TW200301122A

TW200301122A - Kinase inhibitors

Info

Publication number: TW200301122A
Application number: TW91136090A
Authority: TW
Inventors: Qun Li; Keith W Woods; Gui-Dong Zhu; John P Fischer; Jianchun Gong; Tongmei Li; Viraj Gandhi; Sheela A Thomas; Garrick Packard; Xiaohong Song; Jason N Abrams; Robert Diebold; Jurgen Dinges; Charles Hutchins; Vincent S Stoll; Saul H Rosenberg; Vincent L Giranda
Original assignee: Abbott Lab
Priority date: 2001-12-13
Filing date: 2002-12-13
Publication date: 2003-07-01
Also published as: MXPA04005810A; JP2005516927A; AU2002353147A8; EP1463505A2; CA2470214A1; AU2002353147A1

Description

(1) 玖、簽:日月說0I (發明說明應敘明：發明所屬之技術領域、先前技術、内容、實施方式及圖式簡單說明) 技術領域本發明係關於可用於抑制蛋白質激酶之化合物，製造此等化合物之方法，含有此等化合物之組合物，及利用此等化合物之治療方法。先前技術蛋白質激酶已被清楚地証實，在許多因細胞之不適當增生所引致之疾病狀態進展上，係為重要的。已發現此等激酶，在許多過高增生性狀態，譬如癌症中，經常是被提高的。此等激酶在細胞發出訊息上可能是重要的，其中其不適當活化作用會引致細胞增生（例如EGFR、ERBB2、VEGFR 、FGFR、PDGFR、c-Met、IGF-1R、RET、TIE2)。或者，其可能涉及細胞内之訊息轉導（例如c-Src、PKC、Akt、PKA、c-Abl 、PDK-1)。此等訊息轉導基因經常被認為是原致癌基因。許多此等激酶係控制細胞循環進展，在接近G1-S轉變處（例如 Cdk2, Cdk4)，在 G2-M 轉變處（例如 Weel，Mytl，Chkl，Cdc2)，或在纺錘體查核點（Plk，極光體1或2, Bubl或3)。再者，激酶係密切地連接至DNA傷害回應（例如ATM，ATR，Chkl，Chk2)。細胞發出訊息、訊息轉導、細胞循環控制及DN A修補，此等細胞功能之失調，均為過高增生疾病，特別是癌症之正字標記。因此，一或多種激酶之藥理學調制，可能可用於減緩或停止此等疾病中之疾病進展。發明内容在本發明之主要具體實施例中，其係提供式（I)化合物 200301122 (2) R7(1) 玖, Sign: Sun and Moon say 0I (The description of the invention should state: the technical field to which the invention belongs, the prior art, the content, the embodiments, and the schematic description) Technical Field The present invention relates to compounds that can be used to inhibit protein kinases , A method for producing these compounds, a composition containing the compounds, and a method for treating the compounds. Prior art Protein kinases have been clearly demonstrated to be important in the progression of many disease states caused by inappropriate cell proliferation. It has been found that these kinases are often elevated in many hyperproliferative states, such as cancer. These kinases may be important in cell signaling, where inappropriate activation can cause cell proliferation (eg, EGFR, ERBB2, VEGFR, FGFR, PDGFR, c-Met, IGF-1R, RET, TIE2). Alternatively, it may involve intracellular signal transduction (e.g. c-Src, PKC, Akt, PKA, c-Abl, PDK-1). These message-transducing genes are often considered proto-oncogenes. Many of these kinases control cell cycle progression, near G1-S transitions (eg, Cdk2, Cdk4), G2-M transitions (eg, Weel, Mytl, Chkl, Cdc2), or at spindle checkpoints (Plk , Aurora body 1 or 2, Bubl or 3). Furthermore, kinases are tightly linked to DNA damage responses (eg, ATM, ATR, Chkl, Chk2). Cells send messages, message transduction, cell cycle control, and DNA repair. These dysregulations of cell functions are all orthographic signs of hyperproliferative diseases, especially cancer. Therefore, the pharmacological modulation of one or more kinases may be used to slow or stop disease progression in these diseases. SUMMARY OF THE INVENTION In the main embodiment of the present invention, it provides a compound of formula (I) 200301122 (2) R7

(I)，或其治療上可接受之鹽，其中 X係選自包括C(R8)與N ;其中R8係選自包括氫、烷基、胺(I), or a therapeutically acceptable salt thereof, wherein X is selected from the group consisting of C (R8) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, and amine

基、幾基、氯基、鹵基、喪基及酿胺基； X·係選自包括C與N ; Y係選自包括C與N ; YW系選自包括C(R9)與N ;其中R9係選自包括氫與-L2-L3(R3)(R6)； Z係選自包括C與N; 其條件是，X、X’、Y、Y’及Z中之0、1或2個為N; L1係選自包括一個鍵結、-0-、-NR5-、烯基、炔基、-C(O)-、-s-、-s(o)-、-s(o)2-、-s(o)2n(r5)-、-n(r5)s(o)2-、-c(r12)2-、-X, is selected from the group including C and N; Y is selected from the group including C and N; YW is selected from the group including C (R9) and N; R9 is selected from the group consisting of hydrogen and -L2-L3 (R3) (R6); Z is selected from the group consisting of C and N; provided that X, X ', Y, Y' and Z are 0, 1 or 2 Is N; L1 is selected from the group consisting of a bond, -0-, -NR5-, alkenyl, alkynyl, -C (O)-, -s-, -s (o)-, -s (o) 2 -, -S (o) 2n (r5)-, -n (r5) s (o) 2-, -c (r12) 2-,-

C(R12)2N(R5)-、-N(R5)C(0)-及-C(0)N(R5)-;其中各基團係被畫成其左端連接至R1，而其右端連接至芳族環； L2係選自包括一個鍵結、-0-、-C(R12)2-、-S-、-N(R5)-、-N(R5 )C(0)-及-C(0)N(R5)-; L3係選自包括一個鍵結、亞烷基及次烷基，其中亞烷基與次烷基係視情況被一或兩個取代基取代，取代基獨立選自包括烷氧基、胺基、氰基及羥基； R1係選自包括芳基、雜芳基及雜環； R2與R4係獨立為不存在，或選自包括氫、烯基、烷基、 -10- (3) (3)200301122C (R12) 2N (R5)-, -N (R5) C (0)-and -C (0) N (R5)-; where each group is drawn with its left end connected to R1 and its right end connected To aromatic ring; L2 is selected from the group consisting of a bond, -0-, -C (R12) 2-, -S-, -N (R5)-, -N (R5) C (0)-, and -C (0) N (R5)-; L3 is selected from the group consisting of a bond, alkylene, and alkylene, wherein alkylene and alkylene are optionally substituted by one or two substituents, and the substituents are independently selected From alkoxy, amine, cyano and hydroxy; R1 is selected from the group consisting of aryl, heteroaryl and heterocyclic ring; R2 and R4 are independently absent or selected from the group consisting of hydrogen, alkenyl, alkyl, -10- (3) (3) 200301122

炔基、胺基、彡基、芳基炔基、.氰基、氰基埽基、自基、雜芳基、雜環、羥烷基及硝基；或 R2與L1，和彼等所連接之碳原子一起形 #廿、衣選自包括方基、雜方基及雜環；或 R4與L2，和彼等所連接之碳原子一起形芳基、雜芳基及雜環；選自包括其條件是，當L3為亞烷基時，^與。和彼等所連接之碳原子一起形成環，選自包括芳基、雜芳基及雜環； R3為不存在，或選自包括A、芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基垸氧基、雜芳基氧基及雜環； R6係選自包括氫、芳基、芳基烷氧基、芳烷基胺基、芳烷基&基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；其條件是，當L1與L2為鍵結時，R3與R6之至少一個不為氫； R5係選自包括氫、燒基、㈣基、燒基❹基、芳基談籲基、芳基確醯基及雜芳基磺醯基； R為不存在，或選自包括氫、烷基、氰基烯基及-L2-L3(R3)(R6) :或 R7與L1，和彼等所連接之碳原子一起形成環，選自包括芳基、雜芳基及雜環；及各R係選自包括氫、烯基、烷基、炔基、胺基、芳基' 氰基、卣基、雜芳基、雜環及硝基。 -11- (4) 200301122Alkynyl, amine, fluorenyl, arylalkynyl, .cyano, cyanofluorenyl, selfyl, heteroaryl, heterocyclic, hydroxyalkyl, and nitro; or R2 and L1, connected to them The carbon atoms together form # 廿, and the coating is selected from the group consisting of a square group, a heterosquare and a heterocyclic ring; or R4 and L2, together with the carbon atom to which they are attached, form an aryl, a heteroaryl and a heterocyclic ring; The condition is that when L3 is an alkylene group, ^ and. Form a ring with the carbon atoms to which they are attached, selected from the group consisting of aryl, heteroaryl, and heterocyclic ring; R3 is absent or selected from the group consisting of A, aryl, arylalkoxy, and aralkylamino , Aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylfluorenyloxy, heteroaryloxy and heterocyclic ring; R6 is selected from the group consisting of hydrogen, aryl, aryl Alkoxy, aralkylamino, aralkyl &, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy and heterocyclic; The condition is that when L1 and L2 are bonded, at least one of R3 and R6 is not hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, fluorenyl, alkyl, aryl, aryl, and aryl. Fluorenyl and heteroarylsulfonyl; R is absent, or is selected from the group consisting of hydrogen, alkyl, cyanoalkenyl, and -L2-L3 (R3) (R6): or R7 and L1 are connected to each other Carbon atoms together form a ring selected from the group consisting of aryl, heteroaryl, and heterocyclic rings; and each R is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amine, aryl 'cyano, fluorenyl, Heteroaryl, heterocyclic and nitro. -11- (4) 200301122

於另一項具體實施例中本發明係提供式（II)化合物In another embodiment, the present invention provides a compound of formula (II)

R3 或其治療上可接受之鹽，其中係選自包括一個鍵結、•、啊R5)…烯基、炔基、啊R5)C(〇> 及-C(〇)N(R5> ; L係選自包括一個鍵結、、_n(r5)…-離5)c(〇)_及c⑼離5)_ ; _ L3係選自包括一個鍵結、亞烷基及次烷基，其中亞烷基與久'k基係视情況被一或兩個取代基取代，取代基獨立選自包括胺基、氰基及輕基； R1係選自包括芳基、雜芳基及雜環； R2與R4係獨立選自包括氫]希基…决基、芳基決基、胺基、氰基、氰基婦基、自基、羥烷基及雜芳基；其中雜芳基係選自包括呋喃基、吡畊基、噻唑基及噻吩基；或 R2與L1，和彼等所連接之碳原子一起形成環，選自包括_ 二氫说嘻基、p比峻基及苯基；或 R4與L2，和彼等所連接之碳原子一起形成環，選自包括二氫说哈基、苯基、吡啶基及吡咯基；其中環可視情況被酮基取代；其條件是，當L3為亞烷基時，R4與L2和彼等所連接之碳原子一起形成環，選自包括二氫吡咯基、苯基、吡啶基及叶匕洛基；其中環可視情況被酮基取代； -12- 200301122 (5) R3為不存在，或選自包括氫、芳基、芳基烷氧基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環； R6係獨立選自包括氫、芳基、芳基烷氧基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基與雜芳基烷氧基、雜芳基氧基及雜環；其條件是，當L1與L2為键結時，R3與R6之至少一個不為R3 or a therapeutically acceptable salt thereof, which is selected from the group consisting of a bond, •, ah R5) ... alkenyl, alkynyl, ah R5) C (〇 > and -C (〇) N (R5>); L is selected from a group consisting of a bond, _n (r5) ...- Ion 5) c (〇) _ and c⑼Ion 5) _; _ L3 is selected from a group consisting of a bond, alkylene and alkylene, wherein The alkylene group and the Jiu'k group are optionally substituted with one or two substituents, and the substituents are independently selected from the group consisting of amine, cyano, and light group; R1 is selected from the group consisting of aryl, heteroaryl, and heterocyclic; R2 and R4 are independently selected from the group consisting of hydrogen, alkyl, aryl, aryl, alkyl, amine, cyano, cyano, phenyl, hydroxyalkyl, and heteroaryl; wherein heteroaryl is selected from Including furyl, pyryl, thiazolyl, and thienyl; or R2 and L1, together with the carbon atom to which they are attached, form a ring selected from the group consisting of dihydrocarbyl, p-yl, and phenyl; or R4 and L2 form a ring together with the carbon atom to which they are connected, and is selected from the group consisting of dihydrohaloyl, phenyl, pyridyl, and pyrrolyl; wherein the ring may be substituted by a keto group as appropriate; provided that when L3 is For alkylene, R4 and L2 and their The connected carbon atoms together form a ring, selected from the group consisting of dihydropyrrolyl, phenyl, pyridyl, and leafyl; wherein the ring may be substituted by a keto group as appropriate; -12- 200301122 (5) R3 is absent, or selected Including hydrogen, aryl, arylalkoxy, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy and heterocyclic ; R6 is independently selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl and heteroarylalkoxy, heteroaryl Oxygen and heterocyclic ring; provided that when L1 and L2 are bonded, at least one of R3 and R6 is not

氫； R5係選自包括氫、烷基、烷羰基、烷基磺醯基、芳基羰基、芳基磺醯基及雜芳基磺醯基；及 X係選自包括C(R8)與N ;其中R8係選自包括氫、胺基、羧基、氣基及_基。於另一項具體實施例中，本發明係提供式（III)化合物Hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; and X is selected from the group including C (R8) and N ; Wherein R8 is selected from the group consisting of hydrogen, amine, carboxyl, oxo and _. In another embodiment, the present invention provides a compound of formula (III)

L1係選自包括一個鍵結、-0-、-N(R5)-、烯基、炔基及-N(R5 )C(0)-； L2 係選自包括一個键結、-Ο-、-N(R5)-、-N(R5 )C(0)-及-C(0)N(R5)-; L3為次烷基，其中次烷基係被一或兩個獨立選自包括胺基與羥基之取代基取代； R1係選自包括芳基、雜芳基及雜環； R2與R4係獨立選自包括氫與鹵基； -13- 200301122L1 is selected from the group consisting of a bond, -0-, -N (R5)-, alkenyl, alkynyl, and -N (R5) C (0)-; L2 is selected from the group consisting of a bond, -0-, -N (R5)-, -N (R5) C (0)-and -C (0) N (R5)-; L3 is an alkylene group, wherein the alkylene group is independently selected from one or two including amines R1 is selected from the group consisting of aryl, heteroaryl and heterocyclic ring; R2 and R4 are independently selected from the group consisting of hydrogen and halo; -13- 200301122

(6) R3與R6係獨立選自白杠名· 1 包括風、万基、芳基烷氧基及雜芳基 ;其條件{，當L1與L2為鍵結時，r、r6之至少一個不為氫；及 R5係選自包括氫與境基。於另-項具體實施例中，本發明係提供式⑴化合物，其中X係選自包括C(R8)與N，其中r8係選自包括氯、燒基、胺基、幾基、氰基、卣基、輕基及酿胺基；x，係選自包括 C 與 N; Y 為 C; Y，為 c(R9)，其中 R94L2 鄉3)(r6); 2為〇 Li 為烯基；L2係選自包括—個键結、_。_、_c(r12)2·、_s、娜5)_ 、-N(R5)C(〇)-及-C(〇)N(R5)_ ; L3為一個心，或選自包括亞燒基與次燒基，其中亞餘^:冷，A p 1 &、儿基與/人基係視情況被一或兩個取代基取代，取代基獨立選自包括烷氧基、胺基、氰基及羥(6) R3 and R6 are independently selected from white bar names. 1 Including wind, tenyl, arylalkoxy, and heteroaryl; the conditions {when L1 and L2 are bonded, at least one of r and r6 is not Is hydrogen; and R5 is selected from the group consisting of hydrogen and amido. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and r8 is selected from the group consisting of chlorine, alkyl, amine, amino, cyano, Fluorenyl, light and amino; x is selected from the group consisting of C and N; Y is C; Y is c (R9), where R94L2 is 3) (r6); 2 is 〇Li is alkenyl; L2 It is selected from the group consisting of a bond, _. _, _C (r12) 2 ·, _s, Na5) _, -N (R5) C (〇)-and -C (〇) N (R5) _; L3 is a heart, or is selected from the group consisting of alkenylene And secondary alkyl groups, in which the covalent ^: cold, Ap 1 & and phenyl groups are optionally substituted with one or two substituents, the substituents are independently selected from the group consisting of alkoxy, amine, cyano Base and hydroxyl

基，Rl係選自包括菩其 Ν -»·Λ # -ΤΤ V 土 '雜方基及雜環；R2與R4係獨立為不存在，或選自包括氫、婦基、境基、块基、胺基、芳基、芳基块基、氨基、氨基缔基、商基、雜芳基、雜環、經燒基及硝基；R3為不存在，式 Μ …，存在或選自包括氫、芳基、芳基烷R1 is selected from the group consisting of N- »· Λ # -ΤΤ V '' hetero square group and heterocyclic ring; R2 and R4 are independently non-existent, or are selected from the group consisting of hydrogen, feminine, tertiary, and block , Amino group, aryl group, aryl block group, amino group, amino allyl group, commercial group, heteroaryl group, heterocyclic group, alkynyl group and nitro group; R3 is absent, formula M ..., is present or is selected from the group including hydrogen , Aryl, arylalkane

氧基、芳燒基胺基、芳燒其贫I 万烷基硫基、芳氧基、芳硫基、環烷基、㈣基、雜芳基燒氧基、雜芳基氧基及雜環；R6係選自！括：、方基、芳基烷氧基、芳烷基胺基、$烷基硫基、方乳基、芳硫基、環燒基、雜芳基、雜芳基燒氧基、雜 :基乳基及雜環；r5係選自包括冑、燒基、燒幾基 '燒基㈣基：芳基幾基、芳基續酿基及雜芳基績驢l;R7為不存在或選自包括氫、烷基及氰基浠基；及包括氨、缔基、燒基、块基、胺基、芳基自 •14- 200301122Aryl, arylalkylamino, arylthiol-depleted alkylthio, aryloxy, arylthio, cycloalkyl, fluorenyl, heteroaryloxy, heteroaryloxy and heterocyclic ; R6 is selected from! Including :, square, arylalkoxy, aralkylamino, $ alkylthio, square lactyl, arylthio, cycloalkyl, heteroaryl, heteroarylalkyl, hetero: Milk group and heterocyclic ring; r5 is selected from the group consisting of fluorenyl, alkynyl, and alkynyl; alkynyl: aryl, aryl, and aryl; and R7 is absent or selected from Including hydrogen, alkyl, and cyanofluorenyl; and including ammonia, alkenyl, alkynyl, block, amine, and aryl. • 14- 200301122

⑺ 雜芳基、雜環及硝基。於另一項具體實施例中，本發明係提供式⑴化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基、鹵基、羥基及醯胺基；X，係選自包括 C 與 N; Y 為 c; Y’為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ; Z 為 C ; L1 為烯基；L2為; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜環及雜芳基；R2與R4係獨立選自包括氫、埽基、炔基、芳基炔基、胺基、氰基、氰基烯基、i基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吹畊基、者唑基及噻吩基；R3為氫；R6係選自包括氫、芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；及R7為不存在，或選自包括氫、烷基及氰基烯基。於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基、自基、羥基及醯胺基；X，係選自包括 C與 N; Y為 C;Y，為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ; z 為 C ; L1 為晞基；L2為-0- ; L1為烯基；L2為-0- ; L3為次垸基，其中次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri為雜芳基；R2與R4係獨立選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基烯基、卣基、羥燒基及雜芳基，其中雜芳基係選自包括呋喃基、外I： 4基、4峻基及噻吩基；R3為氫；R6係選自包括氫、 -15- 200301122⑺ Heteroaryl, heterocyclic and nitro. In another embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxyl, cyano, and halogen. X, selected from the group consisting of C and N; Y is c; Y 'is C (R9), where R9 is -L2-L3 (R3) (R6); Z is C; L1 is Alkenyl; L2 is; L3 is an alkylene group, wherein the alkylene group is optionally substituted with a substituent, the substituent is selected from the group consisting of alkoxy, amino, cyano and hydroxyl; R1 is selected from the group consisting of aryl, Heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, cyanoalkenyl, iyl, hydroxyalkyl, and heteroaryl, Wherein the heteroaryl group is selected from the group consisting of furanyl, methyl, oxazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamino, and aralkyl Thio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy, and heterocyclic ring; and R7 is absent or is selected from the group consisting of hydrogen, alkyl And cyanoalkenyl. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxy, and cyano. , Self-based, hydroxyl and amido; X is selected from the group consisting of C and N; Y is C; Y is C (R9), where R9 is -L2-L3 (R3) (R6); z is C; L1 is a fluorenyl group; L2 is -0-; L1 is an alkenyl group; L2 is -0-; L3 is a hypofluorenyl group, where the hypocarbyl group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, Amine, cyano and hydroxy; Ri is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, cyanoalkenyl, fluorenyl, hydroxy Alkenyl and heteroaryl, wherein the heteroaryl group is selected from the group consisting of furyl, exo I: 4 group, 4 group and thienyl; R3 is hydrogen; R6 is selected from the group including hydrogen, -15- 200301122

(8) 芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、芳氧基、芳藏基、環燒基、雜芳基、雜芳基燒氧基、雜芳基氧基及雜環，及R3為不存在，或選自包括氫、燒基及氰基婦基。於另一項具體實施例中，本發明係提供式①化合物，其中 X為 N; X，為 c·’ Y 為 C; Y，為 C(R9)，其中 R9 為丄2_L3(R3)(R6) ，Z為C，L1為晞基；L2為; L3為次燒基，其中次挽基係视情況被一個取代基取代，取代基選自包括燒氧基、胺基、氰基及羥基；R1為雜芳基；R2與R4係獨立選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基晞基、鹵基、幾燒基及雜芳基，其中雜芳基係選自包括呋喃基、毗畊基、嘧唑基及嘍吩基；R3為氫；R6為雜芳基；及&7為氫。於另一項具體實施例中，本發明係提供式①化合物，其中X為Ν;且X，為C; γ為C; Υ，為C(R9)，其中，z為c ; L1為晞基；L2為-0- ; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜芳基；R2與R4係獨立選自包括氫、晞基、块基、芳基块基、胺基、氰基、氰基晞基、鹵基、經燒基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嚷唾基及嘍吩基；R3為氫；R6為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基、函基、羥基及醯胺基；且X，係選自包括 C 與 N ; γ 為 c ; Y，為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ; Z 為 C ，L1為缔基；L2為-0- ; L3為一個键結；R1為雜芳基；R2與R4 •16- 2(8) Aryl, arylalkoxy, aralkylamino, aralkylthio, aryloxy, arylzoyl, cycloalkyl, heteroaryl, heteroarylalkyl, heteroaryl Oxy and heterocyclic, and R3 are absent, or are selected from the group consisting of hydrogen, alkyl, and cyano. In another specific embodiment, the present invention provides a compound of formula ①, wherein X is N; X is c · 'Y is C; Y is C (R9), wherein R9 is 丄 2_L3 (R3) (R6 ), Z is C, L1 is fluorenyl; L2 is; L3 is a secondary group, wherein the secondary group is optionally substituted with a substituent, the substituent is selected from the group consisting of alkoxy, amino, cyano and hydroxyl; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, cyanofluorenyl, halo, chicanyl, and heteroaryl, where Heteroaryl is selected from the group consisting of furyl, pyridyl, pyrazolyl, and pyrenyl; R3 is hydrogen; R6 is heteroaryl; and & 7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula ①, wherein X is N; and X is C; γ is C; Υ is C (R9), wherein z is c; L1 is fluorenyl L2 is -0-; L3 is an alkylene group, where the alkylene group is optionally substituted with a substituent selected from alkoxy, amino, cyano, and hydroxyl groups; R1 is a heteroaryl group; R2 And R4 are independently selected from the group consisting of hydrogen, fluorenyl, block, aryl, base, amine, cyano, cyanofluorenyl, halo, fluorenyl, and heteroaryl, wherein heteroaryl is selected from the group consisting of Furanyl, pyrenyl, sialyl, and fluorenyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxy, and cyano. , Functional group, hydroxyl group and amido group; and X is selected from the group consisting of C and N; γ is c; Y is C (R9), where R9 is -L2-L3 (R3) (R6); Z is C , L1 is an allyl group; L2 is -0-; L3 is a bond; R1 is a heteroaryl group; R2 and R4 • 16- 2

係獨互選自包括氫'烯基'块基、芳基炔基、胺基、氰基、氰基烯基、自基、羥烷基及雜芳基，其中雜芳基係選自包括味喃基、响併基、噻唑基及噻吩基；R3為不存在；R6 為雜裱，及R7為不存在，或選自包括氫、烷基及氰基婦基。於另一項具體實施例中，本發明係提供式①化合物，其中 X為 N, X’為 c; Y為 c; Y’為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ，Z為C ; L1為婦基；l2為; L3為一個鍵結；R1為雜芳基 ’ R2與R4為氫；R3為不存在；R6為雜環；及R7為氫。於另一項具體實施例中，本發明係提供式⑴化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基 '自基、羥基及醯胺基；X，係選自包括 C 與 N; Y 為 C; Y’為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ; Z 為 C ; L1 為晞基；L2為-N(R5)C(0)- ; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜環及雜芳基；R2與R4係獨立選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基烯基、南基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、噻唑基及噻吩基；R3為氫；R6係選自包括SL、芳基、芳基燒氧基、芳垸基胺基、芳坑基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；及R7為不存在，或選自包括氫、烷基及氰基烯基。於另一項具體實施例中，本發明係提供式（I)化合物，其中 X為 N;且 X，為 C; Y 為 C; Y，為 C(R9)，其中 R9 為-L2-L3(R3)(R6) -17- 200301122It is independently selected from the group consisting of hydrogen 'alkenyl' block, arylalkynyl, amine, cyano, cyanoalkenyl, self-based, hydroxyalkyl, and heteroaryl, wherein heteroaryl is selected from the group consisting of Weinan R3 is absent; R6 is hetero-framed; and R7 is absent, or is selected from the group consisting of hydrogen, alkyl, and cyanoyl. In another specific embodiment, the present invention provides a compound of formula ①, wherein X is N, X 'is c; Y is c; Y' is C (R9), wherein R9 is -L2-L3 (R3) ( R6), Z is C; L1 is almond; l2 is; L3 is a bond; R1 is heteroaryl 'R2 and R4 are hydrogen; R3 is absent; R6 is heterocyclic; and R7 is hydrogen. In another embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxy, and cyano. X, selected from the group consisting of C and N; Y is C; Y 'is C (R9), where R9 is -L2-L3 (R3) (R6); Z is C; L1 is Fluorenyl; L2 is -N (R5) C (0)-; L3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy, amino, cyano and Hydroxyl; R1 is selected from the group consisting of aryl, heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, south Group, hydroxyalkyl group, and heteroaryl group, wherein the heteroaryl group is selected from the group consisting of furyl, pyryl, thiazolyl, and thienyl; R3 is hydrogen; R6 is selected from the group consisting of SL, aryl, and aryloxy , Arylfluorenylamino, arylpitylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy and heterocyclic ring; and R7 is absent Or selected from the group consisting of hydrogen, alkyl and cyanoalkenyl. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is N; and X is C; Y is C; Y is C (R9), wherein R9 is -L2-L3 ( R3) (R6) -17- 200301122

(ίο) ’ Z為C ’ Ll為晞基；L2為-N(R5)C(〇)- ; L3為次烷基，其中次 &基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri為雜芳基；R2與R4係獨立選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基埽基、自基、#燒基及雜芳基，其中雜芳基係選自包括呋喃基、咐呼基、違峻基及嘧吩基；R3為氫；R6為雜芳基；及r7為氫。於另一項具體實施例中，本發明係提供式⑴化合物，其中 X為 N; X’為 c; Y為 c; Y，為 C(R9)，其中 R9 為-L2-L3(R3)(r6) ，Z為C ; L1為晞基；L2為-N(R5)C(0)'; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為雜芳基；R2與R4係獨立選自包括氫、晞基、块基、芳基炔基、胺基、氰基、氰基晞基、鹵基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吨呼基、嘍唑基及噻吩基；R3為氫；R6為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式①化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基、鹵基、羥基及醯胺基；X，係選自包括 C與 N; Y為 C; Y，為 C(R9)，其中 R9 為丄2 丄 3(r3)(r6); z為 c; L1 為炔基；L2係選自包括一個鍵結、-〇-、c(R12)2-、-S-、-N〇l5；H 、-N(R5 )C(0)-及-C(0)N(R5)- ; L3為一個鍵結，或選自包括亞烷基與次烷基，其中亞烷基與次烷基係視情況被一或兩個取代基取代，取代基獨立選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜芳基及雜環；R2與R4係獨立選 -18- 200301122 (η) 自包括氫、烯基、烷基、炔基、胺基、芳基、芳基块基、氰基、氰基晞基、齒基、雜芳基、雜環、羥烷基及硝基； R3為不存在’或選自包括氫、芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；R6係選自包括氫、芳基、芳基燒氧基、芳:fe基胺基、芳燒基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環’ R5係選自包括氫、fe基、烷羰基、燒基續醯基、芳基羰基、芳基磺醯基及雜芳基磺醯基；R7為不存在，或選自修包括氫、烷基及氰基晞基；及各Rl2係選自包括氫、晞基、烷基、炔基 '胺基、芳基、氰基、鹵基、雜芳基、雜環及硝基。於另一項具體實施例中，本發明係提供式（1)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、垸基、胺基、羧基、氰基、卣基、羥基及醯胺基；X，係選自包括 C 與 Ν;γ 為 C;Y，為 C(r9)，其中 R9 為丄2l3(r3)(r6) ; 2為 c ; Li 為炔基；L2為L3為次烷基，其中次烷基係視情況被一 _ 個取代基取代’取代基選自包括烷氧基、胺基、氰基及幾基，R1係選自包括芳基、雜環及雜芳基；R2與R4係獨立選自包括氫、婦基、決基、芳基炔基、胺基、氰基、氰基缔基、卣基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、咐畊基、噻唑基及噻吩基；R3為氫；R6係選自包括氣、芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基 -19- (12) 及雖環；及R7為不存在，或選自包括氫、虎基及氰基稀基。於另一項具體實施例中，本發明係提供式（1)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基、鹵基、羥基及醯胺基；χ，係選自包括 C 與 Ν; γ為 C; γ，為 C(r9)，其中 r9為仏l3(r3)(r6); qc· ^ 為個鍵結，L2係選自包括一個鍵結、-〇_、_c(r12)2_、$(ίο) 'Z is C' and Ll is a fluorenyl group; L2 is -N (R5) C (〇)-; L3 is an alkylene group, wherein the & group is optionally substituted with a substituent, and the substituent is selected from Including alkoxy, amine, cyano and hydroxyl; Ri is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, and cyanofluorenyl , Self-based, #alkynyl and heteroaryl, wherein the heteroaryl system is selected from the group consisting of furyl, alkyl, phenyl, and pyrenyl; R3 is hydrogen; R6 is heteroaryl; and r7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula VII, wherein X is N; X 'is c; Y is c; Y is C (R9), wherein R9 is -L2-L3 (R3) ( r6), Z is C; L1 is a fluorenyl group; L2 is -N (R5) C (0) '; L3 is an alkylene group, wherein the alkylene group is optionally substituted with a substituent, and the substituent is selected from the group including alkane Oxy, amine, cyano and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, block, arylalkynyl, amine, cyano, cyanofluorenyl, halogen Group, hydroxyalkyl group, and heteroaryl group, wherein the heteroaryl group is selected from the group consisting of furyl, tolyl, oxazolyl, and thienyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxy, cyano, and halogen. X, selected from the group consisting of C and N; Y is C; Y is C (R9), where R9 is 丄 2 丄 3 (r3) (r6); z is c; L1 is Alkynyl; L2 is selected from the group consisting of a bond, -0-, c (R12) 2-, -S-, -N0l5; H, -N (R5) C (0)-, and -C (0) N (R5)-; L3 is a bond, or is selected from the group consisting of alkylene and alkylene, wherein alkylene and alkylene are optionally substituted with one or two substituents, and the substituents are independently selected from Alkoxy, amine, cyano and hydroxyl; R1 is selected from the group consisting of aryl, heteroaryl and heterocyclic ring; R2 and R4 are independently selected -18- 200301122 (η) from hydrogen, alkenyl, alkyl, Alkynyl, amine, aryl, aryl block, cyano, cyanofluorenyl, dentyl, heteroaryl, heterocyclic, hydroxyalkyl and nitro; R3 is absent 'or selected from the group consisting of hydrogen, Aryl, arylalkoxy, aralkylamino, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, Arylalkoxy, heteroaryloxy and heterocyclic ring; R6 is selected from the group consisting of hydrogen, aryl, arylalkyloxy, aryl: feamino, arylthio, aryloxy, arylthio Group, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy and heterocycle 'R5 is selected from the group consisting of hydrogen, fe, alkyl, alkynyl, fluorenyl, arylcarbonyl, aryl R7 is absent, or is selected from the group consisting of hydrogen, alkyl, and cyanofluorenyl; and each R12 is selected from the group consisting of hydrogen, fluorenyl, alkyl, and alkynyl'amine Aryl, aryl, cyano, halo, heteroaryl, heterocyclic and nitro. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, fluorenyl, amine, carboxy, and cyano. , Fluorenyl, hydroxy, and fluorenylamino; X is selected from the group consisting of C and N; γ is C; Y is C (r9), where R9 is 丄 2113 (r3) (r6); 2 is c; Li is Alkynyl; L2 is L3 is an alkylene group, wherein the alkylene group is optionally substituted with one or more substituents. The substituent is selected from the group consisting of alkoxy, amino, cyano and several groups, and R1 is selected from the group consisting of aromatic R2 and R4 are independently selected from the group consisting of hydrogen, feminyl, decyl, arylalkynyl, amine, cyano, cyano, fluorenyl, hydroxyalkyl, and heteroaryl R6 is selected from the group consisting of furyl, aryl, thiazolyl, and thienyl; R6 is hydrogen; R6 is selected from the group consisting of Alkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy-19- (12) and although cyclic; and R7 is absent, or It is selected from the group consisting of hydrogen, tiger and dicyano. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxy, and cyano. , Halo, hydroxyl and amido; χ is selected from the group consisting of C and N; γ is C; γ is C (r9), where r9 is 仏 l3 (r3) (r6); qc · ^ is a bond Knot, L2 is selected from the group consisting of a bond, -〇_, _c (r12) 2_, $

、-N(R5)_、_N(R5)C(0)_ 及 _C(0)N(R5)_ ; p 為一個鍵結或選自包括亞烷基與次烷基，其中亞烷基與次烷基係視情況被一或兩個取代基取代，取代基獨立選自包括烷氧基、胺基' 氰基及羥基；Rl係選自包括芳基、雜芳基及雜環；^與Μ 烯基、烷基、炔基烯基、卣基、雜芳，或選自包括氫、 '胺基、芳基、芳基、雜環、經燒基芳基、芳基烷氧基係獨立選自包括氫、基炔基、氰基、氰基及硝基；R3為不存在, -N (R5) _, _N (R5) C (0) _ and _C (0) N (R5) _; p is a bond or is selected from the group consisting of alkylene and alkylene, wherein alkylene And alkylene are optionally substituted by one or two substituents, the substituents are independently selected from the group consisting of alkoxy, amino 'cyano and hydroxyl; R1 is selected from the group consisting of aryl, heteroaryl and heterocyclic; With M alkenyl, alkyl, alkynyl alkenyl, fluorenyl, heteroaryl, or selected from the group consisting of hydrogen, 'amino, aryl, aryl, heterocyclic, alkynylaryl, arylalkoxy Independently selected from the group consisting of hydrogen, alkynyl, cyano, cyano and nitro; R3 is absent

、芳fe基胺基、芳烷基硫基、芳氧基、芳硫基、環燒基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；％係選自包括氫、芳基、芳基烷氧基、芳烷基胺基 '芳燒基碎其、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；R5係選自包括氫、烷基、烷羰基、燒基續酿基、芳基羰基、芳基磺醯基及雜芳基磺醯基；R7為不存在，或選自包括氫、烷基及氰基晞基；及各Ri 2係選自包括氫、烯基、烷基、炔基、胺基、芳基、氰基、南基、雜芳基、雜環及硝基。於另一項具體實施例中，本發明係提供式①化合物，其中X係選自包括C(R8)與N ,其中R8係選自包括氫、烷基、 -20- 200301122 (13) 股基、幾基、氣基、齒基、喪基及酶胺基；且χι係選自包括 C與 Ν; γ為 c; Y，為 C(R9)，其中 R9 為-L2-L3(r3)(r6) ; z 為 c ’ Ll為一個鍵結；L2為-Ο- ; L3為次燒基，其中次烷基係視情況被_個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜環及雜芳基；#與R4 係獨立選自包括氫、婦基、炔基、芳基炔基、胺基'氨基氣基缔基、鹵基、基及雜芳基，其中雜芳基係選自包括吱喃基、吡畊基、噻唑基及嘍吩基；R3為氫；R6係選自包括氫、芳基、芳基、燒氧基、芳垸基胺基、芳燒基硫基_ 、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；及R7為不存在，或選自包括氫、烷基及葡1基婦基。於另一項具體實施例中，本發明係提供式（1)化合物，其中 X為 N; X，為 C; Y 為 C; γ’ 為 C(r9),其中 R9 為-L2 七3(r3)(r6) ;z為c ; L1為一個鍵結；]^為; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為雜芳基；R2與R4係獨立選自包括_ 風、婦基、決基、芳基炔基、胺基、氰基、氰基晞基、鹵基、^ 基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘍唑基及喳吩基；R3為氫；R6為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（1)化合物，其中 X為 NUC; Y 為 c; γ’為 c(r9)，其中 r9 為·l2.l3(r3)(r6) ’ Z為C ’ L為個鍵結；L2為-ο- ; L3為次烷基，其中次烷基係視隋況被一個取代基取代，$代基選自包括烷氧基、 -21 - 200301122, Arylfeamino, arylalkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy and heterocyclic ring;% is selected from the group consisting of Hydrogen, aryl, arylalkoxy, aralkylamino, aralkyl, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy And heterocycle; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkynyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R7 is absent, or is selected from Hydrogen, alkyl, and cyanofluorenyl; and each Ri 2 is selected from the group consisting of hydrogen, alkenyl, alkyl, alkynyl, amine, aryl, cyano, south, heteroaryl, heterocyclic, and nitro . In another specific embodiment, the present invention provides a compound of formula (1), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, -20- 200301122 (13) , Aryl, aryl, dentate, benzyl, and enzyme amine; and χι is selected from the group consisting of C and N; γ is c; Y is C (R9), where R9 is -L2-L3 (r3) ( r6); z is c 'Ll is a bond; L2 is -0-; L3 is a secondary alkyl group, wherein the alkylene group is optionally substituted with one substituent, and the substituent is selected from alkoxy and amine groups , Cyano and hydroxy; R1 is selected from the group consisting of aryl, heterocyclic and heteroaryl; # and R4 are independently selected from the group consisting of hydrogen, feminyl, alkynyl, arylalkynyl, amino and amino , Halo, aryl, and heteroaryl, wherein heteroaryl is selected from the group consisting of uranyl, pyryl, thiazolyl, and fluorenyl; R3 is hydrogen; R6 is selected from including hydrogen, aryl, aryl, Oxyalkyl, arylamino, arylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryloxy and heterocycle; and R7 is absent, or is selected from the group consisting of hydrogen, alkyl and glucosyl. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is N; X is C; Y is C; γ 'is C (r9), wherein R9 is -L2 seven 3 (r3 ) (r6); z is c; L1 is a bond;] ^ is; L3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy, amine, Cyano and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of: wind, feminyl, decanyl, arylalkynyl, amine, cyano, cyanofluorenyl, halo, ^ and Heteroaryl, wherein the heteroaryl system is selected from the group consisting of furyl, pyrenyl, oxazolyl, and fluorenyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is NUC; Y is c; γ 'is c (r9), where r9 is · 12.l3 (r3) (r6)' Z is C ′ L is a bond; L2 is -ο-; L3 is an alkylene group, wherein the alkylene group is substituted by a substituent as appropriate, and the $ -substituted group is selected from alkoxy, -21-200301122

(14) 胺基、氰基及羥基；Rl為雜芳基；“與尺4係獨立選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基婦基、鹵基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘍唑基及嘧吩基；R3為氫；R6為雜芳基；及R7為氫。於另一項具體實施例中，本發明係提供式⑴化合物，其中X係選自包括C(R8)與N，其中R8為氫；χ，為Ν; γ為c; γ, 為 C(R9) ’ 其中 R9 為-L2-L3(R3)(R6) ; ζ 為 C ; L1為一個鍵結；L2 為-0- ; L3為次：fe基’其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜鲁芳基；R2與R4係獨jl選自包括氫、烯基、炔基、芳基炔基、胺基、氰基、氰基缔基、鹵基、經垸基及芳基，其中雜芳基係選自包括呋喃基、吡畊基、噻唑基及嘍吩基；R3為氫；R6為雜芳基；及R7為不存在。於另一項具體實施例中，本發明係提供式⑴化合物，其中 X為 N; X’為 C; Y為 N; Y，為 c(R9)，其中 R9 為-L2-L3(R3)(R6) ;Z為C ; L1為一個鍵結；l2為; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、φ 胺基、氰基及羥基；R1為雜芳基；R2為不存在；R4係選自包括氫、烯基、炔基、芳基炔基、胺基、氰基、氰基缔基、鹵基、輕燒基及芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘍唑基及噻吩基；R3為氫；R6為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（I)化合物，其中 X為 N; X’為 C; Y 為 N; γ，為 c(R9)，其中 R9 為-L2-L3(R3)(r6) ;Z為C ; L1為一個鍵結；l2為; L3為次烷基，其中次烷 •22- 200301122(14) Amine, cyano, and hydroxyl; R1 is heteroaryl; "independently from the Chi 4 system is selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, cyanoyl, Halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrargyl, oxazolyl, and pyrenyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula ⑴, wherein X is selected from the group consisting of C (R8) and N, where R8 is hydrogen; χ is N; γ is c; γ is C (R9) 'Where R9 is -L2-L3 (R3) (R6); ζ is C; L1 is a bond; L2 is -0-; L3 is sub-: fe-based' where the alkylene is optionally substituted with a substituent The substituent is selected from alkoxy, amine, cyano and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from hydrogen, alkenyl, alkynyl, arylalkynyl, amine, Cyano, cyano, halo, fluorenyl, and aryl, wherein the heteroaryl group is selected from the group consisting of furyl, pyrargyl, thiazolyl, and fluorenyl; R3 is hydrogen; R6 is heteroaryl; And R7 is absent. In another specific embodiment, the present invention is Provide a compound of formula ⑴, where X is N; X 'is C; Y is N; Y is c (R9), where R9 is -L2-L3 (R3) (R6); Z is C; L1 is a bond L2 is; L3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy, φ amino, cyano and hydroxyl; R1 is a heteroaryl; R2 is not Exist; R4 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amine, cyano, cyano, halo, alkynyl, and aryl, wherein heteroaryl is selected from the group including furan R3 is hydrogen; R6 is aryl; and R7 is hydrogen. In another embodiment, the present invention provides a compound of formula (I), wherein X is N X 'is C; Y is N; γ is c (R9), where R9 is -L2-L3 (R3) (r6); Z is C; L1 is a bond; l2 is; L3 is an alkylene group , Of which tane • 22- 200301122

(15) 基係視情況被一個取代基取代，.取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜芳基；R2為不存在；R4係選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基烯基、自基、經燒基及芳基，其中雜芳基係選自包括呋喃基、外匕’基、違峻基及嘍吩基；R3為氫；R6為雜芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（1)化合物，其中X為C(R8)，其中R8為氫；Xf為c ; γ為N ; Y，為c(R9),其中 R9為-L2-L3(R3)(R6) ; Z為C ; L1為一個鍵結；L2為办；L3為次燒基，其中/人fe基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri為雜芳基；R2為不存在；R4係選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基烯基、自基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、噻唑基及噻吩基；R3為氫；R0 為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式①化合物，其中X為C(R8)，其中R8為氫；X，為C ; γ為Ν ; γ，為c(R9)，其中 R9 為-L2-L3(R3)(r6) ; Z 為 C ; Ll 為一個鍵結；^為 _〇· ; l3 為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為雜芳i ; r2為不存在；R4係選自包括氫、缔基、炔基1基炔基、胺基' 氰基、氰基晞基、卣基、羥烷基及芳基，纟中雜芳基係選自包括呋喃基、吡啼基、嘍唑基及噻吩基；y為氫；Μ為雜芳基；及R7為氫。 -23- 200301122 (16)(15) The base is optionally substituted with a substituent. The substituent is selected from the group consisting of alkoxy, amino, cyano, and hydroxyl; R1 is heteroaryl; R2 is absent; R4 is selected from the group consisting of hydrogen and fluorene Alkynyl, alkynyl, arylalkynyl, amine, cyano, cyanoalkenyl, self-radical, alkynyl, and aryl, wherein the heteroaryl group is selected from the group consisting of furyl, exonyl, and acetyl And fluorenyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is C (R8), where R8 is hydrogen; Xf is c; γ is N; Y is c (R9), where R9 -L2-L3 (R3) (R6); Z is C; L1 is a bond; L2 is an office; L3 is a secondary group, where the / human fe group is optionally substituted by a substituent, and the substituent is selected from Including alkoxy, amine, cyano, and hydroxyl; Ri is heteroaryl; R2 is absent; R4 is selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, and cyano Alkenyl, self-based, hydroxyalkyl, and heteroaryl, wherein the heteroaryl group is selected from the group consisting of furyl, pyrargyl, thiazolyl, and thienyl; R3 is hydrogen; R0 is aryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula ①, wherein X is C (R8), wherein R8 is hydrogen; X, is C; γ is N; γ is c (R9), wherein R9 is -L2-L3 (R3) (r6); Z is C; Ll is a bond; ^ is _〇 ·; l3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, and the substituent is selected from Including alkoxy, amine, cyano and hydroxyl; R1 is heteroaryl i; r2 is absent; R4 is selected from the group consisting of hydrogen, alkenyl, alkynyl 1-alkynyl, amine 'cyano, cyano Group, fluorenyl group, hydroxyalkyl group, and aryl group. The heteroaryl group in fluorene is selected from the group consisting of furyl, pyridyl, oxazolyl, and thienyl; y is hydrogen; M is heteroaryl; -23- 200301122 (16)

於另一項具體實施例中，本發明係提供式（i)化合物，其中X為C(R8)，其中R8為氫；X為c ; Y為N ; Y，為C(R9)，其中 R9 為-L2L3(R3)(R6) ; Z 為 N ; L1 為一個鍵結；l2 為-0- ; L3 為次烷基，其中次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜芳基；R4為不存在；R2係選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基晞基、鹵基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘍唑基及噻吩基；R3為氫；R6 為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（I)化合物，其中X為C(R8)，其中R8為氫；X，為c ; γ為N ; γ’為C(R9)，其中 R9 為-L2-L3(R3)(R6) ; Z 為 N ; L1為一個鍵結；L2為; L3 為次境基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜芳基；R4為不存在；R2係選自包括氫、晞基、炔基、芳基炔基、胺基、氰基 '氰基烯基、齒基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡喷基、嘧唑基及p塞吩基；R3為氫；Μ 為雜芳基；及R7為氫。於另項具體實施例中，本發明係提供式（I)化合物，其中X為N ; X’為C ; Y為Ν ; γ，為C(R9)，其中R9為丄2丄3(r3)(r6) ，Z為n ; L1為一個鍵結；L2為L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜芳基；R4為不存在；R2係選自包括氫、烯基、炔基、芳基炔基、胺基、氰基、氰基烯基 -24- (17) 、鹵基、喪燒基及芳基，其中雜芳基係選自包括吱喃基、吡畊基、嘍唑基及嘧吩基；R3為氫；R6為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（I)化合物，其中 X為 N; X’為 c; Y 為 N; Y’為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ;Z為N ; L1為一個鍵結；L2為; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為雜芳基；R4為不存在；R2係選自包括氫、晞基、炔基、芳基炔基、胺基、氰基、氰基烯基、鹵基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘧唑基及p塞吩基；R3為氫；R6為雜芳基；及R7 為氫。於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、幾基、氰基、函基、輕基及醯胺基；X，係選自包括 C 與 N,· Y 為 C; Y’為 C(R9)，其中 R9 為 _L2-L3(R3)(R6); z 為-C-; Ll 為一個鍵結，L2為-N(R5)- ; L3為次统基，其中次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氛基及^基；R1係選自包括芳基、雜環及雜芳基；R2與R4係獨立選自包括氫、烯基、決基、芳基炔基、胺基、氰基、氰基晞基、i基、經烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘧唑基及噻吩基；R3為氫；R5係選自包括風、燒基、燒幾基、：基橫醯基、芳基羰基、芳基橫醯基及雜芳基磺醯基；R6係選自包括氫、芳基、芳基燒氧基、芳烷基胺基、芳燒基硫基、芳氧基、芳硫基、環燒基 200301122 (18) '雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；及R7為不存在’或選自包括氫、垸基及氰基烯基。於另一項具體實施例中，本發明係提供式①化合物，其中 X為 N; X’ 為 C; Y為 c; Yt 為 C(R9),其中 R9 為 _L2_L3(R3)(R6) ’ Z為C ; L1為一個鍵結；L2為-n(r5)-; l3為次烷基，其中次 fe基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為雜芳基；R2與R4係獨立選自包括氫、烯基、炔基、芳基块基、胺基、氰基、氰基晞基、画基為纟元基及雜务基，其中雜芳基係選自包括咬喃基、外匕呼基、噻唑基及噻吩基；R3為氫；R5係選自包括氫、烷基、：fe羰基、烷基磺醯基、芳基羰基、芳基磺醯基及雜芳基橫醯基；R6為雜芳基；及！^為氫。於另一項具體實施例中，本發明係提供式⑴化合物，其中 X為 N; X’為 C; Y 為 c; Y，為 C(R9)，其中 R9 為-L2-L3(R3)(R6) ;Z為C ; L1為一個鍵結；l2為-; l3為次烷基，其中次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri為雜芳基；R2與R4係獨立選自包鲁括氫、烯基、炔基、芳基炔基、胺基、氰基、氰基缔基、鹵基、羥燒基及雜芳基，其中雜芳基係選自包括呋喃基、吡哜基、噻唑基及喳吩基；R3為氫；R5係選自包括氫、烷基、烷羰基、烷基磺醯基、芳基羰基、芳基磺醯基及雜芳基磺醯基；R6為芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、燒基、 -26- (19)In another specific embodiment, the present invention provides a compound of formula (i), wherein X is C (R8), where R8 is hydrogen; X is c; Y is N; Y is C (R9), where R9 -L2L3 (R3) (R6); Z is N; L1 is a bond; l2 is -0-; L3 is an alkylene group, where the alkylene group is optionally substituted with a substituent, and the substituent is selected from the group consisting of Alkoxy, amine, cyano and hydroxyl; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amine, cyano, and cyanofluorene R3 is hydrogen; R6 is aryl; and R7 is hydrogen. Heteroaryl is selected from the group consisting of furyl, pyrido, oxazolyl, and thienyl, halo, hydroxyalkyl, and heteroaryl. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is C (R8), wherein R8 is hydrogen; X, is c; γ is N; γ 'is C (R9), wherein R9 is -L2-L3 (R3) (R6); Z is N; L1 is a bond; L2 is; L3 is a subsitu group, wherein the alkylene group is optionally substituted with a substituent, and the substituent is selected from the group consisting of Alkoxy, amine, cyano, and hydroxyl; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amino, and cyano'cyanoene R3 is hydrogen; M is a heteroaryl group; and R7 is a heteroaryl group selected from the group consisting of furyl, pyrhexyl, pyrazolyl, and p-sphenyl. hydrogen. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is N; X 'is C; Y is N; γ is C (R9), wherein R9 is 丄 2 丄 3 (r3) (r6), Z is n; L1 is a bond; L2 is L3 is an alkylene group, wherein the alkylene group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, amino, cyano and Hydroxy; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amine, cyano, cyanoalkenyl-24- (17), halo , Benzyl, and aryl, wherein the heteroaryl group is selected from the group consisting of uranyl, pyryl, oxazolyl, and pyrenyl; R3 is hydrogen; R6 is aryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is N; X 'is c; Y is N; Y' is C (R9), wherein R9 is -L2-L3 (R3 ) (R6); Z is N; L1 is a bond; L2 is; L3 is an alkylene group, where the alkylene group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy, amino, and cyano And hydroxy; R1 is heteroaryl; R4 is absent; R2 is selected from the group consisting of hydrogen, fluorenyl, alkynyl, arylalkynyl, amino, cyano, cyanoalkenyl, halo, and hydroxyalkyl And heteroaryl, wherein the heteroaryl group is selected from the group consisting of furyl, pyrargyl, pyrazolyl, and p-sphenyl; R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amino, aryl, cyano X, selected from the group consisting of C and N, and Y is C; Y 'is C (R9), where R9 is _L2-L3 (R3) (R6); z Is -C-; Ll is a bond, L2 is -N (R5)-; L3 is a secondary group, where the secondary group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy and amine R2 and R4 are independently selected from the group consisting of aryl, heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, decanyl, arylalkynyl, amine, cyano, and cyano Sulfonyl, i-based, alkyl and heteroaryl, wherein the heteroaryl group is selected from the group consisting of furyl, pyrargyl, pyrazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of wind and alkyl Benzyl, phenyl, sulfonyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamino, Arylthio, aryloxy, arylthio, cycloalkyl200301122 (18) 'heteroaryl Alkoxy, heteroaryl, heteroaryloxy and heterocyclyl; and R7 is absent 'or selected from the group consisting of hydrogen, alkyl with alkenyl group and a cyano group. In another specific embodiment, the present invention provides a compound of formula ①, wherein X is N; X 'is C; Y is c; Yt is C (R9), wherein R9 is _L2_L3 (R3) (R6)' Z is C; L1 is a bond; L2 is -n (r5)-; l3 is an alkylene group, wherein the hypofeline group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, amine, Cyano and hydroxy; R1 is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, aryl block, amine, cyano, cyanofluorenyl, and fluorenyl radicals; A heterogeneous group, wherein the heteroaryl group is selected from the group consisting of sulfanyl, exoyl, thiazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, fecarbonyl, and alkylsulfonyl , Arylcarbonyl, arylsulfonyl, and heteroarylphosphonium; R6 is heteroaryl; and! ^ Is hydrogen. In another specific embodiment, the present invention provides a compound of formula VII, wherein X is N; X 'is C; Y is c; Y is C (R9), wherein R9 is -L2-L3 (R3) ( R6); Z is C; L1 is a bond; l2 is-; l3 is an alkylene group, wherein the alkylene group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, amino, and cyano And hydroxy; Ri is heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amine, cyano, cyano, halo, hydroxy, and Heteroaryl, where heteroaryl is selected from the group consisting of furyl, pyrido, thiazolyl, and fluorenyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aromatic Carbonyl, arylsulfonyl and heteroarylsulfonyl; R6 is aryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, wherein R8 is selected from the group consisting of hydrogen, alkyl, -26- (19)

胺基、羧基、氰基、鹵基、輕基及酿胺基；X，係選自包括 C 與 N ; Y 為 c ; Y，為 C(R9)，其中 r9為丄2-L2(R3)(r6) ; Z 為 C ; L1 為一個鍵結；L2為-N(R5)C(〇)- ; l3為次烷基’其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜環及雜芳基；R2與 R4係獨立選自包括氫、晞基、決基、芳基炔基、胺基、氰基、氰基晞基、i基、羥烷基及雜芳基，其中雜芳基係選自包括吱喃基、吡畊基、嘍唑基及噻吩基；R3為氫；R6係選自包括氫、芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；及R7為不存在，或選自包括氫、烷基及氰基埽基。於另一項具體實施例中，本發明係提供式⑴化合物，其中 X 為 N ; X，為 C，· Y 為 C ; γ，為 C(R9)，其中尺9為 l2_l3(r3)(r6) ;Z為C ; L1為一個鍵結；[2為-N(r5)c(〇> ; l3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl為雜芳基；¥與Μ係獨立選自包括氫、晞基、故其、. 庆基、芳基炔基、胺基、氰基、氰基烯基、鹵基、經垸基及雜名 .^ ® #基’其中雜芳基係選自包括呋喃基、外匕口井基、喧唏其芬+ 、，亡生基及嚯吩基；R3為氫；R6為雜芳基；及 R7為氫。於另^具體實施例中，本發明係提供式(I)化合物，其中X為N，X為c，γ為c; γ，為c(r9卜其中r9為丄2丄»讲6) ,Z為C , L為一個鍵結；L2為啊r5似〇)_; a為次烷基，其 200301122Amino, carboxyl, cyano, halo, light and amino; X is selected from the group consisting of C and N; Y is c; Y is C (R9), where r9 is 丄 2-L2 (R3) (r6); Z is C; L1 is a bond; L2 is -N (R5) C (〇)-; 13 is an alkylene group, wherein the alkylene group is optionally substituted with a substituent, and the substituent is selected from Including alkoxy, amine, cyano and hydroxyl; R1 is selected from the group consisting of aryl, heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, decanyl, arylalkynyl, amine Group, cyano group, cyanofluorenyl group, i group, hydroxyalkyl group, and heteroaryl group, wherein the heteroaryl group is selected from the group consisting of uranyl, pyrargyl, oxazolyl, and thienyl; R3 is hydrogen; R6 is Selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamino, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, hetero Aryloxy and heterocyclic; and R7 is absent or is selected from the group consisting of hydrogen, alkyl and cyanofluorenyl. In another specific embodiment, the present invention provides a compound of formula (I), where X is N; X is C, and Y is C; γ is C (R9), where rule 9 is l2_l3 (r3) (r6 ); Z is C; L1 is a bond; [2 is -N (r5) c (0 >; l3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, and the substituent is selected from the group including Alkoxy, amine, cyano and hydroxy; R1 is heteroaryl; ¥ and M are independently selected from the group consisting of hydrogen, fluorenyl, and so on. Qing, arylalkynyl, amine, cyano, and cyano Alkenyl, halo, fluorenyl, and miscellaneous. ^ ® # 基 'Wherein the heteroaryl group is selected from the group consisting of furyl, exoyl, molybdenyl +, phenyl, and phenylphenyl R3 is hydrogen; R6 is heteroaryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is N, X is c, γ is c; γ, is c (r9, where r9 is 丄 2 丄 »Speaking 6), Z is C, L is a bond; L2 is ah, and r5 is like 0) _; a is an alkylene group, which is 200301122

(20) 中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及經基；Rl為雜芳基；R2與R4係獨立選自包括氫、烯基、炔基、芳基炔基、胺基、氰基、氰基缔基、鹵基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基 '嘍唑基及噻吩基；R3為氫；R6為芳基；及R7(20) The middle alkylene group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, amine, cyano, and meridian; R1 is heteroaryl; R2 and R4 are independently selected from hydrogen, Alkenyl, alkynyl, arylalkynyl, amine, cyano, cyano, alkynyl, halo, hydroxyalkyl, and heteroaryl, wherein the heteroaryl group is selected from the group consisting of furyl, pyridyl 'oxazole And thienyl; R3 is hydrogen; R6 is aryl; and R7

於另一項具體實施例中，本發明係提供式（1)化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、In another specific embodiment, the present invention provides a compound of formula (1), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl,

胺基、羧基、氰基、卣基、羥基及醯胺基；X，係選自包括 C 與 N; Y為 C，Y’為 C(R9)，其中妒為 l2_l3(r3)(r6) ; z 為 c ; l1 為-N(R5)-; L2 係選自包括一個鍵結、_〇·、_c(Rl 2 _、各、_n(r5 >Amine group, carboxyl group, cyano group, fluorenyl group, hydroxy group, and fluorenylamino group; X is selected from the group consisting of C and N; Y is C, and Y 'is C (R9), wherein jealousy is l2-l3 (r3) (r6); z is c; l1 is -N (R5)-; L2 is selected from the group consisting of a bond, _〇 ·, _c (Rl 2 _, each, _n (r5 >

、-N(R5)C(0)-及-C(0)N(R5)- ; L3為一個鍵結，或選自包括亞烷基與次烷基，其中亞烷基與次烷基係視情況被一或兩個取代基取代，取代基獨立選自包括烷氧基、胺基、氰基及羥基，R1係選自包括芳基、雜芳基及雜環；R2與R4係獨立選 2包括氫、晞基、烷基、炔基、胺基、芳基、芳基炔基、' 氰3基、氰基烯基、自基、雜芳基、雜環、#烷基及硝基； R為不存在，或選自包括氫、芳基、芳基烷氧基、芳烷基胺2、芳烷基硫基、芳氧基、芳硫基、環烷基、雜芳基、雜万基烷氧基、雜芳基氧基及雜環；％係選自包括氫、芳基、芳f境氧基、芳燒基胺基、芳燒基硫基、芳氧基、芳硫基、％烷基、雜芳基、雜芳基烷氧基、#芳基氧基及雜環；R5係:選自包括氯、烷基、烷羰基、烷基磺醯基、芳基羰基万基飧醯基及雜芳基磺醯基；R7為不存在，或選 -28- 200301122, -N (R5) C (0)-and -C (0) N (R5)-; L3 is a bond, or is selected from the group consisting of alkylene and alkylene, wherein alkylene and alkylene are Optionally substituted by one or two substituents, the substituents are independently selected from the group consisting of alkoxy, amine, cyano and hydroxyl, R1 is selected from the group consisting of aryl, heteroaryl and heterocyclic ring; R2 and R4 are independently selected 2 Including hydrogen, fluorenyl, alkyl, alkynyl, amine, aryl, arylalkynyl, 'cyano 3, cyanoalkenyl, self-based, heteroaryl, heterocyclic, #alkyl, and nitro R is absent, or is selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamine 2, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, hetero Vanyl alkoxy, heteroaryloxy and heterocyclic ring;% is selected from the group consisting of hydrogen, aryl, aryloxy, arylalkylamino, arylthio, aryloxy, arylthio ,% Alkyl, heteroaryl, heteroarylalkoxy, #aryloxy and heterocyclic ring; R5 series: selected from the group consisting of chlorine, alkyl, alkylcarbonyl, alkylsulfonyl, and arylcarbonylwanyl Fluorenyl and heteroarylsulfonyl; R7 is absent, or select -28- 200301122

(21) 匕括氫、基及氰基烯基；及各Rl 2係選自包括氫、晞基、烷基、炔基、胺基、芳基、氰基、鹵基、雜芳基、雜環及硝基。於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(R8)與N ,其中R8係選自包括氫、烷基、胺基、幾基、氰基、卣基、羥基及醯胺基；χ，係選自包括 C與 N，γ為 c; Y’為 C(R9) ’ 其中 R9 為丄2 丄3(R3)(R6) ; z 為 C ; L1 為-N(R5)- ; L2為-a ; L3為次烷基，其中次烷基係視情況被一個取代基取代’取代基選自包括烷氧基、胺基、氰基及經· 基，R1係選自包括芳基、雜環及雜芳基；R2與R4係獨立選自包括氫、烯基、炔基、芳基炔基、胺基 '氰基、氰基晞基、齒基、羥烷基及芳基，其中雜芳基係選自包括呋喃基、咐畊基、噻唑基及4吩基；R3為氫；R5係選自包括氫、 $元基、燒談基、烷基績醯基、芳基羰基、芳基橫醯基及雜芳基磺醯基；R6係選自包括氫、芳基、芳基烷氧基、芳烷基胺基、芳燒基硫基、芳氧基、芳疏基、環燒基、雜芳基 '雜芳基烷氧基、雜芳基氧基及雜環；及R7為不存在，或 · 選自包括氫、燒基及氰基晞基。於另一項具體實施例中，本發明係提供式⑴化合物，其中 X為 N; X 為 C; Y 為 C; Y’ 為 C(R9)，其中 R9 為丄2-L3(R3)(R6) ’ Z為C ; L1為-N(R5; L2為-0- ; L3為次燒基，其中次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜環及雜芳基；R2與 R4係獨立選自包括氫、婦基、炔基、芳基炔基、胺基、氰 -29- 20030Π22(21) hydrogen, aryl, and cyanoalkenyl; and each R12 is selected from the group consisting of hydrogen, fluorenyl, alkyl, alkynyl, amine, aryl, cyano, halo, heteroaryl, hetero Ring and nitro. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amino, amino, cyano卣, selected from the group consisting of C and N, γ is c; Y 'is C (R9)' where R9 is 丄 2 丄 3 (R3) (R6); z is C L1 is -N (R5)-; L2 is -a; L3 is an alkylene group, wherein the alkylene group is optionally substituted with a substituent; the substituent is selected from the group consisting of alkoxy, amino, cyano and · R1 is selected from the group consisting of aryl, heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amino'cyano, cyanofluorenyl, Dentyl, hydroxyalkyl, and aryl, where heteroaryl is selected from the group consisting of furyl, phenyl, thiazolyl, and 4-phenyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, phenyl, and alkyl , Alkylsulfenyl, arylcarbonyl, arylsulfonyl, and heteroarylsulfonyl; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamino, and arylsulfanyl Aryl, aryloxy, arylalkyl, cycloalkyl, heteroaryl'heteroarylalkoxy Heteroaryl and heterocyclic group; and R7 is absent, or selected from the group consisting of hydrogen-burning Xi group and a cyano group. In another specific embodiment, the present invention provides a compound of formula ⑴, wherein X is N; X is C; Y is C; Y 'is C (R9), wherein R9 is 丄 2-L3 (R3) (R6 ) 'Z is C; L1 is -N (R5; L2 is -0-; L3 is a secondary group, wherein the secondary group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy, amine, Cyano and hydroxy; R1 is selected from the group consisting of aryl, heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, amyl, alkynyl, arylalkynyl, amine, cyano-29- 20030Π22

(22) 基、氰基烯基、自基、羥烷基及芳基，其中雜芳基係選自包括咬喃基、吡畊基、嘍唑基及嘍吩基；R3為氫；R5係選自包括氫、烷基、烷羰基、烷基磺醯基、芳基羰基、芳基 %酿基及雜芳基續醯基；R6為雜芳基；及R7為氫。於另一項具體實施例中，本發明係提供式（1)化合物，其中 X為 N; X，為 C; Y 為 C; Y，為 C(R9)，其中以為-l2_l3(r3)(r6) ’ z為c，L1為-N(R5)- ; L2為-0- ; L3為次燒基，其中次垸基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1係選自包括芳基、雜環及雜芳基；R2與 R4係獨立選自包括氫、烯基、炔基、芳基炔基、胺基、氰基、氰基烯基、自基、羥烷基及芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘍唑基及噻吩基；R3為氫；R5係選自包括氫、烷基、烷羰基、烷基磺醯基、芳基羰基、芳基磺醯基及雜芳基磺醯基；R6為芳基；及尺7為氫。於另一項具體實施例中，本發明係提供式⑴化合物，其中X係選自包括C(R8)與N，其中R8係選自包括氫、烷基、胺基、羧基、氰基、鹵基、羥基及醯胺基；X，係選自包括 C 與 N; Y 為 c; Y’為 C(r9)，其中 R9 為-L2 丄 3(r3)(r6); Z 為 c; L1 為一個鍵結；L2為一個鍵結；L3為一個鍵結；r2與R4係獨立選自包括氫、晞基、块基、芳基炔基、胺基、氰基、氰基稀基、自基、羥烷基及雜芳基，其中雜芳基係選自包括呋喃基、吡畊基、嘧唑基及嘧吩基；R3為不存在；R6為雜環；及R7為不存在，或選自包括氫、烷基及氰基晞基。於另一項具體實施例中，本發明係提供式（1)化合物，其 -30- 200301122(22) aryl, cyanoalkenyl, selfyl, hydroxyalkyl, and aryl, wherein the heteroaryl group is selected from the group consisting of sulfanyl, pyryl, oxazolyl, and fluorenyl; R3 is hydrogen; R5 is It is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, aryl%, and heteroarylcontinyl; R6 is heteroaryl; and R7 is hydrogen. In another specific embodiment, the present invention provides a compound of formula (1), wherein X is N; X is C; Y is C; Y is C (R9), wherein -l2_l3 (r3) (r6 ) 'z is c, L1 is -N (R5)-; L2 is -0-; L3 is a secondary group, wherein the secondary group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, amine R1 is selected from the group consisting of aryl, heterocyclic and heteroaryl; R2 and R4 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, arylalkynyl, amine, cyano, and cyano Alkenyl, self-based, hydroxyalkyl, and aryl, wherein the heteroaryl group is selected from the group consisting of furanyl, pyryl, oxazolyl, and thienyl; R3 is hydrogen; R5 is selected from the group consisting of hydrogen, alkyl, Alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl and heteroarylsulfonyl; R6 is aryl; and R7 is hydrogen. In another embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R8) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxyl, cyano, and halogen. X, selected from the group consisting of C and N; Y is c; Y 'is C (r9), where R9 is -L2 丄 3 (r3) (r6); Z is c; L1 is A bond; L2 is a bond; L3 is a bond; r2 and R4 are independently selected from the group consisting of hydrogen, fluorenyl, bulk, arylalkynyl, amine, cyano, dicyano, and autogenous , Hydroxyalkyl, and heteroaryl, wherein the heteroaryl is selected from the group consisting of furyl, pyrargyl, pyrazolyl, and pyrenyl; R3 is absent; R6 is heterocyclic; and R7 is absent or selected Including hydrogen, alkyl and cyanofluorenyl. In another specific embodiment, the present invention provides a compound of formula (1), which is -30- 200301122

(23)(twenty three)

中X係選自包括C(R8)與N ;其中R8係選自包括氫、烷基、胺基、羧基、氰基、卣基、羥基及醯胺基；X，係選自包括C 與 N ; Y 為 C ; Y’ 為 C(R9)，其中 r9 為-l2-L3(R3)(R6) ; Z 為 C ; L1 係選自包括一個鍵結、-〇-、-N(R5)-、婦基、炔基、-(：(0)-、- S-、-S(O)-、-S(0)2-、-S(0)2N(R5)-、-N(R5)S(0)2-、-C(R12)2-、_ C(R12)2N(R5)-、-N(R5)C(0)-及-C(0)N(R5)-，其中各基團係被畫成其左端連接至R1，而其右端連接至芳族環；L3為亞烷基，其中亞燒基係視情況被一或兩個取代基取代，取代基獨立X is selected from the group consisting of C (R8) and N; R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxyl, cyano, fluorenyl, hydroxy and fluorenyl; X is selected from the group consisting of C and N Y is C; Y 'is C (R9), where r9 is -l2-L3 (R3) (R6); Z is C; L1 is selected from the group consisting of a bond, -0-, -N (R5)- , Feminyl, alkynyl,-(:( 0)-, -S-, -S (O)-, -S (0) 2-, -S (0) 2N (R5)-, -N (R5) S (0) 2-, -C (R12) 2-, _ C (R12) 2N (R5)-, -N (R5) C (0)-, and -C (0) N (R5)-, each of which The group system is drawn with its left end connected to R1 and its right end connected to the aromatic ring; L3 is an alkylene group, where the alkylene group is optionally substituted with one or two substituents, and the substituents are independent

選自包括烷氧基、胺基、氰基及羥基；Ri係選自包括芳基、雜方基及雜環；R4與L2和彼等所連接之碳原子一起形成裱，選自包括芳基、雜芳基及雜環；R3為不存在，或選自Selected from the group consisting of alkoxy, amine, cyano and hydroxyl; Ri is selected from the group consisting of aryl, heterosquare and heterocyclic ring; R4 forms a frame with L2 and the carbon atoms to which they are attached, selected from the group including aryl , Heteroaryl and heterocyclic ring; R3 is absent or selected from

包括氫、芳基、芳基烷氧基、芳烷基胺基、芳烷基硫基、万氧基、芳硫基、環烷基、雜芳基、雜芳基烷氧基、雜芳基氧基及雜環；R6係選自包括氫、芳|、芳基烷氧基、芳烷基胺基、芳烷基硫基 '芳氧基、芳硫基、環烷基、雜芳基、雜芳聽氧基、雜芳基氧基及雜冑；r5係選自包括氯、烷基、烷羰基、烷基磺醯基、芳基羰基、芳基磺醯基及雜芳基磺醯基；R7為不存在，或選自包括氫、、燒基及氰基晞基；及各選自包括氫、缔基、、燒基”失基、胺基、芳基、氰基、#基、雜芳基、雜環及硝基。於另-項具體實施例中，本發明係提供式（ι)化合物，其中X係選自包括C(R8mN，其中r8為氫；Xn· 丫，為 C(R9)，其中 R9 為仏L3(R3)(R6); △局L , L為—個鍵結；l3 為亞烷基，其中亞烷基係被一個 %代暴取代，取代基選自 -31 - (24) (24)20030丄丄22 包括烷氧基、胺基、氰基及羥基；Rl為雜芳基，其中雜芳基為/、奎林基，以與^和彼等所連接之碳原子一起形成雜環，其中雜環為被酮基取代之四氫吡咯基；r3為氫；Μ為雜芳基’其中雜芳基為吲哚基；及R7為氫。於另項具體實施例中，本發明係提供式⑴化合物，其中X係選自包括（：妒）與^其中R8係選自包括氫、烷基、胺基、幾基、氰基、_基、羥基及醯胺基；且X，係選自包括 C 與 N’ Y 為 C，Y’為 C(R9)，其中 R9為-l2-L3(R3)(R6) ; Z 為 C ; R2 與L1和彼等所連接之碳原子一起形成環，其係為芳基，其中方基％為苯基；L2為L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氛基及#i基；Rl為雜芳基；R3為不存在；R6為雜芳基；及R7 為不存在，或選自包括氫、烷基及氰基晞基。於另一項具體實施例中，本發明係提供式（I)化合物，其中 X為 N; X’為 c; γ 為 c; γ，為 c(r9)，其巾 r9 為·l、l3(r3xr6) ，Z為c ; R2與L1和彼等所連接之碳原子一起形成環，其係為芳基其中芳基環為苯基；L2為-0- ; L3為次燒基，其中八烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri為雜芳基；R3為不存在；Μ為雜芳基；及R7為氫。於另一項具體實施例中，本發明係提供式⑺化合物，其為 N X 為 C, Y 為 c; Y’為 c(R9)，其中 R9 為-L2、l3 (r3 )(Ri) 、’ z為c , R與L1和彼等所連接之碳原子一起形成環，其係為芳基，其中芳基環為苯基；G為办；L3為次境基，^中 -32 - (25) 次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為雜芳基；R3為不存在；R6為芳基；及R7為氫。Including hydrogen, aryl, arylalkoxy, aralkylamino, aralkylthio, peroxy, arylthio, cycloalkyl, heteroaryl, heteroarylalkoxy, heteroaryl R6 is selected from the group consisting of hydrogen, aryl |, arylalkoxy, aralkylamino, aralkylthio'aryloxy, arylthio, cycloalkyl, heteroaryl, Heteroaryloxy, heteroaryloxy and heterofluorene; r5 is selected from the group consisting of chlorine, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylsulfonyl and heteroarylsulfonyl R7 is absent, or is selected from the group consisting of hydrogen, alkyl, and cyano; and each is selected from the group consisting of hydrogen, alkenyl, and alkyl ", amyl, amine, aryl, cyano, #, Heteroaryl, heterocyclic and nitro. In another specific embodiment, the present invention provides a compound of formula (ι), wherein X is selected from the group consisting of C (R8mN, where r8 is hydrogen; Xn · y, is C (R9), where R9 is 仏 L3 (R3) (R6); △ local L, L is a bond; l3 is an alkylene group, wherein the alkylene system is substituted with a% substitution, and the substituent is selected from- 31-(24) (24) 20030 丄丄 22 Including alkoxy, amine, cyano and R1 is a heteroaryl group, wherein the heteroaryl group is /, quelinyl, and forms a heterocyclic ring with ^ and the carbon atom to which they are connected, wherein the heterocyclic ring is a tetrahydropyrrolyl group substituted with a keto group; r3 Is hydrogen; M is heteroaryl 'wherein heteroaryl is indolyl; and R7 is hydrogen. In another embodiment, the present invention provides a compound of formula VII, wherein X is selected from the group consisting of (: ^ Wherein R8 is selected from the group consisting of hydrogen, alkyl, amino, amino, cyano, hydroxy, hydroxy, and amido; and X is selected from the group consisting of C and N 'Y is C, and Y' is C ( R9), where R9 is -l2-L3 (R3) (R6); Z is C; R2 forms a ring together with L1 and the carbon atom to which they are attached, which is an aryl group, in which the square group% is phenyl; L2 is L3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, and the substituent is selected from the group consisting of an alkoxy group, an amino group, an aryl group, and a #i group; R1 is a heteroaryl group; R3 is absent R6 is heteroaryl; and R7 is absent, or is selected from the group consisting of hydrogen, alkyl, and cyanofluorenyl. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is N X 'is c; γ c; γ is c (r9), whose r9 is · l, l3 (r3xr6), and Z is c; R2 forms a ring together with L1 and the carbon atoms to which they are attached, which is an aryl group in which an aryl ring Is a phenyl group; L2 is -0-; L3 is a secondary group, wherein the octyl group is optionally substituted with a substituent, and the substituent is selected from the group consisting of alkoxy, amino, cyano and hydroxyl; Ri is heteroaryl R3 is absent; M is heteroaryl; and R7 is hydrogen. In another embodiment, the present invention provides a compound of formula VII, wherein NX is C, Y is c; Y 'is c ( R9), where R9 is -L2, l3 (r3) (Ri), 'z is c, R forms a ring together with L1 and the carbon atom to which they are attached, which is an aryl group, wherein the aryl ring is phenyl G is the office; L3 is a sub-environmental group, and the -32-(25) sub-alkynyl group is optionally substituted by a substituent, and the substituent is selected from the group consisting of alkoxy, amino, cyano and hydroxyl; R1 is Heteroaryl; R3 is absent; R6 is aryl; and R7 is hydrogen.

於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(RS)與N ;其中R8係選自包括氫、烷基、胺基、致基 '氰基、自基、羥基及醯胺基；X’係選自包括C 與 N ; Y 為 C ; γ，為 C(R9)，其中 R9 為丄2-L3(R3)(R6) ; z 為 c ; R2 與L1和彼等所連接之碳原子一起形成環，其係為雜基，一 _ 其中雜芳基為吡唑基；L2為一個鍵結；L3為次烷基，其中零次fe基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri係選自包括芳基、雜環及雜芳基；R3為氫；R6係選自包括芳基、雜環及雜芳基；及R7為不存在，或選自包括氫、烷基及氰基烯基。於另一項具體實施例中，本發明係提供式（I)化合物，其中X為C(R8)，其中r8為氫；X’為n; Y為C; Y，為C(R9)，其中 R9為丄2-L3(R3)(R6) ; z為C ; R2與L1和彼等所連接之碳原子一起形成環，其係為雜芳基，其中雜芳基為吡唑基；L2為一 · 個鍵結，L3為次燒基，其中次燒基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Ri為雜芳基；R3為氫；R6為芳基；及R7為不存在。於另一項具體實施例中，本發明係提供式（I)化合物，其中X為C(R8 )，其中R8為氫；X1為N; Y為c; Y，為C(R9)，其中 R9為-L2-L3(R3)(R6) ; Z為C ; R2與L1和彼等所連接之碳原子一起形成環，其係為雜芳基’其中雜芳基為ϋ比嗤基；L2為一 -33- υ 0301 (26)In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (RS) and N; wherein R8 is selected from the group consisting of hydrogen, alkyl, amine, and alkyl X 'is selected from the group consisting of C and N; Y is C; γ is C (R9), where R9 is 丄 2-L3 (R3) (R6); z is c R2 forms a ring together with L1 and the carbon atoms to which they are attached, which is a hetero group, where _ where heteroaryl is pyrazolyl; L2 is a bond; L3 is an alkylidene group, where zero times fe groups Is optionally substituted by a substituent, the substituent is selected from the group consisting of alkoxy, amine, cyano and hydroxyl; Ri is selected from the group consisting of aryl, heterocyclic and heteroaryl; R3 is hydrogen; R6 is selected from the group consisting of Aryl, heterocyclic and heteroaryl; and R7 is absent or selected from the group consisting of hydrogen, alkyl and cyanoalkenyl. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is C (R8), wherein r8 is hydrogen; X ′ is n; Y is C; Y is C (R9), wherein R9 is 丄 2-L3 (R3) (R6); z is C; R2 forms a ring together with L1 and the carbon atom to which they are attached, which is a heteroaryl group, wherein the heteroaryl group is pyrazolyl; L2 is One bond, L3 is a secondary group, where the secondary group is optionally substituted by a substituent, the substituent is selected from the group consisting of alkoxy, amino, cyano and hydroxyl; Ri is heteroaryl; R3 is Hydrogen; R6 is aryl; and R7 is absent. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is C (R8), wherein R8 is hydrogen; X1 is N; Y is c; Y is C (R9), wherein R9 Is -L2-L3 (R3) (R6); Z is C; R2 forms a ring together with L1 and the carbon atom to which they are connected, which is a heteroaryl group, wherein the heteroaryl group is a fluorenyl group; L2 is Mon-33-υ 0301 (26)

個键結；L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；R1為芳基；R3為風，R6為方基，及R為不存在。於另一項具體實施例中，本發明係提供式（I)化合物，其中X係選自包括C(R )與N，其中R8係選自包括氫、燒基、胺基、羧基、氰基、鹵基、羥基及醯胺基；X，為C;Y為C;Y，為c(R9)，其中R9為-l2-l2(r3)(r6) ; Z為C ; W與L1和彼等所連接之碳原子一起形成環，選自包括芳基、雜芳基及雜環； L2為-0- ; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括烷氧基、胺基、氰基及羥基；Rl係選自包括芳基、雜環及雜芳基；R3為氫；及R6係選自包括芳基、雜環及雜芳基。於另一項具體實施例中，本發明係提供式（I)化合物，其中 X為 N;且 X’為 C; Y 為 C; Y’為 C(R9)，其中 R9 為-L2 -L3 (R3 )(R6) ;Z為C ; R7與L1和彼等所連接之碳原子一起形成環，其係為雜芳基，其中雜芳基為吡啶基；L2為; L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括垸氧基、胺基、氰基及羥基；Ri為雜芳基；R3為氫；及0 為雜芳基。於另一項具體實施例中，本發明係提供式①化合物，其中 X為 N;且 X’為 C; Y為 C; Y’為 c(R9)，其中 R9 為-L2-L3(R3)(R6) ’ Z為c ; R7與L1和彼等所連接之碳原子一起形成環，其係為雜芳基’其中雜芳基為吡啶基；L2為L3為次烷基，其中次烷基係視情況被一個取代基取代，取代基選自包括 -34- 200301122 (27) a^3^sa™aaei8iSHSFji 燒氧基、胺基、氰基及輕基；R1為雜芳基；R3為氫為芳基。於另一項具體實施例中，本發明係提供一種醫藥，其包含式（I)化合物，或其治療上可接受之鹽，且學上可接受之載劑。於另一項具體實施例中，本發明係提供一種在被要治療之病患中抑制蛋白質激酶之方法，其包括對投予治療上可接受量之式（I)化合物或其治療上可接，發明詳述當於本專利說明書中使用時，下列術語具有所指義：於本文中使用之”烯基”一詞，係指衍生自直鏈或烴之基團，具有至高六個原子，含有至少一個雙鍵於本文中使用之π烷氧基”一詞，係指烷基經過氧接至母分子部份基團。於本文中使用之π烷氧烷基π —詞，係指烷氧基經連接至母分子部份基團。於本文中使用之π烷氧羰基π—詞，係指烷氧基經連接至母分子部份基團。於本文中使用之’’燒基’’ 一詞，係指衍生自直鏈或飽和烴之基團，具有一至六個原子。於本文中使用之π次烷基π —詞，係指衍生自直鏈鏈飽和烴之二價基團，具有一至六個原子。於本文中使用之’’烷羰基’’ 一詞，係指烷基經過羰 :及R6 組合物併用藥認定需該病患 $之鹽。示之意分枝鏈〇原子連過烷基過烷基分枝鏈或分枝基連接L3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, the substituent is selected from the group consisting of alkoxy, amino, cyano and hydroxyl; R1 is aryl; R3 is wind, R6 Is a square base, and R is absent. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is selected from the group consisting of C (R) and N, and R8 is selected from the group consisting of hydrogen, alkyl, amine, carboxy, and cyano. , Halo, hydroxyl, and amido; X is C; Y is C; Y is c (R9), where R9 is -l2-l2 (r3) (r6); Z is C; W and L1 and each other And other connected carbon atoms together to form a ring, selected from the group consisting of aryl, heteroaryl and heterocyclic ring; L2 is -0-; L3 is an alkylene group, wherein the alkylene group is optionally substituted by a substituent, the substituent Selected from alkoxy, amine, cyano and hydroxy; R1 is selected from aryl, heterocyclic and heteroaryl; R3 is hydrogen; and R6 is selected from aryl, heterocyclic and heteroaryl. In another specific embodiment, the present invention provides a compound of formula (I), wherein X is N; and X 'is C; Y is C; Y' is C (R9), wherein R9 is -L2 -L3 ( R3) (R6); Z is C; R7 forms a ring together with L1 and the carbon atoms to which they are attached, which is a heteroaryl group in which the heteroaryl group is pyridyl; L2 is; L3 is an alkylene group, in which The alkylene group is optionally substituted with a substituent selected from the group consisting of fluorenyloxy, amine, cyano, and hydroxyl; Ri is heteroaryl; R3 is hydrogen; and 0 is heteroaryl. In another specific embodiment, the present invention provides a compound of formula ①, wherein X is N; and X 'is C; Y is C; Y' is c (R9), wherein R9 is -L2-L3 (R3) (R6) 'Z is c; R7 forms a ring together with L1 and the carbon atoms to which they are attached, which is a heteroaryl' wherein heteroaryl is pyridyl; L2 is L3 is an alkylene group, where the alkylene group is It is optionally substituted by a substituent, and the substituent is selected from the group consisting of -34- 200301122 (27) a ^ 3 ^ sa ™ aaei8iSHSFji thiol, amine, cyano, and light group; R1 is heteroaryl; R3 is hydrogen Is aryl. In another specific embodiment, the present invention provides a medicine comprising a compound of formula (I), or a therapeutically acceptable salt thereof, and a scientifically acceptable carrier. In another embodiment, the present invention provides a method for inhibiting a protein kinase in a patient to be treated, which comprises administering a therapeutically acceptable amount of a compound of formula (I) or a therapeutically accessible amount thereof. DETAILED DESCRIPTION OF THE INVENTION When used in this patent specification, the following terms have meanings: The term "alkenyl" as used herein refers to a group derived from a straight chain or hydrocarbon, having up to six atoms, The term "πalkoxy group containing at least one double bond as used herein" refers to an alkyl group connected to the parent molecular moiety through oxygen. The term "πalkoxyalkylπ" as used herein refers to an alkane An oxy group is connected to the parent molecular moiety. The term πalkoxycarbonylπ, as used herein, refers to an alkoxy group connected to the parent molecular moiety. As used herein, a `` alkyl group '' The term 'refers to a group derived from a linear or saturated hydrocarbon having one to six atoms. As used herein, the π-alkylene group π-the term refers to a divalent group derived from a linear saturated hydrocarbon Has one to six atoms. As used herein, `` alkylcarbonyl '' ‘’ The term refers to the salt of the alkyl group through the carbonyl: and R6 combination and the drug is determined to require the patient's $. The meaning is branched chain 〇 Atom is connected through alkyl alkyl peralkyl branched chain or branched group connected

-35- 20030Π22 1 _ _Μ|" (28) 至母分子部份基團。於本又中使用之”亞烷基”一詞，係指烯基，其中碳-碳雙鍵之一個碳原子，係屬於該晞基所連接之部份基團。於本又中使用之”烷基磺醯基”一詞，係指烷基經過磺醯基連接至母分子部份。 1尔？曰衍生自直鏈或分枝鏈於本文中使用之”炔基烴之基團，具有二至六個原子，含有至少一個參鍵。於本文中使用之”酷胺基，，一詞’係指胺基經過羰基連接至母分子部份基團。於本文中使用之’’胺基”一，，你 ’ 係4曰-NRa Rb，其中Ra與Rb係獨立選自包括氫、埽基、烷荽其 ’ 土砭乳基、烷氧烷基、烷氧羰基、-35- 20030Π22 1 _ _M | " (28) to the parent molecular moiety. As used herein, the term "alkylene" refers to an alkenyl group in which a carbon atom of a carbon-carbon double bond belongs to the group to which the fluorenyl group is attached. As used herein, the term "alkylsulfonyl" refers to an alkyl group attached to the parent molecular moiety through a sulfonyl group. 1? A group derived from a "alkynyl" hydrocarbon, as used herein, which has a straight or branched chain, has two to six atoms and contains at least one reference bond. As used herein, "coolamine," the term 'system Refers to an amine group attached to the parent molecular moiety through a carbonyl group. As used in this article, "Amine", you're 4'-NRa Rb, where Ra and Rb are independently selected from the group consisting of hydrogen, fluorenyl, and alkynyl; Alkoxycarbonyl,

基、坑談基、芳基、苦其法I 矛基烯基、芳烷基、環烷基、函烷基羰基、（NRcRd)燒羰基、雜雖方基、雜芳基烯基、雜芳烷基、雜環、（雜環）烯基及（雜矮）久（雜％)烷基，其中芳基，芳基烯基、芳基烷基之芳基部份，输分 ^ 、雜万基’雜芳基烯基與雜芳基烷基之雜芳基部份，雜環，四 s、（雜環）晞基與（雜環）烷基之雜 %邵份，可視情況被一、二、一 ^ ^ y 一、二、四或五個取代基取代，取代基獨立選自包括烯基、 .^ ^ &乳基、烷氧烷基、烷基、氰基、_基、鹵烷氧基、南# ， 70基、蛵基、羥烷基、硝基及酮基。於本文中使用之”胺基烷基接至母分子部份基團。 ~詞’係指胺基經過烷基連基，’一詞，係指中一或多個祠合於本文中使用之，，芳環狀稠合環系統，其苯基，或雙環狀或三環為苯基。雙環狀稠 -36 - (29)Base, alkynyl, aryl, kuchi alkenyl I, alkynyl, aralkyl, cycloalkyl, alkynylcarbonyl, (NRcRd) carbonyl, heteroalkaline, heteroarylalkenyl, heteroaryl Alkyl, heterocyclic, (heterocyclic) alkenyl and (hetero-dwarf) long (hetero%) alkyl, of which the aryl part of aryl, arylalkenyl, arylalkyl, ^^ Heteroaryl part of the radicals' heteroarylalkenyl and heteroarylalkyl, heterocycle, tetras, (%) heterocycle of (heterocycle) fluorenyl and (heterocycle) alkyl, depending on the situation, Two, one ^ ^ y One, two, four, or five substituents are substituted, and the substituents are independently selected from the group consisting of alkenyl,. ^ ^ &Amp; lactyl, alkoxyalkyl, alkyl, cyano, halo, halogen Alkoxy, South #, 70-based, fluorenyl, hydroxyalkyl, nitro, and keto. As used herein, "aminoalkyl group is attached to the group of the parent molecule. ~ The word" refers to the amino group through the alkyl linker, "the term, refers to one or more of the groups used in this article. ,, Aromatic fused ring system, whose phenyl, or bicyclic or tricyclic is phenyl. Bicyclic fused -36-(29)

合環系統之實例為苯基，經稠合至本另一個苯基。三環狀稠合環系統之實統，經稠合至本文中定義之環烷基或代表性實例包括但不限於蒽基、籃香基、茚基、萘基、苯基及四氫莕基。况被一、二、三、四或五個取代基取包括晞基、烷氧基、烷氧烷基、烷氧、烷硫基、胺基、胺基烷基、第二個芳烷基、芳基羰基、羧基、氰基、環基、自烷基、雜芳基、雜芳基烷氧基 (雜環）’)元氧基、（雜環）燒基、幾基、、·€：(=Ν0Η)ΝΗ2、-C(=NH)NH2 ;其中第二、芳基燒基及芳基羰基之芳基部份，基與雜芳基烷基之雜芳基部份，雜環 (雜環）烷基之雜環部份，可進一步視四或五個取代基取代，取代基獨立選、烷基、鹵基、自烷氧基、_烷基、表於本文中使用之”芳基烯基，，一詞，接至母分子部份基團。於本文中使用之”芳基烷氧基”一詞基連接至母分子部份基團。於本文中使用之”芳烷基”一詞，係至母分子部份基團。於本文中使用之”芳烷基胺基”—詞文中定義之環烷基或例為雙環狀稠合環系另一個苯基。芳基之油烴基、苐基、氫茚本發明之芳基可視情代’取代基獨立選自羧基、烷基、烷羰基芳基、芳基烷氧基、燒基、_基、卣燒氧、雜芳烷基、雜環、羥烷基、硝基、酮基個芳基，芳基烷氧基雜方基’雜芳基燒氧 ’及（雜環）烷氧基與情況被一、二、三、自包括歸基 '燒氧基 I基、羥烷基及硝基。係指方基經過埽基連 ’係指芳基經過烷氧指芳基經過垸基連接 ’係指芳燒基經過氮 -37 - 200301122An example of a ring-binding system is phenyl which is fused to another phenyl group. The actual system of a tricyclic fused ring system fused to a cycloalkyl group or representative examples as defined herein includes, but is not limited to, anthracenyl, lanaryl, indenyl, naphthyl, phenyl, and tetrahydrofluorenyl . It is taken by one, two, three, four or five substituents including fluorenyl, alkoxy, alkoxyalkyl, alkoxy, alkylthio, amine, aminoalkyl, second aralkyl, Arylcarbonyl, carboxyl, cyano, cyclic, self-alkyl, heteroaryl, heteroarylalkoxy (heterocyclic) ')-membered oxy, (heterocyclic) alkyl, aryl, alkoxy, ... (= Ν0Η) ΝΗ2, -C (= NH) NH2; of which, the aryl part of arylalkyl and arylcarbonyl, the heteroaryl part of aryl and heteroarylalkyl, heterocyclic (hetero The heterocyclic part of the ring) alkyl group may be further substituted according to four or five substituents. The substituents are independently selected from the group consisting of alkyl, halo, alkoxy, and alkyl. The term "alkenyl," is attached to the parent molecular moiety. The term "arylalkoxy" used herein is attached to the parent molecular moiety. As used herein, the term "aralkyl" The term refers to the group of the parent molecule. As used herein, "aralkylamino"-a cycloalkyl group as defined in the text or an example is a bicyclic fused ring system of another phenyl group. Oil hydrocarbon group, fluorenyl group The aryl group of the present invention may be independently selected from the substituents of carboxyl, alkyl, alkylcarbonylaryl, arylalkoxy, alkyl, alkynyl, sulfanyl, heteroaralkyl, heterocyclic, Hydroxyalkyl, nitro, keto, aryl, arylalkoxy, heteroaryl, heteroaryl, and (heterocyclic) alkoxy are one, two, three, and self-inclusive. Carbooxy I group, hydroxyalkyl and nitro. Refers to a square group connected via a fluorenyl group. 'Refers to an aryl group via an alkoxy group refers to an aryl group via a fluorenyl group.' Refers to an aryl group via a nitrogen group. -37-200301122

(30) 原子連接至母分子部份基團，其中氮原子係被氫取代。於本文中使用之”芳基亞烷基”一詞，係指芳基經過亞烷基連接至母分子部份基團。於本文中使用之”芳烷基硫基”一詞，係指芳烷基經過硫原子連接至母分子部份基團。於本文中使用之”芳基炔基”一詞，係指芳基經過炔基連接至母分子部份基團。於本文中使用之”芳基羰基”一詞，係指芳基經過羰基連接至母分子部份基團。於本文中使用之”芳氧基"一詞，係指芳基經過氧原子連接至母分子部份基團。於本文中使用之”芳基磺醯基"一詞，係指芳基經過磺醯基連接至母分子部份基團。於本文中使用之’’芳基硫基” 一詞，係指芳基經過硫原子連接至母分子部份基團。於本文中使用之，，羰基，，一詞，係指-c(0)-基團。於本文中使用之”羧基，，一詞，係指-C(0)0H。於本文中使用之”氰基，，一詞，係指-CN。於本文中使用之”氰基烯基”一詞，係指氰基經過晞基連接至母分子部份基團。於本文中使用之π %燒基’’ 一詞，係指飽和單環狀、雙環狀或三環狀烴環系統，具有三至十二個碳原子。環垸基之實例包括環丙基、環戊基、雙環并[3·1·1]庚基、金鋼燒基等。於本文中使用之”（環烷基）亞烷基”一詞，係指環烷基經 (31) 20030Π22 過亞烷基連接至母分子部份基團。於本文中使用之，，函基，，或，，卣素”術語，係指F、α、玢或於本文中使用之’’鹵燒氧基”一啕，伤扣占 4 係扣鹵烷基經過氧原子連接至母分子部份基團。 “ 於本文中使用之"自烷基”一詞，係指烷基被一、二、或四個鹵原子取代。羰於本文中使用之”齒烷基羰基”一詞，仿沪 J 你扣鹵烷基經過基連接至母分子部份基團。於本文中使用之”雜芳基”一詞，係指芳族五-或六·員環，其中：少-個原子係選自包括N、0及S，其餘原子為：。此五員環具有兩個雙鍵，而六員環具有三個雙鍵。雜芳基係經過環中之可取代碳或氮原子連接至母分子基團。二雜芳基” 一詞亦包括一些系統，其中雜芳基環係稠合至本文中足義t芳基、本文中定義之雜環基或另一個雜芳基。雜芳基之貫例為苯并噻吩基、苯并哼二唑、苯并吱喃基、苯并咪唑基、苯并三唑基、嗦啉基、呋喃基、咪唑基、啕唑基、吲哚基、異哼唑基、異喳啉基、異嘍唑基、嗉啶基、崎二唑基、啰二唑基、呤唑基、嘌呤基、嘍唑基、嶁吩并吡啶基、噻吩基、三唑基、嘍二唑基、吡啶基、嗒畊基、嘧啶基、吡畊基、吡唑基、吡咯基、吡啶并[2,3呐嘧啶基、外t嘻并[2,3七]吨啶基、喹唑啉基、喹啉基、噻吩并[2，>cp比啶基、四唑基、三呼基等。本發明之雜芳基可視情況被一、二、三、四或五個取代基取代，取代基獨立選自包栝烯 .39- 200301122(30) An atom is attached to a part of the parent molecule in which the nitrogen atom is replaced by hydrogen. As used herein, the term "arylalkylene" refers to an aryl group attached to the parent molecular moiety through an alkylene group. As used herein, the term "aralkylthio" refers to an aralkyl group attached to the parent molecular moiety through a sulfur atom. As used herein, the term "arylalkynyl" refers to an aryl group attached to the parent molecular moiety through an alkynyl group. As used herein, the term "arylcarbonyl" refers to an aryl group attached to the parent molecular moiety through a carbonyl group. As used herein, the term "aryloxy" refers to an aryl group attached to the parent molecular moiety through an oxygen atom. The term "arylsulfonyl" used herein refers to an aryl group Connected to the parent molecular moiety via a sulfonyl group. As used herein, the term "arylthio" refers to an aryl group attached to the parent molecular moiety through a sulfur atom. As used herein, the term "carbonyl" refers to -c (0 )-Group. As used herein, the term "carboxyl," refers to -C (0) OH. The term "cyano," as used herein, refers to -CN. The term "cyanoalkenyl," as used herein, refers to a cyano group attached to the parent molecular moiety through a fluorenyl group. As used herein The term `` π% alkyl, '' as used herein, refers to a saturated monocyclic, bicyclic, or tricyclic hydrocarbon ring system having three to twelve carbon atoms. Examples of cyclofluorenyl include cyclopropyl, cyclic Amyl, bicyclo [3 · 1 · 1] heptyl, gold-steel, etc. As used herein, the term "(cycloalkyl) alkylene" refers to cycloalkyl via (31) 20030Π22 An alkyl group is attached to the parent molecular moiety. As used herein, the term "functional group", "or", "halogen" means F, α, fluorene, or "halohaloxy" as used herein. For a while, the saccharyl group is connected to the parent molecular moiety through an oxygen atom. The term "from alkyl" as used herein means that the alkyl group is one, two, or four A halogen atom is substituted. Carbonyl is used herein as the term "dental carbonyl", imitated as "J". Haloalkyl is connected to the parent molecular moiety through a radical. In this text The term "heteroaryl" is used to refer to an aromatic five- or six-membered ring, wherein: the fewer-atom system is selected from the group consisting of N, 0, and S, and the remaining atoms are: This five-membered ring has two A double bond, and a six-membered ring with three double bonds. Heteroaryl is attached to the parent molecular group through a substitutable carbon or nitrogen atom in the ring. The term "diheteroaryl" also includes systems in which heteroaryl The ring system is fused to a sufficient sense taryl group herein, a heterocyclic group as defined herein, or another heteroaryl group. Examples of heteroaryl groups are benzothienyl, benzohumidazole, benzocuryl, benzimidazolyl, benzotriazolyl, fluorinyl, furanyl, imidazolyl, oxazolyl, indole Indyl, isoxazolyl, isoxazolyl, isoxazolyl, pyrimidinyl, oxadiazolyl, oxadiazolyl, oxazolyl, purine, oxazolyl, fluorenopyridyl, thiophene Base, triazolyl, amidazolyl, pyridyl, dacrotyl, pyrimidinyl, pyrigyl, pyrazolyl, pyrrolyl, pyrido [2,3napyrimidyl, exopyridine [2,3 G) Tyridyl, quinazolinyl, quinolinyl, thieno [2, > cp than pyridyl, tetrazolyl, trisyl and the like. The heteroaryl group of the present invention may be optionally substituted by one, two, three, four or five substituents, and the substituents are independently selected from the group consisting of pinene. 39-200301122

基 &氧基、燒乳纟元基、燒氣馥基、燒基、块基、境黢基、胺基、胺基烷基、芳基、芳基烷氧基、芳烷基、芳烷基硫基、芳基炔基、芳氧基、羧基、氰基、環烷基、_基、鹵烷氧基、齒烷基、第二個雜芳基、雜芳基烷氧基、雜芳燒基、雜環、（雜環）燒氧基、（雜環）烷基、羥基、幾燒基、硝基及酮基，其中芳基，芳基烷氧基、芳基烷基、芳烷基硫基、芳基炔基及芳基氧基之芳基部份，第二個雜芳基 ’雜芳烷氧基與雜芳烷基之雜芳基部份，雜環，及（雜環）烷氧基與（雜環）烷基之雜環部份，可進一步視情況被一、_ 二、三、四或五個取代基取代，取代基獨立選自包括烯基、烷氧基、烷氧烷基、烷基、氰基、卣基、卣烷氧基、鹵燒基、幾基、經燒基、硝基及鋼基。於本文中使用之”雜芳基烯基，，一詞，係指雜芳基經過烯基連接至母分子部份基團。於本文中使用之"雜芳基烷氧基”一詞，係指雜芳基經過烷氧基連接至母分子部份基團。於本文中使用之"雜芳烷基”一詞，係指雜芳基經過烷基鲁連接至母分子部份基團。於本文中使用之”雜芳基亞烷基”一詞，係指雜芳基經過亞fe基連接至母分子部份基團。於本文中使用之”雜芳基氧基”一詞，係指雜芳基經過氧原子連接至母分子部份基團。於本文中使用之”雜芳基磺醯基”一詞，係指雜芳基經過磺醯基連接至母分子部份基團。 -40- 於本文中使用之”雜環”一詞，係指環狀、非芳族，三_ 、四-、五_、六_或七-員環，含有至少一個選自包括氧、氮及硫之原子。五員環具有零或一個雙鍵，而六·與七·員環具有零、一或兩個雙鍵。本發明之雜環基係經過環中之可取代碳或氮原子連接至母分子基團。，，雜環，，一詞亦包括一些系統，其中雜環之環係稠合至本文中定義之芳基咬另一個雜環基。本發明雜環基之實例為氮丙啶基、一氮四園基、1，3-苯并二氧伍圜晞基、二氫異吲哚基、二氫異峻琳基一氣4琳基、二氛冬并一氧陸圜晞基、二氫[1，3]气嗤并[4 5七] p比啶基、苯并嘧唑基、二氫吲哚基、二氫吡啶基、1 二氧陸圜基、1,4-二氧陸圜基、1，3-二氧伍圜基、異巧嗓琳基、嗎福啉基、六氫毗畊基、四氫吡咯基、四氫吡咬基、六氫吡啶基、硫代嗎福啉基等。本發明之雜環基可視情況被一、二、三、四或五個取代基取代，取代基獨立選自包括烯基、烷氧基、烷氧烷基、烷氧羰基、烷基、烷羰基、亞烷基、胺基、胺基烷基、芳基、芳基烷氧基、芳烷基、芳基亞燒基、氰基、（環烷基）亞烷基、函基、卣烷氧基、函 k基、雜芳基、雜芳基烷氧基、雜芳烷基、雜芳基亞烷基、亞胺基羥基、第二個雜環、（雜環）烷氧基、（雜環）烷基、（雜環）亞烷基、羥基、羥烷基、硝基及酮基，其中芳基，芳基烷氧基與芳基烷基之芳基部份，雜芳基，雜芳基烷氧基、雜芳基烷基及雜芳基亞烷基之雜芳基部份，第二個雜％，及（雜環）烷氧基、（雜環）烷基以及（雜環）亞烷基之雜環部份，可進一步視情況被一、二、三、二二 -41 - 200301122&Amp; oxy, burned fluorenyl group, burned fluorenyl group, burned group, block group, amido group, amino group, aminoalkyl group, aryl group, arylalkoxy group, aralkyl group, aralkyl group Sulfanyl, arylalkynyl, aryloxy, carboxyl, cyano, cycloalkyl, aryl, haloalkoxy, haloalkyl, second heteroaryl, heteroarylalkoxy, heteroaryl Alkyl, heterocycle, (heterocycle) alkoxy, (heterocycle) alkyl, hydroxyl, alkynyl, nitro, and keto, of which aryl, arylalkoxy, arylalkyl, aralkyl Aryl moieties of sulfanylthio, arylalkynyl, and aryloxy, the second heteroaryl 'heteroarylalkoxy and heteroaryl portion of heteroaryl, heterocycle, and (heterocycle ) The heterocyclic part of alkoxy and (heterocyclo) alkyl may be further substituted with one, two, three, four or five substituents as appropriate, and the substituents are independently selected from the group consisting of alkenyl, alkoxy, Alkoxyalkyl, alkyl, cyano, fluorenyl, fluorenyl, haloalkyl, haloyl, alkenyl, nitro, and steel. As used herein, the term "heteroarylalkenyl," refers to a heteroaryl group attached to the parent molecular moiety through an alkenyl group. As used herein, the term "heteroarylalkoxy" Refers to a heteroaryl group attached to the parent molecular moiety through an alkoxy group. As used herein, the term "heteroaralkyl" refers to a heteroaryl group connected to the parent molecular moiety through an alkyl group. As used herein, the term "heteroarylalkylene" is Refers to a heteroaryl group attached to the parent molecular moiety through a fe group. As used herein, the term "heteroaryloxy" refers to a heteroaryl group attached to the parent molecular moiety through an oxygen atom. As used herein, the term "heteroarylsulfonyl" refers to a heteroaryl group attached to the parent molecular moiety through a sulfonyl group. -40- The term "heterocyclic" as used herein refers to A cyclic, non-aromatic, tri-, tetra-, penta-, penta-, or penta-membered ring containing at least one atom selected from the group consisting of oxygen, nitrogen, and sulfur. A penta-membered ring has zero or one double bond, and six Has zero, one, or two double bonds with the seven-membered ring. The heterocyclic group of the present invention is connected to the parent molecular group via a substitutable carbon or nitrogen atom in the ring. The term, heterocycle, also includes Some systems in which a heterocyclic ring system is fused to an aryl group as defined herein and another heterocyclic group. Examples of heterocyclic groups of the present invention are aziridinyl, Tetrazolyl, 1,3-benzodioxoyl, dihydroisoindolyl, dihydroisolinyl, monophenyl 4-yl, dihydrobenzyloxyphenyl, dihydro [ 1,3] pyrido [4 5 seven] p-pyridinyl, benzopyrazolyl, dihydroindolyl, dihydropyridyl, 1 dioxolyl, 1,4-dioxolyl , 1,3-dioxoyl, isoquinolyl, morpholinyl, hexahydropyridyl, tetrahydropyrrolyl, tetrahydropyridyl, hexahydropyridyl, thiomorpholinyl Etc. The heterocyclic group of the present invention may be optionally substituted with one, two, three, four or five substituents, and the substituents are independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, Alkylcarbonyl, alkylene, amino, aminoalkyl, aryl, arylalkoxy, aralkyl, arylalkylene, cyano, (cycloalkyl) alkylene, halide, hafnium Alkoxy, alkoxy, heteroaryl, heteroarylalkoxy, heteroaralkyl, heteroarylalkylene, iminohydroxy, second heterocycle, (heterocyclic) alkoxy, (Heterocyclic) alkyl, (heterocyclic) alkylene, hydroxyl, hydroxyalkyl, nitro and keto Among them, the aryl part of aryl, arylalkoxy and arylalkyl, the heteroaryl part of heteroaryl, heteroarylalkoxy, heteroarylalkyl and heteroarylalkylene, The second hetero%, and the heterocyclic part of (heterocycle) alkoxy, (heterocycle) alkyl, and (heterocycle) alkylene, may be further selected as one, two, three, and two di-41 -200301122

(34) 基取代，取代基獨立選自包括婦基、烷氧基、烷氧烷基、燒基、氰基、函基、函燒氧基、函燒基、輕基、輕垸基、硝基及酮基。於本文中使用之π(雜環）婦基π —詞，係指雜環基經過烯基連接至母分子部份基團。於本文中使用之π(雜環）烷氧基”一詞，係指雜環基經過氧原子連接至母分子基團。(34) group substitution, the substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkynyl, cyano, alkynyl, alkynyl, alkynyl, light-based, light-based And keto. The term π (heterocyclic) alkenyl, as used herein, refers to a heterocyclic group attached to the parent molecular moiety through an alkenyl group. The term "(heterocycle) alkoxy" as used herein refers to a heterocyclic group attached to the parent molecular group through an oxygen atom.

於本文中使用之π(雜環）烷基” 一詞，係指雜環基經過烷基連接至母分子部份基團。於本文中使用之π(雜環）亞烷基π —詞，係指雜環基經過亞烷基連接至母分子部份基團。於本文中使用之π羥基’’ 一詞，係指-ΟΗ。於本文中使用之’’羥烷基π —詞，係指羥基經過烷基連接至母分子部份基團。於本文中使用之π亞胺基羥基π —詞，係指=Ν(ΟΗ)。The term "π (heterocycle) alkyl" as used herein refers to a heterocyclyl group connected to the parent molecular moiety through an alkyl group. The term "π (heterocycle) alkylene", as used herein, Refers to a heterocyclyl group attached to the parent molecular moiety through an alkylene group. The term "πhydroxy" as used herein means -0Η. The term "hydroxyalkylπ" as used herein refers to Refers to the hydroxyl group connected to the parent molecular moiety through an alkyl group. As used herein, π iminohydroxy π — the word means = N (ΟΗ).

於本文中使用之”-NReRdn —詞，係指Re與Rd兩個基團，其係經過氮原子連接至母分子部份基團。Re與Rd各獨立選自氫與烷基。於本文中使用之n(NRcRd)烷基π —詞，係指-NReRd基團經過烷基連接至母分子部份基團。於本文中使用之n(NReRd)烷羰基”一詞，係指（NReRd)烷基經過羰基連接至母分子部份基團。於本文中使用之”硝基π —詞，係指-N02。於本文中使用之”酮基”一詞，係指=〇。 -42- 200301122 (35) 於本文中使用之’f磺醯基π —詞，係指-s(o)2-。本發明化合物可以治療上可接受之鹽存在。The term "-NReRdn" as used herein refers to two groups, Re and Rd, which are connected to the parent molecular moiety through a nitrogen atom. Re and Rd are each independently selected from hydrogen and alkyl. In this article The term "n (NRcRd) alkylπ" is used to refer to the -NReRd group connected to the parent molecular moiety through an alkyl group. As used herein, the term "n (NReRd) alkylcarbonyl" refers to (NReRd) The alkyl group is connected to the parent molecular moiety through a carbonyl group. The term "nitro-π" as used herein refers to -N02. The term "keto" as used herein means = 0. -42- 200301122 (35) 'fsulfonium' as used herein The radical π is a term referring to -s (o) 2-. The compounds of the present invention may exist as therapeutically acceptable salts.

於本文中使用之’’治療上可接受之鹽’’ 一詞，係表示本發明化合物之鹽或兩性離子形式，其係為水或油溶性或可分散性，其適用於治療疾病而無不當毒性、刺激性及過敏性回應；其係伴隨著合理利益/風險比，且其對於其所意欲之用途有效。此等鹽可於化合物之最後單離與純化期間製成，或個別經由使胺基與適當酸反應而製成。代表性酸加成鹽包括醋酸鹽、己二酸鹽、海藻酸鹽、檸檬酸鹽、天冬胺酸鹽、苯曱酸鹽、苯磺酸鹽、酸性硫酸鹽、丁酸鹽、樟腦酸鹽、樟腦磺酸鹽、二葡萄糖酸鹽、甘油磷酸鹽、半硫酸鹽、庚酸鹽、己酸鹽、甲酸鹽、反丁烯二酸鹽、鹽酸鹽、氫溴酸鹽、氫蛾酸鹽、2- #呈基乙燒橫酸鹽（輕乙續酸鹽）、乳酸鹽、順丁烯二酸鹽、1，3,5-三曱苯磺酸鹽、甲烷磺酸鹽、次莕基磺酸鹽、菸鹼酸鹽、2-莕磺酸鹽、草酸鹽、雙羥莕酸鹽、果膠酯酸鹽、過硫酸鹽、3-苯基丙酸鹽、苦味酸鹽、三甲基醋酸鹽、丙酸鹽、琥珀酸鹽、酒石酸鹽、三氯醋酸鹽、三氟醋酸鹽、磷酸鹽、麩胺酸鹽、重碳酸鹽、對-甲苯橫酸鹽及十一燒酸鹽。於本發明化合物中之胺基，亦可以甲基、乙基、丙基及丁基氯化物、溴化物及碘化物；二曱基、二乙基、二丁基及二戊基硫酸鹽；癸基、月桂基、肉豆蔻基及硬脂基氯化物、溴化物及碘化物；以及苄基與苯乙基溴化物四級化。可用以形成治療上可接受加成鹽之酸，其實例包括無機酸類，譬如鹽酸、氫溴酸、硫 -43- 200301As used herein, the term `` therapeutically acceptable salt '' means a salt or zwitterionic form of a compound of the present invention, which is water- or oil-soluble or dispersible, which is suitable for treating diseases without improper Toxic, irritating and allergic responses; it is accompanied by a reasonable benefit / risk ratio and it is effective for its intended use. These salts can be prepared during the final isolation and purification of the compound, or individually by reacting an amine group with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, acid sulfate, butyrate, and camphorate , Camphor sulfonate, digluconate, glyceryl phosphate, hemisulfate, heptanoate, hexanoate, formate, fumarate, hydrochloride, hydrobromide, hydrolysate Salt, 2- # ethane ethanoate (light ethyl acetate), lactate, maleate, 1,3,5-trisenebenzenesulfonate, methanesulfonate, hypofluorene Sulfonate, nicotinic acid salt, 2-hydrazone sulfonate, oxalate, dihydroxygallate, pectinate, persulfate, 3-phenylpropionate, picrate, Methyl acetate, propionate, succinate, tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, p-toluate and undecanoate . The amine group in the compound of the present invention can also be methyl, ethyl, propyl and butyl chloride, bromide and iodide; difluorenyl, diethyl, dibutyl and dipentyl sulfate; decyl Base, lauryl, myristyl and stearyl chloride, bromide and iodide; and quaternization of benzyl and phenethyl bromide. Acids that can be used to form therapeutically acceptable addition salts, examples include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfur -43- 200301

(36) 酸及磷酸，及有機酸類，譬如草酸、順丁烯二酸、琥珀酸及擰檬酸。鹼性加成鹽可於化合物之最後單離與純化期間，經由使羧基與適當鹼，譬如金屬陽離子之氫氧化物、碳酸鹽或重碳酸鹽，或與氨或有機一級、二級或三級胺反應而製成。治療上可接受鹽之陽離子，包括鋰、鈉、鉀、鈣、鎂及鋁，以及無毒性四級胺陽離子，譬如銨、四曱基銨、四乙基銨、甲胺、二甲胺、三甲胺、三乙胺、二乙胺、乙胺、三丁胺、吡啶、N，N-二甲苯胺、N-甲基六氫吡啶、N-曱基嗎福啉、二環己基胺、普魯卡因、二苄胺、N，N-二苄基苯乙胺、1-麻黃胺及Ν，Ν^二芊基乙二胺。其他可用於形成鹼加成鹽之代表性有機胺類，包括乙二胺、乙醇胺、二乙醇胺、六氫ρ比咬及六氫说17井。本發明化合物亦可以治療上可接受之前體藥物存在。π 治療上可接受之前體藥物’'一詞，係指前體藥物或兩性離子，其適用於與病患之組織接觸，而無不當毒性、刺激性及過敏性回應，伴隨著合理利益/風險比，且對於其所意欲之用途有效。”前體藥物π —詞係指在活體内被轉變成式 (I)母體化合物之化合物，例如在血液中藉由水解。當任何變數、取代基或術語（例如芳基、雜環、R12等）在化學式或一般性結構中出現超過一次時，其在每一存在處之定義，係與在每一個其他存在處之定義無關。而且，取代基及/或變數之組合，只有在此種組合會造成安定組合時，才是允許的。 -44- 200301 (37)(36) Acids and phosphoric acids, and organic acids such as oxalic acid, maleic acid, succinic acid, and citric acid. Basic addition salts can be used during the final isolation and purification of the compound by contacting the carboxyl group with a suitable base, such as a hydroxide, carbonate or bicarbonate of a metal cation, or with ammonia or organic primary, secondary or tertiary Made by amine reaction. The cations of therapeutically acceptable salts include lithium, sodium, potassium, calcium, magnesium, and aluminum, and non-toxic quaternary amine cations such as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, and trimethylamine. Amine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N, N-xylylamine, N-methylhexahydropyridine, N-fluorenylmorpholine, dicyclohexylamine, pullul Caine, dibenzylamine, N, N-dibenzylphenylethylamine, 1-ephedrine and N, N ^ difluorenylethylenediamine. Other representative organic amines that can be used to form alkali addition salts include ethylenediamine, ethanolamine, diethanolamine, hexahydrogen ratio, and hexahydrogen 17 wells. The compounds of the invention may also be present in a therapeutically acceptable prodrug. The term `` therapeutic acceptable precursor drug '' refers to a prodrug or zwitterion that is suitable for contact with the patient's tissues without undue toxicity, irritant and allergic responses, with reasonable benefits / risks Ratio, and effective for its intended use. "Prodrug π — The word refers to a compound that is converted into the parent compound of formula (I) in vivo, for example by hydrolysis in blood. When any variable, substituent or term (such as aryl, heterocyclic, R12, etc.) ) When it occurs more than once in a chemical formula or general structure, its definition in each place of existence is independent of its definition in every other place of existence. Moreover, the combination of substituents and / or variables is only in such a combination Permissible only when a combination of stability is created. -44- 200301 (37)

由於碳-碳雙键存在於本發明化合物中，故本發明意欲涵蓋由於取代基環繞此等碳-碳雙鍵之排列所形成之各種幾何異構物及其混合物。應明瞭的是，本發明係涵蓋兩種異構物形式或其混合物，其具有抑制蛋白質激酶之能力。此等取代基係被稱為呈E或Z組態，其中”E” 一詞表示較高序取代基在該碳-碳雙鍵之相反側上，而ΠΖΠ —詞表示較高序取代基在該碳-碳雙鍵之同一側上。Since carbon-carbon double bonds are present in the compounds of the present invention, the present invention is intended to cover various geometric isomers and mixtures thereof formed by the arrangement of substituents around these carbon-carbon double bonds. It should be understood that the present invention encompasses two isomeric forms or mixtures thereof which have the ability to inhibit protein kinases. These substituents are said to be in the E or Z configuration, where the term "E" indicates that the higher-order substituent is on the opposite side of the carbon-carbon double bond, and the word ΠZΠ — indicates that the higher-order substituent The carbon-carbon double bond is on the same side.

不對稱中心存在於本發明化合物中。此等中心係藉由符號”R”或” s”指稱，依環繞對掌性碳原子之取代基組態而定。應明瞭的是，本發明係涵蓋所有立體化學異構物形式或其混合物，其具有抑制蛋白質激酶之能力。化合物之個別立體異構物可以合成方式製自含有對掌中心之市購可得起始物質，或藉由製備對掌異構性產物之混合物，接著分離，譬如轉化成非對映異構物之混合物，接著分離或再結晶、層析技術或對掌異構物在對掌性層析管柱上之直接分離。特定立體化學之起始化合物，係為市購可得，或可藉由此項技藝中已知之技術製成與解析。根據治療方法與本發明之醫藥組合物，此等化合物可單獨或併用其他抗癌劑投藥。當使用此等化合物時，對任何特定病患之特定治療上有效劑量程度，係依一些因素而定，譬如被治療之病症與病症之嚴重性；所使用特定化合物之活性；所採用之特定組合物；病患之年齡、體重、一般健康狀態、性別及飲食；投藥時間；投藥途徑；所採用化合物之排泄速率；治療延續時間；及與所使用化合物合併 -45- (38)Asymmetric centers are present in the compounds of the invention. These centers are designated by the symbol "R" or "s", depending on the configuration of the substituents surrounding the palm carbon atoms. It should be understood that the present invention encompasses all stereochemically isomeric forms or mixtures thereof which have the ability to inhibit protein kinases. Individual stereoisomers of a compound can be prepared synthetically from commercially available starting materials containing the paracentre center, or by preparing a mixture of paraisomeric products and then separating them, such as converting to diastereomers The mixture is then separated or recrystallized, chromatographically or directly separated on the palm chromatography column. The starting compounds for a particular stereochemistry are either commercially available or can be prepared and analyzed by techniques known in the art. Depending on the method of treatment and the pharmaceutical composition of the present invention, these compounds may be administered alone or in combination with other anticancer agents. When using these compounds, the degree of a particular therapeutically effective dose for any particular patient depends on factors such as the severity of the condition and condition being treated; the activity of the specific compound used; the specific combination employed Patients; age, weight, general health, gender, and diet of the patient; time of administration; route of administration; excretion rate of the compound used; duration of treatment; and combination with the compound used -45- (38)

或同時使用4 _ j <樂物。此等化合物可以口服、#經腸、滲透 (鼻噴霧劑）、古 ^甚十，直腸、陰道或局部方式，以含有載浏、佐劑、稀釋劑、捕《詞係包括灌注，媒劑或其組合之單位劑量配方投藥。，，非經腸，，以及皮下、靜脈内、肌内及胸骨内注射以非經胳、奸脈Μ 、万式投予之化合物之水性或油彳生懸浮液，可以月，"’、、或懸浮劑調配。此可注射製劑亦玎為在稀釋劑或溶劑中之、、、 ^ , 〉王射溶液或懸浮液。其中所採用又可接受稀釋劑或溶劑佴W ^ ..Or use 4_ j < These compounds can be taken orally, via the intestine, osmotically (nasal spray), ancient or even in the rectal, vaginal, or topical manner, containing a carrier, an adjuvant, a diluent, or a compound. The combined unit dose formulation is administered. , Parenteral, and subcutaneous, intravenous, intramuscular and intrasternal injection of a non-menstrual, venous M, aqueous or oily suspension of the compound can be monthly, " ', , Or suspending agent. This injectable preparation is also in a diluent or solvent, and is a solution or suspension of Wang She. Among them, diluent or solvent 佴 W ^ is acceptable.

係為水、鹽水、林格氏溶液、缓衝劑、甘油單酉旨、甘油二两匕曰腸肪酸類，譬如油酸，及不揮發/由類’譬如甘油單酯或甘； 1:1 >由二酯。以非經腸太々 ^ 式投予之化合物之抗癌作用，玎藉由減緩其吸收而被延長。、、使特定化合物之吸收減緩之/種方式’是投予可注射乏接、積貯形式，其包含化合物之結晶性、非晶質或其他水不沒：Μ· + 性形式之懸浮液。此化合物之吸收速率係依其溶解速率而令 > ^、夂，其依次視其物理狀態而定。使特疋化合物之吸收減结^It is water, saline, Ringer's solution, buffering agent, glycerol monohydrate, glycerol, intestinal fatty acids, such as oleic acid, and non-volatile / derived from such as monoglycerides or glycerol; > From diester. The anti-cancer effect of a compound administered parenterally is not prolonged by slowing its absorption. The method / mode of slowing the absorption of a specific compound is to administer an injectable depleted, storage form, which contains a crystalline, amorphous, or other water of the compound: a suspension in the form of M · +. The absorption rate of this compound depends on its dissolution rate > ^, 夂, which in turn depends on its physical state. Reduce absorption of special compounds ^

… < 另一種方式，是投予包含作成油質溶液或释浮液之化入〜口物之可注射積貯形式。使特定化合物之吸收減缓之又另_種士斗、 ^ ι ^ ^ Α 禮万式，疋投予可注射積貯形式，其包含福捕獲在微脂粒、與q 、微礼化液或生物可降解聚合體内之化合物之微膠囊基質，与r：c ^ I合體譬如聚内交酯，聚乙交酯、聚原酸酉曰或禾酐類。依藥物對聚合體之比例，及聚合體之組成而定，藥物釋出之速率可加以控制。經皮貼藥亦可提供此等化合可利用速率控制薄膜或經由使物之經控制傳輸。吸收速率化合物捕獲在聚合體基質或 -46-… &Lt; Another way is to administer an injectable storage form that contains an injectable ~ mouthpiece made as an oily solution or release fluid. Slow down the absorption of specific compounds A microcapsule matrix of compounds in a biodegradable polymer, combined with r: c ^ I, such as polylactide, polyglycolide, polyorthoester, or gramic anhydride. Depending on the ratio of drug to polymer and the composition of the polymer, the rate of drug release can be controlled. These compounds can also be provided by transdermal patches, which can use rate-controlling films or controlled delivery via animals. Absorption rate Compounds are trapped in the polymer matrix or -46-

吸收凝膠中而被減緩。反之，口及收增強劑可用以拇供口服投藥之固體劑量形式，包括膠囊、Θ如吸粉末及顆粒。在此等固體劑量形式片釗、丸劑、、丁，右性化厶片及 '' 膠I 丸劑亦可包含緩衝劑，而片劑與丸劑可被製片塗層或其他控制釋出之塗層。粉末與喷霧劑有腸劑，譬如滑石、矽酸、氫氧化鋁、矽酸鈣、^可含有賦牙其混合物。噴霧劑可另外含有習用推進劑：：略，粉束3 或其代用品》 S如氣氟輕I 供口服投藥之液體劑量形式，包括乳化液、微Λ 溶液、懸浮液、糖漿及酏劑，其包含惰性稀釋劑礼化液. 況包含稀釋劑，譬如薦糖、乳糖、澱粉、滑石0物可視情氧化銘、_酸每、聚醯胺粉末、製藥片用酸、氫用助劑’譬如硬脂酸鎂，或微晶性纖維素。I劑及製藥片劑Absorbed in the gel and slowed down. Conversely, oral and oral enhancers can be used in solid dosage forms for oral administration, including capsules, Θ such as powders and granules. In these solid dosage forms, tablets, pills, tinctures, dextrinized tablets, and Glue I pills can also contain buffers, and tablets and pills can be coated with tablets or other controlled release coatings . Powders and sprays include enteric preparations, such as talc, silicic acid, aluminum hydroxide, calcium silicate, and may contain mixtures of teeth. The spray may additionally contain customary propellants :: slightly, powder 3 or its substitutes "such as gas fluoride light I liquid dosage forms for oral administration, including emulsions, micro Λ solutions, suspensions, syrups and elixirs, It contains an inert diluent solution. It also contains diluents, such as recommended sugars, lactose, starch, talc, and other oxidative substances, acid acids, polyamine powder, pharmaceutical tablets, acids, and hydrogen additives. Magnesium stearate, or microcrystalline cellulose. I agent and pharmaceutical tablets

^ 厂 ^Τ'4 此等組合物亦可包含佐劑，譬如潤濕、乳化、譬如懸浮、甜、矯味及芳香劑^ Factory ^ Τ'4 These compositions may also contain adjuvants such as wetting, emulsifying, such as suspension, sweetening, flavoring and fragrance

局部劑量形式包括軟膏 '糊劑、乳t、洗劑、々末、溶液、噴霧劑、吸藥及經皮貼藥。將化合物：膠、件下與載劑及任何所需要之防腐劑或緩衝劑混合菌量形式亦可包含賦形劑’譬如動物與植物脂肪類、2: 墙類 ' 石it '殿粉 ' 西黃蓍樹膠、纖維素衍生物、聚乙醇、聚矽氧、膨土、矽酸、滑石及氧化鋅或其混合物。直腸或陰道投藥用足拴劑，可經由將化合物與適當無刺性賦形劑混合而製成，該賦形劑譬如可可豆脂或聚乙二，其每一個在一般溫度下為固體，但在直腸或陰道中為 •47- 200301122 (40) 體。眼用配方，包括滴眼劑、眼用軟膏、粉末及溶液，亦意欲涵蓋在本發明之範圍内。以單一或分離劑量投予宿主之化合物之總日服劑量，其量可為約0.1至約200毫克/公斤體重，或較佳為約0.25至約 100毫克/公斤體重。單一劑量組合物可含有此等量或其約數，以構成日服劑量。生物活十生之涓!1定酶檢測：此Aktl檢測係使用His-Aktl-S36，其為一種截頭之Aktl，含有His標記在Aktl之N-末端胺基酸139-460處，及下列點突變 :S378A、S381A、T450D 及 S473D。此 His-Aktl-S36 檢測係在 96 井板中操作，其方式是將1 nM His-Aktl-S36, 5 生物素-BAD-肽（生物素）及5 /zM33P-ATP於50微升反應緩衝劑中（20mMHEPES， pH 7.5, 10 mM MgCl2，0.009% Triton X-100)中，在室溫下培養 30 分鐘。藉由添加25微升停止用緩衝劑（4M NaCl與0.1M EDTA)，使反應停止。將試樣轉移至已塗覆鏈黴胺基酸之閃光板。BAD-肽於反應中之鱗酿化作用，係經由以TopCount計數板，進行度量。其他激酶檢測（Akt2、Akt3、PKA、PKC、Erk2、Chkl、 Cdc2、Src、CK2、MAPKAP激酶2及SGK)係以類似方式使用其專一生物素化肽受質與緩衝劑條件進行。本發明化合物在1 濃度下，會抑制Akt達0-100%。較佳化合物於1 下，具有抑制百分比在77與100之間，而更佳化合物在1 下具有抑制百分比在92與100之間。因此，本發明化合物可用於治療因增加之蛋白質激酶含量所造成或加重之病症。 -48- 2〇〇30U22 (41)Topical dosage forms include ointments, creams, lotions, creams, solutions, sprays, inhalants and transdermal patches. Compounds: glue, gelatin, carrier, and any preservatives or buffers needed. Bacterial dosage forms can also include excipients 'such as animal and vegetable fats, 2: wall type', stone it, 'temple powder', west. Sumac gum, cellulose derivatives, polyethanol, polysiloxane, bentonite, silicic acid, talc and zinc oxide or mixtures thereof. Rectal or vaginal foot suppositories can be prepared by mixing the compound with a suitable non-thorny excipient, such as cocoa butter or polyethylene, each of which is solid at ordinary temperatures, but • 47- 200301122 (40) body in the rectum or vagina. Ophthalmic formulations, including eye drops, ointments, powders, and solutions, are also intended to be within the scope of this invention. The total daily dosage of a compound administered to a host in a single or isolated dose may range from about 0.1 to about 200 mg / kg body weight, or preferably from about 0.25 to about 100 mg / kg body weight. Single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. Life is alive! 1 enzyme assay: This Aktl test uses His-Aktl-S36, which is a truncated Aktl containing His tag at the N-terminal amino acid 139-460 of Aktl, and the following Point mutations: S378A, S381A, T450D and S473D. This His-Aktl-S36 assay was performed in a 96-well plate by 1 nM His-Aktl-S36, 5 biotin-BAD-peptide (biotin) and 5 / zM33P-ATP in 50 μl reaction buffer (20mMHEPES, pH 7.5, 10 mM MgCl2, 0.009% Triton X-100), and incubated at room temperature for 30 minutes. The reaction was stopped by adding 25 microliters of a stop buffer (4M NaCl and 0.1M EDTA). The sample was transferred to a glitter plate coated with streptavidin. The scale-making effect of BAD-peptide in the reaction is measured by using a TopCount counting plate. Other kinase assays (Akt2, Akt3, PKA, PKC, Erk2, Chkl, Cdc2, Src, CK2, MAPKAP kinase 2 and SGK) were performed in a similar manner using their specific biotinylated peptide substrate and buffer conditions. The compound of the present invention inhibits Akt by 0 to 100% at a concentration of 1. The preferred compound has a inhibition percentage between 77 and 100 at 1 and the better compound has a inhibition percentage between 92 and 100 at 1. Accordingly, the compounds of the present invention are useful for treating conditions caused or exacerbated by increased protein kinase content. -48- 20000U22 (41)

已被使用於下文圖式與實例之說明文中之縮寫，係為： DEAD為偶氮二羧酸二乙酯；THF為四氫呋喃；MTBE為甲基第三-丁基醚，PPh3為三苯膦；〇Ac為醋酸酯；p(0_to1)3為三-鄰呷笨基膦；dba為二苯亞甲基丙酮；DME為1,2-二甲氧基乙烷；BINAP為2,2，-雙（二苯基膦基）4，1L聯莕；DMAP為4-二甲胺基吡啶；dppf為二苯基膦基二環戊二烯鐵；dppe為二苯基膦基乙烷；EDC為1-乙基-3-[3-(二甲胺基）丙基]碳化二亞胺鹽版鹽；HOBt為1-輕基苯并三峻；DCC為1，3-二環己基碳化二亞胺；DMF為二甲基甲醯胺；NMP為N-甲基四氫吡咯酮； DMSO為二曱亞颯；Boc為第三-丁氧羰基；TFA為三氟醋酸，DIBAL為氫化二異丁基銘；n-BuLi為正-丁基If ; 9-BBN為9-硼雙環并[3·3·1]壬烷；OiPr為異丙氧化物；DMA為二甲基乙醯胺；AIBN為2,2’-偶氮雙異丁腈；TEA為三乙胺；及NBS為诈溴基琥珀醯亞胺。本發明疋化合物與方法，伴隨著下述合成圖式，將更為明瞭，其係說明可藉以製備本發明化合物之方法。基團 ιΛιΛιΛη1，！^，！^ R4 R6A r7 八q如上又定義，除非下文另有指明。本發明係意欲涵蓋當藉由人卜田0成万法或藉由代謝程序製成時，具有式（I)之化合物。本發明化合物藉由代謝程序之製備，係包括發生在人類或動勒物身體中（活體内）之程序，或發生於活體外之過程。 '49, 200301122 (42)The abbreviations used in the descriptions of the following figures and examples are: DEAD is diethyl azodicarboxylate; THF is tetrahydrofuran; MTBE is methyl tertiary-butyl ether; PPh3 is triphenylphosphine; 〇Ac is acetate; p (0_to1) 3 is tris-o-ammonium benzylphosphine; dba is diphenylmethyleneacetone; DME is 1,2-dimethoxyethane; BINAP is 2,2, -bis (Diphenylphosphino) 4,1L bifluorene; DMAP is 4-dimethylaminopyridine; dppf is diphenylphosphinodicyclopentadiene iron; dppe is diphenylphosphinoethane; EDC is 1 -Ethyl-3- [3- (dimethylamino) propyl] carbodiimide salt edition salt; HOBt is 1-light benzotrimethylene; DCC is 1,3-dicyclohexylcarbodiimide DMF is dimethylformamide; NMP is N-methyltetrahydropyrrolidone; DMSO is diamidine; Boc is the third-butoxycarbonyl group; TFA is trifluoroacetic acid and DIBAL is hydrogenated diisobutylammonium; n-BuLi is n-butyl If; 9-BBN is 9-borabicyclo [3 · 3 · 1] nonane; OiPr is isopropoxide; DMA is dimethylacetamide; AIBN is 2,2 '-Azobisisobutyronitrile; TEA is triethylamine; and NBS is bromosuccinimide. The hydrazone compound and method of the present invention will be made clearer along with the following synthetic scheme, which illustrates a method by which the compound of the present invention can be prepared. The group ιΛιΛιΛη1! ^ ,! ^ R4 R6A r7 Eight q are as defined above, unless otherwise specified below. The invention is intended to encompass compounds having formula (I) when made by humans or by metabolic procedures. The compounds of the present invention are prepared by metabolic procedures, including procedures that occur in the body of humans or animals (in vivo), or processes that occur outside the body. '49, 200301122 (42)

圖式ίSchema

如圖式1中所示，式（2)化合物（Ζ為Cl、Br、I或〇Tf)可於：苯膦與活化劑譬如DEAD存在下，經由以式⑶化合物處理，而被轉化成式⑷化合物《此反應可於不含溶劑下或於溶劑存在下進行，譬如THF、乙醚及MTBE。反應溫度典型上為約-10 C至約35°C，且反應時間典型上為約8至約24小時。As shown in Formula 1, a compound of formula (2) (Z is Cl, Br, I, or Otf) can be converted into a formula by treating with a compound of formula ⑶ in the presence of phenylphosphine and an activator such as DEAD This compound can be carried out without solvent or in the presence of a solvent such as THF, ether and MTBE. The reaction temperature is typically about -10 C to about 35 ° C, and the reaction time is typically about 8 to about 24 hours.

式（4)化合物可於鈀觸媒與選用添加劑譬如三乙胺存在下，經由以式⑶化合物（M係選自B(0H)2 ; Sn(Ra)3，其中Ra為烷基或芳基；及氫）處理，而被轉化成式（Ia)化合物。鈀觸媒之實例包括Pd(PPh3)4與Pd(〇Ac)2& P(o-tol)3。代表性溶劑包括甲苯、乙腈及DME。此反應典型上係在約60°C與約110C間之溫度下進行’且反應時間典型上為約4至約12小時。圖式2The compound of formula (4) can be in the presence of a palladium catalyst and an optional additive such as triethylamine by using a compound of formula (M is selected from B (0H) 2; Sn (Ra) 3, where Ra is alkyl or aryl ; And hydrogen), and is converted into a compound of formula (Ia). Examples of the palladium catalyst include Pd (PPh3) 4 and Pd (〇Ac) 2 & P (o-tol) 3. Representative solvents include toluene, acetonitrile, and DME. This reaction is typically carried out at a temperature between about 60 ° C and about 110C 'and the reaction time is typically about 4 to about 12 hours. Schema 2

圖式2顯示式⑹化合物（Z1與Z2係獨立為Cl、Br、I或〇Tf) 可根據圖式1中所述之程序，經由以式⑺化合物處理，而被轉化成式（8)化合物。此等化合物可經由以二苯甲酮亞胺 -50- 200301122Scheme 2 shows that the compound of formula （(Z1 and Z2 are independently Cl, Br, I or 〇tf) can be converted into the compound of formula (8) by treating with the compound of formula 根据 according to the procedure described in formula 1 . These compounds are available via benzophenone imine -50- 200301122

(43) ' &觸媒及驗處理，而被轉化成式⑼化合物。鈀觸媒之實例包括PAdba3，與配位體，譬如BINAp、dppf或dppe。代表性驗包括第二-丁醇锏與第三-丁醇鉀。典型上，此反應係在〉谷赞彳中’譬如曱笨、乙腈或DME ;於溫度約60°C至約90°C下 ,及在約8至約24小時之時間下進行。式⑼化合物可於酸譬如醋酸存在下，以式（10)化合物處理’然後以氰基硼氫化鈉處理，提供式（Ib)化合物。代表性〉谷劑包括甲醇與乙醇。此反應典型上係於約2〇。〇至約7〇。〇下進行’且反應時間典型上為約1至約4小時。圖式3(43) '& catalyst and test treatment, and was converted into a compound of formula (I). Examples of palladium catalysts include PAdba3, and ligands such as BINAp, dppf or dppe. Representative tests included second-butoxide and third-butoxide. Typically, this reaction is carried out in> Guzanjiu ', such as benzene, acetonitrile, or DME; at a temperature of about 60 ° C to about 90 ° C, and for a time of about 8 to about 24 hours. The compound of formula VII can be treated with a compound of formula (10) 'in the presence of an acid such as acetic acid and then treated with sodium cyanoborohydride to provide a compound of formula (Ib). Representative> Cereals include methanol and ethanol. This reaction is typically tied to about 20 °. 〇 to about 70. It is carried out below, and the reaction time is typically about 1 to about 4 hours. Scheme 3

⑴） (12) (ic) 圖式3顯示式（Ic)化合物之製備。式（11)化合物（z為Br)可於 co氣層下，以免觸媒處理，提供式（12)化合物。鈀觸媒之實例包括PdC〗2 · dppf、PdCl2與ΒΙΝΑΡ及PdCl2 · dppe。代表性溶劑包括THF、水、DME及其混合物。此反應典型上係於約8〇。〇至約100°C下進行，且反應時間典型上係在12與24小時之間。式（12)化合物可於偶合劑存在下，經由以經取代之胺處理，而被轉化成式（Ic)化合物。代表性偶合劑包括EDC、H0Bt 、DCC、DMAP及其混合物。所使用溶劑之實例包括二氯曱烷、DMF及DME。此反應典型上係於約ο。至約35它下進行，且反應時間典型上為約12至約24小時。 -51 - 200301Ii) (12) (ic) Scheme 3 shows the preparation of a compound of formula (Ic). The compound of formula (11) (z is Br) can be under the co gas layer to avoid catalyst treatment, so as to provide the compound of formula (12). Examples of palladium catalysts include PdC 2 · dppf, PdCl 2 and BINAP, and PdCl 2 · dppe. Representative solvents include THF, water, DME, and mixtures thereof. This reaction is typically tied to about 80. 0 to about 100 ° C, and the reaction time is typically between 12 and 24 hours. The compound of formula (12) can be converted into a compound of formula (Ic) by treating with a substituted amine in the presence of a coupling agent. Representative coupling agents include EDC, HOBt, DCC, DMAP, and mixtures thereof. Examples of the solvent used include dichloromethane, DMF and DME. This reaction is typically tied to about ο. It is carried out at about 35 and the reaction time is typically about 12 to about 24 hours. -51-200301

(44)(44)

如圖式4中所示，式（13)化合物可被水解，以提供式（14)化合物，使用一般熟諳此藝者已知之方法進行。式（M)化合物可使用圖式3中所述之條件，轉化成式（Id)化合物。圖式5As shown in Formula 4, the compound of formula (13) can be hydrolyzed to provide the compound of formula (14) using a method known to those skilled in the art. The compound of formula (M) can be converted into a compound of formula (Id) using the conditions described in Scheme 3. Scheme 5

(15) h2n R2(15) h2n R2

圖式5顯示式（Ie)化合物之合成。式（15)化合物可經由以還原劑處理，而被轉化成式（16)化合物。還原劑之實例包括Pd/C 與甲酸銨，Pd/C與氫，及pt〇2與氫。代表性溶劑包括甲醇與乙醇。此反應典型上係於約50°C至約70°C下進行，歷經約15 分鐘至约2小時。式（16)化合物可經由以親電子基團，譬如函基取代之雜芳基處理，而被轉化成式（Ie)化合物。使用於此等反應中之溶劑，其實例包括乙醇與甲醇。此反應典型上係於約50°C 至约70°C下進行，歷經約6至約18小時。Scheme 5 shows the synthesis of a compound of formula (Ie). The compound of formula (15) can be converted into a compound of formula (16) by treatment with a reducing agent. Examples of the reducing agent include Pd / C and ammonium formate, Pd / C and hydrogen, and pt02 and hydrogen. Representative solvents include methanol and ethanol. This reaction is typically performed at about 50 ° C to about 70 ° C over a period of about 15 minutes to about 2 hours. The compound of formula (16) can be converted into a compound of formula (Ie) by treatment with an electrophilic group such as a heteroaryl substituted with a functional group. Examples of the solvent used in these reactions include ethanol and methanol. This reaction is typically performed at about 50 ° C to about 70 ° C over a period of about 6 to about 18 hours.

-52- (45) 如圖式6中所示，式⑻化合物可於鈀觸媒與鹼譬如碳酸铯或碳酸鈉存在下，經由以式（17)化合物（M為B(〇Rz)2，其-52- (45) As shown in formula 6, the compound of formula VII can be prepared in the presence of a palladium catalyst and a base such as cesium carbonate or sodium carbonate by using a compound of formula (17) (M is B (〇Rz) 2, its

中R為氲或燒基）處理，而被轉化成式（If)化合物（其中L2為键結）。代表性鈀觸媒包括 PdCl2 .dppf、Pd(PPh3)4 及 PdCl2(PPh3)2 。使用於此等反應中之溶劑，其實例包括DMF、DME及NMP 。此反應典型上係於約3(^c至約1〇〇〇c下進行，歷經約4至約 12小時。圖式7 〇Where R is fluorene or alkynyl), it is converted into a compound of formula (If) (where L2 is a bond). Representative palladium catalysts include PdCl2.dppf, Pd (PPh3) 4 and PdCl2 (PPh3) 2. Examples of solvents used in these reactions include DMF, DME, and NMP. This reaction is typically performed at about 3 ° C to about 1000c, over a period of about 4 to about 12 hours. Scheme 7

如圖式7中所示，式⑼化合物可使用圖式3中所述之條件，與式（18)化合物反應，以提供式（Ig)化合物。現在’伴隨著某些較佳具體實施例說明本發明，其並非意欲限制其範圍。反之，本發明係涵蓋可包含在申請專利範圍之範轉内之所有替代方式、修正及等效事物。因此，下述實例，其包括較佳具體實施例，將說明本發明之較佳實施’應明瞭的是，此等實例係為達說明某些較隹具體實施例之目的，且被提出以提供咸認係為其程序與概念方面之最有用及易於瞭解之說明。 -53- (46) 實例1As shown in Formula 7, a compound of formula (I) can be reacted with a compound of formula (18) using conditions described in Figure 3 to provide a compound of formula (Ig). The invention is now illustrated with certain preferred embodiments, and is not intended to limit its scope. On the contrary, the present invention covers all alternatives, modifications, and equivalents that can be included in the scope of the patent application. Therefore, the following examples, which include preferred embodiments, will illustrate preferred implementations of the present invention. It should be understood that these examples are for the purpose of illustrating some of the more specific embodiments, and are proposed to provide It is the most useful and easy-to-understand description of its procedures and concepts. -53- (46) Example 1

吡啶斗基上^基]吡啶各基}氣基）乙某— 實例1A 土位:[(5_溴羞吡啶各基）氧某1乙基}-N,N-二甲脖將Ν，Ν·二甲基乙醇胺（〇·5毫升）於DMF (10毫升）中之溶液，在1溫下’以氫化鈉（〇·2克，8·4毫莫耳）處理，攪拌3〇分鐘 ’並以3,5-二溴基吡啶（1·〇克，4·2毫莫耳）處理。將混合物在90 C下攪拌8小時，並於醋酸乙酯與水之間作分液處理。將有機層以鹽水洗滌，脫水乾燥@々304)，過濾及在真空下褒縮。於碎膠上藉急驟式管柱層柙純化，使用5〇%醋酸乙酯/己烷，提供所要之產物（〇·8克，78% )。MS (DCI/NH3)m/e 246 (M+H)+ ·Pyridinyl] pyridyl] pyridyl groups} air group) Ethyl — Example 1A Soil position: [(5_bromopyridyl each radical) oxygen certain 1ethyl} -N, N-dimethylamino N, N A solution of dimethylethanolamine (0.5 ml) in DMF (10 ml), 'treated with sodium hydride (0.2 g, 8.4 mmol) at 1 temperature, and stirred for 30 minutes' and Treated with 3,5-dibromopyridine (1.0 g, 4.2 mmol). The mixture was stirred at 90 C for 8 hours and subjected to liquid separation between ethyl acetate and water. The organic layer was washed with brine, dried (@ 々304), filtered and condensed under vacuum. Purification by flash column chromatography on crushed gel using 50% ethyl acetate / hexane provided the desired product (0.8 g, 78%). MS (DCI / NH3) m / e 246 (M + H) + ·

實例IB 迎-二甲基-N-[2-({5-『(EV2-吡啶-4-某乙烯基 >比啶-3-基}氣基）乙基1胺將實例ΙΑ (0.8克，3·27毫莫耳）、4-乙烯基吡啶（0.69克，5.53 毫莫耳）、三-鄰-甲苯基膦（〇·6克，1.96毫莫耳）、醋酸鈀（0.16 克，0·65毫莫耳）及三乙胺（0.66克，6.53毫莫耳）於乙腈（15毫升）中之混合物，在80°C下攪拌8小時。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層以鹽水洗滌，脫水乾燥（Na2S04)，過濾及在真空下濃縮。於矽膠上藉急騾式管柱層析純化，使用10%甲醇/二氯甲烷，提供所要之產物 (0.64 克，73 % )。MS (DCI/NH3) m/e 270 (M+H)+ ; 1 H NMR (DMSO-D6) 5 8.58 (d，>=6·0 Hz，2H)，8.39 (s，1H)，8·24 (s，1H)，7·73 (s，1H)，7.56 (d，J=6.0 Hz， 1H)，7.56 (m，2H)，7.45 (d，J=16.5 Hz，2H)，4·19 (t，J=6.0 Hz，2H)，2.67 (t，J=6.0 Hz， -54- 0301122 (47) 2H)，2·23 (s，6H). 實例2 (LS)-2-(lH-吲哚-3-基）·Η({5-『(Ε)-2-畋啶基 Μ 啶！甚其、Example IB Welcome-dimethyl-N- [2-({5-"(EV2-pyridin-4-some vinyl > pyridin-3-yl) amino) ethyl 1 amine Example IA (0.8 g , 3.27 mmoles), 4-vinylpyridine (0.69 g, 5.53 mmoles), tri-o-tolylphosphine (0.6 g, 1.96 mmoles), palladium acetate (0.16 g, 0 · A mixture of 65 mmol and triethylamine (0.66 g, 6.53 mmol) in acetonitrile (15 ml), stirred at 80 ° C for 8 hours. The reaction solution was made between ethyl acetate and water. Liquid separation. The organic layer was washed with brine, dried (Na2S04), filtered and concentrated under vacuum. Purified by flash column chromatography on silica gel using 10% methanol / dichloromethane to provide the desired product. (0.64 g, 73%). MS (DCI / NH3) m / e 270 (M + H) +; 1 H NMR (DMSO-D6) 5 8.58 (d, > = 6.0 Hz, 2H), 8.39 (s, 1H), 8.24 (s, 1H), 7.73 (s, 1H), 7.56 (d, J = 6.0 Hz, 1H), 7.56 (m, 2H), 7.45 (d, J = 16.5 Hz, 2H), 4.19 (t, J = 6.0 Hz, 2H), 2.67 (t, J = 6.0 Hz, -54-0301122 (47) 2H), 2.23 (s, 6H). Example 2 ( LS) -2- (lH-indole-3-yl) · Η ({5- (Ε) -2- piperidyl Μ Tin piperidine! Very thereof,

甲基1乙胺實例2A (lS)-2-〖(5-羥基吡啶-3-基）氣基1-1-ΠΗ-吲哚；其甲某|脸其甲酸第三-丁酯將3-溴基-5-羥基吡啶（2.0克，11·5毫莫耳）、l-Boc-色胺酸（3.67 克’ 12.6當莫耳）及二苯膦（4.53克’ 17·3毫莫耳）之溶液，於〇 °C下，以DEAD(3.01克，17·3毫莫耳）逐滴處理，溫熱至室溫 ’攪拌過夜及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用己烷/醋酸乙酯（4 : 1),提供所要之產物（4 55克 ’ 88.7% )。MS (DCI/NH3) : m/e 446, 448 (Μ+Η)+ · 實例2Β 吡基乙烯基Μ啶冰基}氣基） 1_基1乙基胺基甲醢第三-丁酯所要之產物係經由以實例2Α取代實例1Β中之實例1Α而製成。MS (DCI/NH3) m/e 471 (Μ+Η)+ ·Examples of methyl 1 ethylamine 2A (1S) -2-[(5-hydroxypyridin-3-yl) aeroyl 1-1-1Η-indole; its a certain | face its third-butyl formate will be 3- Bromo-5-hydroxypyridine (2.0 g, 11.5 mmol), l-Boc-tryptophan (3.67 g '12.6 dmol) and diphenylphosphine (4.53 g' 17.3 mol) The solution was treated dropwise with DEAD (3.01 g, 17.3 mmol) at 0 ° C, warmed to room temperature, stirred overnight, and concentrated. The concentrate was purified by flash column chromatography on silica gel using hexane / ethyl acetate (4: 1) to provide the desired product (4555 g '88 .7%). MS (DCI / NH3): m / e 446, 448 (M + Η) + · Example 2B Pyridinylmethylpyridinyl} Gasyl) 1-yl 1 ethylamino formamidine tert-butyl ester The product was prepared by replacing Example 1A in Example 1B with Example 2A. MS (DCI / NH3) m / e 471 (Μ + Η) + ·

實例2C (jg>2-(lH·^^士[(丨5_「⑹·2·^4_基乙烯某】吡啶各基}氧基）Example 2C (jg > 2- (lH · ^^ 士 [(丨 5_ "⑹ · 2 · ^ 4_ylethene} pyridine each group} oxy)

1.28毫莫耳）於二氯曱烷（2〇毫升）中之在一氧陸圜中之4Ν HC1 (5亳升）處理，。使殘留物溶於水（1.5毫升）中，並凍將實例2Β (603亳克，溶液，在室溫下，以擾摔2小時，及濃縮 -55- (48) 乾，提供所要之產物，為其鹽酸鹽·（610毫克，99% )。MS (DCI/NH3) m/e 371 (M+H) V H NMR (CD3 OD) 5 8·76 (d，J=6.8 Hz，2H)，8·52 (d，J=1.4 Hz， 1H)，8.38 (d，J=2.4 Hz，1H)，8.16 (d，J=7.1 Hz，2H)，7·86 (d，J=16.6 Hz，1H)，7.77 (m， 1H)，7.60 (d，J=8.1 Hz，1H)，7.52 (d5 J=8.1 Hz，1H)，7.50 (d，J=16.6 Hz，1H)，7.39 (d， J=8.1 Hz，1H)，7.28 (s，1H)，7.13 (m，1H)，7.03 (m，1H)，4·39 (dd，J=3.4, 10.5 Hz，1H)， 4.25 (dd，J=5.4, 10.5 Hz，1H)，4.00 (m，1H)，3.30 (m，2H)·1.28 millimolar) in dichloromethane (20 ml) and treated with 4N HC1 (5 ml) in dioxane. Dissolve the residue in water (1.5 ml) and freeze Example 2B (603 g, solution at room temperature, stir for 2 hours, and concentrate -55- (48) dry to provide the desired product, Its hydrochloride salt (610 mg, 99%). MS (DCI / NH3) m / e 371 (M + H) VH NMR (CD3 OD) 5 8 · 76 (d, J = 6.8 Hz, 2H), 8.52 (d, J = 1.4 Hz, 1H), 8.38 (d, J = 2.4 Hz, 1H), 8.16 (d, J = 7.1 Hz, 2H), 7.86 (d, J = 16.6 Hz, 1H ), 7.77 (m, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.52 (d5 J = 8.1 Hz, 1H), 7.50 (d, J = 16.6 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.28 (s, 1H), 7.13 (m, 1H), 7.03 (m, 1H), 4.39 (dd, J = 3.4, 10.5 Hz, 1H), 4.25 (dd, J = 5.4 , 10.5 Hz, 1H), 4.00 (m, 1H), 3.30 (m, 2H) ·

實例2D (lS)-2-(lH-4l 嗓-3-基）-l-f({54(EV2-p比咬-4-基乙婦基比淀-3-基}氧基）甲基1乙胺將實例2B (500毫克，1.06毫莫耳）於二氯甲烷（5毫升）中之溶液，在室溫下，以三氟醋酸（5毫升）處理，攪拌2小時，及濃縮。使殘留物溶於水（1.5毫升）中，並凍乾，提供所要之產物，為三氟醋酸鹽（643毫克，85% )。MS(DCI/NH3)m/e371 (M+H)+ ； 1 H NMR (CD3 OD) δ 8.83 (d, J=7 Hz, 2H), 8.77 (br s, 1H), 8.58 (br s5 1H), 8.39 (br s, 1H), 8.29 (d, J=7 Hz, 2H), 7.98 (d, J=17 Hz, 1H), 7.82 (d3 J=17 Hz, 1H)，7·61 (d，J=7 Hz，1H)，7.48 (d，J=7 Hz，1H)，7.28 (s，1H)，7.09-7.14 (m，1H)， 6.99-7.04 (m，1H)，4.504.57 (m，1H)，4.39-4.45 (m，1H)，4.02-4.08 (m，1H)，3.30-3.38 (m, 2H). 實例3 (1RV2-(1H-吲哚-3-基VH(丨5-mEV2-吡啶斗某乙烯基1吡啶-3-基}氣基）甲基1乙胺所要之產物係經由以D-Boc-色胺酸取代實例2A中之L-Boc-色胺酸，然後按實例2B與2C所述進行，以其鹽酸鹽製成。 MS(DCI/NH3)m/e371 (M+Hf ； 1 H NMR (CD3 OD) 5 8.76 (d, J=6.1 Hz, 2H), -56- 200301122Example 2D (lS) -2- (lH-4l acyl-3-yl) -lf ({54 (EV2-p ratio -4--4-ethylethenylpyridyl-3-yl} oxy) methyl 1ethyl Amine A solution of Example 2B (500 mg, 1.06 mmol) in dichloromethane (5 ml) was treated with trifluoroacetic acid (5 ml) at room temperature, stirred for 2 hours, and concentrated. The residue was allowed to Dissolved in water (1.5 ml) and lyophilized to provide the desired product as trifluoroacetate (643 mg, 85%). MS (DCI / NH3) m / e371 (M + H) +; 1 H NMR (CD3 OD) δ 8.83 (d, J = 7 Hz, 2H), 8.77 (br s, 1H), 8.58 (br s5 1H), 8.39 (br s, 1H), 8.29 (d, J = 7 Hz, 2H ), 7.98 (d, J = 17 Hz, 1H), 7.82 (d3 J = 17 Hz, 1H), 7.61 (d, J = 7 Hz, 1H), 7.48 (d, J = 7 Hz, 1H) , 7.28 (s, 1H), 7.09-7.14 (m, 1H), 6.99-7.04 (m, 1H), 4.504.57 (m, 1H), 4.39-4.45 (m, 1H), 4.02-4.08 (m, 1H), 3.30-3.38 (m, 2H). Example 3 (1RV2- (1H-indol-3-yl VH (5-mEV2-pyridine, a vinyl 1pyridin-3-yl) yl group) methyl group 1 The desired product of ethylamine was obtained by substituting D-Boc-tryptophan for L-Boc-tryptophan in Example 2A, and then proceeding as described in Examples 2B and 2C to Hydrochloride formed MS (DCI / NH3) m / e371 (M + Hf;. 1 H NMR (CD3 OD) 5 8.76 (d, J = 6.1 Hz, 2H), -56- 200301122

(49) 8·52 (m，1Η)，8·37 (m，1H)，8.17 (d，J=6.1 Hz，2H)，7·86 (d，J=16.6 Hz，1H)，7.79 (m， 1H)，7.59 (d，J=7.8 Hz，1H)，7.53 (d，J=16.6 Hz，1H)，7.50 (d，J=16.6 Hz，1H)，7.38 (d， J=8.1 Hz, 1H), 7.23 (s5 1H), 7.12 (m3 1H)5 7.02 (m5 1H), 4.38 (dd3 J=3.13 10.5 Hz, 1H), 4.25 (dd，J=5.4, 10.5 Hz，1H)，3.99, (m，1H)，3.26 (m，2H). 實例4 1-(1H-口弓1 口来-3-基）-3-({5-「(E)-2-口比症-4-基乙婦基1口比咬-3-基}氧基）丙-2-醇將實例2C (150毫克，0.400毫莫耳）於酷酸（2.4毫升）中之溶液，在室溫下，以NaN〇2 (117毫克，1.70毫莫耳）分次處理，攪拌18小時，以水（40微升）使反應淬滅，再攪拌一小時，倒入2N NaOH中，並以異丙醇/二氯曱烷萃取。使合併之萃液濃縮。將殘留物以THF/水（1毫升/ 0.5毫升）中之ϋΟΗ·Η20 (25毫克）處理，加熱至55°C過夜，以二氯甲烷稀釋，以水洗滌，脫水乾燥（MgS04)，過濾及濃縮。使殘留物於C18管柱上藉HPLC純化，使用0-100% CH3CN/H2O/0.1% TFA，提供所要之產物，為三氟醋酸鹽（9.7毫克，5% )。MS(DCI/NH3)m/e372 (M+Hf ； ^NMRCDMSO-^) δ 10.82 (s, 1Η)5 8.85 (d, J=6.6 Hz, 2Η), 8.49 (s, 1H)，8.37 (s，1H)，8.08 (d，J=6.6 Hz，2H)，7.90 (d，J=16.5 Hz，1H)，7.79 (m，1H)，7.65 (d，J=16.6 Hz，1H)，7·56 (d，J=7.8 Hz，1H)，7·32 (d，J=8.1 Hz，1H)，7.18 (d，J=2.2 Hz， 1H)，7.04 (m，1H)，6.95 (m，1H)，4.06 (m，2H)，3.83 (m，1H)，3.03 (dd，J=6.2, 14.5 Hz， 1H)，2.91 (dd，J=6.2, 14.5 Hz，1H)· 實例5 (lS)-2-(l-笨并違吩-3-基VI-[(丨比咬-4-基乙婦基比遠-3-基} 氣基）甲基1乙胺 -57- 200301122(49) 8.52 (m, 1Η), 8.37 (m, 1H), 8.17 (d, J = 6.1 Hz, 2H), 7.86 (d, J = 16.6 Hz, 1H), 7.79 (m , 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 16.6 Hz, 1H), 7.50 (d, J = 16.6 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H ), 7.23 (s5 1H), 7.12 (m3 1H) 5 7.02 (m5 1H), 4.38 (dd3 J = 3.13 10.5 Hz, 1H), 4.25 (dd, J = 5.4, 10.5 Hz, 1H), 3.99, (m , 1H), 3.26 (m, 2H). Example 4 1- (1H-portal arch 1-portal-3-yl) -3-({5-「(E) -2-portal syndrome 4-ylethyl Benzyl-1- (3-yl) oxy) propan-2-ol A solution of Example 2C (150 mg, 0.400 mmol) in picric acid (2.4 ml) at room temperature with NaN. 2 (117 mg, 1.70 mmol), stirred for 18 hours, quenched the reaction with water (40 μl), stirred for an additional hour, poured into 2N NaOH, and mixed with isopropanol / dichloromethane Alkane extraction. The combined extracts were concentrated. The residue was treated with ϋΟϋ · Η20 (25 mg) in THF / water (1 ml / 0.5 ml), heated to 55 ° C overnight, diluted with dichloromethane, and water Washed, dried (MgS04), filtered and concentrated. The residue was taken up in C18 Purified by HPLC on the column using 0-100% CH3CN / H2O / 0.1% TFA to provide the desired product as trifluoroacetate (9.7 mg, 5%). MS (DCI / NH3) m / e372 (M + Hf ^ NMRCDMSO- ^) δ 10.82 (s, 1Η) 5 8.85 (d, J = 6.6 Hz, 2Η), 8.49 (s, 1H), 8.37 (s, 1H), 8.08 (d, J = 6.6 Hz, 2H ), 7.90 (d, J = 16.5 Hz, 1H), 7.79 (m, 1H), 7.65 (d, J = 16.6 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.18 (d, J = 2.2 Hz, 1H), 7.04 (m, 1H), 6.95 (m, 1H), 4.06 (m, 2H), 3.83 (m, 1H) , 3.03 (dd, J = 6.2, 14.5 Hz, 1H), 2.91 (dd, J = 6.2, 14.5 Hz, 1H) · Example 5 (lS) -2- (l-benzyl-phen-3-yl VI- [(丨 Bid-4-ylethenylpyridin-3-yl} amino) methyl 1ethylamine-57- 200301122

(50) 所要之產物係經由以2-第三-丁氧羰基胺基-3-苯并问嘍吩各基-丙-1-醇，取代實例2A中之L-Boc-色胺酸，然後按實例2B 與2D所述進行，以三氟醋酸鹽製成。MS(DCI/NH3)m/e388 (M+H)+ ;1 H NMR (DMSO-d6) 5 8.87 (d，J=6.3 Hz，2H)，8.55 (s，1H)，8·49 (寬廣 s，2H)， 8.40 (d，J=7.2 Hz，1H)，8·10 (d，J=6.3 Hz，2H)，8·02 (d，J=7.2 Hz，1H)，7.96 (d，J=7.2 Hz，1H)，7·90 (d，J=16.2 Hz，1H)，7.80 (m，1H)，7.68 (s，1H)，7.63 (d，J=16.2 Hz，1H)， 7.42 (m5 2H), 4.36 (dd, J=3.1, 10.6 Hz, 1H), 4.20 (dd, J=5.3, 10.6 Hz, 1H)? 3.99 (m3 1H)，3.36 (m，2H). 實例6 (1SV2,2·二苯基-1-「({5-Γ(Ε)-2-吡啶-4-基乙烯基 >比啶-3-基}氳某）甲基1乙胺所要之產物係經由以L-Boc-二苯基丙胺醇取代實例2Α中之 L-Boc-色胺酸，然後按實例2B與2C所述進行，以其鹽酸鹽製成。MS (DCI/NH3) m/e 408 (M+H)+ ; 1H NMR (DMSO-d6) 5 8.89 (d，J=6.8 Hz， 2H), 8.57 (s, 1H), 8.45 (br s, 2H), 8.42 (d, J=2.4 Hz, 1H), 8.16 (d, J=6.8 Hz, 2H), 7.99 (d，J=16.6 Hz，1H)，7.84 (s，1H)，7.73 (d，J=16.6 Hz，1H)，7.62 (m，2H)，7.49 (m， 2H)，7·39 (m，2H)，7.28 (m，3H)，7·18 (m，1H)，4.77 (m，1H)，4.46 (m，2H)，4.03 (m， 1H). 實例7 nSVl-(4-IT2,6-二氣芊基）氧基1芊基丨-2-(丨5-mEV2-吡啶斗基乙烯基1 p比症-3-基丨氧基）乙胺所要之產物係經由以L-Boc-(4-(2,6-二氯芊氧基）苯基）丙胺醇，取代實例2A中之L-Boc-色胺酸，然後按實例2B與2C所述進行，以其鹽酸鹽製成。MS(DCI/NH3)m/e 506,508,510 (M+H)+ ; -58- 200301122 (51) 1 H NMR (CD3 OD) 5 8·81 (d，J=7.1 Hz，2H)，8·71 (d，J=1.0 Hz，1H)，8·55 (d，J=2.7 Hz，1H)，8.28 (d，J=7.1 Hz，2H)，8·25 (m，1H)，7.99 (d，>16·3 Hz，1H)，7.79 (d，J= 16.3 Hz，1H)，7.46 (d，J=1.7 Hz，1H)，7.43 (s，1H)，7.36 (m，1H)，7.30 (m，2H)，7·05 (m，2H)，5·28 (s，2H)，4.45 (dd，J=3.1，10·5 Hz，1H)，431 (dd，J=5.8, 10.5 Hz，1H)， 3.95 (m，1H)，3.21 (m，2H). 實例8 (lS)-2-(卞乳基比咬-4-基乙婦基p比咬-3-基丨氧基）曱基1乙胺所要之產物係經由以L-Boc-3-芊氧基丙胺醇取代實例2A中之L-Boc-色胺酸，然後按實例2B與2C所述進行，以其鹽酸鹽製成。MS (DCI/NH3) m/e 362 (M+H)+; 1 H NMR (CD3 OD) 5 8.80-8.89 (m，4H)， 8.53-8.62 (m，3H)，8.28-8.34 (m，3H)，8.00-8.06 (m，1H)，7.98 (d，J=16.3 Hz，1H)， 7.87(d，J=16.3Hz，lH)，7.28-7.43 (m，3H)，4.66(s，2H)，4.56-4.64(m，2H)，3.94-3.99 (m，1H)，3.83-3.87 (m，2H)· 實例9 N,N-二甲某-N-「(1S,2SH-甲基-2-苯基-2-({5-「(EV2-吡啶-4-基乙烯某 1(50) The desired product was obtained by substituting 2-tert-butoxycarbonylamino-3-benzophenone-propan-1-ol for L-Boc-tryptophan in Example 2A, and then Proceeding as described in Examples 2B and 2D, made from trifluoroacetate. MS (DCI / NH3) m / e388 (M + H) +; 1 H NMR (DMSO-d6) 5 8.87 (d, J = 6.3 Hz, 2H), 8.55 (s, 1H), 8.49 (wide s , 2H), 8.40 (d, J = 7.2 Hz, 1H), 8.10 (d, J = 6.3 Hz, 2H), 8.02 (d, J = 7.2 Hz, 1H), 7.96 (d, J = 7.2 Hz, 1H), 7.90 (d, J = 16.2 Hz, 1H), 7.80 (m, 1H), 7.68 (s, 1H), 7.63 (d, J = 16.2 Hz, 1H), 7.42 (m5 2H ), 4.36 (dd, J = 3.1, 10.6 Hz, 1H), 4.20 (dd, J = 5.3, 10.6 Hz, 1H)? 3.99 (m3 1H), 3.36 (m, 2H). Example 6 (1SV2, 2 · The desired product of diphenyl-1-"({5-Γ (Ε) -2-pyridin-4-ylvinyl > pyridin-3-yl} 氲) methyl 1ethylamine is obtained by the addition of L- Boc-diphenylpropanol was used to replace the L-Boc-tryptophan acid in Example 2A, and then carried out as described in Examples 2B and 2C, using its hydrochloride. MS (DCI / NH3) m / e 408 (M + H) +; 1H NMR (DMSO-d6) 5 8.89 (d, J = 6.8 Hz, 2H), 8.57 (s, 1H), 8.45 (br s, 2H), 8.42 (d, J = 2.4 Hz, 1H ), 8.16 (d, J = 6.8 Hz, 2H), 7.99 (d, J = 16.6 Hz, 1H), 7.84 (s, 1H), 7.73 (d, J = 16.6 Hz, 1H), 7.62 (m, 2H ), 7.49 (m, 2H), 7.39 (m, 2H), 7.28 (m, 3H), 7.18 (m, 1H), 4.77 (m 1H), 4.46 (m, 2H), 4.03 (m, 1H). Example 7 nSVl- (4-IT2,6-difluorofluorenyl) oxy 1fluorenyl 丨 -2- (5-mEV2-pyridine bucket The desired product of phenylvinyl 1 p-pyridin-3-yloxy) ethylamine was replaced by L-Boc- (4- (2,6-dichlorofluorenyloxy) phenyl) propylamine alcohol, replacing Example 2A. L-Boc-tryptophan acid was then prepared as its hydrochloride as described in Examples 2B and 2C. MS (DCI / NH3) m / e 506,508,510 (M + H) +; -58- 200301122 ( 51) 1 H NMR (CD3 OD) 5 8 · 81 (d, J = 7.1 Hz, 2H), 8.71 (d, J = 1.0 Hz, 1H), 8.55 (d, J = 2.7 Hz, 1H ), 8.28 (d, J = 7.1 Hz, 2H), 8.25 (m, 1H), 7.99 (d, > 16.3 Hz, 1H), 7.79 (d, J = 16.3 Hz, 1H), 7.46 (d, J = 1.7 Hz, 1H), 7.43 (s, 1H), 7.36 (m, 1H), 7.30 (m, 2H), 7.05 (m, 2H), 5.28 (s, 2H), 4.45 (dd, J = 3.1, 10.5 Hz, 1H), 431 (dd, J = 5.8, 10.5 Hz, 1H), 3.95 (m, 1H), 3.21 (m, 2H). Example 8 (lS)- The desired product of 2- (fluorenyl-4-methylethenyl-p-pyridyl-3-yloxy) fluorenyl-1ethylamine is replaced by L-Boc-3-fluorenyloxypropylamine L-Boc-tryptophan in 2A, then The Examples 2B with 2C, is made the hydrochloride salt. MS (DCI / NH3) m / e 362 (M + H) +; 1 H NMR (CD3 OD) 5 8.80-8.89 (m, 4H), 8.53-8.62 (m, 3H), 8.28-8.34 (m, 3H ), 8.00-8.06 (m, 1H), 7.98 (d, J = 16.3 Hz, 1H), 7.87 (d, J = 16.3Hz, 1H), 7.28-7.43 (m, 3H), 4.66 (s, 2H) , 4.56-4.64 (m, 2H), 3.94-3.99 (m, 1H), 3.83-3.87 (m, 2H) · Example 9 N, N-dimethyl-N-"-(1S, 2SH-methyl-2 -Phenyl-2-({5-`` (EV2-pyridin-4-ylethylene 1

吡啶-3-基}氧基）乙某1胺實例9A 醋故5->臭基p比淀-3-基酉旨將3-溴基-5-羥基吡啶（9.00克，5L7毫莫耳）、醋酸酐（6.0毫升）及三乙胺（12.0毫升）於THF (50毫升）中之混合物，加熱至回流過夜，冷卻至室溫，以乙醚稀釋，以水、5% NaHC03、水及鹽水洗滌，脫水乾燥（MgS04)，過濾及濃縮，提供所要之產物（9.37 克，84% )。 -59- (52)Pyridin-3-yl} oxy) ethyl 1 amine Example 9A Acetate 5- > Styrolyl p-Hydroxyl-3-yl, 3-Bromo-5-hydroxypyridine (9.00 g, 5L7 mmol) ), A mixture of acetic anhydride (6.0 ml) and triethylamine (12.0 ml) in THF (50 ml), heated to reflux overnight, cooled to room temperature, diluted with ether, water, 5% NaHC03, water and brine Washing, dehydration drying (MgS04), filtration and concentration provided the desired product (9.37 g, 84%). -59- (52)

實例9B 5-「(E)-2-?比症-4-基乙缔基比淀-3-醇將實例9Α (9.37克，43,3毫莫耳）、4-乙烯基吡啶（14.0毫升， 130毫莫耳）、三-鄰-甲苯基膦（13.5克，44.4毫莫耳）、醋酸鈀（2.65 克，11.8毫莫耳）及三乙胺（120毫升，0.861莫耳）於乙腈（40毫升）中之混合物，加熱至回流過夜，並於醋酸乙酯與水之間作分液處理。將有機層以鹽水洗滌，脫水乾燥（Na2S04) ，過濾及在真空下濃縮。於矽膠上藉急騾式管柱層析純化，使用含有0.5%氨之5%甲醇/二氯甲烷，提供醋酸鹽（8.53 克）。將其與LiOH · Η2 Ο (6.00克，143毫莫耳）在THF /水（40毫升 / 20亳升）中，於室溫下攪拌4小時，濃縮，以in HC1 (水溶液）調整至pH 7，及過濾。將濾餅以水洗滌，並於真空及60 °C下乾燥，提供所要之產物（7.23克，84% )。MS (DCI/NH3)m/e 199 (M+H)+ ; 1 H NMR (CD3 OD) ά 8.51 (m，2H)，8·24 (d，J=1.4 Hz，1H)，8·04 (d， J=2.4 Hz，1H)，7·61 (m，2H)，7.50 (m，1H)，7.49 (d，J=16·6 Hz，1H)，7.27 (d，J=16.6Example 9B 5-"(E) -2-?-Bis-4-ylethenylpyridol-3-ol Example 9A (9.37 g, 43,3 mmol), 4-vinylpyridine (14.0 ml , 130 mM), tri-o-tolylphosphine (13.5 g, 44.4 mol), palladium acetate (2.65 g, 11.8 mol) and triethylamine (120 ml, 0.861 mol) in acetonitrile ( 40 ml), heated to reflux overnight, and separated between ethyl acetate and water. The organic layer was washed with brine, dried (Na2S04), filtered and concentrated under vacuum. Borrowed on silica gel Purified by flash column chromatography using 5% methanol / dichloromethane containing 0.5% ammonia to provide the acetate (8.53 g). This was combined with LiOH · H2O (6.00 g, 143 mmol) in THF / In water (40 ml / 20 liters), stir at room temperature for 4 hours, concentrate, adjust to pH 7 with in HC1 (aqueous solution), and filter. Wash the filter cake with water and under vacuum at 60 ° C Dry to provide the desired product (7.23 g, 84%). MS (DCI / NH3) m / e 199 (M + H) +; 1 H NMR (CD3 OD) ά 8.51 (m, 2H), 8.24 ( d, J = 1.4 Hz, 1H), 8.04 (d, J = 2.4 Hz , 1H), 7.61 (m, 2H), 7.50 (m, 1H), 7.49 (d, J = 16 · 6 Hz, 1H), 7.27 (d, J = 16.6

Hz, 1H).Hz, 1H).

實例9C N，N-二甲基-N-「(1S,2SV1-甲基-2-苯基-2-({5-「(EV2-吡啶-4-基、乙烯某 1 p比啶-3-基丨氧基）乙基胺所要之產物係經由以實例9B與（lS，2S)-2-(二曱胺基）-1-苯基丙 -1-醇，個別取代實例2A中之3-溴基-5-羥基吡啶與L-Boc-色胺酸’然後按實例2B與2D所述進行，以三氟醋酸鹽製成。 MS (DCI/NH3) m/e 360 (M+H)+ ； 1 H NMR (DMSO-d6) δ 8.78 (d, 2H), 8.44 (s，1H)，8·33 (d，1H)，7.94 (d，1H)，7·80 (s，1H)，7.75 (d，1H)，7.59 (d，2H)，7.46-7.34 (53)Example 9C N, N-dimethyl-N-"(1S, 2SV1-methyl-2-phenyl-2-({5-" (EV2-pyridin-4-yl, ethylene 1 p-pyridin-3 -Yloxy) ethylamine The desired product was obtained by substituting Example 3B and (1S, 2S) -2- (diamidoamino) -1-phenylpropan-1-ol, individually replacing 3 of Example 2A. -Bromo-5-hydroxypyridine and L-Boc-tryptophanic acid 'were then performed as described in Examples 2B and 2D and made from trifluoroacetate. MS (DCI / NH3) m / e 360 (M + H) +; 1 H NMR (DMSO-d6) δ 8.78 (d, 2H), 8.44 (s, 1H), 8.33 (d, 1H), 7.94 (d, 1H), 7.80 (s, 1H), 7.75 (d, 1H), 7.59 (d, 2H), 7.46-7.34 (53)

(m，5H)，5.84 (d，1H)，3.55-3.45 (m，1H)，2.95 (s，3H)，2.84 (s，3H)，1·02 (d，3H)· 實例10 (lSV2-(2-苯基吡啶-4-基乙烯基1吡啶-3-基丨氧基）甲某1 乙胺所要之產物係經由以L-Boc-(2-莕基）丙胺醇取代實例2A中之 L-Boc-色胺酸，然後按實例2B與2D所述進行，以三氟醋酸鹽製成。MS(DCI/NH3)m/e382 (M+H)+ ; iHNMRpMSO-dS) 5 8.88(d， J=6.8 Hz，2H)，8.57 (d，J=1.0 Hz，1H)，8.43 (d，J=2.4 Hz，1H)，8·15 (d，J=6.8 Hz，2H)， 7.99 (d，J=16.6 Hz，1H)，7.90 (m，5H)，7.73 (d，J=16·6 Hz，1H)，7.50 (m，3H)，4.35 (dd，J=3.4, 10·5 Hz，1H)，4·21 (dd，J=5.4, 10.5 Hz，1H)，3.97 (m，1H)，3.32 (dd，J=5.8, 13·6 Hz，1H)，3.21 (dd，J=9.2, 13.6 Hz，1H). 實例11 N-「(2S)-2-胺基嗓-3-基）丙基 VN-{5-「QE)-2-p比淀-4-基乙婦基 1 吡咬__-3-基}胺實例114 3-溴基-54(E)-2-吡啶-4-某乙烯某1外h啶將3,5-二溴基吡啶（5.56克，23.4毫莫耳）、4-乙烯基吡啶（5.1 毫升）、醋酸鈀（1.05克）、三-鄰-甲苯基膦（5·〇〇克）及三乙胺（33 毫升）於乙腈（100毫升）中之溶液，在80°C下，加熱過夜及濃縮。使殘留物於5% NaHC〇3與二氣甲烷之間作分液處理，及過滤。分離濾、液’並將有機層以水洗蘇，脫水乾燥（MgS04) ，過濾及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用4%甲醇/二氯甲烷’提供所要之產物（218克，36% ) 。（DCI/NH3) m/e 261，263 (M+H)+ · (54)(m, 5H), 5.84 (d, 1H), 3.55-3.45 (m, 1H), 2.95 (s, 3H), 2.84 (s, 3H), 1.02 (d, 3H). Example 10 (lSV2- The desired product of (2-phenylpyridin-4-ylvinyl1pyridin-3-yloxy) methyl 1 ethylamine was obtained by substituting L-Boc- (2-fluorenyl) propanol in Example 2A. L-Boc-tryptophan acid was then carried out as described in Examples 2B and 2D and made from trifluoroacetate. MS (DCI / NH3) m / e382 (M + H) +; iHNMRpMSO-dS) 5 8.88 (d , J = 6.8 Hz, 2H), 8.57 (d, J = 1.0 Hz, 1H), 8.43 (d, J = 2.4 Hz, 1H), 8.15 (d, J = 6.8 Hz, 2H), 7.99 (d , J = 16.6 Hz, 1H), 7.90 (m, 5H), 7.73 (d, J = 16 · 6 Hz, 1H), 7.50 (m, 3H), 4.35 (dd, J = 3.4, 10 · 5 Hz, 1H), 4.21 (dd, J = 5.4, 10.5 Hz, 1H), 3.97 (m, 1H), 3.32 (dd, J = 5.8, 13.6 Hz, 1H), 3.21 (dd, J = 9.2, 13.6 Hz, 1H). Example 11 N-"(2S) -2-Amino-3-yl) propyl VN- {5-" QE) -2-p Bite __- 3-yl} amine Examples 114 3-bromo-54 (E) -2-pyridine-4-an ethylene, an oxidine, 3,5-dibromopyridine (5.56 g, 23.4 mmol) Ear), 4-vinylpyridine (5.1 ml), palladium acetate ( 1.05 g), a solution of tri-o-tolylphosphine (5.0 g) and triethylamine (33 ml) in acetonitrile (100 ml), heated at 80 ° C overnight and concentrated. The residue was concentrated Separate the solution between 5% NaHC03 and methane gas, and filter. Separate the filter, liquid, and wash the organic layer with water, dehydrate and dry (MgS04), filter, and concentrate. Let the concentrate be borrowed on silica gel. Purification by flash column chromatography using 4% methanol / dichloromethane 'provided the desired product (218 g, 36%). (DCI / NH3) m / e 261,263 (M + H) + · (54)

實例11B 比淀-4-基乙烯基 >比症-3-胺將貫例11A (1.88克，7.2毫莫耳）、二苯甲酮亞胺（ι·22毫升）、Pd2(dba)3(66 毫克）、ΒΙΝΑΡ(ι25 毫克）、第三-丁醇鈉（0·97 克）及甲苯（19毫升）之混合物，加熱至8〇c過夜，及濃縮。使殘留物於石夕膠上藉急驟式管柱層析純化，使用醋酸乙酯，提供固體（2.44克）。將其與2N HC1 (水溶液）(5.0毫升）於THF (50毫升）中’在室溫下攪拌2小時，及濃縮。使殘留物溶於〇.5N HC1 ( 水溶液）(100毫升）中，並以醋酸乙酯洗滌三次。以1NNa〇H 將水層調整至pH 11，並以二氯甲烷萃取。將合併之萃液以水洗滌，脫水乾燥（MgS04)，過濾及濃縮，提供所要之產物Example 11B Biyodo-4-ylvinyl > Bisid-3-amine Example 11A (1.88 g, 7.2 mmol), benzophenimine (22 ml), Pd2 (dba) (66 mg), BINAP (25 mg), sodium tert-butoxide (0.97 g) and toluene (19 ml), heated to 80 ° C overnight, and concentrated. The residue was purified by flash column chromatography on Shixi gum using ethyl acetate to provide a solid (2.44 g). It was stirred with 2N HC1 (aqueous solution) (5.0 ml) in THF (50 ml) 'at room temperature for 2 hours, and concentrated. The residue was dissolved in 0.5N HC1 (aq.) (100 ml) and washed three times with ethyl acetate. The aqueous layer was adjusted to pH 11 with 1N NaOH and extracted with dichloromethane. The combined extracts were washed with water, dried (MgS04), filtered and concentrated to provide the desired product.

(1.23 克，87%)。MS(DCI/NH3)m/el98(M+H)+ ; iHNMRpMSO-DJ δ 8.55 (m ； 2H), 8.00 (d, J=1.7 Hz, 1H)? 7.89 (d, J=2.4 Hz, 1H), 7.56 (m5 2H), 7.42 (d，J=16.6 Hz，1H)，7.17 (d，J=16.6 Hz，1H)，7.15 (m，1H). 實例lie 吲哚-3-基VI-「(丨5-「(E)-2-吡啶-4-某乙烯基1吡啶-3-基丨胺基）王基1乙基胺基甲酸第三-丁酯將實例11B (52毫克，0.264毫莫耳）、L-Boc-色胺酸（J. Med. Chem.， 1985, 28 (12)，1874.)(80毫克，0.277毫莫耳）及醋酸（80微升）於甲醇 (4毫升）中之混合物，在室溫下攪摔3小時，回流2小時，冷卻至室溫，以氰基硼氫化鈉（35毫克）處理，攪掉丨小時，及過濾《使濾液濃縮，並使殘留物於C18管柱上藉HPLC純化，使用0-100% CH3CN/H2O/0.1% TFA，提供所意欲之產物（43 毫克，35%)。MS(DCI/NH3)m/e470(M+H)+. -62- (55)(1.23 g, 87%). MS (DCI / NH3) m / el98 (M + H) +; iHNMRpMSO-DJ δ 8.55 (m; 2H), 8.00 (d, J = 1.7 Hz, 1H)? 7.89 (d, J = 2.4 Hz, 1H) , 7.56 (m5 2H), 7.42 (d, J = 16.6 Hz, 1H), 7.17 (d, J = 16.6 Hz, 1H), 7.15 (m, 1H). Example lie Indol-3-yl VI-"(丨 5-"(E) -2-pyridine-4-a vinyl 1-pyridin-3-yl amine group) King-based 1 ethylaminocarboxylic acid tert-butyl ester Example 11B (52 mg, 0.264 mmol) Ear), L-Boc-tryptophan (J. Med. Chem., 1985, 28 (12), 1874.) (80 mg, 0.277 mmol) and acetic acid (80 μl) in methanol (4 ml) The mixture was stirred at room temperature for 3 hours, refluxed for 2 hours, cooled to room temperature, treated with sodium cyanoborohydride (35 mg), stirred for 丨 hours, and filtered. The filtrate was concentrated and the residue was concentrated. Purified by HPLC on a C18 column using 0-100% CH3CN / H2O / 0.1% TFA to provide the desired product (43 mg, 35%). MS (DCI / NH3) m / e470 (M + H) + .-62- (55)

實例liD N-「(2SV2-胺基-3-(1Η-啕哚-3-基）丙基VN-(54(EV2-吡啶-4-基乙烯甚1 口比淀-3-基}胺將實例11C (40毫克，0.085毫莫耳）於二氯甲烷（3·〇毫升）中之溶液，在室溫下，以二氧陸圜（0.5毫升）中之4Ν HC1處理，攪拌1小時，及濃縮，提供所要之產物，為其鹽酸鹽（3〇毫克，74% )。MS(DCI/NH3)m/e370(M+H)+; iHNMRpMSO-dJ 5 11.09 (br s，1H)，8·90 (d，J=5.8 Hz，2H)，8·47 (br s，2H)，8.33 (s，1H)，8.22 (d，J=1.8 Hz，1H)， 8·14 (d，J=5.8 Hz，2H)，7.98 (s5 1H)，7.94 (d，J=16.5 Hz，1H)，7.86 (d，J=16.5 Hz，1H)， 7.62 (d，J=7.9 Hz，1H), 7·37 (d，J=4.5 Hz，1H)，7J6 (s，1H)，7,08 (m，1H)，6.98 (m， 1H)，3.71 (m，1H)，3.67 (m，1H)，3·54 (m，1H)，3.15 (m，2H). 實例12 QS)-2-({2r氯基-5_[(e)-2-p比淀-4·基乙烯某风咬各某丨氣某）小哚-3-基甲基）乙脖實例12Α 20乳基）-5-溴基-2-氧口比症將Μ爷氧基）-5->臭基ρ比淀Ν-氧化物（2·〇克，7.1毫莫耳）於p〇Cl3 (2〇毫升）中溶液，在loot下，攪拌7小時，冷卻至室溫，濃縮，以醋酸乙酯（50毫升）處理，以鹽水洗滌，脫水乾燥（MgS〇4) 過濾及；辰縮。使濃縮物於矽膠上藉急驟式管柱層析純化使用10%醋酸乙酯/己烷，提供所要之產物（1〇克，4〇% ) 。MS (DCI/NH3) m/e 299 (M+H)+ .Example liD N-"(2SV2-amino-3- (1H-pyridin-3-yl) propyl VN- (54 (EV2-pyridin-4-ylethylene) Example 11C (40 mg, 0.085 mmol) in dichloromethane (3.0 ml), treated with 4N HC1 in dioxolane (0.5 ml) at room temperature, stirred for 1 hour, and Concentration provided the desired product as its hydrochloride salt (30 mg, 74%). MS (DCI / NH3) m / e370 (M + H) +; iHNMRpMSO-dJ 5 11.09 (br s, 1H), 8 · 90 (d, J = 5.8 Hz, 2H), 8.47 (br s, 2H), 8.33 (s, 1H), 8.22 (d, J = 1.8 Hz, 1H), 8.14 (d, J = 5.8 Hz, 2H), 7.98 (s5 1H), 7.94 (d, J = 16.5 Hz, 1H), 7.86 (d, J = 16.5 Hz, 1H), 7.62 (d, J = 7.9 Hz, 1H), 7 · 37 (d, J = 4.5 Hz, 1H), 7J6 (s, 1H), 7,08 (m, 1H), 6.98 (m, 1H), 3.71 (m, 1H), 3.67 (m, 1H), 3 · 54 (m, 1H), 3.15 (m, 2H). Example 12 QS) -2-({2r chloro-5 _ [(e) -2-p than yodo-4 · yl vinyl) (A certain gas) small indole-3-ylmethyl) ethyl example 12A 20 lactyl) -5-bromo-2-oxo ratio ratio (Methyloxy) -5- > Oxide (2.0 g 7.1 mmol) in poCl3 (20 ml), stirred for 7 hours under a loot, cooled to room temperature, concentrated, treated with ethyl acetate (50 ml), washed with brine, dehydrated and dried (MgS 〇4) Filtration and filtration. The concentrate was purified on silica gel by flash column chromatography using 10% ethyl acetate / hexane to provide the desired product (10 g, 40%). MS (DCI / NH3) m / e 299 (M + H) +.

實例12B 5_>臭基-2-氯基-3_輕某？比冷Example 12B 5_ > Alkyl-2-chloro-3_light? Than cold

(56) 將實例12A於HBr/HOAc(30%，50毫升）中之混合物’在100°c 下擾拌8小時，冷卻至室溫’及濃縮。使濃縮物於醋酸乙酯與飽和Na2 C03 (水溶液）之間作分液處理。將有機層以鹽水洗滌，脫水乾燥（Na2S04)，過濾及在真空下濃縮。於矽膠上藉急驟式管柱層析純化，使用30%醋酸乙酯/己烷，提供所要之產物（〇·5ΐ 克，72% )。MS(DCI/NH3)m/e209(M+H)+·(56) A mixture of Example 12A in HBr / HOAc (30%, 50 ml) was stirred at 100 ° C for 8 hours, cooled to room temperature, and concentrated. The concentrate was separated between ethyl acetate and saturated Na2C03 (aqueous solution). The organic layer was washed with brine, dried (Na2S04), filtered and concentrated under vacuum. Purified by flash column chromatography on silica gel using 30% ethyl acetate / hexane to provide the desired product (0.5 g, 72%). MS (DCI / NH3) m / e209 (M + H) + ·

12C (lS)-2-「(5-漠基-2-氯基p比症-3-基）氧基口弓丨嗓-3-基甲基）乙基脖某甲酸第三·丁酯所要之產物係經由以實例ΠΒ取代實例2A中之3-溴基-5-羥基吡啶而製成（0·78 克，66% )。MS(DCI/NH3)m/e481 (M+H)+.12C (lS) -2-"(5-Molyl-2-chloro-p-synthesis-3-yl) oxyl-bow 丨 Three-3-ylmethyl) ethyl neck The product was prepared by replacing 3-bromo-5-hydroxypyridine in Example 2A with Example IIB (0.78 g, 66%). MS (DCI / NH3) m / e481 (M + H) +.

實例12D (lSV2-a2-氪基-5-[(EV2-吡啶斗基乙烯基 >比啶-3-基}氧基VH1H-蚓哚-3-基甲基）乙胺所要之產物係經由以實例12C取代實例2B與2D中之實例 2A，以三氟醋酸鹽製成。MS (DCI/NH3) m/e 405, 407 (M+H)+ ; 1 H NMR (DMSO-d6) 5 11.04 (s，1H)，8.72 (d，J=6.0 Hz，2H)，8.30 (s，1H)，8·23 (br s，2H)， 7·84 (s，1H)，7.78 (d，J=6.0 Hz，2H)，7.70 (d，J=16.8 Hz，1H)，7.62 (d，J=8.1 Hz，1H)， 7.50 (d，J=16.8 Hz，1H)，7.38 (d，J=8.1 Hz，1H)，7·28 (s，1H)，7.10 (t，J=7.2 Hz，1H)， 7·00 (t，J=7.2 Hz，1H)，4.38 (m，1H)，4·18 (m，1H)，3.91 (m，1H)，3.20 (m，2H)· 實例13Example 12D (1SV2-a2-fluorenyl-5-[(EV2-pyridinylvinyl > pyridin-3-yl) oxy VH1H-earthin-3-ylmethyl) ethylamine Example 12C was used instead of Example 2A in Examples 2B and 2D, and was made of trifluoroacetate. MS (DCI / NH3) m / e 405, 407 (M + H) +; 1 H NMR (DMSO-d6) 5 11.04 (s, 1H), 8.72 (d, J = 6.0 Hz, 2H), 8.30 (s, 1H), 8.23 (br s, 2H), 7.84 (s, 1H), 7.78 (d, J = 6.0 Hz, 2H), 7.70 (d, J = 16.8 Hz, 1H), 7.62 (d, J = 8.1 Hz, 1H), 7.50 (d, J = 16.8 Hz, 1H), 7.38 (d, J = 8.1 Hz , 1H), 7.28 (s, 1H), 7.10 (t, J = 7.2 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H), 4.38 (m, 1H), 4.18 ( m, 1H), 3.91 (m, 1H), 3.20 (m, 2H) · Example 13

(lS)-2-({6-氯基-5-『(E)-2-p比淀-4-基乙烯基Ip比淀-3-基丨氧基弓I(lS) -2-((6-Chloro-5-"(E) -2-p than Yodo-4-ylvinyl Ip

兔_-3-基甲基）乙胺實例13A -64- (57) 溴基-6-氯基p比遠-3-基）氧基嗓甚甲基）乙基胺基甲酸第三-丁酯將5-溴基-6-氯基-3-¾基p比矣（2.50克，12亳莫耳）、Ν-α-(第三 -丁氧羰基）小色胺酸（3.77克，18亳莫耳）及三苯膦（4.72克，18 晕莫耳）於THF (100毫升）中之落液’在〇°c下攪掉2〇分鐘，以 DEAD (2.83毫升，18毫莫耳）處理，攪拌1小時，溫熱至室溫 ’揽拌15小時’以酷酸乙g§ (300毫升）處理，以鹽水洗務，脫水乾燥（MgS〇4)，過濾及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用25%醋酸乙酯/己烷，提供所要之產物（4.58 克，80% )。MS(APCI)m/e480,482 (M+H)+.Rabbit_-3-ylmethyl) ethylamine Example 13A -64- (57) Bromo-6-chloro p-p-dist-3-yl) oxymethyl) ethylaminocarboxylic acid tert-butyl The ester compared 5-bromo-6-chloro-3-¾yl p to fluorene (2.50 g, 12 mol), N-α- (tertiary-butoxycarbonyl) small tryptophan (3.77 g, 18亳 mol) and triphenylphosphine (4.72g, 18 hamol) in THF (100ml) 's solution was stirred at 0 ° C for 20 minutes with DEAD (2.83ml, 18mmol) Treatment, stirring for 1 hour, warming to room temperature, 'stirring for 15 hours', treatment with ethyl g§ (300 ml), washing with brine, dehydration drying (MgS04), filtration and concentration. The concentrate was purified by flash column chromatography on silica gel using 25% ethyl acetate / hexane to provide the desired product (4.58 g, 80%). MS (APCI) m / e480,482 (M + H) +.

實例13B 氯基-5-「(E)-2-吡啶-4-基乙烯基1峨啶各基}氫某VWm-W 生-3-基甲基）乙基胺基甲酸第三-丁酯將實例 13Α(1·50 克，3.125 毫莫耳）、Pd2(dba)3 (71 毫克，0.078 毫莫耳）及三-鄰-甲苯基膦（71毫克，〇·23毫莫耳）於DMF (30毫升）中之溶液，以4-乙埽基吡啶（492毫克，4·68毫莫耳）與三乙胺（1.30毫升，9.4毫莫耳）處理，以氮滌氣，並加熱至1〇(rc ’歷經4小時。使混合物冷卻至室溫，以醋酸乙酯（2〇〇毫升）處理，以鹽水洗滌，脫水乾燥（MgS〇4)，過濾及濃縮。使濃縮物於秒膠上藉急驟式管柱層析純化，使用75%醋酸乙酯 /己烷，提供所要之產物（L37克，87% )。MS (APCI) m/e 505, 507 (M+H)'Example 13B Chloro-5-"(E) -2-pyridin-4-ylvinyl 1eridine each group} Hydrogen VWm-W 3-Methylmethyl) ethylaminocarboxylic acid tert-butyl ester Example 13A (1.50 g, 3.125 mmol), Pd2 (dba) 3 (71 mg, 0.078 mmol) and tri-o-tolylphosphine (71 mg, 0.23 mmol) were added to DMF (30 ml) of the solution, treated with 4-ethylpyridine (492 mg, 4.68 mmol) and triethylamine (1.30 ml, 9.4 mmol), purged with nitrogen and heated to 1 0 (rc 'over 4 hours. The mixture was cooled to room temperature, treated with ethyl acetate (200 mL), washed with brine, dried (MgS04), filtered and concentrated. The concentrate was placed on a second gel Purified by flash column chromatography using 75% ethyl acetate / hexane to provide the desired product (L37 g, 87%). MS (APCI) m / e 505, 507 (M + H) '

實例13CExample 13C

吡啶-4-基乙烯某1吡啶-3-基}氧基Μ-ΠΗ-W 200301122 (58) 哚-3-基曱基]乙胺所要之產物係經由以實例13B取代實例2D中之實例2B，以三氟醋酸鹽製成。MS (APCI) m/e 405, 407 (M+H)+ ; 1 H NMR (300 MHz， CD3 OD) 5 8.76 (d，J=6.7 Hz，2H)，8.18 (d，J=2.7 Hz，1H)，8.15 (d，J=6.5 Hz，2H)，Pyridin-4-ylethylene 1pyridin-3-yl} oxy M-ΠΗ-W 200301122 (58) indol-3-ylfluorenyl] ethylamine The desired product was obtained by replacing Example 2B in Example 2D with Example 13B Made of trifluoroacetate. MS (APCI) m / e 405, 407 (M + H) +; 1 H NMR (300 MHz, CD3 OD) 5 8.76 (d, J = 6.7 Hz, 2H), 8.18 (d, J = 2.7 Hz, 1H ), 8.15 (d, J = 6.5 Hz, 2H),

7.95 (d, J=16.2 Hz, 1H)3 7.86 (d5 J=3.0 Hz3 1H), 7.58 (d5 J=7.8 Hz, 1H), 7.43 (d5 J= 16·3 Hz，1H)，7.38 (d，J=8.1 Hz，1H)，7.23 (s，1H)，7.13 (t，J=7.1 Hz，1H)，7.03 (t，J= 7·8 Hz，1H)，4.38 (dd，J=10.5, 3.0 Hz，1H)，4.25 (dd，J=10.6, 5·8 Hz，1H)，3.97 (m， 111)，3.31(111，2印；對（：231121(^40*2.3丁?八之分析計算值：〇,49.69 ;H，3.52; Ν，8·40·實測值：C，49·82 ;Η，3·48;Ν，8·32· 實例14 (18)-2-(111-口弓丨嗓-3-基淀-4-基乙块基V比淀-3-基1氧基}甲7.95 (d, J = 16.2 Hz, 1H) 3 7.86 (d5 J = 3.0 Hz3 1H), 7.58 (d5 J = 7.8 Hz, 1H), 7.43 (d5 J = 16 · 3 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 7.13 (t, J = 7.1 Hz, 1H), 7.03 (t, J = 7.8 Hz, 1H), 4.38 (dd, J = 10.5, 3.0 Hz, 1H), 4.25 (dd, J = 10.6, 5.8 Hz, 1H), 3.97 (m, 111), 3.31 (111, 2 marks); analysis and calculation of (: 231121 (^ 40 * 2.3, ?? 8) Value: 〇, 49.69; H, 3.52; N, 8.40. Found: C, 49 · 82; H, 3.48; N, 8.32. Example 14 (18) -2- (111-mouth bow丨 Hydroxy-3-yl lake-4-ylethoxy group

基）乙胺實例14A 丨嗓-3-基V14({5-|T三甲基石夕燒基）乙块基扣比淀各基}氣基）甲基1乙基胺基甲酸第三-丁酉旨Example) 14A 丨 Three-3-yl V14 ({5- | T trimethyl sulphuryl) ethyl group, each group} phenyl group) methyl 1 ethylaminocarboxylic acid tertiary

將實例 2A (500 毫克，1.12 毫莫耳）、Pd2Cl2(PPh3)2 (77 毫克，0.112 毫莫耳）及Cul (52毫克，0.27毫莫耳）之混合物，以氮滌氣，以DMF (7毫升）、三甲基矽烷基乙炔（475微升，3·36毫莫耳）及三乙胺（468微升，3.36毫莫耳）處理，於50°C下攪拌15小時 ’冷卻至室溫，以醋酸乙酯（50毫升）處理，以鹽水洗滌，脫水乾燥（MgS〇4) ’過遽及濃縮。使殘留油於碎膠上藉急驟式管柱層析純化，使用1 : 2醋酸乙酯/己烷，提供所要之產物（417 毫克，80% )。MS(APCI)m/e464(M+H)+.A mixture of Example 2A (500 mg, 1.12 mmol), Pd2Cl2 (PPh3) 2 (77 mg, 0.112 mmol) and Cul (52 mg, 0.27 mmol) was purged with nitrogen and DMF (7 Ml), trimethylsilyl acetylene (475 μl, 3.36 mmol) and triethylamine (468 μl, 3.36 mmol), stirred at 50 ° C for 15 hours, and cooled to room temperature , Treated with ethyl acetate (50 ml), washed with brine, dried (MgS04), dried and concentrated. The residual oil was purified by flash column chromatography on crushed gel using 1: 1 ethyl acetate / hexane to provide the desired product (417 mg, 80%). MS (APCI) m / e464 (M + H) +.

實例14B •66- 0301122 (59)Example 14B66- 0301122 (59)

(jg>2-[(5-乙块基j比呢小(ih_吲哚各基甲某r其眩I ^三-丁酯將實例14Α(400毫克，0別毫莫耳）於THF(6毫升）中之溶液在A/m下，以氟化四丁基銨（於THF中之1〇 M溶液，U 毛升U2毛莫耳）處理，攪拌1小時，以醋酸乙酯（50毫升）處理，以鹽水洗務，脫水乾燥（MgSQ4)，過濾及濃縮。使殘留油於矽膠上藉急驟式管柱層析純化，使用40%醋酸乙酯 /己：k ’ }疋供所要之產物（29〇亳克，86% )。MS (Αρα)牆392 (M+H)+ ·(jg > 2-[(5-Ethyl group j is smaller than iN-indolyl, i. 6 ml) of the solution in A / m, treated with tetrabutylammonium fluoride (10M solution in THF, U 2 liters U 2 moles), stirred for 1 hour, ethyl acetate (50 ml ) Treatment, washing with brine, dehydration drying (MgSQ4), filtration and concentration. The residual oil was purified by flash column chromatography on silica gel using 40% ethyl acetate / hexane: k '} 疋 for the desired product (29.0 g, 86%). MS (Αρα) wall 392 (M + H) + ·

實例14C 基啶斗某乙炔某）毗啶各基〗氣某^甲基基甲醢第二-丁酯將貫例14B (150毫克，〇·384毫莫耳）、4-溴基吡啶鹽酸鹽（75 宅克’ 0·34毫莫耳）、Pd2Cl2(PPh3)2(27毫克，0.0384毫莫耳）及 CuI (18愛克’ 〇 093愛旲耳）之混合物，以氮務氣’以DMF (4 毫升）與三乙胺（214微升，1.54毫莫耳）處理，於5(TC下攪拌20 小時，冷卻至室溫，以醋酸乙酯（5〇毫升）處理，以鹽水洗條’脫水乾燥（MgS04)，過濾及濃縮。使殘留油於矽膠上藉急驟式管柱層析純化，使用2 : 1醋酸乙酯/己烷，提供所要之產物（122 毫克，68% )。MS (APCI) m/e 469 (M+H)+ ·Example 14C Amidinyl group, acetylene group, pyridinyl group, methyl group, methyl methyl formamidine second-butyl ester, Example 14B (150 mg, 0.384 mmol), 4-bromopyridine hydrochloride Mixture of salt (75 gram '0.34 mol), Pd2Cl2 (PPh3) 2 (27 mg, 0.0384 mol) and CuI (18 Aike' 〇093 Amel) with nitrogen gas Treat DMF (4 mL) with triethylamine (214 μl, 1.54 mmol), stir at 5 (TC for 20 hours, cool to room temperature, treat with ethyl acetate (50 mL), and wash the strips with brine 'Dehydrated and dried (MgS04), filtered and concentrated. The residual oil was purified by flash column chromatography on silica gel using 2: 1 ethyl acetate / hexane to provide the desired product (122 mg, 68%). MS (APCI) m / e 469 (M + H) + ·

實例14D (l_S)-2-nH-4丨嘴-3-基卜比咬冬基乙块基）ΐ?比症各基]氧基}甲基）乙胺所要之產物係經由以實例HC取代實例2D中之實例2Β， -67- 200301122Example 14D (l_S) -2-nH-4 丨 Mizol-3-ylbubibenzyl ethyl) bispyridyl] oxy} methyl) ethylamine Example 2B in Example 2D, -67- 200301122

(60) 以三氟醋酸鹽製成。MS (APCI) m/e 369 (M+H)+ ; 1 H NMR (300 MHz， CD3 OD) 5 8·76 (d，>6·5 Hz，2H)，8.47 (d，J=1.7 Hz，1H)，8.42 (d，J=2.7 Hz，1H)， 7.92 (d，J=6.5 Hz，2H)，7.66 (dd，J=2.7, 1·7 Hz，1H)，7.58 (d，J=7.8 Hz，1H)，7·38 (d， J=8.2 Hz，1H)，7.23 (s，1H)，7.13 (td，J=7.1，1·0 Hz，1H)，7·03 (td，J=7.8, 1·1 Hz，1H)， 4.34 (dd，J=10.1，3·0 Hz，1H)，4.19 (dd，J二 10.5, 5.8 Hz，1H)，3·98 (m，1H)，3·28 (m， 2印；對<：23112(^40*3.3丁?八之分析計算值：（：，47/74;11，3.15;凡7.52 實測值：C，47.53 ; H，3·18 ; N，7.48. 實例15 〔lS)-2-(lH-<哚各基VI-「(丨5-「(ZV2-吡啶-4-基乙烯基械啶-3-基}氣某）甲基1乙胺將實例14D(40毫克，0.11毫莫耳）、5% Pd/BaS04(8.1毫克）及喳啉（8.1微升）於曱醇（3毫升）中之混合物，在氫（2〇psi)及室溫下攪拌12分鐘，及過濾。使濾液濃縮，並使殘留油於C18 管柱上藉HPLC純化，使用0-100% CH3CN/H2O/0.1% TFA，提供所要之產物（30 毫克，75% )。MS(APCI)m/e369(M-H)- : iHNMR (300 MHz, CD3 OD) δ 8.57 (d, J=6.8 Hz? 2H)5 8.29 (d, J=2.4 Hz, 1H), 8.04 (s3 1H)3 7.69 (d3 J=6.4 Hz5 2H), 7.57 (d, J=7.8 Hz, 1H), 7.53 (d, J=7.8 Hz, 1H), 7.40 (d, J=8.1 Hz，1H)，7.33 (t，J=1.7 Hz，1H)，7·21 (s，1H)，7·14 (m，2H)，7.02 (td，J=8.1，1.0 Hz， 1H)，6·95 (d，J=12.2 Hz，1H)，4·24 (dd，J=10.5, 3·0 Hz，1H)，4.08 (dd，J=10.5, 5,6 Hz， 1H)，3·92 (m，1H)，3.26 (m，2H);對 C23 H22N4 O · 3.6TFA 之分析計算值 :C，46.45 ; H，3.30; Ν，7·17.實測值·· C，46.56 ; H，3.35; Ν，7·34· 實例16 胺基-4-苯某-N-丨5-『(EV2-吡啶-4-某乙烯基V比啶各基} 丁醯胺(60) Made from trifluoroacetate. MS (APCI) m / e 369 (M + H) +; 1 H NMR (300 MHz, CD3 OD) 5 8 · 76 (d, > 6.5 Hz, 2H), 8.47 (d, J = 1.7 Hz , 1H), 8.42 (d, J = 2.7 Hz, 1H), 7.92 (d, J = 6.5 Hz, 2H), 7.66 (dd, J = 2.7, 1.7 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.23 (s, 1H), 7.13 (td, J = 7.1, 1.0 Hz, 1H), 7.03 (td, J = 7.8, 1.1 Hz, 1H), 4.34 (dd, J = 10.1, 3.0 Hz, 1H), 4.19 (dd, J 2 10.5, 5.8 Hz, 1H), 3.98 (m, 1H), 3.28 (m, 2 prints); <: 23112 (^ 40 * 3.3, but 8) analysis and calculated values: (:, 47/74; 11, 3.15; where 7.52 found: C, 47.53; H, 3 · 18; N, 7.48. Example 15 [lS) -2- (lH- < indolyl VI-"(丨 5-" (ZV2-pyridin-4-ylvinylpyridin-3-yl)) ) Methyl 1 Ethylamine A mixture of Example 14D (40 mg, 0.11 mmol), 5% Pd / BaS04 (8.1 mg), and perylene (8.1 μl) in methanol (3 ml), under hydrogen ( (20 psi) and room temperature for 12 minutes, and filtered. The filtrate was concentrated and the residual oil was purified by HPLC on a C18 column using 0-100% CH3CN / H2O / 0.1% TFA to provide Product (30 mg, 75%). MS (APCI) m / e369 (MH)-: iHNMR (300 MHz, CD3 OD) δ 8.57 (d, J = 6.8 Hz? 2H) 5 8.29 (d, J = 2.4 Hz, 1H), 8.04 (s3 1H) 3 7.69 (d3 J = 6.4 Hz5 2H), 7.57 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.33 (t, J = 1.7 Hz, 1H), 7.21 (s, 1H), 7.14 (m, 2H), 7.02 (td, J = 8.1, 1.0 Hz, 1H) , 6.95 (d, J = 12.2 Hz, 1H), 4.24 (dd, J = 10.5, 3.0 Hz, 1H), 4.08 (dd, J = 10.5, 5,6 Hz, 1H), 3 · 92 (m, 1H), 3.26 (m, 2H); Analytical calculated value for C23 H22N4 O · 3.6TFA: C, 46.45; H, 3.30; Ν, 7.17. Measured value · C, 46.56; H , 3.35; Ν, 7 · 34 · Example 16 Amino-4-benzene-N- 丨 5-"(EV2-pyridin-4-a vinyl V-pyridine group) Butanidine

實例16A -68- 200301122 (61) 胆)_士苯基-l-[({5-「(E)-2-吡症斗基乙烯基滅啶各某}胺基）羰基1丙基胺基甲酸第三-丁酯將實例11B (200毫克，ΐ·〇毫莫耳）、HOBt (210毫克）、EDC (290 毫克）、DMAP (25毫克）及Boc-高苯基丙胺酸之混合物，於室溫下攪摔過夜，及濃縮。使殘留物溶於醋酸乙酯中，相繼以水、5% NaHC03及水洗滌，脫水乾燥（MgS〇4)，過濾及濃縮Example 16A -68- 200301122 (61) Bile) -shifenyl-l-[(({5-"(E) -2-pyridinylvinylpyridinyl) amino) carbonyl 1propylamino Tertiary-butyl formate: A mixture of Example 11B (200 mg, 200 mmol), HOBt (210 mg), EDC (290 mg), DMAP (25 mg), and Boc-homophenylalanine It was stirred overnight at room temperature, and concentrated. The residue was dissolved in ethyl acetate, washed with water, 5% NaHC03 and water, dried (MgS04), filtered and concentrated

。使殘留物於矽膠上藉急驟式管柱層析純化，使用3%甲醇/二氯曱烷，提供所要之產物（192毫克，41% )。MS (DCI/NH3) m/e 459 (M+H)+.. The residue was purified by flash column chromatography on silica gel using 3% methanol / dichloromethane to provide the desired product (192 mg, 41%). MS (DCI / NH3) m / e 459 (M + H) +.

實例16B (2S)-2-胺基-4-苯基外1：淀-4-基乙烯基卜比淀-3-基} 丁酸胺所要之產物係經由以實例16A取代實例2C中之實例2B，以其鹽酸鹽製成（173 毫克，89% )。MS(DCI/NH3)m/e359 (M+H)+ ;1 H NMR (DMSO-d6) 5 12·03 (s，1H)，8.97 (s，1H)，8.91 (d，J=6.6 Hz，2H)，8.85Example 16B (2S) -2-Amino-4-phenylex 1: 1: 4--4-vinylbubbino-3-yl} The desired product of amine butyrate is obtained by replacing the example in Example 2C with Example 16A 2B, made from its hydrochloride (173 mg, 89%). MS (DCI / NH3) m / e359 (M + H) +; 1 H NMR (DMSO-d6) 5 12 · 03 (s, 1H), 8.97 (s, 1H), 8.91 (d, J = 6.6 Hz, 2H), 8.85

(s，1H)，8·70 (d，J=4.1 Hz，2H)，8.60 (s，1H)，8·28 (d，J=6.6 Hz，2H)，8·09 (d，J=16.5 Hz，1H)，7.68 (d，J=16.5 Hz，1H)，7·24 (m，5H)，4.33 (m，1H)，2.78 (m，2H)，2.25 (m， 2H). 實例17 5-{「(2S)-2-胺基吲哚-3-基）丙基1氣某吡啶冬基菸鹼醯胺(s, 1H), 8.70 (d, J = 4.1 Hz, 2H), 8.60 (s, 1H), 8.28 (d, J = 6.6 Hz, 2H), 8.09 (d, J = 16.5 Hz, 1H), 7.68 (d, J = 16.5 Hz, 1H), 7.24 (m, 5H), 4.33 (m, 1H), 2.78 (m, 2H), 2.25 (m, 2H). Example 17 5 -{"(2S) -2-Aminoindol-3-yl) propyl

實例17A 5-{「(2SV2-『(第三-丁氣羰基）胺基-3-ΠΗ-吲哚-3-某）丙基1氣基}菸鹼酸將實例2Α(1·30克，3·02毫莫耳）與PdCl2.dppf(123毫克）於THF /水（6·3毫升/ 6·3毫升）中之溶液，在CO (800 psi)下，加熱至100 °C，歷經19小時，冷卻至室溫，並以水稀釋。以二氯曱烷 -69- 200301122Example 17A 5-{((2SV2-[(Third-butanecarbonyl) amino-3-III-indol-3-indole) propyl 1aeroyl} nicotinic acid) Example 2A (1.30 g, 3.02 mmol) and PdCl2.dppf (123 mg) in THF / water (6.3 ml / 6.3 ml), heated to 100 ° C under CO (800 psi) for 19 Hour, cool to room temperature and dilute with water. Dichloromethane-69- 200301122

(62) 萃取混合物，並將合併之萃液以水洗滌，脫水乾燥（MgS〇4) ’過濾及濃縮，提供所要之產物（912亳克，76% )。MS (DCI/NH3) m/e 396 (M+H)+ ·(62) The mixture is extracted and the combined extracts are washed with water, dried (MgS04) 'filtered and concentrated to provide the desired product (912 g, 76%). MS (DCI / NH3) m / e 396 (M + H) + ·

實例17B -3-基M-价5-f(吡啶-4-某胺基读基桃啶各基m甚、里基1乙基胺基甲酸第三-丁酯將實例17A (410毫克，1.0毫莫耳）' 4-胺基吡啶（100毫克，1.0 毫莫耳）、EDC (960毫克）及HOBt (680毫克）於DMF (10毫升）中之溶液，在室溫下攪拌過夜，以二氯甲烷稀釋，以水洗滌 ’脫水乾燥（MgS04)，過濾及濃縮。使殘留物於矽膠上藉急驟式管柱層析純化，使用醋酸乙酯/甲醇（8 : 1)，提供所要之產物（87 毫克，18% )。MS (DCI/NH3) m/e 488 (M+H)+ ·Example 17B-3-yl M-valent 5-f (pyridine-4-an amino group of pyridine, each group m, phenyl 1 ethylaminocarboxylic acid third-butyl ester Example 17A (410 mg, 1.0 MM) '4-aminopyridine (100 mg, 1.0 mM), EDC (960 mg) and HOBt (680 mg) in DMF (10 ml), stirred overnight at room temperature, Diluted with methyl chloride, washed with water, dried (MgS04), filtered and concentrated. The residue was purified by flash column chromatography on silica gel using ethyl acetate / methanol (8: 1) to provide the desired product ( 87 mg, 18%). MS (DCI / NH3) m / e 488 (M + H) + ·

實例17CExample 17C

胺基-3-ΠΗ-吲嗓-3-基）丙基1氣基^比淀-4-基於驗醯胺所要之產物係經由以實例17B取代實例2C中之實例2B，以其鹽酸鹽製成（27 毫克，31% )。MS(DCI/NH3)m/e 388 (M+H)+ ; 1HNMR(DMSO-D6) δ 11.32(brs, 1Η), 11.04 (brs,lH), 8.83 (d5J=l.4 Ηζ51Η)3 8·69 (表觀 d，J=6.8 Hz，2H)，8·59 (d，J=2.7 Hz，1H)，8.15 (br s，2H)，8.08 (表觀 d， J=6.8 Hz，2H)，7.85 (dd，J=l，4, 2.7 Hz，1H)，7.61 (d，J=7.8 Hz，1H)，7.38 (d，J=8.12 Hz，1H)，7·29 (d，J=2.7 Hz，1H)，7.10 (m，1H)，7·01 (m，1H)，4.33 (m，1H)，4.16 (m， lH)，3.87(m，lH)，3.16(m，2H). 實例18 N-(胺基乙基比淀-4-基乙缔基1於驗臨胺Amino-3-ΠΗ-indox-3-yl) propyl 1-amino ^ Biyodo-4- The desired product based on the test amine was obtained by replacing Example 2B in Example 2C with Example 17B, and its hydrochloride salt. Made (27 mg, 31%). MS (DCI / NH3) m / e 388 (M + H) +; 1HNMR (DMSO-D6) δ 11.32 (brs, 1Η), 11.04 (brs, lH), 8.83 (d5J = l.4 Ηζ51Η) 3 8 · 69 (apparent d, J = 6.8 Hz, 2H), 8.59 (d, J = 2.7 Hz, 1H), 8.15 (br s, 2H), 8.08 (apparent d, J = 6.8 Hz, 2H), 7.85 (dd, J = 1, 4, 2.7 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.12 Hz, 1H), 7.29 (d, J = 2.7 Hz , 1H), 7.10 (m, 1H), 7.01 (m, 1H), 4.33 (m, 1H), 4.16 (m, lH), 3.87 (m, lH), 3.16 (m, 2H). Example 18 N- (aminoethylpyridine-4-ylethylene 1

實例18A -70- (63) 5-[(垃：2-?^ -4-基乙烯基芬驗酸乙酷所要之產物係經由以3-溴基-5-乙氧羰基吡啶取代實例1B 中之實例 1A 而製成。MS (DC1/NH3) m/e 355 CM+Hf ·Example 18A -70- (63) 5-[(R: 2-? ^-4-ylvinylphenoxyacetate The desired product is obtained by replacing Example 1B with 3-bromo-5-ethoxycarbonylpyridine Example 1A. MS (DC1 / NH3) m / e 355 CM + Hf ·

實例18B 5-[(E)-2-p比淀-4-基乙婦基1於驗酸將實例 18A (1·60 克，6.3 毫莫耳）與 LiOH · H2 0 (2.64 克）於 THF / 水（50毫升/ 50毫升）中之混合物，於室溫下攪拌2小時。在真空下移除THF，並以1NHC1(水溶液）使水層酸化。藉過濾收集固體，並乾燥，提供所要之產物。MS (DCI/NH3) m/e 227 (M+H)+.Example 18B 5-[(E) -2-p Biyodo-4-ylethynyl 1 in acid test Example 18A (1.60 g, 6.3 mmol) with LiOH · H2 0 (2.64 g) in THF / Water (50ml / 50ml) and stir at room temperature for 2 hours. The THF was removed under vacuum and the aqueous layer was acidified with 1NHC1 (aq.). The solid was collected by filtration and dried to provide the desired product. MS (DCI / NH3) m / e 227 (M + H) +.

實例18C N-(胺基乙基）-5-『(E)-2-p比淀-4-基乙缔基於驗酿胺所要之產物係經由以實例18Β與Ν-第三-丁氧羰基胺基乙胺，個別取代實例ΠΒ與HC中之實例ΠΑ與4_胺基吡啶，以其鹽酸鹽製成。MS(DCI/NH)m/e384(M+H)+ ; iHNMRiDMSO-A) 5 9·19 (t，J=5.4 Hz，1H)，9.09 (d，J=1.7 Hz，1H)，9·01 (d，J=2.0 Hz，1H)，8.89 (d，J=6.5 Hz，2H)，8.82 (dd，J=1.7, 2.0 Hz，1H)，8.18 (d，J=6.5 Hz，2H)，8.07 (d，J=16.6 Hz，1H)， 7.87 (d, J=16.6 Hz, 1H), 3.72 (br s, 2H), 3.59 (m, 2H), 3.05 (m, 2H). 實例19 1>1-『(2£)-3-(4->臭苯基）丙-2-婦基1-1^-[2-(丨5-[(£)-2-外1：淀-4-基乙缔基117比Example 18C N- (Aminoethyl) -5-"(E) -2-p Biyodo-4-ylethylene is based on the desired product of amine test by using Example 18B with N-tertiary-butoxycarbonyl Aminoethylamine, examples of ΠA and HC in the individual substitution examples ΠA and 4-aminopyridine, are prepared from their hydrochloride salts. MS (DCI / NH) m / e384 (M + H) +; iHNMRiDMSO-A) 5 9 · 19 (t, J = 5.4 Hz, 1H), 9.09 (d, J = 1.7 Hz, 1H), 9.01 (d, J = 2.0 Hz, 1H), 8.89 (d, J = 6.5 Hz, 2H), 8.82 (dd, J = 1.7, 2.0 Hz, 1H), 8.18 (d, J = 6.5 Hz, 2H), 8.07 (d, J = 16.6 Hz, 1H), 7.87 (d, J = 16.6 Hz, 1H), 3.72 (br s, 2H), 3.59 (m, 2H), 3.05 (m, 2H). Example 19 1 > 1 -"(2 £) -3- (4- > Oxyphenyl) propan-2-yl 1-1 ^-[2- (丨 5-[(£) -2-outside 1: Yodo-4- Glycol 117 ratio

啶-3-基丨氣基）乙基1胺實例19A (2EV3-(4-溴苯基）丙-2-烯-1-醇將乙基4-溴基桂皮醯胺（5.430克，22.07毫莫耳）於甲苯（2〇毫 20G301122Pyridin-3-yl 丨 carbyl) ethyl 1 amine Example 19A (2EV3- (4-bromophenyl) prop-2-en-1-ol. Ethyl 4-bromocinnamidine (5.430 g, 22.07 mmol) Moore) in toluene (20 mmol 20G301122

(64) 升）中之溶液，在-78°c下，以DIBAL(1.5M，於甲苯中，37.0 毫升，55.5亳莫耳）處理10分鐘，於-78°C下攪拌30分鐘，溫熱至室溫’攪拌1小時，以1〇% HC1 (水溶液）使反應淬滅，並以乙醚萃取兩次。將合併之萃液以水及鹽水洗滌，脫水乾燥（MgS〇4)，過濾及濃縮，提供所要之產物（4463克，95% ) ° MS (DCI/NH3) m/e 212, 214 (M+H)+，228, 230 (M+18)+ ·(64) liters), treated with DIBAL (1.5M in toluene, 37.0 ml, 55.5 mol) at -78 ° C, stirred at -78 ° C for 30 minutes, warm Stir to room temperature for 1 hour, quench the reaction with 10% HC1 (aq.), And extract twice with diethyl ether. The combined extracts were washed with water and brine, dried (MgS04), filtered and concentrated to provide the desired product (4463 g, 95%) ° MS (DCI / NH3) m / e 212, 214 (M + H) +, 228, 230 (M + 18) + ·

實例19BExample 19B

1-溴基-4-「nEV3-盡.基丙-1-烯基1苯將實例19Α(2·0克，9.387毫莫耳）與S0C12(3.5毫升，47.9毫莫耳）於苯（10毫升）中之混合物，在室溫下攪拌24小時，及濃縮，提供所要之產物（2.167 克，99% )。（DCI/NH3) m/e 231，233, 235 (M+H)'1-Bromo-4- "nEV3-Jin.propylprop-1-enyl-1benzene Example 19A (2.0 g, 9.387 mmol) and SOC12 (3.5 ml, 47.9 mmol) in benzene (10 Ml), stirred at room temperature for 24 hours, and concentrated to provide the desired product (2.167 g, 99%). (DCI / NH3) m / e 231, 233, 235 (M + H) '

實例19CExample 19C

2-(丨5-『(EV2-吡啶-4-基乙烯基 >比啶各基}氧基）乙胺所要之產物係經由以實例9B與N-第三-丁氧基羰基胺基乙醇（200毫克，1.00毫莫耳），個別取代實例2A與2C中之3-溴基 -5-羥基吡啶與L-Boc-色胺酸，以其鹽酸鹽製成。MS (DCI/NH3) m/e 242 (M+H)+ ; 1 H NMR (CD3 OD) δ 8·88 (d，J=6.1 Hz，2H)，8·59 (s，1H)，8.43 (s， 1H)，8.19 (d，J=6.1 Hz，2H)，8·03 (d，J=16.3 Hz，1H)，8·01 (s，1H)，7.82 (d，J=16.3 Hz， 1H), 4.42 (t, J=4.9 Hz, 2H), 3.28 (m3 2H).The desired product of 2- (丨 5-"(EV2-pyridin-4-ylvinyl > pyridinyl) oxy) ethylamine is obtained by using Example 9B and N-third-butoxycarbonylaminoethanol. (200 mg, 1.00 millimolar), the 3-bromo-5-hydroxypyridine and L-Boc-tryptophanic acid in Examples 2A and 2C were individually substituted with the hydrochloride salt. MS (DCI / NH3) m / e 242 (M + H) +; 1 H NMR (CD3 OD) δ 8 · 88 (d, J = 6.1 Hz, 2H), 8.59 (s, 1H), 8.43 (s, 1H), 8.19 (d, J = 6.1 Hz, 2H), 8.03 (d, J = 16.3 Hz, 1H), 8.01 (s, 1H), 7.82 (d, J = 16.3 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 3.28 (m3 2H).

實例19D N-『(2EKH4-溴苯基）丙-2-烯基丨5-『(EV2-吡啶-4-基乙烯基 >比啶-3-基}氧基）乙基1胺將實例19C (100毫克，0.285毫莫耳）、實例19B (66.0毫克，0.285 -72- (65)Example 19D N-"(2EKH4-bromophenyl) prop-2-enyl 5-" (EV2-pyridin-4-ylvinyl > pyridin-3-yl} oxy) ethyl 1 amine 19C (100 mg, 0.285 mmol), Example 19B (66.0 mg, 0.285 -72- (65)

毫莫耳）及三乙胺（250微升，1.79毫莫耳）於DMF (5亳升）中之溶液，在室溫下攪拌3天，並倒入水中。將水層以二氯甲烷萃取三次，並將合併之萃液以水洗滌，脫水乾燥（MgS〇4) ，過濾及濃縮。使殘留物於矽膠上層析，使用二氯甲燒/ 甲醇/ NH4〇H(100 : 5 : 0.5)，提供自由態驗。將此物質以2M HCl/Et20處理，提供其鹽酸鹽（34.0 毫克，22% )。MS(DCI/NH3)m/e 436, 438 (M+H)+ ; 1H NMR (CDC13) 5 8.61 (m，2H)，8·37 (d，J=1.7 Hz，1H)，8·27 (d，J=2.7 Hz，1H)，7·37 (m，4H)，7·26 (m，5H)，7·25 (d，J=16.3 Hz，1H)，7·05 (d，J= 16.3 Hz, 1H), 6.53 (d, J=15.9 Hz, 1H), 6.31 (dt, J=6.1, 15.9 Hz, 1H), 4.23 (t, J-5.1 Hz, 2H)，3.53 (dd，J=l.l，6·1 Hz，1H)，3.13 (t，J=5.1 Hz，1H). 實例20 N4-(3-{『(2S)-2-胺基丨嗓-3-基）丙基1氣基丨笨基 >密淀-2,4-二胺MM) and triethylamine (250 μl, 1.79 mmol) in DMF (5 μl), stirred at room temperature for 3 days, and poured into water. The aqueous layer was extracted three times with dichloromethane, and the combined extracts were washed with water, dried (MgS04), filtered and concentrated. The residue was chromatographed on silica gel using dichloromethane / methanol / NH4OH (100: 5: 0.5) to provide a free state test. Treatment of this material with 2M HCl / Et20 provided its hydrochloride (34.0 mg, 22%). MS (DCI / NH3) m / e 436, 438 (M + H) +; 1H NMR (CDC13) 5 8.61 (m, 2H), 8.37 (d, J = 1.7 Hz, 1H), 8.27 ( d, J = 2.7 Hz, 1H), 7.37 (m, 4H), 7.26 (m, 5H), 7.25 (d, J = 16.3 Hz, 1H), 7.05 (d, J = 16.3 Hz, 1H), 6.53 (d, J = 15.9 Hz, 1H), 6.31 (dt, J = 6.1, 15.9 Hz, 1H), 4.23 (t, J-5.1 Hz, 2H), 3.53 (dd, J = ll, 6.1 Hz, 1H), 3.13 (t, J = 5.1 Hz, 1H). Example 20 N4- (3-{"(2S) -2-amino group voc-3-yl) propyl 1 gas Benzene > Mito-2,4-diamine

實例20A (lS)-2-(lH-沔丨嗓-3-基V1-IY3-硝基苯氧基）甲基1乙基胺基甲酸第三_ 丁酯所要之產物係經由以3-硝基酚取代實例2A中之3-溴基-5-羥基吡啶而製成（257 毫克，61% )。MS(DCI/NH3)m/e412(M+H)+，419 (Μ+18)+· 實例20ΒExample 20A (lS) -2- (lH- 沔丨 -3-yl V1-IY3-nitrophenoxy) methyl 1 ethylaminocarboxylic acid tertiary-butyl ester It was prepared by substituting 3-bromo-5-hydroxypyridine in Example 2A (257 mg, 61%). MS (DCI / NH3) m / e412 (M + H) +, 419 (Μ + 18) + · Example 20B

ClS)-2-(3-胺某笟氩某Vl-ilHWl哚各基甲基）乙基胺基甲酸第三- 丁酉旨將實例20Α (247毫克，0.600毫莫耳）、曱酸銨（400毫克，6.34 毫莫耳）及10% Pd/C (25毫克）於曱醇（1〇毫升）中之溶液，加熱至回流，歷經30分鐘，冷卻至室溫，經過矽藻土（Celite®)過 (66) 200301122ClS) -2- (3-amine, argon, argon, Vl-ilHWl, indole methyl) ethylaminocarboxylic acid, tert-butylamine, Example 20A (247 mg, 0.600 mmol), ammonium phosphonate (400 Mg, 6.34 mmol) and 10% Pd / C (25 mg) in methanol (10 ml), heated to reflux, cooled to room temperature over 30 minutes, and passed through celite (Celite®) Over (66) 200301122

遽及丨辰縮。使濃縮物於碎膠上葬多上精驟式管柱層析純化，使用醋酸乙酯/己烷（1 : n，柃糾π 1、、 )彳疋供所要之產物（200毫克，87% ) 〇 MS (DCI/NH3) m/e 382 (Μ+Η)+遽 and 丨 shrink. The concentrate was purified by gel column chromatography on crushed gel, and ethyl acetate / hexane (1: n, π, 1,) was used to supply the desired product (200 mg, 87% ) 〇MS (DCI / NH3) m / e 382 (Μ + Η) +

實例20C (is)-2-{.H(g:胺基基 μι·Γ1Η^ 甲芊 Κ 羞甲酸第三-丁酷將貫例20B (41·2耄克，0·108毫莫耳）與厶胺基斗氯基嘧啶〇4 〇毫克，0.108毫莫耳）於乙醇（〇·5毫升）中之溶液，加熱至8〇它，歷經13小時，並於矽膠上藉急騾式管柱層析純化，使用二氯甲燒/曱醇/ NKOH(100 : 5 : 〇·5)，提供所要之產物（5〇毫克，98% )。MS (DCI/NH3) m/e 475 (Μ+Η)+ ·Example 20C (is) -2-{. H (g: Amino group μ · Γ1Η ^ Formamidine carboxylic acid third-butanol Cooling Example 20B (41.2 g, 0.18 mmol) Amidinochlor chloropyrimidine (0.4 mg, 0.108 mmol) in ethanol (0.5 ml), heated to 80 ° C. for 13 hours, and borrowed from a silica gel column layer on silica gel Analytical purification using dichloromethane / methanol / NKOH (100: 5: 0.5) provided the desired product (50 mg, 98%). MS (DCI / NH3) m / e 475 (Μ + Η) + ·

實例20D N4-(3-{[(gS)-2:胺基-3-(1Η-Μΐ噪-3-基）丙基1氧基}笨基）喊咬_2,4-二胺所要之產物係經由以實例20C取代實例2C中之實例2B，以其鹽酸鹽製成（33 毫克，81% )。MS(DCI/NH3)m/e 375 (M+H)+ ;Example 20D N4- (3-{[((gS) -2: amino-3- (1Η-Μΐ noise-3-yl) propyl 1oxy} benzyl)) screams for what _2,4-diamine requires The product was prepared from Example 2C by replacing Example 2B in Example 2C with its hydrochloride salt (33 mg, 81%). MS (DCI / NH3) m / e 375 (M + H) +;

1 H NMR (DMSO-d6) δ 12.3 (br s3 1H), 10.8 (br s5 1H)5 8.35 (br s, 4H)? 7.85 (d, J= 7·1 Hz，1H)，7·61 (d，J=7.8 Hz，1H)，7.45 (br s，2H)，7.37 (d，J=7.8 Hz，1H)，7.30 (m， 2H)，7.09 (m，1H)，6.99 (m，1H)，6.75 (m，1H)，6.35 (m，1H)，4.17 (dd，J=3.4, 10.5 Hz， 1H)，4.03 (dd，J=5.8, 10.5 Hz，1H)，3.77 (m，1H)，3.18 (d，J=7.5 Hz，2H)· 實例21 (lRV3-{6-氯基口比淀-4-基乙婦基 1 口比淀-3-基口弓 1 口朵-3- 某甲基）丙胺1 H NMR (DMSO-d6) δ 12.3 (br s3 1H), 10.8 (br s5 1H) 5 8.35 (br s, 4H)? 7.85 (d, J = 7.1 Hz, 1H), 7.61 (d , J = 7.8 Hz, 1H), 7.45 (br s, 2H), 7.37 (d, J = 7.8 Hz, 1H), 7.30 (m, 2H), 7.09 (m, 1H), 6.99 (m, 1H), 6.75 (m, 1H), 6.35 (m, 1H), 4.17 (dd, J = 3.4, 10.5 Hz, 1H), 4.03 (dd, J = 5.8, 10.5 Hz, 1H), 3.77 (m, 1H), 3.18 (d, J = 7.5 Hz, 2H) · Example 21 (lRV3- {6-chloro-based bipyridine-4-ylethynyl 1-port biyid-3-yl-portal bow 1-portal -3- some methyl group ) Amine

實例21A 6-氣基-5-『(EV2w比啶-4_基乙烯基V比啶·3_胺 -74- (67) 將3-胺基j溴基各氯吡啶（2〇克.，9·64毫莫耳）、pd2(dba)3(44〇 t克，0.48亳莫耳）、三-鄰·曱苯基膦（438毫克，丨44毫莫耳）、4-乙晞基吡啶（2 〇8毫升，19·28毫莫耳）及三乙胺（4 〇3毫升 ’ 29毫莫耳）於DMF (30毫升）中之溶液，在1〇〇。〇下攪拌15小時’冷卻至室溫，以醋酸乙酯（2〇〇毫升）處理，以鹽水洗滌兩次’脫水乾燥（MgSCU)，過濾及濃縮。使殘留固體自己烷 /二氯甲烷再結晶，提供所要之產物（186克，84% )。MS (APCI) m/e 232 (M+H)+.Example 21A 6-amino-5-[(EV2w than pyridin-4-ylvinyl V than pyridine · 3-amine-74- (67) 3-amino j bromo each chloropyridine (20 g., 9.64 millimoles), pd2 (dba) 3 (44 gram, 0.48 millimoles), tri-o-pyrophenylphosphine (438 mg, 44 millimoles), 4-ethylpyridine (2.0 mL, 19.28 mmol) and a solution of triethylamine (403 mL '29 mmol) in DMF (30 mL), stirred for 15 hours at 100 ° C, cooled Treat to room temperature, treat with ethyl acetate (200 mL), wash twice with brine 'dry (MgSCU), filter, and concentrate. Recrystallize the residual solid from hexane / dichloromethane to provide the desired product (186 G, 84%). MS (APCI) m / e 232 (M + H) +.

實例21B g：氯基_5-碘基吡啶_4-基乙烯基扣比啶將實例21Α(1·0克，4.3毫莫耳）於30% H2S04(1〇毫升）中之溶液，在0 C下’以NaN〇2 (386毫克，5·6毫莫耳）處理，授拌5小時，以Nal(2.1克，14毫莫耳）於叱0(2毫升）中之溶液處理，攪拌2小時，以另外之Nal (2.1克，14毫莫耳）處理，攪拌2小時，倒入0°C下之30% NaOH (水溶液）(200毫升）中，並以1〇% 曱醇/醋酸乙醋萃取三次。使合併之有機相脫水乾燥（MgS〇4) ，過濾及濃縮。使殘留固體於矽膠上藉急驟式管柱層析純化，使用70%醋酸乙酯/己烷，提供所要之產物（1〇3克，7〇 % ) 〇 MS (DCI) m/e 343 (M+H)+ ·Example 21B g: Chloro_5-iodopyridin_4-ylvinylbipyridine A solution of Example 21A (1.0 g, 4.3 mmol) in 30% H2S04 (10 ml) was added at 0 Under C, treat with NaNO2 (386 mg, 5.6 mmol), stir for 5 hours, treat with a solution of Nal (2.1 g, 14 mmol) in 叱 0 (2 ml), and stir 2 Hour, treat with additional Nal (2.1 g, 14 mmol), stir for 2 hours, pour into 30% NaOH (aqueous solution) (200 ml) at 0 ° C, and add 10% methanol / ethyl acetate Extract three times with vinegar. The combined organic phases were dried (MgS04), filtered and concentrated. The residual solid was purified by flash column chromatography on silica gel using 70% ethyl acetate / hexane to provide the desired product (103 g, 70%). MS (DCI) m / e 343 (M + H) + ·

實例21C 嗓-3-基甲基）丙-2-烯基胺一 -丁酯將漠化甲基三苯基鱗（5.65克’ 15·81毫莫耳）於THF(5〇毫升）中之懸浮液，在〇°C下，以11-BuLi(於己烷中之25M溶液，633 毫升’ 15.81毫莫耳）處理，攪拌1〇分鐘，溫熱至室溫，檀掉 -75- (68) (68)200301122Example 21C Benzol-3-ylmethyl) prop-2-enylamine mono-butyl ester. Methyltriphenylscale (5.65 g '15 .81 mmol) in THF (50 ml) The suspension was treated with 11-BuLi (25M solution in hexane, 633 ml '15 .81 mmol) at 0 ° C, stirred for 10 minutes, warmed to room temperature, ) (68) 200301122

30分鐘，冷；§卩$ p至〇 C，以L-Boc-色胺酸（3.80克，13.2毫莫耳）在 THF (10毫升）中夕a、丨；甲 < 洛液處理，攪掉2小時，以乙醚（200毫升）處理，以鹽氽、、土％ π水先滌，脫水乾燥（MgS〇4)，過濾及濃縮。使殘田’由於發膠上藉急驟式管柱層析純化，使用20%醋酸乙酯 /己k ’提供所要之產物（700毫克，18% )。MS(DCI)m/e287 (M+H)+ ·30 minutes, cold; § $ p to 0 ° C, treated with L-Boc-tryptophan (3.80 g, 13.2 mmol) in THF (10 ml); a < Luo solution treatment, stir It was dropped for 2 hours, treated with diethyl ether (200 ml), washed with salt water, soil% π water, dried (MgS04), filtered and concentrated. Residual field was purified by flash column chromatography on a hair spray using 20% ethyl acetate / hexane to provide the desired product (700 mg, 18%). MS (DCI) m / e287 (M + H) + ·

實例21D 吡啶-4-基乙烯某1毗啶各墓Vl-ΠΗ-吲哚-3-羞^1_基）丙基胺基甲醢第三-丁酯將實例21C (1〇〇毫克，〇·35毫莫耳）於THF (3毫升）中之溶液 ’在〇 C下’以9-BBN (於THF中之〇·5 Μ溶液，0.70毫升，0.35 宅莫耳）處理’揽掉過夜’同時慢慢地溫熱至室溫，以套管加入實例21Β (108毫克，0.32毫莫耳）、PdCl2(dppf)(26毫克，0.032 毫莫耳）及Cs2 C03 (228毫克，〇·7毫莫耳）於DMF中之混合物内 ’以氮滌氣’並於50。(：下攪拌8小時。將混合物以醋酸乙酯 (50毫升）處理，以鹽水洗滌，脫水乾燥（MgS〇4)，過濾及濃縮。使殘留油於矽膠上藉急驟式管柱層析純化，使用80% 醋酸乙酯/己烷’提供所要之產物（69毫克，40% )。Example 21D Pyridine-4-ylethylene, 1-pyridine, 1-pyridine, 1-pyridinyl-indole-3-yl-1-propyl) propylaminoformamidine, tert-butyl ester Example 21C (100 mg, • 35 millimolar) solution in THF (3 ml) 'at 0 ° C' treated with 9-BBN (0.5 M solution in THF, 0.70 ml, 0.35 mol) overnight At the same time, slowly warm to room temperature, and add 21B (108 mg, 0.32 mmol), PdCl2 (dppf) (26 mg, 0.032 mmol) and Cs2 C03 (228 mg, 0.7 mmol) in a cannula. Moore) 'Clean with nitrogen' in a mixture in DMF at 50 ° C. (: Stirred for 8 hours. The mixture was treated with ethyl acetate (50 ml), washed with brine, dried (MgS04), filtered and concentrated. The residual oil was purified by flash column chromatography on silica gel, The use of 80% ethyl acetate / hexane 'provided the desired product (69 mg, 40%).

實例21E (1这)->{6-氯基-5-『(E)-2-吡啶·4-基乙烯某 >比啶-3-某[H1H，哚-3- 基甲基）丙胺所要之產物係經由以實例21D取代實例2D中之實例2Β，以三氟醋酸鹽製成。MS (APCI) m/e 403, 405 (Μ+Η)+; 1 H NMR (300 ΜΗζ， CD3 OD) δ 8.78 (d, J=6.8 Hz, 2H), 8.19 (d, J=1.7 Hz, 1H)5 8.18 (d, J=6.S Hz, 2H), -76- 200301122Example 21E (1This)-> {6-Chloro-5-[(E) -2-pyridine · 4-ylethylene> > Bipyridin-3-& [H1H, indol-3-ylmethyl] The desired product of propylamine was made from trifluoroacetate by substituting Example 21D for Example 2B in Example 2D. MS (APCI) m / e 403, 405 (Μ + Η) +; 1 H NMR (300 ΜΗζ, CD3 OD) δ 8.78 (d, J = 6.8 Hz, 2H), 8.19 (d, J = 1.7 Hz, 1H ) 5 8.18 (d, J = 6.S Hz, 2H), -76- 200301122

(69) 7.97 (d，J=2.4 Hz，1Η)，7·93 (d，J=16.3 Hz，1Η)，7·48 (d，J=7.8 Hz, 1Η)，7·34 (d，J= 9·5 Hz，1H)，7.33 (d，J=16.0 Hz，1H)，7.20 (s，1H)，7.11 (td，J=7.1，1·0 Hz，1H)，7.00 (td，J=6.8, 1·0 Hz，1H)，3·55 (p，J=6.4 Hz，1H)，3.16 (m，2H)，2.82 (m，2H)，2.06 (m， 2H);對 C24H23C1N4 .2.8TFA之分析計算值：C，49.23; Η，3·60; Ν，7·76. 實測值：C，49.11 ; H，3.64; Ν，7·66. 實例22 4-(5-m2S)-2-胺基-3-ΠΗ-蚓哚-3-基）丙基1氣基}吡啶-3-基）笨甲腈(69) 7.97 (d, J = 2.4 Hz, 1Η), 7.93 (d, J = 16.3 Hz, 1Η), 7.48 (d, J = 7.8 Hz, 1Η), 7.34 (d, J = 9.5 Hz, 1H), 7.33 (d, J = 16.0 Hz, 1H), 7.20 (s, 1H), 7.11 (td, J = 7.1, 1.0 Hz, 1H), 7.00 (td, J = 6.8, 1.0 Hz, 1H), 3.55 (p, J = 6.4 Hz, 1H), 3.16 (m, 2H), 2.82 (m, 2H), 2.06 (m, 2H); for C24H23C1N4 .2.8TFA Analytical calculated value: C, 49.23; Η, 3.60; Ν, 7.76. Found: C, 49.11; H, 3.64; Ν, 7.66. Example 22 4- (5-m2S) -2- Amino-3-Πfluorene-earthin-3-yl) propyl 1-amino} pyridin-3-yl) benzonitrile

實例22Α (lS)-2]f5-(4-氰基茉某V比啶-3-基1氧基μΐ-(1Η-吲哚-3-基甲基）乙基胺基甲酸第三-丁酯Example 22A (1S) -2] f5- (4-Cyanosupperone V than pyridin-3-yl 1oxy μΐ- (1Η-indole-3-ylmethyl) ethylaminocarboxylic acid tert-butyl ester

將實例2Α (250毫克，0.56毫莫耳）於乙二醇二甲基醚（20.0毫升）中之溶液，在室溫下以肆（三苯膦）鈀⑼(32毫克，0.03毫莫耳）處理，攪拌10分鐘，以（4-氰基苯基）二羥基硼烷（123毫克，0.84毫莫耳）於乙醇（5.0毫升）中之溶液處理，攪拌15分鐘，以2Μ Na2 C03 (水溶液）(1·4毫升）處理，加熱至回流，歷經4小時，冷卻至室溫及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用己烷/醋酸乙酯（1 : 1)，提供所要之產物（230 毫克，88% )。MS(DCI/NH3)m/e469(M+H)+.A solution of Example 2A (250 mg, 0.56 mmol) in ethylene glycol dimethyl ether (20.0 ml) was treated with tris (triphenylphosphine) palladium (32 mg, 0.03 mmol) at room temperature. Treat, stir for 10 minutes, treat with a solution of (4-cyanophenyl) dihydroxyborane (123 mg, 0.84 mmol) in ethanol (5.0 ml), stir for 15 minutes, and use 2M Na2C03 (aqueous solution) (1.4 ml), heated to reflux for 4 hours, cooled to room temperature and concentrated. The concentrate was purified by flash column chromatography on silica gel using hexane / ethyl acetate (1: 1) to provide the desired product (230 mg, 88%). MS (DCI / NH3) m / e469 (M + H) +.

實例22B 4-(5-{『(2S)-2-胺某-3-ΠΗ-吲哚各基）丙篡1氧某}吡啶-3-基）苯甲腈將實例22A (20毫克，0.043毫莫耳）於二氯甲烷（2.0毫升）中之溶液，在0°C下，以三氟醋酸（0.5毫升）逐滴處理，並攪拌 2小時，同時溫熱至室溫。使反應混合物濃縮，提供所要之產物，為三氟醋酸鹽（27毫克，88% )。MS(DCI/NH3)m/e369 -77- (70)Example 22B 4- (5-{"(2S) -2-Amine-3-ΠΗ-Indolyl) propanone 1oxy} pyridin-3-yl) benzonitrile Example 22A (20 mg, 0.043 A solution of mol) in dichloromethane (2.0 ml) was treated dropwise with trifluoroacetic acid (0.5 ml) at 0 ° C and stirred for 2 hours while warming to room temperature. The reaction mixture was concentrated to provide the desired product as trifluoroacetate (27 mg, 88%). MS (DCI / NH3) m / e369 -77- (70)

(M+H)+ ； ^NMRCDMSO-dg) 5 11.02 (s, 1H)? 8.63 (d5 J=l.9 Hz, 1H)5 8.42 (d? J二2·8 Hz，1H)，8.21 (br s，2H)，7.99-7.92 (m，4H)，7.73 (t，J=1.9 Hz，1H)，7.61 (d，J= 8.1 Hz，1H)，7.38 (d，J=8.1 Hz，1H)，7.29 (d，J=2.5 Hz，1H)，7.10 (m，1H)，7.01 (m， 1H)，4.36 (dd，J=10.6, 3.1 Hz，1H)，4.19 (dd，J=10.9, 5.9 Hz，1H)，3.89-3.82 (m，1H)， 3.16 (d, J=7.2 Hz, 2H). 實例23 1^-[(28)-2-胺基-3-(111-1^丨嗓-3-基）丙某1->||-異4淋-5-基？比淀-3,5-二胺(M + H) +; ^ NMRCDMSO-dg) 5 11.02 (s, 1H)? 8.63 (d5 J = 1.9 Hz, 1H) 5 8.42 (d? J 2 · 8 Hz, 1H), 8.21 (br s, 2H), 7.99-7.92 (m, 4H), 7.73 (t, J = 1.9 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 2.5 Hz, 1H), 7.10 (m, 1H), 7.01 (m, 1H), 4.36 (dd, J = 10.6, 3.1 Hz, 1H), 4.19 (dd, J = 10.9, 5.9 Hz , 1H), 3.89-3.82 (m, 1H), 3.16 (d, J = 7.2 Hz, 2H). Example 23 1 ^-[(28) -2-amino-3- (111-1 ^ 丨 throat- 3-based) Bing 1- > || -Iso-4-L-5-yl? Pyodo-3,5-diamine

實例23A 異喹〃林....二5·基三氟甲烷磺酸鹽將5-羥基異喹啉（1.6克；11.0毫莫耳）與三乙胺（138克；13 6 耄莫耳）於二氯甲烷（25毫升）中之混合物，在〇°c下，以三氟甲烷磺酐（3.35克；12.1毫莫耳）慢慢地處理，攪摔過夜，同時溫熱至室溫，以二氯甲烷稀釋，以水及飽和腿4 α (水洛液）洗條兩次’以水及鹽水洗滌一次，脫水乾燥^s〇4) ’過濾及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用7%醋酸乙酯/二氯甲烷，提供所要之產物（1·54克； 50% ) 〇Example 23A Isoquinazine .... Di-5-yltrifluoromethanesulfonate. 5-Hydroxyisoquinoline (1.6 g; 11.0 mmol) and triethylamine (138 g; 13 6 gmol) The mixture in dichloromethane (25 ml) was slowly treated with trifluoromethanesulfonic anhydride (3.35 g; 12.1 mmol) at 0 ° C and stirred overnight while warming to room temperature to Diluted with dichloromethane, washed the strips twice with water and saturated legs 4α (water solution), 'washed once with water and brine, dried and dried ^ s04)', filtered and concentrated. The concentrate was purified by flash column chromatography on silica gel using 7% ethyl acetate / dichloromethane to provide the desired product (1.54 g; 50%).

^1L23B 基吡啶將3M NaOH(250毫升）之溶液，於室溫下，以溴（25 9克’ 162 毫莫耳）處理，攪拌15分鐘，以5_溴基於驗酿胺（25克，124 毫莫耳）處理，攪拌45分鐘，加熱至85_1〇〇t：，歷經3小時，冷卻至室溫，〃1〇%Ηα(水落液）調整至pH1，以乙醚洗務兩次。以固體Na〇H將水層調整至pH〜1〇_n，並以乙醚萃取 -78- 200301122^ 1L23B based pyridine. A solution of 3M NaOH (250 ml) was treated with bromine (25 9 g '162 mmol) at room temperature, stirred for 15 minutes, and 5-bromo-based amine (25 g, 124 Millimol) treatment, stirred for 45 minutes, heated to 85-100 t: cooled to room temperature over 3 hours, adjusted to pH 1 with 10% α (water falling solution), and washed twice with ether. Adjust the aqueous layer to pH ~ 10_n with solid NaOH and extract with ether -78- 200301122

(71) 燥(％s〇4) 四次’及以二氯甲烷兩次。使合併之萃液脫水乾 ’過濾及濃縮，提供所要之產物（13.3克，62% )。(71) Dry (% s04) four times' and twice with dichloromethane. The combined extracts were dried and filtered 'and concentrated to provide the desired product (13.3 g, 62%).

實例23C N-(5-溴基吡啶-3-基）異口奎淋-5-胺將實例23A(500毫克，1·8毫莫耳）、實例23B (600亳克，3 5 亳莫耳）、Pd2(dba)3 (42 毫克；0.045 毫莫耳）、ΒΙΝΑΡ (56 亳克；〇.09 亳莫耳）及第三-丁醇鈉（350毫克；3.6毫莫耳）於1〇毫升甲苯中之混合物，加熱至回流，歷經2小時，以水稀釋，並以醋酸乙酯萃取三次。將合併之萃液以飽和NaHC〇3、水及鹽水連續洗滌，脫水乾燥（Na2S04)，及濃縮。使濃縮液於矽膠上藉急驟式管柱層析純化，使用3%曱醇/二氯甲燒，提供所要之產物（97毫克，18% )。Example 23C N- (5-Bromopyridin-3-yl) isoquinone-5-amine Example 23A (500 mg, 1.8 mmol), Example 23B (600 mg, 3 5 mmol) ), Pd2 (dba) 3 (42 mg; 0.045 mmol), BINAP (56 μg; 0.009 mmol) and sodium tert-butoxide (350 mg; 3.6 mmol) in 10 ml The mixture in toluene was heated to reflux for 2 hours, diluted with water, and extracted three times with ethyl acetate. The combined extracts were washed successively with saturated NaHC03, water and saline, dried (Na2S04), and concentrated. The concentrate was purified by flash column chromatography on silica gel using 3% methanol / dichloromethane to provide the desired product (97 mg, 18%).

實例23D ϋ-(二苯亞甲基yNL異喹啉-5-某吡咗_3,5_二胺將實例23C (175毫克，〇·58毫莫耳）、二苯甲酮亞胺（150毫克，0.83 毫莫耳）、Pd2(dba)3(54 毫克，0.06 毫莫耳）、BINAP(55 毫克’ 0.09愛莫耳）及第三-丁醇鈉（8〇毫克，〇·82毫莫耳）於3毫升甲苯中之混合物，加熱至75-80°C，歷經4小時，及濃縮。使濃縮液於碎膠上藉急驟式管柱層析純化，使用3%甲醇 /二氯甲烷，提供所要之產物（150毫克，64% )。Example 23D hydrazone- (diphenylmethylene yNL isoquinoline-5-some pyridonium-3,5-diamine Example 23C (175 mg, 0.58 mmol), benzophenimine (150 Mg, 0.83 mmoles), Pd2 (dba) 3 (54 mg, 0.06 mmoles), BINAP (55 mg '0.09 emolles), and tertiary-butoxide (80 mg, 0.82 mmoles Ear) in 3 ml of toluene, heated to 75-80 ° C over 4 hours, and concentrated. The concentrated solution was purified by gel chromatography on crushed gel using 3% methanol / dichloromethane, Provided the desired product (150 mg, 64%).

實例23E N-異口奎琳-5-基口比咬-3,5-二fe 將貫例23D (145耄克；〇·36毫莫耳）於3毫升丁 HF中之混合物 ’在室溫下，以10滴水與3滴濃HC1處理，攪拌2小時，及 •79- (72) n &殘留物於醋酸乙酿與濃NaHC〇3(水溶液）之間作分液處理冑7欠層以醋酸乙醋萃取三次。將合併之萃液以鹽務脫水乾燥（MgS〇4)，過渡、及濃縮。使濃縮液於碎膠上藉急驟式管柱層析純化，使用10%甲醇/二氯甲燒，提供所要之產物（59毫克，68% )。Example 23E A mixture of N-Isoqueline Quirin-5-base ratio bite-3,5-dife Example 23D (145 g; 0.36 mmol) in 3 ml of HF at room temperature Next, treat with 10 drops of water and 3 drops of concentrated HC1, stir for 2 hours, and • 79- (72) n & residues were separated between ethyl acetate and concentrated NaHC0 (aqueous solution). 7 underlayer Extract three times with ethyl acetate. The combined extracts were dried (MgS04) with salt, transitioned, and concentrated. The concentrate was purified on a gel by flash column chromatography using 10% methanol / dichloromethane to provide the desired product (59 mg, 68%).

實例23F 基胺某 Μ 咗二其 I 丨田羞^基胺基i酸第三_丁酯將貫例23E (55耄克，〇·23耄莫耳）與ε·Β(Χ;•色胺酸（科毫克，〇·29 毛莫耳）於2笔升二氯甲烷中之混合物，在室溫下，以Ti(iPrO)4 (1笔升）處理，攪拌2小時，及濃縮。使殘留物溶於2毫升乙醇中，以NaBH3CN(30毫克；〇·46毫莫耳）處理，攪拌2小時 ’以水稀釋及過濾。將濾餅以甲醇洗滌，並使濾液濃縮。使殘留物懸浮於甲醇/二氯甲烷中，及過濾。使濾液濃縮 ’並使濃縮液於矽膠上藉急驟式管柱層析純化，使用5% 曱醇/二氯曱烷，提供所要之產物（28毫克，24% )。Example 23F A certain amino group of a methylamine, a tertiary butyl amine amino acid, a tertiary butyl ester of aminoamino acid, Example 23E (55 g, 0.23 mole) and ε · Β (X; • tryptamine A mixture of an acid (Kg, 0.29 momol) in 2 liters of dichloromethane, treated with Ti (iPrO) 4 (1 liter) at room temperature, stirred for 2 hours, and concentrated. Residue The material was dissolved in 2 ml of ethanol, treated with NaBH3CN (30 mg; 0.46 mmol), stirred for 2 hours', diluted with water and filtered. The filter cake was washed with methanol, and the filtrate was concentrated. The residue was suspended in Methanol / dichloromethane, and filtered. The filtrate was concentrated, and the concentrate was purified by flash column chromatography on silica gel using 5% methanol / dichloromethane to provide the desired product (28 mg, 24 %).

實例23G 吐[(25)-2-胺基各(1沁吲哚-3-基）丙某柯，-異崦啉-5-基吡啶-3,5-二胺將實例23F (26毫克，0.05毫莫耳）於2毫升二氯甲烷中之溶液，在室溫下，以〇·5毫升TFA處理，攪拌3小時，及濃縮。使濃縮液於C18管拄上，藉逆相HPLC純化，使用0-100% CHsCN/E^O/O.l% TFA，並使殘留物溶於水中，及；東乾，提供所要之產物，為三氟醋酸鹽（27毫克，70% )。MS (ESI(+)) m/e 409 (M+H)+ ; 1 H NMR (DMSO-D6，500 MHz) 5 1L02 (s，1H)，9·44 (s，1H)，9.07 (s， -80- (73) 1H)，8·57 (d，J=9 Hz，1H)，7.95-8.01 (m，2H)，7.88-7.93 (m，2H)，7.68-7.73 (m，3H)， 7.57-7.59 (m，1H)，7·53 (d，J=8 Hz，1H)，7.38 (d，J=8 Hz，1H)，7.24-7.27 (m，1H)， 7.09 (t, J=9 Hz, 1H), 6.89 (t3 J=9 Hz, 1H), 6.92 (s? 1H), 6.83 (br s5 1H)5 3.33-3.40 (m, lH)，3.00-3.14(m，4H);對 C25H24N6 ·3ΤΡΑ·3Η20 之分析計算值： C，46.28; Η，4·13; N，10.44 ; F，21.25.實測值：C，46.32; Η，3·54·; Ν，10·02 ；F? 21.58. 實例24 N-「(2SV2-胺基-3-ΠΗ-吲哚-3-基）丙基VN-「5-(異4啉-5-基氧基）吡啶-Example 23G Toss [(25) -2-amino group (1 indolin-3-yl) propanone, -isophosphon-5-ylpyridin-3,5-diamine Example 23F (26 mg, 0.05 millimolar) in 2 ml of dichloromethane, treated with 0.5 ml of TFA at room temperature, stirred for 3 hours, and concentrated. The concentrated solution was purified on a C18 tube and purified by reverse-phase HPLC using 0-100% CHsCN / E ^ O / Ol% TFA and the residue was dissolved in water, and Donggan provided the desired product as three Fluoroacetate (27 mg, 70%). MS (ESI (+)) m / e 409 (M + H) +; 1 H NMR (DMSO-D6, 500 MHz) 5 1L02 (s, 1H), 9.44 (s, 1H), 9.07 (s, -80- (73) 1H), 8.57 (d, J = 9 Hz, 1H), 7.95-8.01 (m, 2H), 7.88-7.93 (m, 2H), 7.68-7.73 (m, 3H), 7.57-7.59 (m, 1H), 7.53 (d, J = 8 Hz, 1H), 7.38 (d, J = 8 Hz, 1H), 7.24-7.27 (m, 1H), 7.09 (t, J = 9 Hz, 1H), 6.89 (t3 J = 9 Hz, 1H), 6.92 (s? 1H), 6.83 (br s5 1H) 5 3.33-3.40 (m, lH), 3.00-3.14 (m, 4H); yes Analytical calculated values of C25H24N6 · 3TPA · 3Η20: C, 46.28; Η, 4.13; N, 10.44; F, 21.25. Found: C, 46.32; Η, 3.54 ·; Ν, 10 · 02; F? 21.58. Example 24 N-"(2SV2-Amino-3-Πfluorene-indol-3-yl) propyl VN-" 5- (iso4-line-5-yloxy) pyridine-

3-基1胺實例24A 54(5-溴基吡啶-3-基）氣基1異4啉於密封管中裝填5-羥基異喳啉（0.15克，1.03毫莫耳）、3,5-二溴基吡啶（0.24克，L03毫莫耳）、碳酸鉀（0.27克，2.0毫莫耳）及DMF (4毫升）。將反應物於個人用化學微波爐中，加熱至240°C，歷經10分鐘。使反應物於水與醋酸乙酯之間作分液處理。將水層以醋酸乙酯萃取兩次。使合併之萃液濃縮，並使殘留物於矽膠上藉急驟式管柱層析純化，使用2 :1醋酸乙酯/己烷，提供所要之產物（0.071克，23% )。Example of 3-yl 1 amine 24A 54 (5-bromopyridin-3-yl) amino 1 iso4 morpholine Sealed tube was filled with 5-hydroxyisoxoline (0.15 g, 1.03 mmol), 3,5- Dibromopyridine (0.24 g, L03 mmol), potassium carbonate (0.27 g, 2.0 mmol) and DMF (4 ml). The reaction was heated in a personal chemical microwave oven to 240 ° C for 10 minutes. The reaction was partitioned between water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined extracts were concentrated and the residue was purified by flash column chromatography on silica gel using 2: 1 ethyl acetate / hexane to provide the desired product (0.071 g, 23%).

實例24B N-『(2SV2-胺基丨嘴-3-基）丙基1-Ν-「5-(異4 ?林-5-基氧基V比咬- 3-基1胺所要之產物係經由以實例24A取代實例23D中之實例23C，然後按實例23E、23F及23G所述進行而製成。MS (ESI) m/e 410 (M+H)+; 1 H NMR (DMSO-D6，300 MHz) 5 11.00 (br s，1H)，9.47 (br s，1H)，8·58 (74)Example 24B The desired product of N-"(2SV2-amino group-l--3-yl) propyl 1-N-" 5- (iso4-?-5-yloxyV is more than that of 3-yl-1 amine Prepared by replacing Example 23C in Example 23D with Example 24A, and then proceeding as described in Examples 23E, 23F, and 23G. MS (ESI) m / e 410 (M + H) +; 1 H NMR (DMSO-D6, 300 MHz) 5 11.00 (br s, 1H), 9.47 (br s, 1H), 8.58 (74)

(d，J=8 Hz，1H)，7.97-8.03 (m，1H)，7.92-7.94 (m，1H)，7.85-7.87 (m，1H)，7.79-7.82 (m，2H)，7.66-7.72 (m，2H)，7.51-7.54 (m，1H)，7.26-7.36 (m，3H)，7.02-7.08 (m，1H)， 6.94-6.98 (m，1H)，6.68-6.71 (m，1H)，6.39 (br s，1H)，3.73-3.80 (m，1H)，3·43-3·52 (m，2H)，3.16-3.19 (m，2H);對 C25H23N5CU3TFA 之分析計算值：C，49.53 ;Η，3·46; Ν，9·30; F，22.76·實測值：C，49.44; Η，3·58; Ν，9·14; F，22.30· 實例25 (2S)-2-胺基-3-ΠΗ-Θ丨嗓-3-基）奈咬-2-基V比咬-3-基1丙醯胺實例25Α 2,2-二甲基-Ν-ρ比咬-4-基丙醯胺使4-胺基吡啶（1〇克，1〇6毫莫耳）與氯化三甲基乙醯（丨2.9克，107毫莫耳）於200毫升二氯曱烷中之混合物冷卻至〇。〇，並以三乙胺（1〇·9克，108毫莫耳）慢慢地處理，溫熱至室溫 ’攪拌過夜，並以水稀釋。將水層以二氯曱烷萃取三次，並將合併之萃液以鹽水洗滌，脫水乾燥（NhSOj，過濾及濃縮。使產物自甲苯再、結晶，提供所要之產物（14克，74% )。(d, J = 8 Hz, 1H), 7.97-8.03 (m, 1H), 7.92-7.94 (m, 1H), 7.85-7.87 (m, 1H), 7.79-7.82 (m, 2H), 7.66-7.72 (m, 2H), 7.51-7.54 (m, 1H), 7.26-7.36 (m, 3H), 7.02-7.08 (m, 1H), 6.94-6.98 (m, 1H), 6.68-6.71 (m, 1H) , 6.39 (br s, 1H), 3.73-3.80 (m, 1H), 3.43-3.52 (m, 2H), 3.16-3.19 (m, 2H); Analysis and calculation of C25H23N5CU3TFA: C, 49.53 Η, 3.46; Ν, 9.30; F, 22.76. Found: C, 49.44; Η, 3.58; Ν, 9.14; F, 22.30. Example 25 (2S) -2-amino -3-ΠΗ-Θ 丨 Hydroxy-3-yl) Benzene-2-yl V than Benzyl-3-yl 1 propionamine Example 25A 2,2-dimethyl-N-ρ Ratio phenyl-4-ylpropyl Amidine cools a mixture of 4-aminopyridine (10 g, 106 mmol) and trimethylacetamidine (2.9 g, 107 mmol) in 200 ml of dichloromethane. 〇. 〇, and slowly treated with triethylamine (10.9 g, 108 mM), warmed to room temperature ′ stirred overnight, and diluted with water. The aqueous layer was extracted three times with dichloromethane, and the combined extracts were washed with brine, dried (NhSOj, filtered, and concentrated. The product was recrystallized from toluene to provide the desired product (14 g, 74%).

實例25B 甲酿羞，外斗基）-2,2-二甲基丙醯胺使實例25A (11·4克，64亳莫耳）於2〇〇毫升THF中之混合物冷卻至-78°C ’以己烷中之l 6MnBuLi(1〇〇毫升，ι6〇毫莫耳）處理 ’溫熱至0°C ’攪拌1小時，以dmF (22克，215毫莫耳）於100 毫升THF中之溶液處理，溫熱至室溫，攪拌1小時，以鹽水稀釋，並以醋酸乙酯萃取三次。將合併之萃液以水洗滌，以鹽水洗務兩次’脫水乾燥（MgS〇4),過濾及濃縮。使濃縮液於碎膠上藉急驟式管柱層析純化，使用甲醇/二氯 -82- 200301122 (75) 甲烷，提供所要之產物（9·1克，69% ) ° 實例25C 4-胺某菸鹼醛將實例25B (870毫克，4.2毫莫耳）於3N HC1 (水溶液）(1〇毫升）中之溶液，加熱至回流過夜，並以乙醚萃取三次。以固體 K2 C03將水層調整至pH >7，並以20%異丙醇/氯仿萃取六次。使合併之萃液脫水乾燥（Na2S04)，過濾及濃縮，提供所Example 25B Formamidine, exoyl) -2,2-dimethylpropanamide. The mixture of Example 25A (11.4 g, 64 mol) in 200 ml of THF was cooled to -78 ° C. 'Treat with 1 6 MnBuLi (100 mL, ΙΟΟmmol) in hexane' 'Warm to 0 ° C' and stir for 1 hour with dmF (22 g, 215 mmol) in 100 mL of THF The solution was treated, warmed to room temperature, stirred for 1 hour, diluted with brine, and extracted three times with ethyl acetate. The combined extracts were washed with water, washed twice with brine and dried (MgS04), filtered and concentrated. The concentrated solution was purified on a gel by flash column chromatography using methanol / dichloro-82- 200301122 (75) methane to provide the desired product (9.1 g, 69%) ° Example 25C 4-amine Nicotinaldehyde. A solution of Example 25B (870 mg, 4.2 mmol) in 3N HC1 (aqueous) (10 mL) was heated to reflux overnight and extracted three times with ether. The aqueous layer was adjusted to pH > 7 with solid K2 C03 and extracted six times with 20% isopropanol / chloroform. The combined extracts were dried (Na2S04), filtered and concentrated to provide

要之產物（450毫克；87% )。Essential product (450 mg; 87%).

實例25D 5-乙醯基菸鹼醯胺Example 25D 5-Acetyl nicotinamide

將5-溴基菸鹼醯胺（2.5克，12.4毫莫耳）、三丁基（1-乙氧基乙晞基）鍚（5.0克，13.8毫莫耳）及二氯雙（三苯膦）鈀（11)(800毫克，1.1毫莫耳）於25毫升甲苯中之混合物，加熱至回流，歷經3小時。使混合物冷卻至室溫，以25毫升2N HC1 (水溶液）處理，並攪拌1小時。將水層以醋酸乙酯洗滌，以固體 K2 C03調整至pH >7，並在20%異丙醇/氯仿中萃取六次。使合併之萃液脫水乾燥（Na2S〇4)，過濾及濃縮，提供所要之產物（1.6 克，78% )。實例25E 3-(1，6-哈淀-2-基）於驗酿胺將實例25C (450毫克，3·68毫莫耳）與實例25D (605毫克，3.68 毫莫耳）於20毫升乙醇與1·2毫升10% NaOH (水溶液）中之混合物’加熱至回流，歷經3小時，及濃縮。收集固體，並以酷酸乙酯沖洗，提供所要之產物（740毫克，80% )。 -83- 0301122 (76) t 例 25F -2-某）吡啶各胺所要之產物係經由以實例25E取代實例23B中之5-溴基菸鹼醯胺而製成。Add 5-bromo nicotinamide (2.5 g, 12.4 mmol), tributyl (1-ethoxyethylfluorenyl) europium (5.0 g, 13.8 mmol) and dichlorobis (triphenylphosphine) ) A mixture of palladium (11) (800 mg, 1.1 mmol) in 25 ml of toluene was heated to reflux for 3 hours. The mixture was cooled to room temperature, treated with 25 ml of 2N HC1 (aqueous solution), and stirred for 1 hour. The aqueous layer was washed with ethyl acetate, adjusted to pH > 7 with solid K2 C03, and extracted six times in 20% isopropanol / chloroform. The combined extracts were dried (Na2SO4), filtered and concentrated to provide the desired product (1.6 g, 78%). Example 25E 3- (1,6-Harden-2-yl) in amines Example 25C (450 mg, 3.68 mmol) and Example 25D (605 mg, 3.68 mmol) in 20 ml of ethanol With a mixture of 1.2 ml of 10% NaOH (aq.) Was heated to reflux for 3 hours, and concentrated. The solid was collected and rinsed with ethyl picrate to provide the desired product (740 mg, 80%). -83- 0301122 (76) t Example 25F -2-A) Pyridine amine The desired product was prepared by substituting Example 25E for 5-bromonicotinamide amine in Example 23B.

f 例 25G 嗓·3·基_里表^{「5孔6_嘧啶冬基）吡啶净基1胺甚卜酮基—.乙羞胺某甲鹼第三-丁酯所要之產物係經由以實例25F (100毫克，〇·45毫莫耳）與L-Boc-色胺酸（150毫克，0.49毫莫耳），個別取代實例16A中之實例 11B與Boc-高苯基丙胺酸而製成。f Example 25G Thyme · 3 · Lyridine ^ {"5-hole 6_pyrimidyl winteryl) pyridinyl 1 amine and ketone ketone —. The desired product of ethyl methyl tertiary-butyl ester is Example 25F (100 mg, 0.45 mmol) and L-Boc-tryptophan (150 mg, 0.49 mmol) were prepared by substituting Example 11B and Boc-homophenylalanine in Example 16A. .

實例25H (^)-2-胺基-3-(lH-p?丨嗓各基VN-[~5-(l，6-哈淀-2-基Hb淀-3-基1丙醯胺所要之產物係經由以實例25G取代實例2D中之實例2B，以三氟醋酸鹽製成。MS(ESI)m/e409(M+H)+ ; 1HNMR(DMSO-D6, 500 MHz) δ 11.04 (br s, 1H), 10.91 (s, 1H), 9.50 (s, 1H), 9.23 (d, J=3 Hz, 1H), 8.95 (d，J=3 Hz，1H)，8.77-8.83 (m，3H)，8.42 (d，J=8Ηζ，1Η)，8·28-8·32(πι，2Η)，7·97-8.00 (m, 1H), 7.65-7.69 (m, 1H), 7.37 (d, J=8 Hz, 1H), 7.26-7.28 (m5 1H), 7.06-7.11 (m，1H)，6.96-7.01 (m，1H)，4.18-4.25 (m，1H)，3·25-3·45 (m，2H);對 C24H20N6O • 3TFA· 1H20 之分析計算值：C，46·88 ; Η，3·28 ; N，10.93 ; F，22.25. 實測值：C，47.19 ; H，3.39; N，1U4; F，21.81. 實例26Example 25H (^)-2-Amino-3- (lH-p? 丨 All groups VN- [~ 5- (l, 6-Harden-2-ylHbYid-3-yl-1propanamide) The product was made from trifluoroacetate by replacing Example 2B in Example 2D with Example 25G. MS (ESI) m / e409 (M + H) +; 1HNMR (DMSO-D6, 500 MHz) δ 11.04 (br s, 1H), 10.91 (s, 1H), 9.50 (s, 1H), 9.23 (d, J = 3 Hz, 1H), 8.95 (d, J = 3 Hz, 1H), 8.77-8.83 (m, 3H ), 8.42 (d, J = 8Ηζ, 1Η), 8.28-8 · 32 (π, 2Η), 7.97-8.00 (m, 1H), 7.65-7.69 (m, 1H), 7.37 (d, J = 8 Hz, 1H), 7.26-7.28 (m5 1H), 7.06-7.11 (m, 1H), 6.96-7.01 (m, 1H), 4.18-4.25 (m, 1H), 3.25-3 · 45 (m, 2H); Analytical calculated value for C24H20N6O • 3TFA · 1H20: C, 46 · 88; Η, 3.28; N, 10.93; F, 22.25. Found: C, 47.19; H, 3.39; N, 1U4; F, 21.81. Example 26

N-「(2S)-2-胺基-3-ΠΗ-吲哚-3-某）丙基VN-f5-(l，6-喑啶-2-基）吡啶-3-基1胺所要之產物係經由以實例25F取代實例23F與23G中之實例 23E，以三氟醋酸鹽製成。MS(ESI)m/e 395 (M+H)+ ; hNMR -84- (77)N-"(2S) -2-Amino-3-ΠΗ-indole-3-some" propyl VN-f5- (l, 6-pyridin-2-yl) pyridin-3-yl 1amine The product was prepared from trifluoroacetate by substituting Example 25F in Examples 23F and 23G with Example 25F. MS (ESI) m / e 395 (M + H) +; hNMR -84- (77)

(DMSOD6，500 MHz) 5 11·07 (br s，1H)，9:51 (s，1H)，8·74-8·83 (m，3H)，8·27 (d， J=9 Hz，1H)，8.18 (d，J=4 Hz，1H)，7.93-7.97 (m，4H)，7.60-7.64 (m，1H)，7.39 (d，J= 9 Hz，1H)，7.34 (d，J=4 Hz，1H)，7.06-7.12 (m，1H)，6.96-7.02 (m，1H)，6.78 (br s， 1H)，3.40-3.67 (m，3H)，3.11-3.16 (m，2H);對 C24H22N6 ·3·25ΤΡΑ 之分析計算值：C，47.88; Η，3·33; N，10.98; F，24,21.實測值：C，47.51 ; H，3.29 ；N, 10.94； F, 24.16. 實例27 (lS)-2-(lH-H丨嗓-3-基）-l-{[(5-異p奎琳-6-基p比淀-3-基）氣基"I甲基}乙胺(DMSOD6, 500 MHz) 5 11 · 07 (br s, 1H), 9:51 (s, 1H), 8.74-8 · 83 (m, 3H), 8 · 27 (d, J = 9 Hz, 1H), 8.18 (d, J = 4 Hz, 1H), 7.93-7.97 (m, 4H), 7.60-7.64 (m, 1H), 7.39 (d, J = 9 Hz, 1H), 7.34 (d, J = 4 Hz, 1H), 7.06-7.12 (m, 1H), 6.96-7.02 (m, 1H), 6.78 (br s, 1H), 3.40-3.67 (m, 3H), 3.11-3.16 (m, 2H) ; Analysis and calculation value for C24H22N6 · 3.25TPA: C, 47.88; Η, 3.33; N, 10.98; F, 24, 21. Found: C, 47.51; H, 3.29; N, 10.94; F, 24.16 Example 27 (lS) -2- (lH-H 丨 Hydr-3-yl) -l-{[(5-Iso-p-quelin-6-yl p ratio lake-3-yl) Ethylamine

實例27A 6-(三甲基錫烷某4 將6-溴基異唼啉（0·35克，1.7毫莫耳）於DMA (6毫升）中之溶液，以六曱基二錫（〇·55毫升，1.9毫莫耳）與Pd(PPh3)4(〇.23克， 0·2毫莫耳）處理，在l〇〇°C下攪拌1小時，以水稀釋，並以醋酸乙酯萃取三次。使合併之萃液濃縮，並使殘留物於矽膠上藉急驟式管柱層析純化，使用1 : 1己烷/醋酸乙醋，提供所要之產物（0·247克，50% )。實例27Β 啕哚-3-碁）士1£(5-異j淋-6-基吡啶各基）氧基1甲基^乙基...胺基甲酸第三-丁酯將實例27A(0.25克，0.86毫莫耳）與實例2Α(〇·444克，1〇〇毫莫耳）於6毫升DMF中之溶液，以Pd2(dba)3(〇〇8克，〇〇86毫莫耳）、三-鄰-甲苯基膦（0.02克，〇.〇4毫莫耳）及三乙胺（〇15毫升’ 1·〇毫莫耳）處理’在密封管中加熱至75°C，歷經8小時，及濃縮。使殘留物於矽膠上藉急驟式管柱層析純化，使 •85- (78) 200301122 用2.5%甲醇/二氯甲烷，提供所要之產物（0.125克，30% )。Example 27A 6- (trimethylstannane 4) A solution of 6-bromoisophosphonium (0.35 g, 1.7 mmol) in DMA (6 ml), with hexafluorenyl ditin (0 · 55 ml, 1.9 mmol) with Pd (PPh3) 4 (0.23 g, 0.2 mmol), stirred at 100 ° C for 1 hour, diluted with water, and extracted with ethyl acetate Three times. The combined extracts were concentrated and the residue was purified by flash column chromatography on silica gel using 1: 1 hexane / ethyl acetate to provide the desired product (0.247 g, 50%). Example 27B Indole-3- 碁) 1 ((5-isopyridin-6-ylpyridinyl) oxy 1methyl ^ ethyl ... amino carboxylic acid third-butyl ester Example 27A (0.25 G, 0.86 mmol) with Example 2A (0.444 g, 100 mmol) in 6 ml of DMF, Pd2 (dba) 3 (0.08 g, 0.0086 mmol) , Tri-o-tolylphosphine (0.02 g, 0.04 mmol) and triethylamine (0.15 ml '1.0 mmol) were heated in a sealed tube to 75 ° C for 8 Hours, and concentrated. The residue was purified by flash column chromatography on silica gel using 85- (78) 200301122 with 2.5% methanol / dichloromethane to provide the desired product (0.125 g, 30%).

實例27C (lS)-2-(lH-吲哚-3-基V1-{|T5-異喳啉-6-某毗凃-3-基）氣基1甲某i乙胺將實例27Β (0.125克，0.25毫莫耳）於二氯甲烷（3毫升）中之溶液，在室溫下，以TFA (400微升）處理，攪拌1小時，及濃縮。使用乙醚，使濃縮物以共沸方式蒸餾兩次，並使殘留物於C18管柱上藉逆相HPLC純化，使用0-100% CH3CN/H2 0/0.1Example 27C (lS) -2- (lH-indole-3-yl V1- {| T5-isofluorin-6-6-pyrimidin-3-yl) amino 1methyl certain ethylamine Example 27B (0.125 G, 0.25 mmol) in dichloromethane (3 ml), treated with TFA (400 µl) at room temperature, stirred for 1 hour, and concentrated. Using ether, the concentrate was distilled azeotropically twice, and the residue was purified by reverse phase HPLC on a C18 column using 0-100% CH3CN / H2 0 / 0.1

% TFA，提供所要之產物，為二-三氟醋酸鹽（o.iio克，70% ) 。MS (ESI) m/e 395 (M+H)+; 1 H NMR (DMSO-D6，300 MHz) 5 11.02 (br s，1H)， 9.52 (s，1H)，8.76 (d，J=3 Hz，1H)，8.62 (d，J=8 Hz，1H)，8.44-8.46 (xn，2H)，8.38 (d， J=9 Hz，1H)，8.11-8.20 (m，3H)，8.04-8.08 (m，1H)，7.83-7.86 (m，1H)，7.62 (d，J=9 Hz, 1H), 7.37-7.40 (τη, 1H), 7.31 (d, J=3 Hz, 1H), 7.08-7.12 (m, 1H)5 6.99-7.03 (m； 1H)，4.37-4.41 (m，1H)，4.18-4.23 (m，1H)，3·86-3·91 (m，1H)，3.16-3.20 (m，2H)；對 C25H22N40.2TFA*H20之分析計算值：C，49.35; Η，3·61; Ν，7·43 ;F，22·67·實測值：C，49.04 ; H，3·55 ; N，7·42 ; F，22.28. 實例28% TFA, which provides the desired product as di-trifluoroacetate (o.iio g, 70%). MS (ESI) m / e 395 (M + H) +; 1 H NMR (DMSO-D6, 300 MHz) 5 11.02 (br s, 1H), 9.52 (s, 1H), 8.76 (d, J = 3 Hz , 1H), 8.62 (d, J = 8 Hz, 1H), 8.44-8.46 (xn, 2H), 8.38 (d, J = 9 Hz, 1H), 8.11-8.20 (m, 3H), 8.04-8.08 ( m, 1H), 7.83-7.86 (m, 1H), 7.62 (d, J = 9 Hz, 1H), 7.37-7.40 (τη, 1H), 7.31 (d, J = 3 Hz, 1H), 7.08-7.12 (m, 1H) 5 6.99-7.03 (m; 1H), 4.37-4.41 (m, 1H), 4.18-4.23 (m, 1H), 3.86-3 · 91 (m, 1H), 3.16-3.20 ( m, 2H); Analytical calculated value for C25H22N40.2TFA * H20: C, 49.35; Η, 3.61; Ν, 7.43; F, 22 · 67 · Measured value: C, 49.04; H, 3.55 N, 7.42; F, 22.28. Example 28

(lR)-2-(lH-H丨嗓-3-基奎琳-6-基外1：淀-3-基）氧基~[甲基}乙胺(lR) -2- (lH-H 丨 Hex-3-ylquinine-6-ylex 1: 1: 3-yl) oxy ~ [methyl} ethylamine

實例28A (lR)-2-[(5-鹿基外1：啶-3-基）氫某哚-3-基甲基）乙甚眩其甲酸第三-丁酯所要之產物係經由以D-Boc-色胺酸取代實例2A中之L-Boc色胺酸而製成。Example 28A (lR) -2-[(5-Arylexyl 1: pyridin-3-yl) hydrosome indole-3-ylmethyl) ethoxyzine and its third-butyl formate are obtained via D -Boc-tryptophan was prepared in place of L-Boc tryptophan in Example 2A.

實例28B (lR)-2-(lH-口弓1嗓-3-基奎淋-6-基p比咬-3-基）氧某1甲基}乙胳 -86- 0301 0301Example 28B (lR) -2- (lH-portal arch 1-3-ylquinol-6-yl p ratio bite-3-yl) oxy-1methyl} ethyl -86- 0301 0301

(79) 所要之產物係經由以28A取代實例27B中之2A，然後按實例27C移除6〇〇基團，以三氟醋酸鹽製成。^^作81)11^ 395 (^1+11)+ ;1H NMR (DMSO-D6,500 ΜΗζ) δ 11.02 (s, 1Η), 8.97-9.00 (m, 1Η), 8.74 (d5 J= 3 Hz，1H)，8.50-8.54 (m，1H)，8.39-8.42 (m，2H)，8·18-8·23 (m，3H)，8.13-8.17 (m， 1H)，7.81-7.83 (m，1H)，7.61-7.66 (m，2H)，7.39 (d，J=8 Hz，1H)，7.31 (d，J=3 Hz，1H)， 7.07-7.10 (m, 1H), 6.99-7.02 (m, 1H), 4.38-4.41 (m, 1H), 4.21-4.24 (m, 1H), 3.79-3.83 (m，1H)，3.16-3.19 (m，2H)· 實例29 (lS)-2-f(6-氯基-5-異口奎淋-6-基外匕咬-3-基）氧基弓I 口来-3-基甲基）乙胺所要之產物係經由以實例13A取代實例27中之實例2A，以三氟醋酸鹽製成。MS (APCI) m/e 429, 431 (M+H)+; 1 H NMR (300 MHz， CD3 OD) 5 9.77 (s，1H)，8.63 (d，J=6.4 Hz，1H)，8.54 (d，J=88 Hz，1H)，8.43 (d，J= 6.4 Hz，1H)，8·30 (s，1H)，8.27 (d，J=3.1 Hz，1H)，8.06 (dd，J=8.4, 1.7 Hz, 1H)，7.58 (s， 1H)，7.56 (d，J=5.4 Hz，1H)，7·35 (d，J=8.1 Hz，1H)，7.22 (s，1H)，7.10 (td，J=7」，1.4 Hz，1H)，7.00 (td，J=7.8, 1.0 Hz，1H)，4.37 (dd，J=10.5, 3·4 Hz，1H)，4.24 (dd，J=10.5, 5.8 Hz，1H)，3.98 (m，1H)，3·27 (m，2H);對 C2 5 H2 ! C1N4 O · 2.25TFA 之分析計算值：C，51.69 ; H，3.42; Ν，8·17·實測值：C，51.75 ; Η，3·39; N，8.13· 實例30 (lS)-2-[(2-氣基-5-異喹啉-6-某吡啶-3-基）氣基哚-3-基曱某）乙胺所要之產物係經由以實例12C取代實例27中之實例2A，以三氟醋酸鹽製成（0.02 克，80% )。MS(DCI/NH3)m/e429,431 (M+H)+ ;1 H NMR (DMSO-D6) 5 11·04 (s，1H)，9.50 (s，1H)，8.62 (d，J=6.0 Hz，1H)，8·57 -87- (80)(79) The desired product was prepared from trifluoroacetate by substituting 28A for 2A in Example 27B and then removing the 600 group according to Example 27C. ^^ 作 81) 11 ^ 395 (^ 1 + 11) +; 1H NMR (DMSO-D6,500 ΜΗζ) δ 11.02 (s, 1Η), 8.97-9.00 (m, 1Η), 8.74 (d5 J = 3 Hz , 1H), 8.50-8.54 (m, 1H), 8.39-8.42 (m, 2H), 8.18-8 · 23 (m, 3H), 8.13-8.17 (m, 1H), 7.81-7.83 (m, 1H), 7.61-7.66 (m, 2H), 7.39 (d, J = 8 Hz, 1H), 7.31 (d, J = 3 Hz, 1H), 7.07-7.10 (m, 1H), 6.99-7.02 (m , 1H), 4.38-4.41 (m, 1H), 4.21-4.24 (m, 1H), 3.79-3.83 (m, 1H), 3.16-3.19 (m, 2H) · Example 29 (lS) -2-f ( 6-Chloro-5-Isoquinone-6-yl-exo-3-yl) oxybladder I orallyl-3-ylmethyl) ethylamine The desired product was obtained by replacing Example 27 with Example 13A Example 2A was made from trifluoroacetate. MS (APCI) m / e 429, 431 (M + H) +; 1 H NMR (300 MHz, CD3 OD) 5 9.77 (s, 1H), 8.63 (d, J = 6.4 Hz, 1H), 8.54 (d , J = 88 Hz, 1H), 8.43 (d, J = 6.4 Hz, 1H), 8.30 (s, 1H), 8.27 (d, J = 3.1 Hz, 1H), 8.06 (dd, J = 8.4, 1.7 Hz, 1H), 7.58 (s, 1H), 7.56 (d, J = 5.4 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 7.10 (td, J = 7 ", 1.4 Hz, 1H), 7.00 (td, J = 7.8, 1.0 Hz, 1H), 4.37 (dd, J = 10.5, 3.4 Hz, 1H), 4.24 (dd, J = 10.5, 5.8 Hz, 1H), 3.98 (m, 1H), 3.27 (m, 2H); Analytical calculated value for C2 5 H2! C1N4 O · 2.25TFA: C, 51.69; H, 3.42; Ν, 8 · 17 · Found: C, 51.75; Rhenium, 3.39; N, 8.13. Example 30 (lS) -2-[(2-Gasyl-5-isoquinoline-6-a pyridin-3-yl) aerodole The desired product of -3-ylsulfonium) ethylamine was prepared by replacing Example 2A in Example 27 with Example 12C and using trifluoroacetate (0.02 g, 80%). MS (DCI / NH3) m / e429,431 (M + H) +; 1 H NMR (DMSO-D6) 5 11 · 04 (s, 1H), 9.50 (s, 1H), 8.62 (d, J = 6.0 Hz, 1H), 8.57 -87- (80)

(s，1H)，8.44 (s，1H)，8·35 (d，J=9.0 Hz，1H)，8·22 (s，2H)，8·13 (d，J=9.0 Hz，1H)， 8.00 (d，J=6.0 Hz，1H)，7·98 (s，1H)，7.64 (d，J=7.5 Hz，1H)，7.38 (d，J=7.5 Hz, 1H)， 7.30 (s，1H)，7.10 (t，J=7.2 Hz，1H)，7.00 (t，J=7.2 Hz，1H)，4.46 (m，1H)，4.30 (m， 1H)，3.92 (m，1H)，3.21 (m，2H). 實例31 (1R)-1-(1H-沔丨嗓-3-基甲基V3-(5-異口套琳-6-基外匕淀-3-基）丙胺(s, 1H), 8.44 (s, 1H), 8.35 (d, J = 9.0 Hz, 1H), 8.22 (s, 2H), 8.13 (d, J = 9.0 Hz, 1H), 8.00 (d, J = 6.0 Hz, 1H), 7.98 (s, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.30 (s, 1H ), 7.10 (t, J = 7.2 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H), 4.46 (m, 1H), 4.30 (m, 1H), 3.92 (m, 1H), 3.21 (m , 2H). Example 31 (1R) -1- (1H- 沔丨 -3-methylmethyl V3- (5-isoortholine-6-yl exo-3-yl) propylamine

實例31A 6-(5-溴基吡啶各基）異4啉將3,5_二溴基吡啶供4毫克，I·2毫莫耳）、Pd2(dba)3(110毫克，0.12毫莫耳）及三-鄰-甲苯基膦（110毫克，0·36毫莫耳）於DMF (15毫升）中之溶液，以實例27A (500毫克，1·2毫莫耳）與三乙胺（500微升，3.6毫莫耳）處理，以氮滌氣，加熱至70°C，歷經6小時，冷卻至室溫，以醋酸乙酯（100毫升）處理，以鹽水洗滌，脫水乾燥（MgS04)，過濾及濃縮。使殘留油於矽膠上藉急驟式管柱層析純化，使用醋酸乙酯，提供所要之產物（110 毫克，32%)。MS(APCI)m/e285,287 (M+H)+·Example 31A 6- (5-bromopyridine each group) iso4-line provided 3,5-dibromopyridine for 4 mg, 1.2 mmol, Pd2 (dba) 3 (110 mg, 0.12 mmol) ) And tri-o-tolylphosphine (110 mg, 0.36 mmol) in DMF (15 ml), using Example 27A (500 mg, 1.2 mmol) and triethylamine (500 Microliter, 3.6 millimolar), nitrogen purged, heated to 70 ° C, cooled to room temperature over 6 hours, treated with ethyl acetate (100 ml), washed with brine, dehydrated and dried (MgS04), Filtered and concentrated. The residual oil was purified by flash column chromatography on silica gel using ethyl acetate to provide the desired product (110 mg, 32%). MS (APCI) m / e285,287 (M + H) + ·

實例31B 哚-3-某甲基）-3-(5-異崦啉-6-基吡啶-3-基）丙胺所要之產物係經由以實例31A取代實例21D中之實例21B，然後按實例21E所述，移除Boc保護基，以三氟醋酸鹽製成。MS (DCI/NH3) m/e 458 (M+H)+ ; 1 H NMR (CD3 OD) 5 9.78 (s, 1H), 8.97 (d, J=l.l Hz，1H)，8·64 (d，J=6.4 Hz，1H)，8·61 (d，J=8.9 Hz，1H)，8.55 (s，1H)，8·53 (s， 1H)，8.47 (d，J=6.5 Hz，1H)，8.25 (dd，J=8.4, 1.7 Hz，1H)，8.23 (s，1H)，7·49 (d，J=7.9 Hz，1H)，7.30 (d，J=8.2 Hz，1H)，7.22 (s，1H)，7.06 (td，J=7.1，1.0 Hz，1H)，6.97 (td， 200301122 (81) J=7.1,1.0 Hz, 1H), 3.59 (p, J=6.5 Hz, 1H), 3.18 (dd? J=7.1, 3.4 Hz, 2H), 2.99 (m5 2H), 2.15 (m5 2H). 實例32 5-(5-{[(2S)-2-胺基嗓-3-基）丙基愾某 Uk A -3-基 MH-異 <Example 31B The desired product of indole-3-somemethyl) -3- (5-isopyridin-6-ylpyridin-3-yl) propylamine was obtained by substituting Example 31A for Example 21B in Example 21D and then following Example 21E. As mentioned above, the Boc protecting group is removed and made of trifluoroacetate. MS (DCI / NH3) m / e 458 (M + H) +; 1 H NMR (CD3 OD) 5 9.78 (s, 1H), 8.97 (d, J = ll Hz, 1H), 8.64 (d, J = 6.4 Hz, 1H), 8.61 (d, J = 8.9 Hz, 1H), 8.55 (s, 1H), 8.53 (s, 1H), 8.47 (d, J = 6.5 Hz, 1H), 8.25 (dd, J = 8.4, 1.7 Hz, 1H), 8.23 (s, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.30 (d, J = 8.2 Hz, 1H), 7.22 (s , 1H), 7.06 (td, J = 7.1, 1.0 Hz, 1H), 6.97 (td, 200301122 (81) J = 7.1, 1.0 Hz, 1H), 3.59 (p, J = 6.5 Hz, 1H), 3.18 ( dd? J = 7.1, 3.4 Hz, 2H), 2.99 (m5 2H), 2.15 (m5 2H). Example 32 5- (5-{[((2S) -2-aminomethyl-3-yl) propyl) propyl hydrazone Uk A -3-yl MH-iso <

哚-1，3(2HV二酮實例32A (lS)-2-(lH-沔|嗓-3-基三甲基錫燒基）口比淀_3-基氧基}甲基）乙基胺基甲酸第三-丁西a 將實例2A (1克，2·23毫莫耳）於DMA (15毫升）中之溶液，以六甲基二錫（1.8毫升，5.6毫莫耳）與pd(pph3)4(0.4克，〇·2毫莫耳）處理’加熱至75C ’歷經L5天’添加至水中，並以醋酸乙酯萃取三次。使合併之萃液濃縮，並使殘留物於矽膠上藉急騾式管拄層析純化，使用1 : 1己烷/醋酸乙酯，提供所要之產物（0.4克，34% )。實例32Β (j_S)-2-{「5-(l，3-二嗣基-2,3-士―氫-1Η-異吲哈-5-某 >比淀-3-甚 1氡基[μ (1Η-吲哚-3-基甲D乙^基甲酸第三-丁酷^ 將實例32A (0·2克’ 0.31愛莫耳）與6-溴基鄰苯二甲酿亞胺 (0.084克，0.4毫莫耳）於DMF (2毫升）中之溶液，以pd2(〇〇4 克，0.02毫莫耳）、三-鄰-甲苯基膦〇2克，〇·〇〗亳莫耳）及三乙胺（0·06毫升，0.4毫莫耳）處理。將反應物在密封管中加熱至75 C，歷經6小時，及濃縮。使殘留物於；?夕膠上藉急驟式管柱層析純化’使用1 · 1己燒/醋酸乙酯，提供所要之產物（0.116 克，55% )。 -89- 200301122Indole-1,3 (2HV diketone example 32A (lS) -2- (lH-fluorene | trimethyl-3-methyltrimethyltin)) Hipido_3-yloxy} methyl) ethylamine Tertiary-butanyl carbamate A solution of Example 2A (1 g, 2.23 mmol) in DMA (15 ml) was prepared with hexamethylditin (1.8 ml, 5.6 mmol) and pd ( pph3) 4 (0.4 g, 0.2 mmol) was heated 'to 75C' over L5 days and added to water and extracted three times with ethyl acetate. The combined extracts were concentrated and the residue was purified on silica gel by flash tube chromatography using 1: 1 hexane / ethyl acetate to provide the desired product (0.4 g, 34%). Example 32B (j_S) -2-{"5- (l, 3-Difluorenyl-2,3-Shih-hydro-1H-isoindha-5-some > Biyodo-3-veryl1 [ μ (1′-indole-3-ylmethyl D ethyl carbamic acid tertiary butyl butyl ^ ^ Example 32A (0.2 g '0.31 Amor) and 6-bromophthalimide (0.084 G, 0.4 mmol) in DMF (2 ml), pd2 (0.04 g, 0.02 mmol), tri-o-tolylphosphine (0.2 g, 0.0 mmol) And triethylamine (0.06 ml, 0.4 mmol). The reaction was heated to 75 C in a sealed tube for 6 hours, and concentrated. The residue was immersed in a flash column on a gel column. Chromatographic purification 'using 1.1 · hexane / ethyl acetate to provide the desired product (0.116 g, 55%). -89- 200301122

(82)(82)

實例32C 5-(5J「(2S)冬胺基哚-3-基）丙基1氧基丨吡啶-3-基V1H-異哚-1，3(2H)-二酮所要之產物係經由以實例32B取代實例27C中之實例27B，以三氟醋酸鹽製成。MS(ESI)m/e413(M+H)+ ; iHNMRpMSO-Do 300 MHz) δ 11·43 (s，1Η)，11.02 (br s，1Η)，8·67 (d，J=3 Ηζ，1Η)，8.42 (d，J=6 Ηζ， 1H)，8·14-8·18 (m，4H)，7.92-7.96 (m，1H)，7·79-7·81 (m，1H)，7·61 (d，J=9 Hz，1H)， 7.38 (d，J=9 Hz，1H)，7·30 (d，J=3 Hz，1H)，7·08-7·12 (m，1H)，6·98-7·03 (m，1H)， 4.35-4.40 (m，1H)，4.17-4.22 (m，1H)，3.83-3.88 (m，1H)，3.13-3.17 (m，2H). 對 C24H20N4O3 d.lTFA 之分析計算值：C，51.96 ; Η，3·42 ; N，8.59 ;F，18·30·實測值：C，51·45 ; H，3·46 ; N，8.56 ; F，17·47· 實例33 5-(5-{「(2S)-2-胺基-3-(lH-4|嗓-3-基）丙基1氧基丨p比咬-3·基）異W嗓-1-酮Example 32C 5- (5J "(2S) Hydroxyaminoindol-3-yl) propyl 1oxy 丨 pyridin-3-yl V1H-isodol-1,3 (2H) -dione The desired product is Example 32B replaced Example 27B in Example 27C with trifluoroacetate. MS (ESI) m / e413 (M + H) +; iHNMRpMSO-Do 300 MHz) δ 11 · 43 (s, 1Η), 11.02 ( br s, 1Η), 8.67 (d, J = 3 Ηζ, 1Η), 8.42 (d, J = 6 Ηζ, 1H), 8.14-8 · 18 (m, 4H), 7.92-7.96 (m , 1H), 7.79-7 · 81 (m, 1H), 7.61 (d, J = 9 Hz, 1H), 7.38 (d, J = 9 Hz, 1H), 7.30 (d, J = 3 Hz, 1H), 7.08-7 · 12 (m, 1H), 6.98-7 · 03 (m, 1H), 4.35-4.40 (m, 1H), 4.17-4.22 (m, 1H) , 3.83-3.88 (m, 1H), 3.13-3.17 (m, 2H). Analysis and calculation of C24H20N4O3 d.lTFA: C, 51.96; Η, 3.42; N, 8.59; F, 18 · 30 · Measured Value: C, 51 · 45; H, 3.46; N, 8.56; F, 17.47. Example 33 5- (5-{"(2S) -2-amino-3- (lH-4 | -3-yl) propyl 1oxy 丨 p than bite-3 · yl) iso-W-1--1-one

實例33A 4-、✓臭基-2-甲基笨甲酸甲酉旨將4-溴基-2-甲基苯甲酸（1·〇克，4.7毫莫耳）於甲醇（24毫升）中之溶液，以20滴HC1處理，於回流下加熱6小時，及濃縮，提供所要之產物（1.07克，1〇〇% )。Example 33A 4-, ✓Amino-2-methylbenzylformate. A solution of 4-bromo-2-methylbenzoic acid (1.0 g, 4.7 mmol) in methanol (24 ml). It was treated with 20 drops of HC1, heated under reflux for 6 hours, and concentrated to provide the desired product (1.07 g, 100%).

實例33B t溴基溴基甲某）苯甲酸甲酯將實例33A (1.02克，4·47毫莫耳）於CC14(22毫升）中之溶液，以AIBN (0.065克，0.4毫莫耳）與nbS (〇·955克，5.4毫莫耳）處理 ’加熱至回流，歷經4小時，以水洗滕，脫水乾燥^s〇4) ’過濾及濃縮，提供所要之產物（u克，79% )。 -90- 200301122 (83)Example 33B tBromobromomethyl) methyl benzoate A solution of Example 33A (1.02 g, 4.47 mmol) in CC14 (22 ml) was mixed with AIBN (0.065 g, 0.4 mmol) and nbS (0.055 g, 5.4 millimoles) treatment 'heated to reflux for 4 hours, washed with water, dried and dried ^ s04)' filtered and concentrated to provide the desired product (u g, 79%). -90- 200301122 (83)

實例33C 5-溴基異4丨哚-1-酮將實例33B (U克，3.57毫莫耳）於THF (20毫升）中之溶液，在室溫下，以甲醇中之IN NH3 (7.14毫升，7·14毫莫耳）處理，攪拌24小時及過濾。將濾餅以乙醚（100毫升）洗滌，提供所要之產物（0.4克，52% )。Example 33C 5-bromoiso4-indol-1-one A solution of Example 33B (U g, 3.57 mmol) in THF (20 ml) was treated with IN NH3 (7.14 ml) in methanol at room temperature. , 7.14 millimoles), stirred for 24 hours and filtered. The filter cake was washed with diethyl ether (100 ml) to provide the desired product (0.4 g, 52%).

實例33DExample 33D

5-(5-{「(2S)-2-胺基嗓-3-基）丙基1氧基比咬-3-基）異p呆-1-酉同所要之產物係經由以實例33C取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (ESI) m/e 399 (M+H)+ ; 1 H NMR (DMSO-D6，300 MHz) (5 11.03 (br s，1H)，8·63 (s，1H)，8·57 (s，1H)，8·35 (br s，3H)，7.90 (s，1H)，7.78 (s，2H)，7·67 (s，1H)，7.61 (d，J=8 Hz，1H)，7·37 (d，J=8 Hz，1H)，7.79 (d，J=2 Hz，1H)，7.03-7.10 (m，1H)，6·96-7·01 (m，1H)，4.32-4.36 (m， 1H), 4.17-4.22 (m, 1H), 3.80-3.83 (m, 1H), 3.18 (d, J=8 Hz, 2H), 2.50 (s, 2H). 實例34 (lS)-2:[(5-蟑啉-6-基吡啶-3-某）氲基1-H1H-吲哚-3-基曱某）乙fe5- (5-{"(2S) -2-Amino-3-yl) propyl 1oxy is more than 3--3-yl) iso-p-1-one, and the desired product was substituted by Example 33C 6-Bromophthalimide of Example 32, made from trifluoroacetate. MS (ESI) m / e 399 (M + H) +; 1 H NMR (DMSO-D6, 300 MHz) (5 11.03 (br s, 1H), 8.63 (s, 1H), 8.57 (s, 1H), 8.35 (br s, 3H), 7.90 (s, 1H), 7.78 (s, 2H ), 7.67 (s, 1H), 7.61 (d, J = 8 Hz, 1H), 7.37 (d, J = 8 Hz, 1H), 7.79 (d, J = 2 Hz, 1H), 7.03 -7.10 (m, 1H), 6.96-7 · 01 (m, 1H), 4.32-4.36 (m, 1H), 4.17-4.22 (m, 1H), 3.80-3.83 (m, 1H), 3.18 ( d, J = 8 Hz, 2H), 2.50 (s, 2H). Example 34 (lS) -2: [(5-cockolin-6-ylpyridin-3-some) fluorenyl 1-H1H-indole- 3- 基曱某）乙 fe

實例34A N二(2-乙醯基笨基）乙醯胺將2’-胺基苯乙酮（5.0克，37毫莫耳）於二氯甲烷（15〇毫升）中之溶液，在室溫下，以三乙胺毫升，4〇毫莫耳）與氯化乙醯（3.2毫升，45毫莫耳）處理，攪拌3小時，然後以水洗滌。將水層以醋酸乙酯萃取（2 χ 2〇毫升），並使合併之萃液濃縮，提供所要之產物（6 5克，1〇〇% )。實例34Β -91 - (84) -4-溴苯基）乙醯胺將實例34A (6·5克，37亳莫耳）於醋酸（100毫升）中之溶液，在室溫下，以Βγ2(4毫升，84毫莫耳）處理，攪拌1小時又15 分鐘’倒入水（200毫升）中，並過濾。將固體以水（2 χ 1〇〇毫升）與己烷（2 X100毫升）洗滌，溶於乙醚中，以鹽水（5〇毫升）洗滌及濃縮，提供所要之產物（8 5克，89% )。Example 34A A solution of 2'-aminoacetophenone (5.0 g, 37 mmol) in dichloromethane (15 ml) at room temperature at room temperature Next, it was treated with triethylamine ml, 40 mmoles) and acetamidine chloride (3.2 ml, 45 mmoles), stirred for 3 hours, and then washed with water. The aqueous layer was extracted with ethyl acetate (2 x 20 ml), and the combined extracts were concentrated to provide the desired product (65 g, 100%). Example 34B -91-(84) -4-bromophenyl) acetamidine A solution of Example 34A (6.5 g, 37 mol) in acetic acid (100 ml) was treated at room temperature with βγ2 ( 4 ml, 84 mmol), stir for 1 hour and 15 minutes' into water (200 ml) and filter. The solid was washed with water (2 x 100 ml) and hexane (2 x 100 ml), dissolved in ether, washed with brine (50 ml) and concentrated to provide the desired product (85 g, 89%) .

實例34C Μ臭基嗱啉-4(ΊΗ)-酿1Example 34C

將實例34Β (6.28克，24.4毫莫耳）於THF (75毫升）中之溶液，以濃HC1 (水溶液）(15毫升）與水（15毫升）處理，加熱至回流，歷經1小時，並濃縮以移除THF。將水溶液以另外之水（5 愛升）與濃HC1 (5¾:升）處理’冷卻至〇°c，以NaN〇2(i.85克，26.84 笔吴耳）在水（10笔升）中之}谷液’以5份處理，慢慢溫熱至室溫，歷經2小時期間，並於室溫下攪拌過夜。將反應物加熱至回流，歷經6小時，並過濾。將固體以水（5〇毫升）與乙醚（50毫升）洗滌，並於真空下乾燥，提供所要之產物（3 〇克，54% )。A solution of Example 34B (6.28 g, 24.4 mmol) in THF (75 ml) was treated with concentrated HC1 (aqueous solution) (15 ml) and water (15 ml), heated to reflux for 1 hour, and concentrated To remove THF. The aqueous solution was treated with additional water (5 liters) and concentrated HC1 (5¾: liters) and cooled to 0 ° C, and NaNO 2 (i.85 g, 26.84 pens) in water (10 pens) Zhi} Valley 'was treated in 5 parts, slowly warmed to room temperature over a period of 2 hours, and stirred overnight at room temperature. The reaction was heated to reflux for 6 hours and filtered. The solid was washed with water (50 mL) and ether (50 mL) and dried under vacuum to provide the desired product (30 g, 54%).

實例34D 6-溴基-4-氯基峰成將實例34C (0.4克，1.8毫莫耳）於p〇ci3(2.5毫升）中之溶液，加熱至100°C，歷經2小時，且慢慢傾倒在冰上。使水層冷卻至0°C ’並以50% NaOH調整至pH5-7。將水層以醋酸乙醋萃取（2 χ 50毫升），並使合併之有機層濃縮。使殘留物於碎膠上藉急驟式管柱層析純化，使用4 : 1己烷/酷酸乙g旨， -92- (85) (85)20030Π22 提供所要之產物（〇 19〇克，43% )。Example 34D The 6-bromo-4-chloroyl peak formed a solution of Example 34C (0.4 g, 1.8 mmol) in poci3 (2.5 ml), heated to 100 ° C for 2 hours, and slowly Dump on ice. The aqueous layer was cooled to 0 ° C 'and adjusted to pH 5-7 with 50% NaOH. The aqueous layer was extracted with ethyl acetate (2 x 50 ml), and the combined organic layers were concentrated. The residue was purified by flash column chromatography on crushed gel using 4: 1 hexane / ethyl acetate, -92- (85) (85) 20030Π22 to provide the desired product (019 g, 43 %).

實例34E 6->臭基-4-月井基蜂口林將實例34D (2.6克，10.6毫莫耳）於乙醇（70毫升）中之溶液，以肼單水合物（3毫升，90%溶液）處理，在室溫下授掉3夭，及過濾。將固體以水（50毫升）與乙醚（50毫升）洗滌，並在真空下乾燥，提供所要之產物（2.5克，100% )。實例34F 6-溴基啦將貫例34E (3.5克，14毫莫耳）於水（50毫升）中之溶液加熱至回"ιυ ’以CuS〇4(2.8克’ 17.5愛莫耳）在水（20毫升）中之溶液逐滴處理，回流2小時，冷卻至室溫，以飽和NaHC03 (水溶液）調整至pH 7，並以醋酸乙酯萃取（2 X 25毫升）。使合併之萃液濃縮，並使殘留物於矽膠上藉急驟式管柱層析純化，使用1 : 1己烷/醋酸乙酯，提供所要之產物（〇.7克，24% )。Example 34E 6- > Alkyl-4-Yukiki based bee-mouth forest A solution of Example 34D (2.6 g, 10.6 mmol) in ethanol (70 ml) was treated with hydrazine monohydrate (3 ml, 90%) Solution), bleed for 3 hours at room temperature, and filter. The solid was washed with water (50 ml) and diethyl ether (50 ml) and dried under vacuum to provide the desired product (2.5 g, 100%). Example 34F 6-Bromo. A solution of conventional Example 34E (3.5 g, 14 mmol) in water (50 ml) was heated back to " ιυ'4. (2.8 g '17.5 Amor) The solution in water (20 ml) was treated dropwise, refluxed for 2 hours, cooled to room temperature, adjusted to pH 7 with saturated NaHC03 (aqueous solution), and extracted with ethyl acetate (2 X 25 ml). The combined extracts were concentrated and the residue was purified by flash column chromatography on silica gel using 1: 1 hexane / ethyl acetate to provide the desired product (0.7 g, 24%).

實例34G (l_S)-2-『(5-4啉-6-基吡啶-3-基）氣某哚-3-基甲基）乙胺所要之產物係經由以實例34F取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (ESI) m/e 396 (Μ+Η)4* ; 1 H NMR (DMSO-D6,300 MHz) δ 11.04 (s, 1H), 9.43 (d, J=6 Hz, 1H), 8.78 (d5 J= 2 Hz，1H)，8.60 (d，J=8 Hz，1H)，8.45-8.49 (m，2H)，8.30-8.34 (m，1H)，8.26 (d，J=6 Hz，1H)，8.21-8.25 (m，2H)，7·89 (t，J=2 Hz，1H)，7.63 (d，J=8 Hz，1H)，7.39 (d，J=8 Hz，1H)，7.31 (d，J=2 Hz，1H)，7.08-7.12 (m，1H)，7.01-7.04 (m，1H)，4·38·4·42 (m， 1H), 4.22-4.26 (m, 1H), 3.83-3.88 (m, 1H), 3.17-3.20 (m5 2H). -93· 20030Π22 (86) 實例35 (lS)-2-{T5-(lH-4|峻-5-基 >比症各基1氧基嗓-3-基甲基）乙脖實例35A 5-溴基-1H-W唑將5-漠基-2-氟基苯甲趁（1〇克，49.2毫莫耳）與98%肼（20毫升）之混合物加熱至回流，歷經5小時，傾倒於冰上，及過濾。使固體自H20 /甲醇再結晶，提供所要之產物（3.7克，38Example 34G (l_S) -2-[(5-4Phenyl-6-ylpyridin-3-yl) aindol-3-ylmethyl) ethylamine The desired product was obtained by replacing Example 6 with Example 34F. -Bromophthalimide, made from trifluoroacetate. MS (ESI) m / e 396 (Μ + Η) 4 *; 1 H NMR (DMSO-D6, 300 MHz) δ 11.04 (s, 1H), 9.43 (d, J = 6 Hz, 1H), 8.78 (d5 J = 2 Hz, 1H), 8.60 (d, J = 8 Hz, 1H), 8.45-8.49 (m, 2H), 8.30-8.34 (m, 1H), 8.26 (d, J = 6 Hz, 1H), 8.21-8.25 (m, 2H), 7.89 (t, J = 2 Hz, 1H), 7.63 (d, J = 8 Hz, 1H), 7.39 (d, J = 8 Hz, 1H), 7.31 (d , J = 2 Hz, 1H), 7.08-7.12 (m, 1H), 7.01-7.04 (m, 1H), 4.38 · 4 · 42 (m, 1H), 4.22-4.26 (m, 1H), 3.83 -3.88 (m, 1H), 3.17-3.20 (m5 2H). -93 · 20030Π22 (86) Example 35 (lS) -2- {T5- (lH-4 | 1oxymethyl-3-ylmethyl) Ethyl Example 35A 5-Bromo-1H-Wazole uses 5-benzyl-2-fluorobenzyl (10 g, 49.2 mmol) with 98% A mixture of hydrazine (20 ml) was heated to reflux for 5 hours, poured onto ice, and filtered. The solid was recrystallized from H20 / methanol to provide the desired product (3.7 g, 38

實例35B (lS)-2-{f5-(lH-吲唑-5-某）吡啶-3-基1氧基卜H1H-吲哚各某甲某）乙脖所要之產物係經由以實例35A取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (ESI) m/e 384 (M+H)+ ; 1 H NMR (DMSO-D6,300 MHz) δ 13.22 (br s, 1H), 11.04 (br s, 1H), 8.62 (d, J=2Example 35B (lS) -2- {f5- (lH-indazole-5-a) pyridin-3-yl1oxyb H1H-indole each aa) The desired product was replaced by Example 35A The 6-bromophthalimide of Example 32 was prepared from trifluoroacetate. MS (ESI) m / e 384 (M + H) +; 1 H NMR (DMSO-D6, 300 MHz) δ 13.22 (br s, 1H), 11.04 (br s, 1H), 8.62 (d, J = 2

Hz，1H)，8·33 (d，J=3 Hz，1H)，8.13-8.21 (m，3H)，8.12 (s，1H)，7.67-7.72 (m，3H)， 7.64 (d，J=8 Hz，1H)，7.39 (d，J=8 Hz，1H)，7.30 (d，J=2 Hz，1H)，7.06-7.13 (m，1H)， 6.98-7.04 (m，1H)，4·14-4·39 (m，2H)，3.33-3.38 (m，1H)，3.13-3.16 (m，2H)；對 C23H21N50.2TFA.H20之分析計算值·· C，51.52; Η，4·00; N，11.13. 實測值：C，51.80 ; H，3.61; Ν，11·03· 實例36 5-(5-m2SV2-胺基-3-ΠΗ-吲哚-3-基）丙基1氣基Wl：啶各基H，3-二氫- 2H-吲哚-2-酮所要之產物係經由以5-溴基氧化吲哚取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/e 399 (M+H)+ ; 1 H NMR (300 MHz，CD3 OD) 5 8.59 (s，1H)，8.35 (s，1H)，7.92 (s，1H)， -94- 200301122Hz, 1H), 8.33 (d, J = 3 Hz, 1H), 8.13-8.21 (m, 3H), 8.12 (s, 1H), 7.67-7.72 (m, 3H), 7.64 (d, J = 8 Hz, 1H), 7.39 (d, J = 8 Hz, 1H), 7.30 (d, J = 2 Hz, 1H), 7.06-7.13 (m, 1H), 6.98-7.04 (m, 1H), 4 · 14-4 · 39 (m, 2H), 3.33-3.38 (m, 1H), 3.13-3.16 (m, 2H); Analytical calculated value for C23H21N50.2TFA.H20 ·· C, 51.52; Η, 4.00 N, 11.13. Found: C, 51.80; H, 3.61; N, 11.03. Example 36 5- (5-m2SV2-Amino-3-ΠΗ-indole-3-yl) propyl 1-amino W1: the desired product of pyridyl H, 3-dihydro-2H-indole-2-one is via substitution of 6-bromophthalimide in Example 32 with 5-bromooxyindole, Made from trifluoroacetate. MS (APCI) m / e 399 (M + H) +; 1 H NMR (300 MHz, CD3 OD) 5 8.59 (s, 1H), 8.35 (s, 1H), 7.92 (s, 1H), -94- 200301122

(87) 7·60 (d，J=6.9 Hz，1H)，7.58 (s，1H)，7.55 (d，JN10.1 Hz，1H)，7.38 (d，J=8.1 Hz，1H)， 7.24 (s，1H)，7.13 (t，J=7.6 Hz，1H)，7.03 (d，J=8.0 Hz，1H)，7·03 (t，J=7.5 Hz，1H)， 4.45 (dd，J=10.5, 3.2 Hz，1H)，4,31 (dd，>10.5, 5·8 Hz，1H)，4·01 (m，1H)，3.62 (s， 2H)，3·32 (m，1H)，3.29 (m，1H);對 C24H22N402 · 2.5TFA 之分析計算值 :C，50.96 ; H，3.61 ; N，8.20.實測值：C，50.96 ; H，3·62 ; N，8·12· 實例37 (1SV2-丨[5-(2,1,3-苯并吟二唑基）吡啶-3-基1氧基糾哚-3-基甲基）乙胺(87) 7.60 (d, J = 6.9 Hz, 1H), 7.58 (s, 1H), 7.55 (d, JN 10.1 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.24 ( s, 1H), 7.13 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 4.45 (dd, J = 10.5 , 3.2 Hz, 1H), 4,31 (dd,> 10.5, 5.8 Hz, 1H), 4.01 (m, 1H), 3.62 (s, 2H), 3.32 (m, 1H), 3.29 (m, 1H); Analytical calculated values for C24H22N402 · 2.5TFA: C, 50.96; H, 3.61; N, 8.20. Found: C, 50.96; H, 3.62; N, 8.12. Example 37 (1SV2- 丨 [5- (2,1,3-benzodiazolyl) pyridin-3-yl1oxypyridin-3-ylmethyl) ethylamine

所要之產物係經由以5-氯基-2，1，3-苯并哼二唑取代實例32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/e 386 (M+H)+ ； 1 H NMR (300 MHz, CD3 OD) δ 8.64 (s, 1H), 8.44 (s? 1H)? 8.18 (s，1H)，8.05 (d，J=10.4 Hz，1H)，7.81 (d，J=10.9 Hz，1H)，7.78 (s，1H)，7.59 (d，J=6.7 Hz，1H)，7·37 (d，J=7.1 Hz，1H)，7.24 (s，1H)，7·12 (t，J=8-l Hz，1H)，7.03 (t，J=6.9 Hz， 1H)，4.44 (dd，J=10.5, 3.1 Hz，1H)，4.29 (dd，J=10.6, 5·8 Hz，1H)，3.99 (m，1H)，3.32 (s, 1H), 3.30 (s, 1H) ； # C22H19N5〇2 ·2.45ΤΡΑ^ ^ # ϋ : C5 48.60 ;H，3·25 ; N，10.53·實測值：C，48.68 ; H，3·48 ; N，10.58·The desired product was prepared by replacing the 6-bromophthalimidine in Example 32 with 5-chloro-2,1,3-benzohumidazole and using trifluoroacetate. MS (APCI) m / e 386 (M + H) +; 1 H NMR (300 MHz, CD3 OD) δ 8.64 (s, 1H), 8.44 (s? 1H)? 8.18 (s, 1H), 8.05 (d , J = 10.4 Hz, 1H), 7.81 (d, J = 10.9 Hz, 1H), 7.78 (s, 1H), 7.59 (d, J = 6.7 Hz, 1H), 7.37 (d, J = 7.1 Hz , 1H), 7.24 (s, 1H), 7.12 (t, J = 8-1 Hz, 1H), 7.03 (t, J = 6.9 Hz, 1H), 4.44 (dd, J = 10.5, 3.1 Hz, 1H), 4.29 (dd, J = 10.6, 5.8 Hz, 1H), 3.99 (m, 1H), 3.32 (s, 1H), 3.30 (s, 1H); # C22H19N502 · 2.45TPA ^ ^ # ϋ: C5 48.60; H, 3.25; N, 10.53. Found: C, 48.68; H, 3.48; N, 10.58.

(lS)-2-(lH^l哚-3-基）小{「(5-嘧吩并「2,3-cM啶-2-基吡啶-3-基）氧基1 甲基丨乙胺(lS) -2- (lH ^ l indol-3-yl) small {"(5-pyrimido" 2,3-cM pyridin-2-ylpyridin-3-yl) oxylmethyl ethylamine

實例38A 2-(三甲基錫烷某）喧吩#『2,3-cl吡啶將嘧吩并[2,3-c]吡啶（J.Wikel 等人，J.Heterocycl. Chem·，1993,30,289) (2.0克，14·8毫莫耳）於THF(50毫升）中之溶液，在-78X：下，以正-丁基鋰（於己烷中之2·5 Μ溶液，7·1毫升，17,8毫莫耳） -95· 20^3〇Π22 (88) 處理，溫熱至〇°C，攪拌15分鐘’冷卻至-78°C ’以THF (10毫升）中之氯化三甲基錫（3.54克，17·8毫莫耳）慢慢地處理’溫熱至室溫，歷經2小時，並於醋酸乙酯與鹽水之間作分液處理。將酷酸乙酯溶液以水洗滌，及濃縮。使殘留物藉急騾式層析純化（於己烷中之10-35%醋酸乙酯），提供所要之產物（3.15 克，71%)。MS(APCI)m/e298 (M+H)+·Example 38A 2- (Trimethylstannane) oxophene # 『2,3-cl pyridine pyrimido [2,3-c] pyridine (J. Wikel et al., J. Heterocycl. Chem., 1993, 30,289) (2.0 g, 14.8 mmol) in THF (50 ml) at -78X: n-butyllithium (2.5 M solution in hexane, 7.1 Ml, 17,8 mmoles) -95 · 20 ^ 3〇Π22 (88) treated, warmed to 0 ° C, stirred for 15 minutes 'cooled to -78 ° C' with chlorination in THF (10 ml) Trimethyltin (3.54 g, 17.8 millimoles) was slowly treated and warmed to room temperature for 2 hours, and separated between ethyl acetate and saline. The ethyl acetate solution was washed with water and concentrated. The residue was purified by flash chromatography (10-35% ethyl acetate in hexane) to provide the desired product (3.15 g, 71%). MS (APCI) m / e298 (M + H) + ·

實例38BExample 38B

哚-3-基）-1-(ΙΤ5-屢吩并「2,3-cl吡啶-2-基吡啶-3-基）氧基1 甲基丨乙胺所要之產物係經由以實例38A取代實例27B與27C中之實例 27A，以三氟醋酸鹽製成。MS(APCI)m/e402(M+H)+ ; 1HNMR (300 MHz，CD3 OD) δ 9.58 (s，1H)，8.78 (s，1H)，8·63 (d，J=6.4 Hz，1H)，8.49 (s，Indole-3-yl) -1- (Ι5-5-pheno "2,3-clpyridin-2-ylpyridin-3-yl) oxy 1methyl 丨 ethylamine The desired product was obtained by substituting the example with Example 38A Example 27A in 27B and 27C, made of trifluoroacetate. MS (APCI) m / e402 (M + H) +; 1HNMR (300 MHz, CD3 OD) δ 9.58 (s, 1H), 8.78 (s, 1H), 8.63 (d, J = 6.4 Hz, 1H), 8.49 (s,

1H)，8.36 (d，J=6.4 Hz，1H)，8.20 (s，1H)，7·86 (s，1H)，7·60 (d，J=8.6 Hz，1H)，7.38 (d， J=8.1 Hz，1H)，7·25 (s，1H)，7.12 (t，J=8.1 Hz，1H)，7.03 (t，J=7.5 Hz，1H)，4.45 (dd， JN10.6, 3.2 Hz，1H)，4·30 (dd，J=10.5, 5·7 Hz，1H)，4.02 (m，1H)，3.32 (s，1H)，3.30 (s， 1H);對 C23H20N4OS.3.6TFA之分析計算值：C，44.73; Η，2·93; Ν，6·91· 實測值·· C，44.74 ; H，2.91; N，6.77. 實例39 (3Z)-5-(5-m2SV2-胺基各ΠΗ-吲哚-3-基）丙基1氧基}吡啶-3-基V3-(1H-吡咯冬基亞甲基VU-二氫-2H-吲哚-2-酮所要之產物係經由以三氟醋酸鹽取代實例32中之5-溴基-3-(1H-吡咯-2-基亞甲基）-1，3-二氫，哚-2-酮6-溴基鄰苯二甲醯亞胺（L. Sun 等人，J· Med· Chem·，1998, 41，2588·)而製成。MS (APCI) m/e 476 (M+H)+ ； 1 H NMR (400 MHz, DMSO-d6) δ 13.33 (br s, 1H), 11.05 (s5 1H), 11.04 -96- 200301122 (89) (d，J=6.5 Hz，1H)，8·64 (s，1H)，8·34 (s，1H)，8:22 (br s，2H)，8·09 (s，1H)，7.91 (s，1H)， 7.74 (br s，1H)，7.62 (d，J=7.7 Hz，1H)，7·51 (dd，J=8.3 Hz，1H)，7.40 (s，1H)，7.38 (d， J=8.3 Hz，1H)，7.30 (d，J=2.2 Hz，1H)，7.1 (dd，J=7.9 Hz，1H)，7.01 (d，J=7.7 Hz，1H)， 7.00 (d，J=8.0 Hz，1H)，6.85 (br s，1H)，6·39 (s，1H)，4.37 (dd，J=12.00, 3·1 Hz，1H)， 4·20 (dd，J=8.00, 6.0 Hz，1H)，3.15-3.21 (m，1H);對 C2 9 H2 5 N5 02 · 2.6TFA 之分析計算值：C，53.21 ; H，3.60 ; N，9.07.實測值：C，53.36 ; H，3.67 ；N, 8.92. 實例40 6-(5-m2RV2-胺基·3-(1Η-吲哚各基）丙基1氧基丨吡啶-3-基Vl，3-苯并嘧唑-2(3H)-酮所要之產物係經由以6-溴基-2-苯并噻唑啉酮取代實例32中之6-溴基鄰苯二甲醯亞胺而製成。MS(APCI)m/e417(M+H)+ ; 1 H NMR (300 MHz, CD3 OD) 5 8.52 (s，1H)，8.31 (d，J=2.4 Hz，1H)，7.77 (d，J= 1·7 Hz, 1H)，7·71 (t，J=1.7 Hz，1H)，7.59 (d，J=7.8 Hz，1H)，7·56 (dd，J=6.0, 1.7 Hz， 1H), 7.39 (d5 J=8.2 Hz, 1H)? 7.25 (d, J=8.2 Hz, 1H), 7.23 (s, 1H), 7.14 (t? J=7.2 Hz, 1H)，7.03 (t，J=7.2 Hz，1H)，4.41 (dd，J=12.0, 3.4 Hz，1H)，4.26 (dd，J=9.0, 5.7 Hz， lH)，3.97-4.〇2(m，1H);對 C23H20N4O2 .1.9TFA之分析計算值：C，5〇.84 ;H，3·49; Ν，8·85·實測值：C，51·22 ; H，3.67; Ν，8·49· 實例411H), 8.36 (d, J = 6.4 Hz, 1H), 8.20 (s, 1H), 7.86 (s, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.25 (s, 1H), 7.12 (t, J = 8.1 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 4.45 (dd, JN10.6, 3.2 Hz , 1H), 4 · 30 (dd, J = 10.5, 5.7 Hz, 1H), 4.02 (m, 1H), 3.32 (s, 1H), 3.30 (s, 1H); Analysis of C23H20N4OS.3.6TFA Calculated: C, 44.73; Η, 2.93; Ν, 6.91. Found, C, 44.74; H, 2.91; N, 6.77. Example 39 (3Z) -5- (5-m2SV2-amino Each ΠΗ-indol-3-yl) propyl 1oxy} pyridin-3-yl V3- (1H-pyrrolidonylmethylene VU-dihydro-2H-indole-2-one is Replace 5-bromo-3- (1H-pyrrole-2-ylmethylene) -1,3-dihydro, indol-2-one 6-bromophthalate with trifluoroacetate in Example 32 Hydrazone (L. Sun et al., J. Med. Chem., 1998, 41, 2588 ·). MS (APCI) m / e 476 (M + H) +; 1 H NMR (400 MHz, DMSO-d6) δ 13.33 (br s, 1H), 11.05 (s5 1H), 11.04 -96- 200301122 (89) (d, J = 6.5 Hz, 1H), 8.64 (s, 1H), 8.34 (s, 1H), 8:22 (br s, 2H), 8.09 (s, 1H) , 7.91 (s, 1H), 7.74 (br s, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.51 (dd, J = 8.3 Hz, 1H), 7.40 (s, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.30 (d, J = 2.2 Hz, 1H), 7.1 (dd, J = 7.9 Hz, 1H), 7.01 (d, J = 7.7 Hz, 1H), 7.00 (d , J = 8.0 Hz, 1H), 6.85 (br s, 1H), 6.39 (s, 1H), 4.37 (dd, J = 12.00, 3.1 Hz, 1H), 4.20 (dd, J = 8.00, 6.0 Hz, 1H), 3.15-3.21 (m, 1H); Analytical calculated value for C2 9 H2 5 N5 02 · 2.6TFA: C, 53.21; H, 3.60; N, 9.07. Found: C, 53.36 H, 3.67; N, 8.92. Example 40 6- (5-m2RV2-amino · 3- (1Η-indolyl) propyl 1oxy 丨 pyridin-3-yl Vl, 3-benzopyrazole The desired product of -2 (3H) -one was prepared by replacing the 6-bromophthalimide in Example 32 with 6-bromo-2-benzothiazolinone. MS (APCI) m / e417 (M + H) +; 1 H NMR (300 MHz, CD3 OD) 5 8.52 (s, 1H), 8.31 (d, J = 2.4 Hz, 1H), 7.77 (d, J = 1 · 7 Hz, 1H), 7.71 (t, J = 1.7 Hz, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.56 (dd, J = 6.0, 1.7 Hz, 1H), 7.39 (d5 J = 8.2 Hz, 1H)? 7.25 (d, J = 8.2 Hz, 1H), 7.23 (s, 1H), 7.14 (t? J = 7.2 Hz, 1H), 7.03 (t, J = 7.2 Hz , 1H), 4.41 (dd, J = 12.0, 3.4 Hz, 1H), 4.26 (dd, J = 9.0, 5.7 Hz, 1H), 3.97-4.〇2 (m, 1H); for C23H20N4O2.1.9TFA Analytical calculated value: C, 50.84; H, 3.49; Ν, 8.85. Found: C, 51.22; H, 3.67; Ν, 8.49. Example 41

沔1 口朵-3-基）-2彳5-異口奎淋-6-基说畦-3-基）乙胺實例41A 3-(氰基甲基V1H-㈤哚小藉酸第三-丁醋_ 將3-氰基曱基啕哚（7.50克，48毫莫耳）、二碳酸二-第三-丁酯（11·5克，52.8毫莫耳）及DMAP (300毫克）於二氯甲烷（2〇〇毫 -97- 200301122沔 1 Ortho-3-yl) -2 彳 5-Isoquinone-6-yl said 畦 -3-yl) Ethylamine Example 41A 3- (Cyanomethyl V1H-pyridine small borrow acid third- Butyl vinegar_ Combine 3-cyanoamidinium indole (7.50 g, 48 mmol), di-tertiary-butyl dicarbonate (11.5 g, 52.8 mmol) and DMAP (300 mg) Chloromethane (200 milli-97- 200301122

(90) 升）中之溶液，在室溫下攪拌過夜。使混合物濃縮，並使殘留物於碎膠上藉急驟式管柱層析純化，使用二氯甲燒，提供所要之產物（11.44 克，93% )。MS(DCI/NH3)m/e257(；M+H)+.(90) liters), and stirred at room temperature overnight. The mixture was concentrated and the residue was purified by flash column chromatography on crushed gel using dichloromethane to provide the desired product (11.44 g, 93%). MS (DCI / NH3) m / e257 (; M + H) +.

實例41B 34(5-漠某p比咬-3-基）(果基）甲基嗓小藉酸第三·丁酉旨將實例41Α (5.46克，21.3毫莫耳）與3,5·二溴基吡啶（5·〇3克， 21.3毫莫耳）於DMF (25毫升）中之溶液，在室溫下，以數份 NaH (60%，於礦油中，1.08克，25.6毫莫耳）處理。將反應物在室溫下攪拌20分鐘，加熱至60°C，歷經2小時，並倒入水修中。將水層以乙醚萃取’並將合併之萃液以水洗滌，脫水乾燥（MgS〇4)，過滤及濃縮。使殘留物於；?夕膠上藉急驟式管柱層析純化，使用醋酸乙酯/己烷（1 : 7)，提供所要之產物（336 毫克，4%)。MS(DCI/NH3)m/e413(M+H)+.Example 41B 34 (5- Mo-p-ratio-3-yl) (fruit group) methyl acetic acid third butyl cyanide Example 41A (5.46 g, 21.3 mmol) and 3,5 · dibromo Of pyridine (5.03 g, 21.3 mmol) in DMF (25 ml) at room temperature with several portions of NaH (60% in mineral oil, 1.08 g, 25.6 mmol) deal with. The reaction was stirred at room temperature for 20 minutes, heated to 60 ° C for 2 hours, and poured into water repair. The aqueous layer was extracted with ether 'and the combined extracts were washed with water, dried (MgS04), filtered and concentrated. The residue was purified by flash column chromatography on silica gel using ethyl acetate / hexane (1: 7) to provide the desired product (336 mg, 4%). MS (DCI / NH3) m / e413 (M + H) +.

實例41C 3-[氰基（5-異ρ奎琳-6-基p比咬-3-基）曱基1-1Η-Θ1嚷-μ卷酸第三-丁 g皆所要之產物係經由以實例41B取代實例27B中之實例2A而製成。MS (DCI/NH3) m/e 461 (Μ+Η)+ . ·Example 41C 3- [Cyano (5-Isoquinolin-6-yl p-ratio-3-yl) fluorenyl 1-1Η-Θ1 嚷 -μ volume acid tertiary-butyl g all desired products Example 41B was prepared in place of Example 2A in Example 27B. MS (DCI / NH3) m / e 461 (Μ + Η) +.

實例41D 2-(lH-哎嗓-3-基）-2-(5-異p奎琳-6-基p比哈各基）乙胺將實例41C(159毫克，〇,345毫莫耳）、RaNi28〇〇(525亳克）、氨（2毫升）及三乙胺（2毫升）於曱醇（20毫升）中之混合物，在氫（60psi)及室溫下攪拌73小時，並濃縮。將殘留物以醋酸乙酯與曱醇研製。使所形成之固體溶於三氟醋酸（1毫升）中，在室溫下授摔5分鐘，及濃縮。使殘留物於C18管柱上 -98- 200301122Example 41D 2- (lH-Hou-3-yl) -2- (5-isop-quelin-6-yl-p-biharyl) ethylamine Example 41C (159 mg, 0.345 mmol) , RaNi280 (525 g), a mixture of ammonia (2 ml) and triethylamine (2 ml) in methanol (20 ml), stirred under hydrogen (60 psi) at room temperature for 73 hours, and concentrated. The residue was triturated with ethyl acetate and methanol. The formed solid was dissolved in trifluoroacetic acid (1 ml), allowed to stand for 5 minutes at room temperature, and concentrated. Put residue on C18 column -98- 200301122

(91) 藉HPLC純化，使用0-100% CH3CN/H2O/0.1% TFA，提供所要之產物，為三氟醋酸鹽（64 毫克，26% )。MS (DCI/NH3) m/e 365 (M+H)+ ；1 H NMR (CD3 OD) 5 9·80 (s，1H)，9.12 (br s，1H)，8·87 (br s，1H)，8.68 (s，1H)， 8·64 (m，3H)，8·51 (d，J=6.6 Hz，1H)，8·35 (dd，J=1.6, 8·4 Hz，1H)，7.52 (d，J=8.1 Hz， 1H)，7.50 (s，1H)，7.42 (d，J=8.4 Hz，1H)，7.15 (m，1H)，7.03 (m，1H)，4.95 (t，J=7.8(91) Purified by HPLC using 0-100% CH3CN / H2O / 0.1% TFA to provide the desired product as trifluoroacetate (64 mg, 26%). MS (DCI / NH3) m / e 365 (M + H) +; 1 H NMR (CD3 OD) 5 9 · 80 (s, 1H), 9.12 (br s, 1H), 8.87 (br s, 1H ), 8.68 (s, 1H), 8.64 (m, 3H), 8.51 (d, J = 6.6 Hz, 1H), 8.35 (dd, J = 1.6, 8 · 4 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.50 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.15 (m, 1H), 7.03 (m, 1H), 4.95 (t, J = 7.8

Hz，1H)，3.91 (m，2H). 實例42 2-(lH-蜊嗓-3-基）-3-(5-異口奎口林-6-基口比淀-3-基）丙-1-胳Hz, 1H), 3.91 (m, 2H). Example 42 2- (lH-clam-3-yl) -3- (5-isokouqueline-6-based acetic acid-3-yl) c -1- tick

實例42A (2Z)-3-(5-溴基吡啶-3-基V2-(1H-吲哚各基）丙烯赔Example 42A (2Z) -3- (5-Bromopyridin-3-yl V2- (1H-indolyl) propene)

將3-氰基甲基吲哚（156毫克，1.0毫莫耳）於無水乙醇（1.5毫升）中之溶液，在室溫下，以乙醇（450微升）中之21%乙醇鈉處理，攪拌1小時，以3-溴基吡啶-5-羧醛（J. HeterocycL Chem.，1995, 32, 1801.)(187毫克，1·0毫莫耳）處理，攪拌過夜，及濃縮。使殘留物於矽膠上藉急驟式管柱層析純化，使用2%甲醇/ 二氯曱烷，提供所要之產物（52毫克，16% )。MS (DCI/NH3)m/e 325 (M+H)+.A solution of 3-cyanomethylindole (156 mg, 1.0 mmol) in absolute ethanol (1.5 ml) was treated with 21% sodium ethoxide in ethanol (450 µl) at room temperature, and stirred After 1 hour, it was treated with 3-bromopyridine-5-carboxaldehyde (J. HeterocycL Chem., 1995, 32, 1801.) (187 mg, 1.0 mmol), stirred overnight, and concentrated. The residue was purified by flash column chromatography on silica gel using 2% methanol / dichloromethane to provide the desired product (52 mg, 16%). MS (DCI / NH3) m / e 325 (M + H) +.

實例42B 2-(1Η-吲哚各基V3-(5-異口奎啉-6-基吡啶-3-基）丙小胺所要之產物係經由以實例42A取代實例41C與41D中之實例 41B，以三氟醋酸鹽製成。MS(DCI/NH3)m/e379(M+H)+ ; hNMR (CD3 OD) δ 9.70 (s, 1H), 8.88 (s, 1H), 8.61 (d5 J=6.6 Hz, 1H), 8.47 (m, 2H)? 8.86 (d, J=6.6 Hz，1H)，8.03 (s，1H)，7.86 (s，1H)，7·83 (dd，J=1.6, 8.4 Hz，1H)，7·54 (d，J=7.8 Hz，1H)，7.45 (d5 J=8.1 Hz，1H)，7.21 (s，1H)，7.17 (m，1H)，7.04 (m，1H)，8.82 (m， -99- 200301122 (92) 1H)，3·61 (m，2H)，3,36 (dd，J=4.1，13·4 Hz，1H)，3.30 (m，1H)· 實例43 (1SV2-(1H-吲哚-3-基毗啶_4-基4啉-3-基）氣某1甲墓}乙胺實例43A 6-溴甚各羥基喹啉-4-#酸Example 42B 2- (1H-Indolyl V3- (5-Isoquinolin-6-ylpyridin-3-yl) propanamine The desired product was obtained by replacing Example 41B in Examples 41C and 41D with Example 42A , Made of trifluoroacetate. MS (DCI / NH3) m / e379 (M + H) +; hNMR (CD3 OD) δ 9.70 (s, 1H), 8.88 (s, 1H), 8.61 (d5 J = 6.6 Hz, 1H), 8.47 (m, 2H)? 8.86 (d, J = 6.6 Hz, 1H), 8.03 (s, 1H), 7.86 (s, 1H), 7.83 (dd, J = 1.6, 8.4 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.45 (d5 J = 8.1 Hz, 1H), 7.21 (s, 1H), 7.17 (m, 1H), 7.04 (m, 1H) , 8.82 (m, -99- 200301122 (92) 1H), 3.61 (m, 2H), 3,36 (dd, J = 4.1, 13.4 Hz, 1H), 3.30 (m, 1H) · Examples 43 (1SV2- (1H-indol-3-ylpyridin_4-yl4-line-4-yl-3-yl) methyl-1methyl)} Ethylamine Example 43A 6-Bromoxylhydroxyquinoline-4- # acid

使5-溴基啕哚醌（2.26克，1〇毫莫耳）與氫氧化鉀（4.48克，80 毫莫耳）於水（1〇毫升）中之溶液温熱，直到物質溶解，然後冷卻至室溫，以溴基丙酮酸（2.3克，14毫莫耳）處理，攪掉 6天，以濃HC1調整至pH <7及過濾。將固體以水與乙醇洗滌，並乾燥，提供所要之產物（1.5克，58% )。MS(DCI/NH3)m/e269 (M+H)+ · 實例43B 6-邊基3-#至基4淋A solution of 5-bromopyridoquinone (2.26 g, 10 mmol) and potassium hydroxide (4.48 g, 80 mmol) in water (10 ml) was warmed until the material was dissolved and then cooled to Treat with bromopyruvic acid (2.3 g, 14 mmol) at room temperature, stir for 6 days, adjust to pH < 7 with concentrated HC1 and filter. The solid was washed with water and ethanol and dried to provide the desired product (1.5 g, 58%). MS (DCI / NH3) m / e269 (M + H) + Example 43B 6-side group 3- # to base 4

使實例43A (1·5克，5.6毫莫耳）於硝基苯（10毫升）中之溶液回流5分鐘，過濾，冷卻至室溫，並再過濾一次。將固體以己烷洗滌，並乾燥，提供所要之產物（0.68克，55% )。 MS (DCI/NH) m/e 225 (Μ+Η)+ ·A solution of Example 43A (1.5 g, 5.6 mmol) in nitrobenzene (10 ml) was refluxed for 5 minutes, filtered, cooled to room temperature, and filtered again. The solid was washed with hexane and dried to provide the desired product (0.68 g, 55%). MS (DCI / NH) m / e 225 (Μ + Η) + ·

實例43C (lSV2-『(6-溴基喹啉-3-基）氳基1-Η1Η-吲哚-3-某甲某）乙基胺基甲酸第三-丁酯所要之產物係經由以實例43B取代實例2A中之3-溴基-5·羥基吡啶而製成。於矽膠上藉急驟式管柱層析純化，使用100 %醋酸乙酯，提供所要之產物（〇·89克，72% )。MS (DCI/NH3) m/e 497 (M+H)+ · -100- 200301122Example 43C (1SV2-[(6-Bromoquinolin-3-yl) fluorenyl 1-fluorene 1 indole-3-indol-3-somemethyl) ethylaminocarboxylic acid tert-butyl ester 43B was prepared by substituting 3-bromo-5.hydroxypyridine in Example 2A. Purification by flash column chromatography on silica gel using 100% ethyl acetate provided the desired product (0.89 g, 72%). MS (DCI / NH3) m / e 497 (M + H) +--100- 200301122

(93)(93)

實例43D (lS)-2-(lH-4l嗓-3-基）小丨IT6-P比淀-4-基。奎琳-3-基）氣基1甲基丨乙基胺基甲酸第三-丁 ^ 將實例43C (0.33克’ 0·67愛莫耳）、p比咬二經基侧燒（ο ι) 克，0.99毫莫耳）、氟化铯（0.2克，L34毫莫耳）及肆三苯膦鈀 (0.038克，0.034毫莫耳）於DMF (10毫升）中之混合物，在1〇〇。〇下攪拌8小時，以醋酸乙酯（10毫升）處理，以鹽水洗條，脫水乾燥（MgS〇4 )，過濾，及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用ίο%甲醇/二氯曱烷，提供所要之 ® 產物（0.25 克，76%)。MS(DCI/NH3)m/e495 (M+H)+.Example 43D (lS) -2- (lH-4lH-3-yl) IT6-P is smaller than Yodo-4-yl. Quelin-3-yl) 1-methyl-1-ethylaminocarboxylic acid tert-butyl ^ Example 43C (0.33 g '0.67 Emole), p-bitumen side burned (ο ι) G, 0.99 mmol, cesium fluoride (0.2 g, L34 mmol) and triphenylphosphine palladium (0.038 g, 0.034 mmol) in DMF (10 mL) at 100. Stir at 0 ° C for 8 hours, treat with ethyl acetate (10 mL), wash the strips with brine, dry (MgS04), filter, and concentrate. The concentrate was purified on silica gel by flash column chromatography using 5% methanol / dichloromethane to provide the desired product (0.25 g, 76%). MS (DCI / NH3) m / e495 (M + H) +.

實例43E (1SV2-(1H-41嗓-3-基）-1-{『(6-ρ比淀-4-基g套琳-3-基）氣基1甲基]乙胺所要之產物係經由以實例43D取代實例27C中之實例27B，以三氟醋酸鹽製成。MS(DCI/NH3)m/e395 (M+H)+; iHNMR^DMSOO 510.89 (s，1H)，8.74 (d，J=3.0 Hz，1H)，8·71 (d，J=5.0 Hz，2H)，8.25 (s，1H)，8.07 (d， J=9.0 Hz，1H)，7.99 (d，J=9.0 Hz，1H)，7.83 (d，J=5.0 Hz，2H)，7.72 (d5 J=3.0 Hz，1H)， 7.58 (d ; J=7.5 Hz，1H)，7.35 (d，J=8.4 Hz，1H)，7.23 (s，1H)，7·06 (t，J=7.5 Hz，1H)，籲 6.95 (t, J=8.4 Hz, 1H), 4.05 (m, 2H), 3.53 (m, 1H), 3.01 (dd, J=6.3, 14.9 Hz, 1H), 2.87(dd，J=6.9, 14.9 Hz，1H). 實例44 (3Z)-3-|~(2S)-2-胺基丨嗓-3-基）亞丙基 1-5-異居琳-6-基-1,3-二氬Example 43E (1SV2- (1H-41H-3--3-yl) -1-{"(6-ρ 比 Lake-4-ylg taolin-3-yl) Gas 1methyl] ethylamine desired product system By replacing Example 27B in Example 27C with Example 43D and making it with trifluoroacetate. MS (DCI / NH3) m / e395 (M + H) +; iHNMR ^ DMSOO 510.89 (s, 1H), 8.74 (d, J = 3.0 Hz, 1H), 8.71 (d, J = 5.0 Hz, 2H), 8.25 (s, 1H), 8.07 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 9.0 Hz, 1H), 7.83 (d, J = 5.0 Hz, 2H), 7.72 (d5 J = 3.0 Hz, 1H), 7.58 (d; J = 7.5 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.23 (s, 1H), 7.06 (t, J = 7.5 Hz, 1H), 6.95 (t, J = 8.4 Hz, 1H), 4.05 (m, 2H), 3.53 (m, 1H), 3.01 ( dd, J = 6.3, 14.9 Hz, 1H), 2.87 (dd, J = 6.9, 14.9 Hz, 1H). Example 44 (3Z) -3- | ~ (2S) -2-amino group ) Propylene 1-5-isocurene-6-yl-1,3-diargon

-2H-吡咯并[2,3-bl吡啶-2-酮實例44A (!S，2g)-2-(5胃溪基-2-酮基·1，2-二氫-3H-p比洛并 |~2,3-bl亞 ρ比淀-3-基）-1- -101 - (94)-2H-pyrrolo [2,3-bl pyridin-2-one Example 44A (! S, 2g) -2- (5 Gasketyl-2-keto · 1,2-dihydro-3H-p Billow And | ~ 2,3-bl sub-p-pyridine-3-yl) -1- -101-(94)

基甲基）乙某胺基甲酸第三J：Zj^ 使5-溴基1氮-氧化⑻哚（D. Mazeas等人，雜環1999, 50, ι〇65 )(213 毫克，1.0毫莫耳）、L_B0C_色胺酸（29〇毫克，1 〇亳莫耳）及六氫说咳：（40微升）於乙醇中之混合物，回流2 5小時，並濃縮。將殘留物以二氯甲烷（1毫升）與己烷（6毫升）研製，並乾燥，提供所要之產物⑸2毫克）。MS(DCI/NH3)m/e483,485 (M+H)+Methyl methyl) ethyl aminocarbamic acid third J: Zj ^ make 5-bromo 1-nitrogen-oxindole (D. Mazeas et al., Heterocyclic 1999, 50, ι〇65) (213 mg, 1.0 mmol) Ear), L_B0C_ tryptophan (29 mg, 10 mol) and hexahydro cough: (40 microliters) of a mixture in ethanol, refluxed for 25 hours, and concentrated. The residue was triturated with dichloromethane (1 ml) and hexane (6 ml) and dried to give the desired product (2 mg). MS (DCI / NH3) m / e483,485 (M + H) +

實例44B Z_l-3-[(2S)-2-胺基各(1H-吲哚！某）亞丙基1-5-異4呲二新 -2Η-ρ比嘻并「2,3-b>比咬-2-酮所要之產物係經由以實例44A (260毫克）取代實例27中之實例 2A 而製成。MS(DCI/NH3)m/e432(M+H)+ ; hNMRfDsOD) 3 9.57 (s，1H)，8.64 (d，J=2.5 Hz，1H)，8.52 (d，J=7.6 Hz，1H)，8.26 (s，1H)，8·24 (s，1H)， 8.08 (d，J=6.4 Hz，1H)，7.64 (s，1H)，7.60 (dd，J=8.7，1.7 Hz，1H)，7.55 (d，J=6.6 Hz， 1H)3 7.54 (d, J=7.1 Hz, 1H), 7.33 (dd5 J=7.0, 1.1 Hz, 1H), 7.29 (dd, J=3.3, 1.3 Hz? 1H)，7.26 (dd，J=7.1，1.0 Hz，1H)，6.26 (d，J=2.2 Hz，1H)，4.20 (s，1H)，3.94 (d，J=6.8 Hz，1H)，3.61 (s，1H)，2.78 (d，J=14.7 Hz，1H)，2.68 (dd，J=16.3, 6·9 Hz，1H).新穎實例按照實例1中所述之程序，使用適當醇類，製成下列化合物。實例45 3-丁氫基-542-(4-吡啶基）乙烯基1吡啶 MS (DCI/NH3) m/e 255 (M+1)· 1 H NMR (DMS〇-d6): δ 8.58 (d； J=6.0 Hz, 1H), 8.39(s; lH)，8.22(s; 1H)，7.70 (s; lH)，7.56(d; J=6.0Hz，1H)，7.56 (d，J=16.5 Hz, 1H), 7.45 (d ； J=16.5 Hz, 2H), 4.12 (t ； J=8.6 Hz? 3H), 1.74 (m ； 2H), 1.47 20030Π22 (95) (m ; 2H)，0·96 (t ; J=8.6 Hz，2H). 實例46 3-甲氧基比咬基）乙歸r基p比淀 MS (DCI/NH3 ) m/e 213 (M+l). 1H NMR (DMS0-d6): (5 ppm 8,58 (m，2H)，8·41 (d， J=1.7 Hz，1H)，8·24 (d，J=2.7 Hz，1H)，7·71 (m，1H) 7·57 (m，3H)，7.47 (d，J=16.5 Hz， 1H)，3.89 (s，3H). 實例47Example 44B Z_l-3-[(2S) -2-Amino groups (1H-indole! Some) propylene group 1--5-iso-4 'dioxin-2'-ρ ratio and "2,3-b > The desired product of bibitan-2-one was prepared by replacing Example 2A in Example 27 with Example 44A (260 mg). MS (DCI / NH3) m / e432 (M + H) +; hNMRfDsOD) 3 9.57 ( s, 1H), 8.64 (d, J = 2.5 Hz, 1H), 8.52 (d, J = 7.6 Hz, 1H), 8.26 (s, 1H), 8.24 (s, 1H), 8.08 (d, J = 6.4 Hz, 1H), 7.64 (s, 1H), 7.60 (dd, J = 8.7, 1.7 Hz, 1H), 7.55 (d, J = 6.6 Hz, 1H) 3 7.54 (d, J = 7.1 Hz, 1H ), 7.33 (dd5 J = 7.0, 1.1 Hz, 1H), 7.29 (dd, J = 3.3, 1.3 Hz? 1H), 7.26 (dd, J = 7.1, 1.0 Hz, 1H), 6.26 (d, J = 2.2 Hz, 1H), 4.20 (s, 1H), 3.94 (d, J = 6.8 Hz, 1H), 3.61 (s, 1H), 2.78 (d, J = 14.7 Hz, 1H), 2.68 (dd, J = 16.3 , 6.9 Hz, 1H). Novel Examples The following compounds were prepared using the appropriate alcohols using the procedure described in Example 1. Example 45 3-Buthydro-542- (4-pyridyl) vinyl 1pyridine MS (DCI / NH3) m / e 255 (M + 1) · 1 H NMR (DMS〇-d6): δ 8.58 (d; J = 6.0 Hz, 1H), 8.39 (s; lH), 8.22 (s; 1H), 7.70 (s; lH), 7.56 (d; J = 6.0Hz, 1H), 7.56 (d, J = 16.5 Hz, 1H), 7.45 (d; J = 16.5 Hz, 2H), 4.12 (t; J = 8.6 Hz? 3H), 1.74 ( m; 2H), 1.47 20030Π22 (95) (m; 2H), 0.96 (t; J = 8.6 Hz, 2H). Example 46 3-methoxy-l-phenyl group) ethylazine r-group p-Hydro MS ( DCI / NH3) m / e 213 (M + 1). 1H NMR (DMS0-d6): (5 ppm 8,58 (m, 2H), 8.41 (d, J = 1.7 Hz, 1H), 8 · 24 (d, J = 2.7 Hz, 1H), 7.71 (m, 1H) 7.57 (m, 3H), 7.47 (d, J = 16.5 Hz, 1H), 3.89 (s, 3H). Example 47

S-3-|"2-胺基-3-苯基-丙氧基比咬基）乙婦基V比淀鹽酸鹽 MS (DCI/NH3) m/e 332 (M+l). 1H NMR (DMS0-d6) ： δ 8.58 (d ； J=6.0 Hz, 2H), 8.40 (s； 1H), 8.25(s； lH),7.69(s； lH),7.56(d； J=6.0 Hz, 1H), 7.56 (d； J=16.5 Hz, 1H), 7.43 (d； J=16.5 Hz, 1H), 7.26 (m； 5H), 3.94 (m； 2H), 3.28 (m； 1H), 2.87 (dd ; J=6.0 Hz，與 13·5 Hz，1H)，2.65 (dd ; J=9 Hz，13.5 Hz，1H)· 實例48 嗓基V乙乳基比症基）乙婦基比淀鹽酸鹽 MS (DCI/NH3) ： m/z 342 (M+l). 1 HNMR (DMSO-d6) ： δ 10.39 (brs, 1H), 8.60 (d，J=6.6 Hz，2H)，8.38 (d，J=2.5 Hz，1H)，8·25 (d，>3·3 Hz，1H)，7.72 (dd，J=2.5，S-3- | " 2-Amino-3-phenyl-propoxy specific octyl) ethynyl V ratio lake hydrochloride MS (DCI / NH3) m / e 332 (M + l). 1H NMR (DMS0-d6): δ 8.58 (d; J = 6.0 Hz, 2H), 8.40 (s; 1H), 8.25 (s; lH), 7.69 (s; lH), 7.56 (d; J = 6.0 Hz, 1H), 7.56 (d; J = 16.5 Hz, 1H), 7.43 (d; J = 16.5 Hz, 1H), 7.26 (m; 5H), 3.94 (m; 2H), 3.28 (m; 1H), 2.87 ( dd; J = 6.0 Hz, with 13.5 Hz, 1H), 2.65 (dd; J = 9 Hz, 13.5 Hz, 1H) · Example 48 Acetyl-V-ethyl-lactylate-based) Ethyl-pyridine hydrochloride Salt MS (DCI / NH3): m / z 342 (M + 1). 1 HNMR (DMSO-d6): δ 10.39 (brs, 1H), 8.60 (d, J = 6.6 Hz, 2H), 8.38 (d, J = 2.5 Hz, 1H), 8.25 (d, > 3.3 Hz, 1H), 7.72 (dd, J = 2.5,

3·3 Hz，1H)，7.62 (d，J=8,5 Hz，1H)，7.55 (d，J=17.4 Hz，1H)，7.36 (d，J=8.1 Hz, 1H)， 7·54 (d，J=6.6 Hz，2H)，7.28 (d, J=3.3 Hz，1H)，4.36 (t，J=7.5 Hz，2H)，3.11 (t，J=3.11 Hz, 2H). 實例49 3-「2-(lH-3-吲哚基V丙氧基l-5-「2-(4-吡啶基）乙烯基 >比啶 MS (DCI/NH3 )： m/z 356 (M+l). 1 HNMR (DMSO-d6)： 6 10.79 (br s? 1H), 8.57 (m5 2H)，8·39 (d，J=1.7 Hz，1H)，8·25 (d，J=3.1 Hz，1H)，7.69 (t，J=2.0 Hz，1H)，7.56 (m， 2H)，7·55 (d，J=16.6 Hz，1H)，7·52 (m，1H)，7.43 (d，J=16.6 Hz，1H)，7.33 (d，J=8.1 -103- (96)3 · 3 Hz, 1H), 7.62 (d, J = 8, 5 Hz, 1H), 7.55 (d, J = 17.4 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.54 ( d, J = 6.6 Hz, 2H), 7.28 (d, J = 3.3 Hz, 1H), 4.36 (t, J = 7.5 Hz, 2H), 3.11 (t, J = 3.11 Hz, 2H). Example 49 3- "2- (lH-3-indolyl V propoxyl-5-" 2- (4-pyridyl) vinyl > pyridine MS (DCI / NH3): m / z 356 (M + 1) 1 HNMR (DMSO-d6): 6 10.79 (br s? 1H), 8.57 (m5 2H), 8.39 (d, J = 1.7 Hz, 1H), 8.25 (d, J = 3.1 Hz, 1H ), 7.69 (t, J = 2.0 Hz, 1H), 7.56 (m, 2H), 7.55 (d, J = 16.6 Hz, 1H), 7.52 (m, 1H), 7.43 (d, J = 16.6 Hz, 1H), 7.33 (d, J = 8.1 -103- (96)

Hz，1H)，7.15 (d，J=2.4 Hz，1H)，7.06 (m，1H)，6.96 (m，1H)，4·16 (t，J=6.5 Hz，2H)， 2.89 (t，J=8.1 Hz，2H)，2.14 (m，2H)· 實例50 S-3-『2-胺基-3-(4-芊氧基笨基V丙氣基1-542-(4-吡啶基）乙烯某1吡症鹽酸鹽 MS (DCI/NH3): m/z 438 (M+1)· 1 H NMR (DMSO-d6): 5 10·04 (br s，3H)，8.86 (d， J=7.5 Hz, 2H), 8.54 (s, 1H), 8.39 (d5 J=3.3 Hz, 1H), 8.13 (d, J=7.5 Hz, 2H), 7.98 (d, J=17.4 Hz，1H)，7.88 (m，1H)，7.73 (d，J=17.4 Hz，1H)，7.39 (m，5H)，7.24 (d，J=9.0 Hz, 2H), 6.99 (d5 J=9.0 Hz, 2H), 4.28 (dd, J=3.9, 11.5 Hz, 1H)? 5.07 (s, 2H), 4.12 (dd, J=6.5, 11.5 Hz，1H)，3.29 (m，1H)，3.05 (m，2H). 實例51 3-(穴乳口比咬·4_基）-5-『2-(4-口比淀基）乙婦基]口比淀 MS (DCI/NH3) ： m/z 282 (M+l). 1 H NMR (DMSO-d6) ： δ 8.55 (m, 2H), 8.34 (d, J=1.7 Hz, 1H), 8.18 (d, J=2.7 Hz, 1H)? 7.72 (m, 1H), 7.62 (m5 2H)5 7.52 (d=16.3 Hz, 1H)，7.35 (d，J=16.3 Hz，1H)，4.66 (m，1H)，3.10 (m，2H)，2.78 (m，2H)，2·06 (m，2H)， 1.70 (m，2H)· 實例52 R-3-丨2-胺基-3-卞乳基丙乳基比淀基）乙綠基比淀鹽酸鹽 MS (DCI/NH3): m/z 362 (M+1)· 1 H NMR (CD3 CD): <5 8.84 (m，2H)，8.81 (m，1H)， 8.58 (m，1H)，8.53 (m，1H)，8.32 (m，2H)，7·98 (d，J=16.3 Hz，1H)，7.87 (d，J=16.3 Hz， 1H)，7.35 (m，5H)，4.66 (s，2H)，3·95 (m，2H)，3.85 (m，1H)· 實例53 3-(1-曱基-咪唑-4-甲氧基）-542-(4-吡啶基）乙烯基扣比啶 MS (DCI/NH3) ： m/z 393 (M+l). 1 H NMR (CD3 OD) ： 5 8.52 (m, 2H), 8.39 (d, J= (97) 1.6 Hz，1H)，8·27 (d，J=2.5 Hz，1Η)，7·84 (m，1H)，7.69 (s，1H)，7.62 (m，2H)，7·53 (d， J=16.5 Hz，1H)，7·88 (d，J=16.5 Hz，1H)，7.15 (s，1H)，5·29 (s，2H)，3.78 (s，3H)· 實例54 S-3-{2-胺基-3-『3-羥基笨基丙氧基}-5-『2-(4-吡啶基）乙烯基扣比啶三氟醋酸鹽 MS (DCI/NH3)： m/z 348 (M+l). 1 H NMR (DMS0-d6) ： δ 8.84 (d, J=6.8 Hz, 2H),Hz, 1H), 7.15 (d, J = 2.4 Hz, 1H), 7.06 (m, 1H), 6.96 (m, 1H), 4.16 (t, J = 6.5 Hz, 2H), 2.89 (t, J = 8.1 Hz, 2H), 2.14 (m, 2H) · Example 50 S-3- "2-Amino-3- (4-methoxyoxybenzyl V-propenyl 1-542- (4-pyridyl) MS (DCI / NH3): m / z 438 (M + 1) · 1 H NMR (DMSO-d6): 5 10 · 04 (br s, 3H), 8.86 (d, J = 7.5 Hz, 2H), 8.54 (s, 1H), 8.39 (d5 J = 3.3 Hz, 1H), 8.13 (d, J = 7.5 Hz, 2H), 7.98 (d, J = 17.4 Hz, 1H), 7.88 (m, 1H), 7.73 (d, J = 17.4 Hz, 1H), 7.39 (m, 5H), 7.24 (d, J = 9.0 Hz, 2H), 6.99 (d5 J = 9.0 Hz, 2H), 4.28 ( dd, J = 3.9, 11.5 Hz, 1H)? 5.07 (s, 2H), 4.12 (dd, J = 6.5, 11.5 Hz, 1H), 3.29 (m, 1H), 3.05 (m, 2H). Example 51 3 -(Acupoint milk mouth ratio bite · 4_base) -5- 『2- (4-Mouth ratio lake base) Otome] Mouth lake MS (DCI / NH3): m / z 282 (M + l). 1 H NMR (DMSO-d6): δ 8.55 (m, 2H), 8.34 (d, J = 1.7 Hz, 1H), 8.18 (d, J = 2.7 Hz, 1H)? 7.72 (m, 1H), 7.62 ( m5 2H) 5 7.52 (d = 16.3 Hz, 1H), 7.35 (d, J = 16.3 Hz, 1H), 4.66 (m, 1H), 3.10 (m, 2H), 2.78 (m, 2H), 2.06 (m, 2H), 1.7 0 (m, 2H) · Example 52 R-3- 丨 2-Amino-3-fluorenyl-acryloyl-propionyl-pyridyl) Ethyl-green-pyridyl hydrochloride MS (DCI / NH3): m / z 362 (M + 1) · 1 H NMR (CD3 CD): < 5 8.84 (m, 2H), 8.81 (m, 1H), 8.58 (m, 1H), 8.53 (m, 1H), 8.32 (m, 2H ), 7.98 (d, J = 16.3 Hz, 1H), 7.87 (d, J = 16.3 Hz, 1H), 7.35 (m, 5H), 4.66 (s, 2H), 3.95 (m, 2H) , 3.85 (m, 1H) · Example 53 3- (1-fluorenyl-imidazol-4-methoxy) -542- (4-pyridyl) vinylpiperidine MS (DCI / NH3): m / z 393 (M + l). 1 H NMR (CD3 OD): 5 8.52 (m, 2H), 8.39 (d, J = (97) 1.6 Hz, 1H), 8.27 (d, J = 2.5 Hz, 1Η ), 7.84 (m, 1H), 7.69 (s, 1H), 7.62 (m, 2H), 7.53 (d, J = 16.5 Hz, 1H), 7.88 (d, J = 16.5 Hz, 1H), 7.15 (s, 1H), 5.29 (s, 2H), 3.78 (s, 3H). Example 54 S-3- {2-Amino-3- "3-hydroxybenzylpropoxy} -5- "2- (4-pyridyl) vinylbipyridine trifluoroacetate MS (DCI / NH3): m / z 348 (M + 1). 1 H NMR (DMS0-d6): δ 8.84 ( d, J = 6.8 Hz, 2H),

8.54 (m，1H)，8·37 (d，J=2.7 Hz，1H)，8.06 (d，J=6.8 Hz，2H)，7.91 (m，J=16.6 Hz，1H)， 7.62 (d，J=16.6 Hz，1H)，7·09 (d，J=8.5 Hz，2H)，6.73 (d，J=8.5 Hz，2H)，4.22 (dd， 3.1，10.5 Hz，1H)，4.06 (dd，J=5.4, 10·5 Hz，1H)，3.77 (m，1H)，2.93 (m，2H). 實例55 S-3-{2-胺基氨基苯基1-丙乳基}-5-「2-(4-口比淀基）乙婦基1外匕淀鹽酸鹽 MS (DCI/NH3)： m/z 357 (M+l). 1 H NMR (DMSO-d6)： δ 8.92 (d5 J=6.4 Hz, 2H),8.54 (m, 1H), 8.37 (d, J = 2.7 Hz, 1H), 8.06 (d, J = 6.8 Hz, 2H), 7.91 (m, J = 16.6 Hz, 1H), 7.62 (d, J = 16.6 Hz, 1H), 7.09 (d, J = 8.5 Hz, 2H), 6.73 (d, J = 8.5 Hz, 2H), 4.22 (dd, 3.1, 10.5 Hz, 1H), 4.06 (dd, J = 5.4, 10 · 5 Hz, 1H), 3.77 (m, 1H), 2.93 (m, 2H). Example 55 S-3- {2-aminoaminophenyl 1-propanoyl} -5- "2 -(4-methylpyridyl) ethynyl 1 hydrochloride MS (DCI / NH3): m / z 357 (M + 1). 1 H NMR (DMSO-d6): δ 8.92 (d5 J = 6.4 Hz, 2H),

8.66 (s，1H)，8·49 (d，J=1.8 Hz，1H)，8.21 (d，J=6.4 Hz，2H)，8.13 (s，1H)，8.06 (d，J二 16.5 Hz, 1H), 7.90 (d, J=16.5 Hz, 1H), 7.83 (d, J=8.2 Hz, 2H)3 7.59 (d, J=8.2 Hz, 2H), 4·40 (dd，J=3.4, 10.7 Hz，1H)，4.24 (dd，J=5.8, 10·7 Hz，1H)，3.91 (m，1H)，3.29 (dd， J=6.1, 13.7 Hz, 1H), 3.16 (dd, J=8.5, 13.7 Hz, 1H). 實例56 341-(4-氰基芊基）-咪唑-4-甲氧基l-5-f2-(4-吡啶基）乙烯基1吡啶 MS (DCI/NH3) ： m/z 394 (M+l). 1 H NMR (CD3 OD) δ 8.51 (d ； J=6.1 Hz, 2H), 8.33 (d，J=1.5 Hz，1H)，7·94 (d，J=2.5 Hz，1H)，7.93 (s，1H)，7·67 (d，J=8.2 Hz，2H)， 7.62 (d，J=6.1 Hz，2H)，7·48 (m，1H)，7.47 (d，J=16.5 Hz，1H)，7·30 (d，J=16.5 Hz， 1H)，7.27 (s，1H)，7.25 (d，J=8.2 Hz，2H)，5.47 (s，2H)，5.26 (s，2H)· 實例57 •105- 200301122 (98) S-3-〖2-胺基-3-α-甲基-1H-3-吲哚基）-丙氧基l-5-「2-(4-吡啶基）乙烯基 >比淀鹽酸鹽 MS (DCI/NH3) ： m/z 385 (M+l). 1H NMR (CD3 OD) δ 8.87 (d ； J=6.8 Hz, 2H), 8.55 (s, 1H), 8.41 (d, J=2.7 Hz, 1H), 8.13 (d, J=6.8 Hz, 2H), 7.96 (d, J=6.8 Hz, 2H), 7.96 (d，J=16.6 Hz，1H)，7.86 (m，1H)，7·71 (d，J=16.6 Hz，1H)，7.65 (d，J=8.1 Hz， 1H)，7·42 (d，J=8.1 Hz，1H)，7·29 (s，1H)，7.17 (m，1H)，7.04 (m，1H)，4.84 (dd，J=3.4, 10.5 Hz，1H)，4.21 (dd，J=5.8, 10·5 Hz，1H)，3.90 (m，1H)，3.19 (m，2H)，3.17 (s，3H)·8.66 (s, 1H), 8.49 (d, J = 1.8 Hz, 1H), 8.21 (d, J = 6.4 Hz, 2H), 8.13 (s, 1H), 8.06 (d, J = 16.5 Hz, 1H ), 7.90 (d, J = 16.5 Hz, 1H), 7.83 (d, J = 8.2 Hz, 2H) 3 7.59 (d, J = 8.2 Hz, 2H), 4.40 (dd, J = 3.4, 10.7 Hz , 1H), 4.24 (dd, J = 5.8, 10.7 Hz, 1H), 3.91 (m, 1H), 3.29 (dd, J = 6.1, 13.7 Hz, 1H), 3.16 (dd, J = 8.5, 13.7 Hz, 1H). Example 56 341- (4-cyanofluorenyl) -imidazole-4-methoxyl-5-f2- (4-pyridyl) vinyl1pyridine MS (DCI / NH3): m / z 394 (M + l). 1 H NMR (CD3 OD) δ 8.51 (d; J = 6.1 Hz, 2H), 8.33 (d, J = 1.5 Hz, 1H), 7.94 (d, J = 2.5 Hz , 1H), 7.93 (s, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.62 (d, J = 6.1 Hz, 2H), 7.48 (m, 1H), 7.47 (d, J = 16.5 Hz, 1H), 7.30 (d, J = 16.5 Hz, 1H), 7.27 (s, 1H), 7.25 (d, J = 8.2 Hz, 2H), 5.47 (s, 2H), 5.26 ( (s, 2H) · Example 57 • 105- 200301122 (98) S-3- 〖2-amino-3-α-methyl-1H-3-indolyl) -propoxyl-5- "2- (4-Pyridyl) vinyl group> Hydrochloride MS (DCI / NH3): m / z 385 (M + 1). 1H NMR (CD3 OD) δ 8.87 (d; J = 6.8 Hz, 2 H), 8.55 (s, 1H), 8.41 (d, J = 2.7 Hz, 1H), 8.13 (d, J = 6.8 Hz, 2H), 7.96 (d, J = 6.8 Hz, 2H), 7.96 (d, J = 16.6 Hz, 1H), 7.86 (m, 1H), 7.71 (d, J = 16.6 Hz, 1H), 7.65 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.29 (s, 1H), 7.17 (m, 1H), 7.04 (m, 1H), 4.84 (dd, J = 3.4, 10.5 Hz, 1H), 4.21 (dd, J = 5.8, 10 · 5 Hz, 1H), 3.90 (m, 1H), 3.19 (m, 2H), 3.17 (s, 3H) ·

實例58 S-342-二甲胺基-3-(lH-3-吲哚基V丙氧基l-5-『2-(4-吡啶基）乙烯某1 外匕淀鹽酸鹽 MS (DCI/NH3) ： m/z 399 (M+l). 1 H NMR (DMSO-d6) δ 8.88 (d ； J=6.6 Hz, 2H), 8.58 (s，1H)，8.45 (s，1H)，8·16 (d，J=6.6 Hz，2H)，7.96 (d，J=16.5 Hz，1H)，7.95 (s， 1H)，7.76 (d，J=16.5 Hz，1H)，7.74 (d，J=7.8 Hz，1H)，7·35 (d，J=8.1 Hz，1H)，7·29 (d， J=2.2 Hz，1H)，7.07 (m，1H)，6.97 (m，1H)，4.54 (dd，J=1.6, 11.9 Hz)，4.35 (dd，J=5.0, 11.9 Hz，1H)，3·95 (m，1H)，3.51 (dd，J=3.1，13.7 Hz，1H)，3.29 (dd，J=11.5, 13.7 Hz， 1H)，2.96 (s，6H).Example 58 S-342-dimethylamino-3- (lH-3-indolyl V propoxyl-5- "2- (4-pyridyl) ethene 1 hydrochloride MS (DCI / NH3): m / z 399 (M + 1). 1 H NMR (DMSO-d6) δ 8.88 (d; J = 6.6 Hz, 2H), 8.58 (s, 1H), 8.45 (s, 1H), 8 16 (d, J = 6.6 Hz, 2H), 7.96 (d, J = 16.5 Hz, 1H), 7.95 (s, 1H), 7.76 (d, J = 16.5 Hz, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 2.2 Hz, 1H), 7.07 (m, 1H), 6.97 (m, 1H), 4.54 ( dd, J = 1.6, 11.9 Hz), 4.35 (dd, J = 5.0, 11.9 Hz, 1H), 3.95 (m, 1H), 3.51 (dd, J = 3.1, 13.7 Hz, 1H), 3.29 (dd , J = 11.5, 13.7 Hz, 1H), 2.96 (s, 6H).

實例59 g-3-[2-胺基-3-(1-茬墓V丙氣基1-542-(4-吡啶墓）乙烯基1吡啶鹽酸鹽 MS (DCI/NH3) ·· m/z 382 (M+1)· 1H NMR (DMSO-d6) 5 8.66 (d; J=6.1 Hz，2H)， 8·48 (d，J=1.4 Hz，1H)，8·32 (d，J=2.7 Hz，1H)，8.20 (m，1H)，7.98 (m，1H)，7.90 (m， 1H)，7.69 (m，3H)，7·60 (m，3H)，7.46 m，3H)，4.25 (dd，J=2.7, 10·5 Hz，1H)，4.09 (dd， J=5.1，10.5 Hz，1H)，3·92 (m，1H)，3.53 (m，2H)· 實例60 g-i2-胺基乙氧基V5-[2-(4-吡啶基）乙烯某械啶鹽酸鹽 -106- 200301122 (99) MS (DCI/NH3) m/e 242 (M+l): 1 H NMR (CD3 OD) : 5 8.88 (d，J=6.1 Hz，2H)， 8·59 (s，1H)，8.43 (s，1H)，8.19 (d，J=6.1 Hz，2H)，8.03 (d，J=16.3 Hz，1H)，8.01 (s， 1H)，7.82 (d，J=16.3 Hz，1H)，4·42 (t，J=4.9 Hz，2H)，3·28 (m，2H)· 實例61Example 59 g-3- [2-Amino-3- (1-stump V propanyl 1-542- (4-pyridine tomb) vinyl 1 pyridine hydrochloride MS (DCI / NH3) · m / z 382 (M + 1) · 1H NMR (DMSO-d6) 5 8.66 (d; J = 6.1 Hz, 2H), 8.48 (d, J = 1.4 Hz, 1H), 8.32 (d, J = 2.7 Hz, 1H), 8.20 (m, 1H), 7.98 (m, 1H), 7.90 (m, 1H), 7.69 (m, 3H), 7.60 (m, 3H), 7.46 m, 3H), 4.25 (dd, J = 2.7, 10.5 Hz, 1H), 4.09 (dd, J = 5.1, 10.5 Hz, 1H), 3.92 (m, 1H), 3.53 (m, 2H) · Example 60 g-i2 -Aminoethoxy V5- [2- (4-pyridyl) ethene hydrochloride-106- 200301122 (99) MS (DCI / NH3) m / e 242 (M + 1): 1 H NMR (CD3 OD): 5 8.88 (d, J = 6.1 Hz, 2H), 8.59 (s, 1H), 8.43 (s, 1H), 8.19 (d, J = 6.1 Hz, 2H), 8.03 (d, J = 16.3 Hz, 1H), 8.01 (s, 1H), 7.82 (d, J = 16.3 Hz, 1H), 4.42 (t, J = 4.9 Hz, 2H), 3.28 (m, 2H) · Example 61

3-(3-胺基丙氧基比症基）乙婦基比淀鹽酸鹽 MS (DCI/NH3) m/e 256 (M+l). 1 H NMR (DMSO-d6) ： δ 8.88 (d ； J=6.4 Hz, 2H), 8.53 (d ; J=1.4 Hz，1H)，8.40 (d，J=2.7 Hz，1H)，8.15 (d，J=6.4 Hz，2H)5 8.00 (d，J= 16.6 Hz，1H)，7.93 (m，1H)，7.78 (d，J=16.6 Hz，1H)，4·27 (t，J=6.1 Hz，2H)，2.99 (m， 2H)，2.10m (m，2H). 實例62 S-3-(2-胺基3-甲基丁氣基）-542-(4-吡啶基）乙烯基1吡啶鹽酸鹽 MS (DCI/NH3) m/e 284 (M+l). 1 H NMR (DMSO-d6) ： δ 8.85 (d ； J=6.5 Hz, 2H), 8.54 (d ; ·4 Hz，1H)，8.40 (d，J=3.1 Hz，1H)，8.09 (d，J=6.5 Hz，2H)，7.95 (d，J= 16·3 Hz，1H)，7·90 (m，1H)，7.71 (d，J=16.3 Hz, 1H)，4·39 (m，1H)，4.24 (m，1H)， 3.08 (m，1H)，2.10 (m，1H)，1.06 (d，J=8.1 Hz，3H)，1.03 (d，J=7.8 Hz，3H)· 實例63 3-(1-甲基各六氫吡啶基氧基V5-『2-(4-吡啶基）乙烯基M啶三氟 · 醋酸鹽 MS (OCmm3) m/z 296 (M+H). 1H NMR (DMSO-d6) ： 5 8.82 (d, 2H), 8.53 (s3 1H)，8·41 (d，1H)，8.00 (t，2H)，7.88 (dd，2H)，7.59 (dd，2H)，4.53 (dd，1H)，4.37 (dd， 1H)，3.89 (bs，1H)，3.64 (bs，1H)，3.24-3.13 (m，1H)，3.01 (s，3H)，2·35-2·28 (m，1H)， 2.13-2.07 (m5 1H), 2.02-1.93 (m5 1H), 1.90-L83 (in, 1H). 實例64 3-(2-氯芊基V5-『2-(4-吡啶基）乙烯基1吡啶三氟醋酸鹽 -107- 2003011223- (3-Aminopropoxypyridyl) ethynyl hydrochloride MS (DCI / NH3) m / e 256 (M + 1). 1 H NMR (DMSO-d6): δ 8.88 ( d; J = 6.4 Hz, 2H), 8.53 (d; J = 1.4 Hz, 1H), 8.40 (d, J = 2.7 Hz, 1H), 8.15 (d, J = 6.4 Hz, 2H) 5 8.00 (d, J = 16.6 Hz, 1H), 7.93 (m, 1H), 7.78 (d, J = 16.6 Hz, 1H), 4.27 (t, J = 6.1 Hz, 2H), 2.99 (m, 2H), 2.10m (m, 2H). Example 62 S-3- (2-Amino3-methylbutanyl) -542- (4-pyridyl) vinyl 1pyridine hydrochloride MS (DCI / NH3) m / e 284 (M + 1). 1 H NMR (DMSO-d6): δ 8.85 (d; J = 6.5 Hz, 2H), 8.54 (d; · 4 Hz, 1H), 8.40 (d, J = 3.1 Hz, 1H ), 8.09 (d, J = 6.5 Hz, 2H), 7.95 (d, J = 16 · 3 Hz, 1H), 7.90 (m, 1H), 7.71 (d, J = 16.3 Hz, 1H), 4 39 (m, 1H), 4.24 (m, 1H), 3.08 (m, 1H), 2.10 (m, 1H), 1.06 (d, J = 8.1 Hz, 3H), 1.03 (d, J = 7.8 Hz, 3H) · Example 63 3- (1-Methylhexahydropyridyloxy V5- "2- (4-pyridyl) vinylMidine trifluoro · acetate MS (OCmm3) m / z 296 (M + H). 1H NMR (DMSO-d6): 5 8.82 (d, 2H), 8.53 (s3 1H), 8.41 (d, 1H), 8.00 (t, 2H) , 7.88 (dd, 2H), 7.59 (dd, 2H), 4.53 (dd, 1H), 4.37 (dd, 1H), 3.89 (bs, 1H), 3.64 (bs, 1H), 3.24-3.13 (m, 1H ), 3.01 (s, 3H), 2.35-2 · 28 (m, 1H), 2.13-2.07 (m5 1H), 2.02-1.93 (m5 1H), 1.90-L83 (in, 1H). Example 64 3 -(2-chlorofluorenyl V5- "2- (4-pyridyl) vinyl 1 pyridine trifluoroacetate-107- 200301122

(100) MS (DCI/NH3) m/z 323 (M+H)· 1H NMR (DMSO-d6): 5 8.84 (d，2H)，8.53 (s，1H)， 8.44 (d，1H)，8.07 (d，2H)，7.96-7.92 (m，2H)，7.70-7.67 (m，2H)，7.57-7.55 (m，1H)， 7.46-7.43 (m, 2H), 5.33 (s, 2H). 實例65 3-(N-卞基-N-甲胺基乙乳基）-5-f2-(4-p比症基）乙婦基扣比淀三氟醋酸鹽(100) MS (DCI / NH3) m / z 323 (M + H) · 1H NMR (DMSO-d6): 5 8.84 (d, 2H), 8.53 (s, 1H), 8.44 (d, 1H), 8.07 (d, 2H), 7.96-7.92 (m, 2H), 7.70-7.67 (m, 2H), 7.57-7.55 (m, 1H), 7.46-7.43 (m, 2H), 5.33 (s, 2H). Examples 65 3- (N-fluorenyl-N-methylamino ethyl ethynyl) -5-f2- (4-p specific sympto) ethynyl trifluoroacetate

MS (DCI/NH3) m/z 346 (M+H)·1H NMR (DMSO-d6): 5 8.80 (d，2H)，8·53 (s，1H)， 8.37 (d，1H)，7·98 (d，2H)，7·87 (d，1H)，7·81 (s，1H)，7.60 (d，1H)，7.58-7.47 (m，5H)， 4.58-4.50 (m，2H)，3.59-3.56 (m，2H)，2.85 (s，3H)，2.79 (t，2H)· 實例66 3-(6-(N，N-二甲胺基）己氧基吡啶基）乙烯基1吡啶三氣醋酸鹽 MS (DCI/NH3) m/z 326 (M+H). 1 H NMR (DMSO-D6) ： δ 8.82 (d, 2H)? 8.49 (d, 1H)，8.33 (d，1H)，8·04 (d，2H)，7.89 (d，1H)，7.80 (t，1H)，7.66 (d，1H)，4.14 (t，2H)， 3.06-3.02 (m, 2H), 2.78 (s, 3H), 2.77 (s, 3H), 1.82-1.76 (m, 2H)3 1.68-1.62 (m, 2H), L51-4.45 (m5 2H), 1.40-1.34 (m, 2H).MS (DCI / NH3) m / z 346 (M + H) · 1H NMR (DMSO-d6): 5 8.80 (d, 2H), 8.53 (s, 1H), 8.37 (d, 1H), 7. · 98 (d, 2H), 7.87 (d, 1H), 7.81 (s, 1H), 7.60 (d, 1H), 7.58-7.47 (m, 5H), 4.58-4.50 (m, 2H), 3.59-3.56 (m, 2H), 2.85 (s, 3H), 2.79 (t, 2H) · Example 66 3- (6- (N, N-dimethylamino) hexyloxypyridyl) vinyl 1pyridine Three gas acetate MS (DCI / NH3) m / z 326 (M + H). 1 H NMR (DMSO-D6): δ 8.82 (d, 2H)? 8.49 (d, 1H), 8.33 (d, 1H) , 8.04 (d, 2H), 7.89 (d, 1H), 7.80 (t, 1H), 7.66 (d, 1H), 4.14 (t, 2H), 3.06-3.02 (m, 2H), 2.78 (s , 3H), 2.77 (s, 3H), 1.82-1.76 (m, 2H) 3 1.68-1.62 (m, 2H), L51-4.45 (m5 2H), 1.40-1.34 (m, 2H).

3-(2-硫代苯氧基-乙氧基比咬基）乙烯基比咬三氟醋酸鹽 MS (DCI/NH3) m/z 335 (M+H). 1H NMR (DMSO-d6 )： δ 8.76 (d5 2H), 8.46 (s3 1H), 8.27 (d, 1H), 7.93 (d, 1H), 7.80 (d3 1H), 7.77-7.74 (m, 2H), 7.59 (d5 1H), 7.43-742 (m3 1H), 736-7.31 (m，3H), 7.24-7.16 (m，1H), 4.33 (t，2H)，3.43 (t，2H)· 實例68 3-〇甲基-g-四氫吡咯基氧基）-542-(4-吡啶基）乙烯某減啶三氟醋酸鹽 -108- (101) MS (DCI/NH3) m/z 282 (M+H). 1 H NMR (DMSO-D6) : 5 8.75 (d，2H)，8·52 (s， 1H)，8·31 (d，1H)，7.88 (d，2H)，7.80-7.77 (m，2H)，7·57 (d，1H)，5·36-5·30 (m，1H)， 3.46-3,39 (m，1H)，3.23-3.15 (m，1H)，2.97-2.95 (m，1H)，2.91 (s，3H)，2.73-2.63 (m， 1H), 2.36-2.25 (m5 1H)? 2.17-2.09 (m, 1H). 實例69 3-「(l-甲基-2-六氫吡啶基）甲氣基l-5-「2-(4-吡啶基）乙烯某扣比啶三氟醋酸鹽 MS (DCI/NH3) m/z 310 (M+H). 1 H NMR (DMSO-d6) ： δ 8.81 (d? 2H)5 8.54-8.53 (m，1H)，8.40-8.38 (m，1H)，8·01-7·99 (m，2H)，7.91-7.85 (m，2Η)，7·64-7·59 (m，1H)， 4.55-4.52 (m, 1H), 4.38-4.31 (m, 1H), 3.71-3.62 (m, 1H), 3.55-3.45 (m, 1H), 3.35-3.23 (m，1H)，2.91 (s，3H)，2.88 (dt，1H)，2.10-L52 (m，5H)· 實例70 3-Π-吡啶基-乙氧基V5-『2-(44比啶基）乙烯基 >比淀三氟醋酸輮 MS (DCI/NH3) m/z 304 (M+H). 1 H NMR (DMSO-d6) 5 8.81 (d, 2H), 8.73 (d5 2H), 8.48 (s，1H)，8.34 (d，1H)，8.01 (d，1H)，7.85-7.81 (m，2H)，7·74 (d，2H)，7.57 (d，1H)， 5.89 (q，lH)，1.65 (d，3H). 實例71 4-{5-『(2S)-2-胺基-3-(1_ΐυ嗓-3-基V丙氣基1-吡啶-3-基某-草_3- (2-thiophenoxy-ethoxy group) vinyl group trifluoroacetate MS (DCI / NH3) m / z 335 (M + H). 1H NMR (DMSO-d6): δ 8.76 (d5 2H), 8.46 (s3 1H), 8.27 (d, 1H), 7.93 (d, 1H), 7.80 (d3 1H), 7.77-7.74 (m, 2H), 7.59 (d5 1H), 7.43- 742 (m3 1H), 736-7.31 (m, 3H), 7.24-7.16 (m, 1H), 4.33 (t, 2H), 3.43 (t, 2H) · Example 68 3-〇methyl-g-tetrahydro Pyrrolyloxy) -542- (4-pyridyl) ethene trifluoroacetate-108- (101) MS (DCI / NH3) m / z 282 (M + H). 1 H NMR (DMSO- D6): 5 8.75 (d, 2H), 8.52 (s, 1H), 8.31 (d, 1H), 7.88 (d, 2H), 7.80-7.77 (m, 2H), 7.57 (d , 1H), 5.36-5 · 30 (m, 1H), 3.46-3, 39 (m, 1H), 3.23–3.15 (m, 1H), 2.97-2.95 (m, 1H), 2.91 (s, 3H), 2.73-2.63 (m, 1H), 2.36-2.25 (m5 1H)? 2.17-2.09 (m, 1H). Example 69 3-"(l-methyl-2-hexahydropyridyl) methanyl l-5- "2- (4-pyridyl) ethene trifluoroacetate MS (DCI / NH3) m / z 310 (M + H). 1 H NMR (DMSO-d6): δ 8.81 ( d? 2H) 5 8.54-8.53 (m, 1H), 8.40-8.38 (m, 1H), 8.01-7 · 99 (m, 2H), 7.91-7.85 ( m, 2Η), 7.64-7 · 59 (m, 1H), 4.55-4.52 (m, 1H), 4.38-4.31 (m, 1H), 3.71-3.62 (m, 1H), 3.55-3.45 (m , 1H), 3.35-3.23 (m, 1H), 2.91 (s, 3H), 2.88 (dt, 1H), 2.10-L52 (m, 5H) · Example 70 3-Π-pyridyl-ethoxy V5- "2- (44 than pyridyl) vinyl group> Bidodotrifluoroacetate 輮 MS (DCI / NH3) m / z 304 (M + H). 1 H NMR (DMSO-d6) 5 8.81 (d, 2H) , 8.73 (d5 2H), 8.48 (s, 1H), 8.34 (d, 1H), 8.01 (d, 1H), 7.85-7.81 (m, 2H), 7.74 (d, 2H), 7.57 (d, 1H), 5.89 (q, 1H), 1.65 (d, 3H). Example 71 4- {5-『(2S) -2-amino-3- (1_ΐυTh-3-yl V propanyl 1-pyridine -3-yl-grass_

Oi三氟醋醢鳑實例71A 4^H(2S)-2-BOC胺基士(1HW丄兔各基v丙氫某]-吡啶-3-某μΝ-色^ 苯曱胱於實例22 (200毫克，0.43毫莫耳）在曱苯（7 〇毫升）與甲醇（〇 5 毫升）中之溶液内，添加羥胺鹽酸鹽（33毫克，〇·48毫莫耳） 200301122 (102) 與第三-丁醇鉀（54毫克，0.48毫莫耳），並將混合物於室溫及氮大氣下攪拌8小時。添加另一份羥胺鹽酸鹽（33毫克，0.48 毫莫耳）與第三-丁醇鉀（54毫克，0.48毫莫耳），並將混合物加熱至80°C ’歷經16小時。使混合物濃縮，並於碎膠上藉管柱層析純化，使用二氯甲烷/甲醇（15 : 1)作為溶劑系統。獲得130毫克（61% )產物，為白色粉末。 MS (DCI/NH3) m/z 487 (M-OH+2H).Oi Trifluoroacetamidine Example 71A 4 ^ H (2S) -2-BOC amino group (1HW 丄 rabbit groups v propyl hydrogen) -pyridine-3-some μN-color ^ phenylacetamide Example 22 (200 Mg, 0.43 mmol) in a solution of toluene (70 ml) and methanol (05 ml), hydroxylamine hydrochloride (33 mg, 0.48 mmol) was added 200301122 (102) and a third -Potassium butoxide (54 mg, 0.48 mmol) and stir the mixture at room temperature under nitrogen for 8 hours. Add another portion of hydroxylamine hydrochloride (33 mg, 0.48 mmol) with tertiary butane Potassium alkoxide (54 mg, 0.48 mmol) and the mixture was heated to 80 ° C. for 16 hours. The mixture was concentrated and purified by column chromatography on crushed gel using dichloromethane / methanol (15: 1) As a solvent system. 130 mg (61%) of the product was obtained as a white powder. MS (DCI / NH3) m / z 487 (M-OH + 2H).

實例71BExample 71B

4-{5-fX2S)-2-胺基嗓-3-基丙氧基1^比咬-3-基i-N-經基-苯甲脒三氣醋酸鹽所要之產物係經由以實例71Α取代實例22Β中之實例22Α而製成。MS (DCI/NH3 ) m/z 369 (Μ-ΝΗΟΗ)· 1H NMR (DMSO-d6) δ 11.02 (s，1Η)， 8.63 (d，1Η)，8.40 (d，1Η)，8·23 (bs，2Η)，8.01-7.91 (m，2Η)，7·85-7·79 (m，2Η), 7·71 (t，1H)，7.62 (d, 1H)，7·38 (d，1H)，7·29 (d，1H)，7·10 (t，1H)，7.01 (q，1H)，4·35 (dd， 1H), 4.19 (dd, 1H), 3.85-3.82 (m5 1H), 3.16 (m5 2H). 實例724- {5-fX2S) -2-Amino-3-ylpropoxy 1 ^ specific thio-3-yl iN-acyl-benzyltriazine triacetate The desired product is obtained by replacing Example 71A with Example 71A Example 22A of 22B was prepared. MS (DCI / NH3) m / z 369 (M-NΗΟΗ) · 1H NMR (DMSO-d6) δ 11.02 (s, 1Η), 8.63 (d, 1Η), 8.40 (d, 1Η), 8.23 (bs , 2Η), 8.01-7.91 (m, 2Η), 7.85-7 · 79 (m, 2Η), 7.71 (t, 1H), 7.62 (d, 1H), 7.38 (d, 1H) , 7.29 (d, 1H), 7.10 (t, 1H), 7.01 (q, 1H), 4.35 (dd, 1H), 4.19 (dd, 1H), 3.85-3.82 (m5 1H), 3.16 (m5 2H). Example 72

4-{5-「(2S)-2-胺基-3-ΠΗ-41嗓-3-基）-丙氧基比咬-3-基丨-苯甲腺三4- {5-"(2S) -2-Amino-3-ΠΗ-41a-3-yl) -propoxy-ratio-3-yl 丨 -benzylidene

氟醋酸鹽實例72A 4-{5-[(2S)-2-BOC-胺某-3-(lH-4l嗓-3-基）-丙乳基比咬-3-基卜笨甲脉^ 於實例71之產物（110毫克，0.22毫莫耳）在冰醋酸（5.0毫升）中之溶液内，添加醋酸酐（0.15毫升，1·6毫莫耳），並將混合物於環境溫度下攪拌2小時。藉由添加水（0.1毫升）使醋酸酐水解，添加10%鈀/炭（25毫克），並將混合物於氫大氣 -110- (103) (1大氣壓）下激烈攪拌4小時。將混合物經過矽藻土（Celite®) 墊片過濾，並將濾餅以醋酸洗滌。使合併之濾液於高真空中蒸發，並將殘留物以醋酸乙酯研製，而得80毫克（39% ) 產物，為米黃色粉末。 MS (DCI/NH3) m/z 486 (M+H). 1 H NMR (DMSO-d6) ： 6 10.93 (s，1H)，8.56 (s， 1H)，8·32 (d，1H)，7.93-7.88 (m，4H)，7.66 (s，1H)，7.57 (d，1H)，7.34 (d，1H)，7.17 (s，1H)，7.07-7.05 (m，2H)，6·96 (t，1H)，4.17-4.11 (m，2H)，4.09-4.05 (m，1H)，3·00 (dd，1H)，2.92 (dd，1H)，1.36 (s，9H).Example of Fluoroacetate 72A 4- {5-[(2S) -2-BOC-Amine-3- (lH-4lh-3-yl) -propionyl group than bityl-3-yl-methyl To a solution of the product of Example 71 (110 mg, 0.22 mmol) in glacial acetic acid (5.0 ml), acetic anhydride (0.15 ml, 1.6 mmol) was added, and the mixture was stirred at ambient temperature for 2 hours . The acetic anhydride was hydrolyzed by adding water (0.1 ml), 10% palladium / charcoal (25 mg) was added, and the mixture was vigorously stirred under a hydrogen atmosphere -110- (103) (1 atm) for 4 hours. The mixture was filtered through a Celite® pad and the filter cake was washed with acetic acid. The combined filtrate was evaporated in high vacuum and the residue was triturated with ethyl acetate to give 80 mg (39%) of the product as a beige powder. MS (DCI / NH3) m / z 486 (M + H). 1 H NMR (DMSO-d6): 6 10.93 (s, 1H), 8.56 (s, 1H), 8.32 (d, 1H), 7.93 -7.88 (m, 4H), 7.66 (s, 1H), 7.57 (d, 1H), 7.34 (d, 1H), 7.17 (s, 1H), 7.07-7.05 (m, 2H), 6.96 (t , 1H), 4.17-4.11 (m, 2H), 4.09-4.05 (m, 1H), 3.00 (dd, 1H), 2.92 (dd, 1H), 1.36 (s, 9H).

實例72B 4-{5-丨(2SV2-胺基-3-ΠΗ-啕哚-3-基）-丙氣基1-吡啶-3-基丨-笨甲脒三氟醋酸鹽所要之產物係經由以實例72A取代實例22B中之實例22A而製成。MS (DCI/NH3) m/z 386 (M+H)· 1 H NMR (DMSO-d6): 5 11·03 (s，1H)， 9.38 (s，2Η)，9.24 (s，2Η)，8.65 (d，1Η)，8.42 (d，1Η)，8·25 (bs，2Η)，8·00-7·94 (m，4Η)， 7·74 (t，1H)，7·62 (d，1H)，7.38 (d，1H)，7.29 (d，1H)，7.10 (t，1H)，7.01 (t，1H)，4.36 (dd，1H)，4.20 (dd，1H)，3.90-3.82 (m5 1H)，3.17 (m，2H)· 實例73 3-「(2S)-2-胺基-3-ΠΗ-3-啕哚基）-丙氣基1-6-(3-吡啶基）-喹啉所要之產物係經由以吡啶各二羥基硼烷取代實例43中之吡啶·4-二羥基硼烷而製成。MS (DCI/NH3 )111^ 395 (^1+1).1 H NMR (DMSO-d6) ： δ 10.89 (s ； 1H), 9.02 (s ； 1H), 8.72 (d ； J=3.0 Hz, 1H)? 8.62 (d ； J=5.0 Hz, 1H), 8.20 (d ； J=7.5 Hz, 1H), 8.15 (s ； 1H), 8.06 (d ； J=9.0 Hz, 1H), 7.95 (d; J=9.0 Hz，1H)，7.70 (s ; 1H)，7.59 (d; J=6.0 Hz，1H)，7·57 (m; 1H)，7.35 (d; J=8.4 Hz，1H)，7.22 (s; 1H)，7.06 (t; J=7.5 Hz，1H)，6.95 (t; J=7.5 Hz，1H)，4.05 (104) (m； 2H), 3.53 (m； 1H)? 3.01 (dd； J=6.3, 14.9 Hz, 1H), 2.87 (dd； J=6.9, 14.9 Hz, 1H) 實例74 3-『(2SV2-胺基-3-(lH-3-吲哚基V丙氧基1-6-(3-喳啉基啉所要之產物係經由以喹啉-3-二羥基硼烷取代實例43中之吡啶-4-二羥基硼烷而製成。MS (DCI/NH3 (DMSO-d6) ： (5 0.89 (s ; 1H)，9·49 (s ; 1H)，8·80 (s ; 1H)，8.74 (s ; 1H)，8·31 (s; 1H)，8.10 (m; 4H)，7.82 (t; J=6.6 Hz，1H)，7·73 (s; 1H)，7.69 (t; J=6.6 Hz，1H)， 7.49 (d； J=8.4Hz, lH),7.35(d； J=8.4 Hz, 1H), 7.23 (s ； 1H), 7.06 (t ； J=7.5 Hz, 1H)3 6.95 (t； J=7.5 Hz, 1H), 4.05 (m； 2H), 3.52 (m； 1H), 3.01 (dd； J=6.3, 14.9 Hz, 1H), 2.87 (dd ； J=6.9, 14.9 Hz, 1H). 實例75 ^：[(gS)-2-胺基-3-ΠΗ-3-4卜朵某V丙氧基l-5-「2-(2-胺基比咬某）乙烯Example 72B 4- {5- 丨 (2SV2-Amino-3-ΠΗ-amidin-3-yl) -propanyl 1-pyridin-3-yl 丨 -benzidine trifluoroacetate Example 72A was prepared in place of Example 22A in Example 22B. MS (DCI / NH3) m / z 386 (M + H) · 1 H NMR (DMSO-d6): 5 11 · 03 (s, 1H), 9.38 (s, 2Η), 9.24 (s, 2Η), 8.65 (d, 1Η), 8.42 (d, 1Η), 8.25 (bs, 2Η), 8.00-7.94 (m, 4Η), 7.74 (t, 1H), 7.62 (d, 1H), 7.38 (d, 1H), 7.29 (d, 1H), 7.10 (t, 1H), 7.01 (t, 1H), 4.36 (dd, 1H), 4.20 (dd, 1H), 3.90-3.82 (m5 1H), 3.17 (m, 2H) · Example 73 3-"(2S) -2-amino-3-ΠΗ-3-fluorinyl) -propanyl 1-6- (3-pyridyl) -quine The desired product was prepared by replacing the pyridine · 4-dihydroxyborane in Example 43 with pyridine dihydroxyborane. MS (DCI / NH3) 111 ^ 395 (^ 1 + 1). 1 H NMR ( DMSO-d6): δ 10.89 (s; 1H), 9.02 (s; 1H), 8.72 (d; J = 3.0 Hz, 1H)? 8.62 (d; J = 5.0 Hz, 1H), 8.20 (d; J = 7.5 Hz, 1H), 8.15 (s; 1H), 8.06 (d; J = 9.0 Hz, 1H), 7.95 (d; J = 9.0 Hz, 1H), 7.70 (s; 1H), 7.59 (d; J = 6.0 Hz, 1H), 7.57 (m; 1H), 7.35 (d; J = 8.4 Hz, 1H), 7.22 (s; 1H), 7.06 (t; J = 7.5 Hz, 1H), 6.95 (t; J = 7.5 Hz, 1H), 4.05 (104) (m; 2H), 3.53 (m; 1H)? 3.01 (dd; J = 6.3, 14.9 Hz, 1H), 2.87 (dd; J = 6.9, 14.9 Hz, 1H) Example 74 3-"(2SV2-amino-3- (lH-3-indolylVpropoxy1-6- (3-fluoroline The desired product of the quinoline was prepared by replacing the pyridine-4-dihydroxyborane in Example 43 with quinoline-3-dihydroxyborane. MS (DCI / NH3 (DMSO-d6): (5 0.89 (s 1H), 9.49 (s; 1H), 8.80 (s; 1H), 8.74 (s; 1H), 8.31 (s; 1H), 8.10 (m; 4H), 7.82 (t; J = 6.6 Hz, 1H), 7.73 (s; 1H), 7.69 (t; J = 6.6 Hz, 1H), 7.49 (d; J = 8.4Hz, lH), 7.35 (d; J = 8.4 Hz, 1H ), 7.23 (s; 1H), 7.06 (t; J = 7.5 Hz, 1H) 3 6.95 (t; J = 7.5 Hz, 1H), 4.05 (m; 2H), 3.52 (m; 1H), 3.01 (dd ; J = 6.3, 14.9 Hz, 1H), 2.87 (dd; J = 6.9, 14.9 Hz, 1H). Example 75 ^: [(gS) -2-amino-3-ΠΗ-3-4 Budow V Propoxyl-5- "2- (2-amino group)

某扣比啶三氟醋酸鹽實例75A 2-胺某-4-琪基口比咬將2-花香斗碘基吡啶（3·〇克，13.5毫莫耳）、乙醯基醯胺（15.8 克’ 269毫莫耳）及碳酸鉀（9.2克，67毫莫耳）之混合物，於⑽ C下攪拌7小時，倒入冰（1〇〇克）中，以醋酸乙酯萃取，以鹽水洗滌，脫水乾燥（MgS04)，過濾及濃縮。使濃縮物於矽膠上藉急驟式管柱層析純化，使用50%醋酸乙酯/己烷，提供標題化合物（u 克，37% )。MS(DCI/NH3)nl/e221 (m+h)Example of a certain ratio of pyridinium trifluoroacetate 75A 2-Amine-4-kikiyl ratio of 2-aminopyridine (3.0 g, 13.5 mmol), acetamidinium (15.8 g '269 millimoles) and potassium carbonate (9.2 g, 67 millimoles), stirred at 小时 C for 7 hours, poured into ice (100 grams), extracted with ethyl acetate, washed with brine, Dehydrate and dry (MgS04), filter and concentrate. The concentrate was purified on silica gel by flash column chromatography using 50% ethyl acetate / hexane to provide the title compound (u g, 37%). MS (DCI / NH3) nl / e221 (m + h)

實例75B 拉士雙（第三-丁氫某羰基）胺基冬破某毗咗將得自上述實例75A之產物（1·〇克，4.5毫莫耳）於THF (25毫Example 75B Russbis (third-butane carbonyl) amine tetrodepyrazine The product obtained from the above Example 75A (1.0 g, 4.5 mmol) was dissolved in THF (25 mmol

(105) 升）中之溶液，以1.0M LiHMDS (9.0毫升，9.0毫莫耳）逐滴處理 ’攪拌30分鐘，以二碳酸二-第三-丁酯（ι·96克，9.0毫莫耳）處理’並攪拌1小時。以水（1〇毫升）使混合物淬滅，溫熱至主溫’並以醋酸乙酯萃取。將合併之萃液以鹽水洗滌，脫水乾燥（MgS04)，過濾及濃縮。將濃縮物以1 : 1己烷/醋酸乙醋研製，提供所要之產物（1.〇克，53% )。MS (DCI/NH3)m/z421 (M+H).(105) liters), treated dropwise with 1.0 M LiHMDS (9.0 ml, 9.0 mmol) and stirred for 30 minutes with di-tertiary-butyl dicarbonate (ι · 96 g, 9.0 mmol) ) Process' and stir for 1 hour. The mixture was quenched with water (10 ml), warmed to main temperature 'and extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered and concentrated. The concentrate was triturated with 1: 1 hexane / ethyl acetate to provide the desired product (1.0 g, 53%). MS (DCI / NH3) m / z421 (M + H).

實例75C Ν,Ν-雙（第三-丁氣基羰某）胺基-4-乙烯基吡啶將得自上述實例75Β之產物（0.7克，1.67毫莫耳）、乙婦基三丁基錫（0.83克，2.6毫莫耳）及肆-(三苯膦）-鈀⑼(0.12克，0.11 毫莫耳）之混合物，於100°C下加熱6小時，冷卻至室溫，以醋酸乙酯（10毫升）處理，以鹽水洗滌，脫水乾燥（MgS04)，過濾及濃縮。使濃縮物於矽膠上藉急騾式管柱層析純化，使用20%醋酸乙酯/己烷，提供標題化合物（0.4克，75% )。 MS (DCI/NH3) m/e 321 (M+H).Example 75C Ν, Ν-bis (tertiary-butoxycarbonyl) amino-4-vinylpyridine will be obtained from the product of Example 75B (0.7 g, 1.67 mmol), triethyltin (0.83 G, 2.6 mmoles) and tris- (triphenylphosphine) -palladium europium (0.12 g, 0.11 mmoles), heated at 100 ° C for 6 hours, cooled to room temperature, and washed with ethyl acetate (10 Ml), washed with brine, dried (MgSO4), filtered and concentrated. The concentrate was purified on silica gel by flash column chromatography using 20% ethyl acetate / hexane to provide the title compound (0.4 g, 75%). MS (DCI / NH3) m / e 321 (M + H).

實例75D 3-f(2SV2-(N-第三-丁氣基羰基）胺基-3-ΠΗ-3-巧哚基V丙氧基1-5-企丨謦〔第三-丁氣基羰基）胺基-4-吡啶基1乙烯基丨吡啶所要之產物係經由以75C實例取代實例2B中之4_乙烯基外匕啶而製成。於矽膠上純化’以100%醋酸乙醋溶離’提供標題化合物（0.15 克，49% )。MS (DCI/NH3)m/e 685 (M+H)·Example 75D 3-f (2SV2- (N-Third-butyroylcarbonyl) amino-3-ΠΗ-3-carolinyl Vpropoxy 1-5-- ) Amino-4-pyridyl 1vinyl. The desired product of pyridine was prepared by substituting the 4-vinylexopyridine in Example 2B with a 75C example. Purification on silica ‘dissociated with 100% ethyl acetate’ provided the title compound (0.15 g, 49%). MS (DCI / NH3) m / e 685 (M + H)

實例75E 基弓 1 u朵-3-基丙氧基比淀-3-基卜乙躁基）- -113- (106)Example 75E 1-bend-3-ylpropoxy group Bid-3-ylb-ethoxy) -113- (106)

吡啶-2-基胺所要之產物係經由以實例75D取代實例2C中之實例邡而製成。於HPLC上純化，提供標題化合物（0.06克，70% )。 MS (DCI/NH3) m/e 386 (M+l). 1H NMR (DMSO-d6) ： 5 11.05 (s； 1H)? 8.50 (s; 1H)，8.35 (s; 1H)，8.23 (bs; 2H)，8.13 (bs; 2H)，7,95(d; J=6.3Hz，1H)，7.72 (s ; 1H)，7·65 (d ; J=15.9 Hz，1H)，7.61 (d ; J=6.3 Hz)，7.42 (d ; J=15.9 Hz，1H)， 7.38(d; J=6.9Hz，lH)，7.28(s; lH)，7.18(d; J=6.9Hz，lH)，7.10(t; J=6.9Hz， lH)，7.00(t; J=6.9Hz，1H)，6.93 (s; 1H)，4.29 (m; 1Η)，4·14(ιη; 1Η)，3·87 (m; lH)，3.17(m; 2H). 實例76 5-f(2SV2-(胺基-3-(lH-3-巧哚基）-丙氧基1-342-(2-胺篡-4-毗啶基）乙烯基1-2-氯-吡啶三氟醋酸鹽所要之產物係經由以3-溴基-2-氯基-5-羥基吡啶取代實例75 中之3-溴基-5-羥基吡啶而製成。MS (DCI/NH) m/e 420 (M+1)· 1 H NMR (DMSO-d6)： 5 11.05 (s； 1H), 8.21 (s ； 1H)5 8.21 (bs ； 2H)5 8.04 (bs ； 2H), 7.95 (d； J-6.3Hz51H),7.93(s； lH)37.61(d； J=6.3 Hz, 1H), 7.58 (d； J=15.9 Hz, 1H), 7.39 (d； J=15.9 Hz, 1H)3 7.39 (d； J=6.9 Hz, 1H)? 7.28 (s； 1H), 7.18 (d； J=6.9 Hz, lH),7.10(t； J=6.9 Hz, 1H), 7.00 (t ； J=6.9 Hz, 1H), 6.99 (s ； 1H), 4.32 (m ； 1H), 4.16 (m ； 1H), 3.87 (m ； lH),3.17(m； 2H). 實例77 (lS)-l-(lH-钊哚-3-基甲基）-2·(5-苯-2-基w比啶-3-基氣基）-乙胺所要之產物係經由以2-溴莕取代實例27中之6-溴基異喹啉而製成。111丽11((16-〇]\^〇,5001^1^)(5: 11.02 (s，1Η)，8.74 (s，1Η)， 8·38 (s，1H)，8·30 (s，1H)，8.18-8.21 (m，2H)，8.04 (d，J=8 Hz，1H)，7.97-8.01 (m，2H)， (107) 8.85(d，J=8Hz，lH)，7.81(s，lH)，7.62(d，J=8Hz，lH)，7.50-7.58 (m，lH)，7.35-7.39 (m，1H)，7·23-7·31 (m，1H)，7.08-7.12 (m，1H)，6.96-7.03 (m，2H)，4.18-4.41 (m， 2H)，3.82-3.87 (m，1H)，3.17-3.21 (m，2H). MS : (ESI) (M+H)+m/z = 394 實例78 (lS)-l-(lH-^哚-3-基甲基）-2-(5-異4。林-5-基^比啶-3-某氧基V乙胺實例78A 5-溴基異4 4 於5-胺基異喳啉（2.0克，13.8毫莫耳）與48% HBr (6毫升）在20 毫升水中，經冷卻至〇°C之溶液内，添加亞硝酸鈉（〇 95克， 13.8毫莫耳）於6毫升水中之溶液。將此溶液在下攪拌2〇分鐘。在使溶液保持於0°C下時，將其添加至CuBr (2.11克，15.9 耄莫耳）於48% ΗΒγ (4·77毫升）與水（1〇毫升）中之溶液内。將反應物在室溫下再攪拌1小時。以NaOH (50% )使反應中和，並以醋酸乙醋萃取（3X)。使合併之有機層於真空中濃縮，並層析，使用1 : 1己烷/醋酸乙酯，而得1.4克產物（50% )。Pyridin-2-ylamine The desired product was prepared by replacing Example VII in Example 2C with Example 75D. Purification on HPLC provided the title compound (0.06 g, 70%). MS (DCI / NH3) m / e 386 (M + 1). 1H NMR (DMSO-d6): 5 11.05 (s; 1H)? 8.50 (s; 1H), 8.35 (s; 1H), 8.23 (bs; 2H), 8.13 (bs; 2H), 7,95 (d; J = 6.3Hz, 1H), 7.72 (s; 1H), 7.65 (d; J = 15.9 Hz, 1H), 7.61 (d; J = 6.3 Hz), 7.42 (d; J = 15.9 Hz, 1H), 7.38 (d; J = 6.9Hz, lH), 7.28 (s; lH), 7.18 (d; J = 6.9Hz, lH), 7.10 ( t; J = 6.9Hz, lH), 7.00 (t; J = 6.9Hz, 1H), 6.93 (s; 1H), 4.29 (m; 1Η), 4.14 (ιη; 1Η), 3.87 (m lH), 3.17 (m; 2H). Example 76 5-f (2SV2- (amino-3- (lH-3-carolinyl) -propoxy1-342- (2-amine Pyridinyl) vinyl 1-chloro-pyridine trifluoroacetate The desired product is obtained by replacing the 3-bromo-5-hydroxy group in Example 75 with 3-bromo-2-chloro-5-hydroxypyridine Made from pyridine. MS (DCI / NH) m / e 420 (M + 1) · 1 H NMR (DMSO-d6): 5 11.05 (s; 1H), 8.21 (s; 1H) 5 8.21 (bs; 2H ) 5 8.04 (bs; 2H), 7.95 (d; J-6.3Hz51H), 7.93 (s; lH) 37.61 (d; J = 6.3 Hz, 1H), 7.58 (d; J = 15.9 Hz, 1H), 7.39 (d; J = 15.9 Hz, 1H) 3 7.39 (d; J = 6.9 Hz, 1H)? 7.28 (s; 1H), 7.18 (d; J = 6.9 Hz, lH), 7.10 (t; J = 6.9 Hz, 1H), 7.00 (t; J = 6.9 Hz, 1H), 6.99 (s; 1H), 4.32 (m; 1H), 4.16 (m; 1H), 3.87 (m; lH), 3.17 (m; 2H ). Example 77 (lS) -l- (lH-zolin-3-ylmethyl) -2 · (5-phenyl-2-yl w than pyridin-3-ylamino) -ethylamine Prepared by replacing 6-bromoisoquinoline in Example 27 with 2-bromofluorene. 111 M11 ((16-〇) \ ^ 〇, 5001 ^ 1 ^) (5: 11.02 (s, 1Η), 8.74 (s, 1Η), 8.38 (s, 1H), 8.30 (s, 1H), 8.18-8.21 (m, 2H), 8.04 (d, J = 8 Hz, 1H), 7.97-8.01 ( m, 2H), (107) 8.85 (d, J = 8Hz, lH), 7.81 (s, lH), 7.62 (d, J = 8Hz, lH), 7.50-7.58 (m, lH), 7.35-7.39 ( m, 1H), 7.23-7.31 (m, 1H), 7.08-7.12 (m, 1H), 6.96-7.03 (m, 2H), 4.18-4.41 (m, 2H), 3.82-3.87 (m , 1H), 3.17-3.21 (m, 2H). MS: (ESI) (M + H) + m / z = 394 Example 78 (lS) -l- (lH- ^ in-3-ylmethyl)- 2- (5-different 4. Lin-5-yl ^ bipyridin-3-ethoxy V ethylamine Example 78A 5-bromoiso4 4 in 5-aminoisophosphorin (2.0 g, 13.8 mmol) with 48% HBr (6 ml ) In 20 ml of water, after cooling to 0 ° C, a solution of sodium nitrite (0 95 g, 13.8 mmol) in 6 ml of water was added. This solution was stirred for 20 minutes. While keeping the solution at 0 ° C, it was added to a solution of CuBr (2.11 g, 15.9 mol) in 48% ΗΒγ (4.77 ml) and water (10 ml). The reaction was stirred for an additional hour at room temperature. The reaction was neutralized with NaOH (50%) and extracted with ethyl acetate (3X). The combined organic layers were concentrated in vacuo and chromatographed using 1: 1 hexane / ethyl acetate to give 1.4 g of product (50%).

實例78B (lS)-l-(lH-吲哚-3-基甲基）-2-(5-異崦啉-5-基-吡啶-3-某氣基乙胺所要之產物係經由以實例78A取代實例27中之6-溴基異喹啉而製成。MS (ESI) m/z 395 (M+H)+ ; 1H NMR (d6 -DMSO, 300 ΜΗζ) δ 11.02 (bs，1H)，9.53 (s，1H)，8.52 (d，J=8 Hz，1H)，8.49 (d，J=4 Hz，1H)，8·37 (d，J=3 Hz, 1H)，8.30-8.34 (m，1H)，8.15-8.19 (m，2H)，7.84-7.88 (m，2H)，7.68 (d5 J=8 Hz， 1H)，7.56-7.60 (m，2H)，7.47 (d，J=8 Hz，1H)，7.28 (d，J=4 Hz，1H)，7.60-7.12 (m，1H)， 6.94-6.99 (m，1H)，4.12-4.32 (m，2H)，3·82-3·87 (m，1H)，3.13-3.17 (m，2H)·Example 78B (lS) -l- (lH-indole-3-ylmethyl) -2- (5-isophosphon-5-yl-pyridine-3-a-aminoethylamine) The desired product is described by way of example. 78A was prepared in place of 6-bromoisoquinoline in Example 27. MS (ESI) m / z 395 (M + H) +; 1H NMR (d6 -DMSO, 300 ΜΗζ) δ 11.02 (bs, 1H), 9.53 (s, 1H), 8.52 (d, J = 8 Hz, 1H), 8.49 (d, J = 4 Hz, 1H), 8.37 (d, J = 3 Hz, 1H), 8.30-8.34 (m , 1H), 8.15-8.19 (m, 2H), 7.84-7.88 (m, 2H), 7.68 (d5 J = 8 Hz, 1H), 7.56-7.60 (m, 2H), 7.47 (d, J = 8 Hz , 1H), 7.28 (d, J = 4 Hz, 1H), 7.60-7.12 (m, 1H), 6.94-6.99 (m, 1H), 4.12-4.32 (m, 2H), 3.82-3 · 87 (m, 1H), 3.13-3.17 (m, 2H) ·

200301122 (108) 6-{5-「(25)-2-胺基-3-(1沁口弓卜朵-3-基）-丙氣基1-吡啶-3-基}-211-異喳啉- 1-酮所要之產物係經由以2- #呈基異p奎淋取代實例27中之6-溴基異喹啉而製成。MS(ESI)m/z411(M+H)+ ; iHNMRCDMSO-Dh 300 MHz) (5 1L30 (bs，1H)，11.04 (bs，1H)，8·66-8·68 (m，1H)，8.41 (d，J=3 Hz，1H)， 8.27 (d，J=8 Hz，1H)，8.17-8.20 (m，2H)，8.02-8.03 (m，1H)，7.76-7.81 (m，2H)，7.62 (d，J=8Hz，lH)，7.38(d，J=8Hz，lH)，7.29-7.31(m，lH)，7.20-7.26(m，lH)，7.07-7.12 (m，1H)，6.98-7.04 (m，1H)，6·60 (d，J=8 Hz，1H)，4.14-4.39 (m，2H)，3.33-3.38 (m，lH)，3.13-3.16(m，2H)·對 C25H22N40.2TFA之分析計算值：C，54.54 ;Η，3·78; N，8.78; F，17.86·實測值：C，54·54; Η，4·00; N，8.56; F，17.10. 實例80 (lS)-2-「5-(3-氯-異p奎琳-6-基Vp比咬-3-基氧基卜朵-3-基曱甚乙胺200301122 (108) 6- {5-"(25) -2-Amino-3- (1 Qinkoubudol-3-yl) -propanyl 1-pyridin-3-yl} -211-isoamidine The desired product of quinolin-1-one was prepared by substituting 6-bromoisoquinoline in Example 27 with 2- # for isoisoquinine. MS (ESI) m / z411 (M + H) +; iHNMRCDMSO-Dh 300 MHz) (5 1L30 (bs, 1H), 11.04 (bs, 1H), 8.66-8 · 68 (m, 1H), 8.41 (d, J = 3 Hz, 1H), 8.27 (d , J = 8 Hz, 1H), 8.17-8.20 (m, 2H), 8.02-8.03 (m, 1H), 7.76-7.81 (m, 2H), 7.62 (d, J = 8Hz, 1H), 7.38 (d , J = 8Hz, lH), 7.29-7.31 (m, lH), 7.20-7.26 (m, lH), 7.07-7.12 (m, 1H), 6.98-7.04 (m, 1H), 6.60 (d, J = 8 Hz, 1H), 4.14-4.39 (m, 2H), 3.33-3.38 (m, 1H), 3.13-3.16 (m, 2H) · Analysis and calculation of C25H22N40.2TFA: C, 54.54; Η, 3.78; N, 8.78; F, 17.86. Measured value: C, 54.54; Η, 4.00; N, 8.56; F, 17.10. Example 80 (lS) -2- "5- (3-chloro -Iso-p-quelin-6-yl-Vp

實例80A 6-溴-氫茚-1,2-二酮1-月亏使5->臭基-1-氫莽酮（1.8克，8.5毫莫耳）於乙醇（150毫升）中之溶液，冷卻至0°C，以亞硝酸第三-丁酯（2.1毫升）處理，在室溫下攪拌2小時，過濾，並以醚洗滌所要之產物。產率為 76%。MS(DCI/NH3)m/e242(M+l)+·Example 80A A solution of 6-bromo-hydroindene-1,2-dione 1-monthly depleted 5- > Stanyl-1-hydromonone (1.8 g, 8.5 mmol) in ethanol (150 ml) , Cooled to 0 ° C, treated with tert-butyl nitrite (2.1 ml), stirred at room temperature for 2 hours, filtered, and washed the desired product with ether. The yield was 76%. MS (DCI / NH3) m / e242 (M + l) + ·

實例80B 6-溴基-1,3-二氯-異4呲將實例80Α(1·5克，6.2毫莫耳）於P〇C13(40毫升）中之懸浮液 ’以PC15(L55克，7.4毫莫耳）處理，並引進HC1氣體，直到、、容液飽和。將反應物於60°C下攪拌6小時，在真空下濃一项。精 200301122 (109) 由添加水使殘留物慢慢水解，以醋酸乙酯（200毫升）處理，以鹽水洗滌，脫水乾燥（Mgs〇4),過濾及濃縮。使濃縮物於矽膠上藉急騾式管柱層析純化，使用1〇%醋酸乙酯/己烷，提供標題化合物（I·7 克，100% )。MS (Da/NH3)m/e278 (Μ+Η)+·Example 80B A suspension of Example 80A (1.5 g, 6.2 mmol) in PO13 (40 ml) was treated with PC15 (L55 g, 7.4 millimolars), and introduce HC1 gas until the liquid volume is saturated. The reaction was stirred at 60 ° C for 6 hours and concentrated under vacuum. Fine 200301122 (109) The residue was slowly hydrolyzed by adding water, treated with ethyl acetate (200 ml), washed with brine, dried (Mgs04), filtered and concentrated. The concentrate was purified on silica gel by flash column chromatography using 10% ethyl acetate / hexane to provide the title compound (1.7 g, 100%). MS (Da / NH3) m / e278 (Μ + Η) + ·

f 例 80C 氯-異4啉使實例80Β (1.8克，6·5毫莫耳）、ρ (〇·48克，15·5毫莫耳）及(3 毫升，48% )於醋酸（20毫升）中之混合物，回流8小時，在熱狀態下過濾，並於真空下濃縮。藉由添加氫氧化卸溶液使殘留物鹼化，以醋酸乙酯（200毫升）處理，以鹽水洗條，脫水乾燥（MgS〇4)，過濾及濃縮。使濃縮物於矽膠上藉夸、驟式管柱層析純化，使用30%醋酸乙酯/己烷，提供標題& 合物（0.81 克，50%)。MS(DCI/NH3)m/e244(M+H)+·f Example 80C Chloro-iso4-morpholine Example 80B (1.8 g, 6.5 mmol), ρ (0.48 g, 15.5 mmol) and (3 mL, 48%) in acetic acid (20 mL The mixture in) was refluxed for 8 hours, filtered under heat, and concentrated under vacuum. The residue was basified by adding a hydrogen hydroxide solution, treated with ethyl acetate (200 ml), washed with brine, dried (MgS04), filtered and concentrated. The concentrate was purified on silica gel by flash column chromatography using 30% ethyl acetate / hexane to provide the title compound (0.81 g, 50%). MS (DCI / NH3) m / e244 (M + H) + ·

實例80D 3-氣基-6-三甲基錫烷基-異4啉Example 80D 3-Gasyl-6-trimethylstannyl-isotetraline

所要之產物係經由以實例80C取代實例27A中之孓漠基異喹啉而製成。MS (DCI/NH3) m/e 327 (M+H)+.The desired product was prepared by substituting Example 80C for the isopropyl isoquinoline in Example 27A. MS (DCI / NH3) m / e 327 (M + H) +.

實例80E (lSH2-『5-(3-氯·異 4 啉-6-某吡啶二3-基氧基 H-〇H，乙某1-胺甲基酸第三-丁所要之產物係經由以實例80D取代實例27B中之實例27A而製成。MS (DCI/NH3) m/e 530 (M+H)+ ·Example 80E (1SH2- "5- (3-Chloroisoisophthaloline-6-pyridinedi-3-yloxy H-OH, ethyl 1-aminomethyl acid third-but Example 80D was prepared in place of Example 27A in Example 27B. MS (DCI / NH3) m / e 530 (M + H) + ·

實例80F (lSV2-「5-(3-氯-異崦琳-6-基：Kl味各基氧基HX1.斤吸 -117- (110) 乙胺’ 所要之產物係經由以實例80E取代實例27C中之實例27B而製成。MS(DCI/NHB)m/e429(M+l)+ ; 1H NMR (DMSO-D6 5 300 MHz) δ 11.04 (s ; 1Η)，9.28 (s ; 1H)，8.72 (s ; 1H)，8.44 (s ; 1H)，8.33 (s ; 1H), 8.32 (d ; 1H ; J=8.4 Hz)，8.17 (s ; 2H)，8.07 (s ; 1H)，8.05 (d ; 1H ; J=8.4 Hz)，7.80 (s ； lH),7.63(d； 1H； J=7.5 Hz), 7.48 (d ； 1H ； J=7.5 Hz), 7.30 (s ； 1H), 7.10 (t； 1H； J=7.2 Hz), 7.00 (t ； 1H ； J=7.2 Hz), 4.38 (m ； 1H), 4,20 (m ； 1H), 3.88 (m; lH)，3.18(m; 2H). 實例81 (15)-2-(「3,41聯吡啶净基氧基）-1-(1沁峭哚-3-基甲基）-乙胺三氟醋酸所要之產物係經由以4-三丁基錫烷基吡啶取代實例27中之實例 27A 而製成。MS(APCI)m/z345 (M+l)+ ; 1 H NMR (CD3 OD, 300 MHz) 5 8.85 (d, J=6.8 Hz, 2H), 8.73 (d, J=1.7 Hz, 1H), 8.53 (d51=2 J Hz, 1H), 8.20 (d, J=6.8 Hz, 2H)? 7.84 (t, J=1.7 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.38 (d5 J=8.2 Hz，1H)，7.24 (s，1H)，7.12 (t，J=6.8 Hz，1H)，7.01 (t，J=8.1 Hz，1H)，4·44 (dd，JN10.8, 3·4 Hz，1H)，4.30 (dd，J=10.5, 5.8 Hz，1H)，4·01 (m，1H)，3.33 (m，2H); 對（：21112(^40.2.7丁?八之分析計算值：（：，48.61;11，3.51;凡8.59· 實測值：C，48.69 ; H，3.50; Ν，8·46· 實例82 (1S)-1-(1H-吲哚-3-基甲基吡啶-2-基-乙烯基V吡啶-3-基氧基乙胺所要之產物係經由以2-乙烯基吡啶取代實例2中之4-乙烯基吡啶而製成。MS (APCI) m/z 371 (M+l)+ ; 1 H NMR (CD3 OD，300 MHz) 5 8.72 (d，J=5.5 Hz，1H)，8.55 (s，1H)，8.39 (d，J=2.4 Hz，1H)，8.34 (td，J=7.8,1·7 Hz，Example 80F (1SV2- "5- (3-Chloro-isoamylin-6-yl: Kl syloxy group HX1. Jin-117- (110) ethylamine 'The desired product was replaced by Example 80E 27C by Example 27B. MS (DCI / NHB) m / e429 (M + 1) +; 1H NMR (DMSO-D6 5 300 MHz) δ 11.04 (s; 1Η), 9.28 (s; 1H), 8.72 (s; 1H), 8.44 (s; 1H), 8.33 (s; 1H), 8.32 (d; 1H; J = 8.4 Hz), 8.17 (s; 2H), 8.07 (s; 1H), 8.05 (d ; 1H; J = 8.4 Hz), 7.80 (s; lH), 7.63 (d; 1H; J = 7.5 Hz), 7.48 (d; 1H; J = 7.5 Hz), 7.30 (s; 1H), 7.10 (t ; 1H; J = 7.2 Hz), 7.00 (t; 1H; J = 7.2 Hz), 4.38 (m; 1H), 4,20 (m; 1H), 3.88 (m; lH), 3.18 (m; 2H) Example 81 (15) -2-("3,41 Bipyridinyloxy) -1- (1Qindol-3-ylmethyl) -ethylamine trifluoroacetic acid Tributyltin alkylpyridine was prepared in place of Example 27A in Example 27. MS (APCI) m / z345 (M + 1) +; 1 H NMR (CD3 OD, 300 MHz) 5 8.85 (d, J = 6.8 Hz, 2H), 8.73 (d, J = 1.7 Hz, 1H), 8.53 (d51 = 2 J Hz, 1H), 8.20 (d, J = 6.8 Hz, 2H)? 7.84 (t, J = 1.7 Hz, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.3 8 (d5 J = 8.2 Hz, 1H), 7.24 (s, 1H), 7.12 (t, J = 6.8 Hz, 1H), 7.01 (t, J = 8.1 Hz, 1H), 4.41 (dd, JN10. 8, 3.4 Hz, 1H), 4.30 (dd, J = 10.5, 5.8 Hz, 1H), 4.01 (m, 1H), 3.33 (m, 2H); pair (21112 (^ 40.2.7 丁) ? The calculated value of the analysis: (:, 48.61; 11, 3.51; Where 8.59 · Found: C, 48.69; H, 3.50; Ν, 8.46 · Example 82 (1S) -1- (1H-indole- The desired product of 3-ylmethylpyridin-2-yl-vinylVpyridin-3-yloxyethylamine was prepared by substituting 4-vinylpyridine in Example 2 with 2-vinylpyridine. MS (APCI) m / z 371 (M + l) +; 1 H NMR (CD3 OD, 300 MHz) 5 8.72 (d, J = 5.5 Hz, 1H), 8.55 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 8.34 (td, J = 7.8,1.7 Hz,

(Ill) 1H)，8.12 (d，J=8.2 Hz，1H)，7.88 (t，J=1.7 Hz，1H)，7·82 (d，J=16.3 Hz，1H)，7.74 (t， J=6.7 Hz，1H)，7·59 (d，J=7.8 Hz，1H)，7·53 (d，J=16.3 Hz，1H)，7·38 (d，J=8.1 Hz， 1H)，7.24 (s，1H)，7·12 (td，J=7.1, 1.0 Hz，1H)，7.03 (td，J=7.1，1.0 Hz，1H)，4.41 (tt， J=10.5, 3·4 Hz，1H)，4.27 (dd，J=10.5, 5·5 Hz，1H)，4.00 (m，1H)，3.33 (m，2H);對 C23H22N40.3.8TFA 之分析計算值·· C，45.73 ; H，3·24 ; N，6.97·實測值：C，45.60 ; H，3·34 ; N，6·86. 實例83 (lS)-l-(lH-W哚-3-基甲基）-2-(5-吡啶-3-基乙炔基-吡啶-3-基氧基）- 乙胺三氟醋酸鹽(Ill) 1H), 8.12 (d, J = 8.2 Hz, 1H), 7.88 (t, J = 1.7 Hz, 1H), 7.82 (d, J = 16.3 Hz, 1H), 7.74 (t, J = 6.7 Hz, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 16.3 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.24 ( s, 1H), 7 · 12 (td, J = 7.1, 1.0 Hz, 1H), 7.03 (td, J = 7.1, 1.0 Hz, 1H), 4.41 (tt, J = 10.5, 3.4 Hz, 1H) , 4.27 (dd, J = 10.5, 5.5 Hz, 1H), 4.00 (m, 1H), 3.33 (m, 2H); Analytical calculated value for C23H22N40.3.8TFA · C, 45.73; H, 3 · 24; N, 6.97. Found: C, 45.60; H, 3.34; N, 6.86. Example 83 (lS) -l- (lH-Win-3-ylmethyl) -2- (5 -Pyridin-3-ylethynyl-pyridin-3-yloxy) -ethylamine trifluoroacetate

所要之產物係經由以3-溴基吡啶取代實例14中之4-溴基吡啶而製成。MS(APCI)m/z367(M-l：T ; iHNMRfDsODJOOMHz) δ 8·80 (s，1Η)，8.62 (br d，J=4.7 Ηζ，1Η)，8.42 (s，1Η)，8·36 (d，J=2.7 Ηζ，1Η)，8.12 (dt，J=8.2, 1.7 Hz，1H)，7.60 (m，3H)，7,39 (d，J=8.1 Hz，1H)，7.22 (s，1H)，7.14 (td， J=7.1, 1.4 Hz, 1H), 7.04 (td, J=8.25 1.1 Hz, 1H), 4.33 (dd? J=10.5, 3.0 Hz, 1H), 4.19 (dd, J=10.5, 5.4 Hz, 1H), 3.97 (m, 1H), 3.29 (m, 2H)；對 C2 3 H2 〇N4 O · 3.0TFA 之分析計算值：C，49.02 ; H, 3.26 ; N，7.89.實測值：C，48.86 ; H，3.14 ；N, 8.01. 實例84 (18)-2-「5-(2-耽-口比淀-4-基乙決基）-p比淀-3-基氧基丨嗓-3-基甲基乙胺三氟醋酸鹽所要之產物係經由以4-碘基-2-氟基吡啶取代實例14中之4-溴基吡啶而製成。MS (APCI) m/z 385 (M-l)-; 1 H NMR (CD3 OD，300 MHz) 5 8.42 (d，J=1.4 Hz，1H)，8·38 (d，J=2.7 Hz，1H)，8·26 (d，J=5.1 Hz，1H)，7·61 (dd， 2·7, 1.7 Hz，1H)，7.58 (d，J=7.8 Hz，1H)，7·43 (dt，J=5.1，1.7 Hz，1H)，7.38 (d，J二8.1 2〇〇3〇1i?9 **- w ς^.The desired product was prepared by replacing 4-bromopyridine in Example 14 with 3-bromopyridine. MS (APCI) m / z367 (Ml: T; iHNMRfDsODJOOMHz) δ 8 · 80 (s, 1Η), 8.62 (br d, J = 4.7 Ηζ, 1Η), 8.42 (s, 1Η), 8.36 (d, J = 2.7 Ηζ, 1Η), 8.12 (dt, J = 8.2, 1.7 Hz, 1H), 7.60 (m, 3H), 7,39 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 7.14 (td, J = 7.1, 1.4 Hz, 1H), 7.04 (td, J = 8.25 1.1 Hz, 1H), 4.33 (dd? J = 10.5, 3.0 Hz, 1H), 4.19 (dd, J = 10.5, 5.4 Hz, 1H), 3.97 (m, 1H), 3.29 (m, 2H); Analytical calculated values for C2 3 H2 ON4O · 3.0TFA: C, 49.02; H, 3.26; N, 7.89. Measured value: C , 48.86; H, 3.14; N, 8.01. Example 84 (18) -2- "5- (2-Dan-Kapido-4-ylethoxy) -p-Kido-3-yloxy The desired product of 3-ylmethylethylamine trifluoroacetate was prepared by replacing 4-bromopyridine in Example 14 with 4-iodo-2-fluoropyridine. MS (APCI) m / z 385 (Ml)-; 1 H NMR (CD3 OD, 300 MHz) 5 8.42 (d, J = 1.4 Hz, 1H), 8.38 (d, J = 2.7 Hz, 1H), 8.26 (d, J = 5.1 Hz, 1H), 7.61 (dd, 2 · 7, 1.7 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.43 (dt, J = 5.1, 1.7 Hz, 1H), 7.38 (d, J 2: 8.1 20003i? 9 **- w ς ^.

(112) HZ，1H)，7.23 (m，2H)，7.13 (td，J=7.1, 1·3 Hz，1H)，7·04 (td，J=7.8, 1·3 Hz，1H)，4.33 (dd5 J=l〇.5, 3.4 Hz, 1H), 4.18 (dd, J=10.5, 5.8 Hz, 1H), 3.97 (m> iH), 3.30 (m5 2H)；對 C23H19FN4CN2.3TFA之分析計算值：C，5Ll〇; η，3·31; Ν，8·64· 實測值：C，51.06 ; H，3·32 ; N，8.69· 實例85 (lS)-4-{5-「2-胺基口木-3-基）-丙乳基1-口比咬-3-基乙快基卜口比啶-2-醇三氟醋酸鹽將N-BOC保護之實例84 (45毫克，0.093毫莫耳））於醋酸（5毫升）中之溶液，在801下加熱15小時，且於l〇〇°c下5小時。使溶液濃縮，並使殘留油溶於CH2C12(5毫升）中。於〇°C下添加三氟醋酸（1.25毫升）。將溶液在0°C下攪拌10分鐘，並於室溫下30分鐘，並濃縮。使殘留物質於HPLC (Zorbax，C-18)上純化，提供標題化合物（15毫克，33% )。MS (APCI)m/z383 (M-l)_ ;^NMR^OD^OOMHz) δ 8.40 (s, 1H), 8.36 (d, J=2.3 Hz, 1H), 7.58 (m, 2H)，7.46 (d，J=6.8 Hz，1H)，7.39 (d，J=8.2 Hz，1H)，7.22 (s，1H)，7.14 (td，J=7.1，1·0 Hz，1H)，7·03 (td，J=8.2, 1·1 Hz，1H)，6.69 (brs，1H)，6.46 (dd，J=6.8, 1.7 Hz，1H)， 4.32 (dd，J=10.5, 3·4 Hz，1H)，4.18 (dd，J=10.5, 5.8 Hz，1H)，3.98 (m，1H)，3·34 (m， 2H). 實例86 (1SV246-氣基-5·(1·氣-異崦啉-6·基）-吡啶-3-基氧基哚-3- 某甲基V乙胺三氟醋酸鹽標題化合物係經由以實例13A取代實例27中之實例2A，並以實例80D取代實例27中之實例27八而製成。MS (APCI) m/z 464 (M+l)+ ; 1H NMR (CD3 OD, 300 MHz) δ 8.44 (d5 J=8.8 Hz, 1H), 8.31 (d, J= -120- (113) 5·8 Hz，1H)，8.22 (d，J=3.1 Hz，1H)，8.03 (d，J二 1·7 Hz，1H)，7.84 (m，2H)，7·57 (dt，J= 7.8, 1.0 Hz, 1H), 7.53 (d? J=3.0 Hz, 1H), 7.34 (d3 J=7.2 Hz, 1H), 7.22 (s, 1H), 7.10 (td5 J=7.2, 1.4 Hz，1H)，7.01 (td，J=7.7, 1·0 Hz，1H)，4,36 (dd，J=10.5, 3.0 Hz，1H)，4.22 (dd，J=10.5, 5.7 Hz，1H)，3·97 (m，1H)，3.27 (m，2H);對 C2 5 H2 0 Cl2 N4 O · 2.05 TFA 之分析計算值：C，50]4 ; Η，3·19 ; Ν，8·04·實測值：C，50.16 ;H，3.03 ; Ν，7·88. 實例87 雙-[3-(4-漠苯基）-烯丙基1-丨2-[~5-(2-外1：淀-4-基-乙烯基比症-3-基氧基1-乙基丨-胺鹽酸鹽標題化合物係得自實例19D中之較低極性產物（5.3毫克，3 % )。MS (DCI/NH3) m/z 630, 632, 634 (Μ+Η)+ ; 1 H NMR (CDCI3，300 MHz) (5 8·62 (m，2Η)，8·36 (s，1Η)，8·26 (d，J=2.7 Hz, 1Η)，7.0-7.5 (m，13Η)，6·52 (m，2Η)， 6.35 (m，2H)，4.25 (m，2H)，3.49 (m，4H)，3.08 (m，2H). 實例88 N4-[3-(2-胺基-乙氧基苯基1-p密淀-2Λ-二胺鹽酸鹽標題化合物係經由以N-Boc-胺基乙醇取代實例20中之BOC-色胺酸而製成。MS(DCI/NH3)m/z246(M+l)+ ; 1HNMR(DMSO-d6, 300 MHz) δ 12·4 (br s，1Η)，11·0 (br s，1Η)，8·26 (br，5Η)，7·86 (d，J=7.1 Ηζ，1Η)， 7·55 (m，1H)，7.44 (m，1H)，7·31 (t，J=8,l Hz，1H)，6.79 (d，J=8.1 Hz，1H)，6.46 (d，J= 7.1 Ha，1H)，4·22 (t，J=5.1 Hz，2H)，3.22 (m，2H)· 實例89 反式-「4-(2-{5-「(2SV2-胺基-3-ΠΗ-峭哚-3-基V丙胺基V吡啶-3-基}-乙烯基）嘧啶-2-基1-胺甲基酸乙酯三氟醋酸鹽(112) HZ, 1H), 7.23 (m, 2H), 7.13 (td, J = 7.1, 1.3 Hz, 1H), 7.04 (td, J = 7.8, 1.3 Hz, 1H), 4.33 (dd5 J = 10.5, 3.4 Hz, 1H), 4.18 (dd, J = 10.5, 5.8 Hz, 1H), 3.97 (m > iH), 3.30 (m5 2H); Analytical calculated value for C23H19FN4CN2.3TFA : C, 5L10; η, 3.31; N, 8.64. Found: C, 51.06; H, 3.32; N, 8.69. Example 85 (lS) -4- {5- "2-amine Benzyl-3-yl) -Prolactyl 1-methylpyridyl-3-ylpyridyl-2-pyridyl-2-ol trifluoroacetate Example of protecting N-BOC 84 (45 mg, 0.093 mmol) Mol)) solution in acetic acid (5 ml), heated at 801 for 15 hours, and at 100 ° C for 5 hours. The solution was concentrated and the residual oil was dissolved in CH2C12 (5 ml). Trifluoroacetic acid (1.25 ml) was added at 0 ° C. The solution was stirred at 0 ° C for 10 minutes, and at room temperature for 30 minutes, and concentrated. The residue was purified by HPLC (Zorbax, C-18), Provide the title compound (15 mg, 33%). MS (APCI) m / z383 (Ml) _; ^ NMR ^ OD ^ OOMHz) δ 8.40 (s, 1H), 8.36 (d, J = 2.3 Hz, 1H), 7.58 (m, 2H), 7.46 (d, J = 6.8 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.22 (s, 1H), 7.14 (td, J = 7.1, 1.0 Hz, 1H), 7.03 (td, J = 8.2, 1.1 Hz, 1H ), 6.69 (brs, 1H), 6.46 (dd, J = 6.8, 1.7 Hz, 1H), 4.32 (dd, J = 10.5, 3.4 Hz, 1H), 4.18 (dd, J = 10.5, 5.8 Hz, 1H), 3.98 (m, 1H), 3.34 (m, 2H). Example 86 (1SV246-Gasyl-5 · (1 · Gas-Isophosphorin-6 · yl) -pyridin-3-yloxy Indole-3- a methyl V ethylamine trifluoroacetate title compound was prepared by replacing Example 2A in Example 27 with Example 13A and replacing Example 27A in Example 27 with Example 80D. MS (APCI) m / z 464 (M + l) +; 1H NMR (CD3 OD, 300 MHz) δ 8.44 (d5 J = 8.8 Hz, 1H), 8.31 (d, J = -120- (113) 5 · 8 Hz, 1H) , 8.22 (d, J = 3.1 Hz, 1H), 8.03 (d, J = 1.7 Hz, 1H), 7.84 (m, 2H), 7.57 (dt, J = 7.8, 1.0 Hz, 1H), 7.53 (d? J = 3.0 Hz, 1H), 7.34 (d3 J = 7.2 Hz, 1H), 7.22 (s, 1H), 7.10 (td5 J = 7.2, 1.4 Hz, 1H), 7.01 (td, J = 7.7 , 1.0 Hz, 1H), 4,36 (dd, J = 10.5, 3.0 Hz, 1H), 4.22 (dd, J = 10.5, 5.7 Hz, 1H), 3.97 (m, 1H), 3.27 ( m, 2H); Analysis of C2 5 H2 0 Cl2 N4 O · 2.05 TFA Calculated: C, 50] 4; Η, 3.19; Ν, 8.04. Found: C, 50.16; H, 3.03; Ν, 7.88. Example 87 Bis- [3- (4- Mobenzene Group) -Allyl 1- 丨 2- [~ 5- (2-External 1: Yodo-4-yl-vinyl ratio-3-yloxy 1-ethyl 丨 -amine hydrochloride) Obtained from the less polar product from Example 19D (5.3 mg, 3%). MS (DCI / NH3) m / z 630, 632, 634 (M + Η) +; 1 H NMR (CDCI3, 300 MHz) (5 8 · 62 (m, 2Η), 8.36 (s, 1Η), 8 · 26 (d, J = 2.7 Hz, 1Η), 7.0-7.5 (m, 13Η), 6.52 (m, 2Η), 6.35 (m, 2H), 4.25 (m, 2H), 3.49 (m, 4H), 3.08 (m, 2H). Example 88 N4- [3- (2-Amino-ethoxyphenyl 1-p dense lake-2Λ-diamine hydrochloride The title compound was prepared via N-Boc- Aminoethanol was produced in place of BOC-tryptophan in Example 20. MS (DCI / NH3) m / z246 (M + 1) +; 1HNMR (DMSO-d6, 300 MHz) δ 12 · 4 (br s, 1Η), 11.0 (br s, 1Η), 8.26 (br, 5Η), 7.86 (d, J = 7.1 Ηζ, 1Η), 7.55 (m, 1H), 7.44 (m, 1H ), 7.31 (t, J = 8, 1 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.46 (d, J = 7.1 Ha, 1H), 4.22 (t, J = 5.1 Hz, 2H), 3.22 (m, 2H). Example 89 trans- "4- (2- {5-" (2SV2-amino-3-ΠΗ-achido-3-yl V-propylamino V-pyridine- 3-yl} -vinyl) pyrimidin-2-yl 1-aminomethyl acetate ethyl trifluoroacetate

實例89A (114) 200301122Example 89A (114) 200301122

1全胺基淀將5-溴-p比淀-3-#甲總：山、、 · （ 36耄克，2.34毫莫耳）與2_胺基j甲基口备咬（246晕克，215古笔旲耳）於曱酸（96% , 3亳升）中之溶液加熱18小時。於冷卻 w 衫益並甘王至/m後，接者將其以水稀釋，並以INNaOH鹼化至pH〜13 〇 ^ 然後，將混合物以二氯甲烷萃取將口併之萃液以水洗滌（1X)，以MgS〇4脫水乾燥及濃縮。1 All-amino-based lakes will be 5-bromo-p than yodo-3- # A total: Shan ,, · (36 g, 2.34 mmol) and 2-amino-J methyl mouth preparation (246 halo, 215 Gu Bi Er) heated in a solution of acetic acid (96%, 3 liters) for 18 hours. After cooling the shirt, and then diluting it to / m, it was diluted with water and alkalized with INNaOH to pH ~ 13. Then, the mixture was extracted with dichloromethane, and the extracted solution was washed with water. (1X), dried over MgS04 and concentrated.

使殘留物於々膠上層析’以CH2Cl2: MeOH: NH4〇H(觸·· 5: 0.5)溶離’而得標題化合物（463毫克，7i% )。ms(dci細 279 (M+l)+.The residue was chromatographed on a gelatin 'dissolved in CH2Cl2: MeOH: NH4OH (touch · 5: 0.5)' to give the title compound (463 mg, 7i%). ms (dci fine 279 (M + l) +.

實例89B 基1-2-「雙（第三-丁氣.基）胺某扣嘧珐將實例 89Α(439 毫克，L58 毫莫耳）、（B〇C)2〇(1〇4〇克，4 77 笔莫耳）、DMAP (50毫克，〇·4ΐ毫莫耳）及三乙胺（67〇微升4 81 笔莫耳）於丁HF (10毫升）中之懸浮液，在室溫下攪拌過夜。使反應物濃縮，並於矽膠上層析，以Ac〇Et ••己烷（1 ··丨）溶離’而得標題化合物（511 毫克，68% )。MS(DCI/NH3)m/z477,479 (M+1)·Example 89B Based on 1-2- "bis (tertiary-butane.yl) amine, a certain pyrimide, Example 89A (439 mg, L58 mmol), (BOC) 20 (104 g), A suspension of 4 77 pen moles), DMAP (50 mg, 0.4 μmol) and triethylamine (67 μl of 4 81 pen moles) in DHF (10 ml) at room temperature Stir overnight. The reaction was concentrated, chromatographed on silica gel, and dissolved with AcOH • hexane (1 ·· 丨) to give the title compound (511 mg, 68%). MS (DCI / NH3) m / z477,479 (M + 1) ·

實例89C 呈_立_-44(5-胺基比淀-3-基乙烯基1-2-(第三-丁氧談基）胺基-p密症根據實例51步驟4與5中所述之程序，使實例89B轉化成標題化合物。MS (DCI/NH3) m/z 314 (M+l)+ ·Example 89C presents Li-44 (5-aminopyridine-3-ylvinyl 1- 2- (tertiary-butoxy) amino-p-dense) according to Example 51, steps 4 and 5 Procedure to convert Example 89B to the title compound. MS (DCI / NH3) m / z 314 (M + 1) + ·

實例89D ΚΛ -[4-(2-{5-「(2SV2-胺基-3-ΠΗ-41哚各基上丙胺基1-吡啶-3-基[乙烯基V嘧啶-2-基V胺甲基酸乙酯三氟醋酸鹽 -122- 200301122 (115) 標題化合物係經由以實例89C取代實例11中之實例11B而製成。（DCI/NH3) m/z 458 (M+lf; NMR (DMSO-d6): 5 8.58 (d5 J=5.3 Hz, 1H)， 8.17 (s，1H)，7.91 (d，J=2.2 Hz，1H)，7.75 (d，J=15.9 Hz，1H)，7.58 (m，1H)，7.35 (m， 2H)，7·32 (s，1H)，7·22 (d，J=5.3 Hz，1H)，7.15 (d，J=15.9 Hz，1H)，7·11 (m，1H)，7.04 (m，1H)，4·28 (q，J=7.2 Hz，2H)，3.80 (m，1H)，3.62 (dd，J=4.4, 14.7 Hz，1H)，3·50 (dd， J=8.1，14.7 Hz，1H)，3·20 (m，2H)，1.35 (t，J=7.2 Hz，3H)· 〆實例90 1-胺基-6]5-f(2S)-2-胺基巧哚-3-基V丙氧基V吡啶-3-某μ異4Example 89D κΛ- [4- (2- {5-"(2SV2-amino-3-ΠΗ-41 indole on each base propylamino 1-pyridin-3-yl [vinyl Vpyrimidin-2-yl V amine methyl Ethyl trifluoroacetate-122- 200301122 (115) The title compound was prepared by replacing Example 11B in Example 11 with Example 89C. (DCI / NH3) m / z 458 (M + lf; NMR (DMSO -d6): 5 8.58 (d5 J = 5.3 Hz, 1H), 8.17 (s, 1H), 7.91 (d, J = 2.2 Hz, 1H), 7.75 (d, J = 15.9 Hz, 1H), 7.58 (m , 1H), 7.35 (m, 2H), 7.32 (s, 1H), 7.22 (d, J = 5.3 Hz, 1H), 7.15 (d, J = 15.9 Hz, 1H), 7.11 ( m, 1H), 7.04 (m, 1H), 4.28 (q, J = 7.2 Hz, 2H), 3.80 (m, 1H), 3.62 (dd, J = 4.4, 14.7 Hz, 1H), 3.50 (dd, J = 8.1, 14.7 Hz, 1H), 3.20 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H) · Example 90 1-amino-6] 5-f (2S) -2-Aminoquinol-3-yl V-propoxy V-pyridine-3-some μ iso-4

淋三氟醋酸鹽實例90Α 6->臭基-1-氯基異口奎口林Trifluoroacetate Example 90A 6- > Styrol-1-chloroisoisoquinone

將6-溴基小羥基異喹啉（9.205克，41.0毫莫耳）於p〇Cl3 (100毫升）中之溶液，加熱至l〇〇°C，歷經4小時。使反應物濃縮至乾涸。使殘留物溶於醋酸乙酯中，並將有機層以5% NaHC03 、水、鹽水洗滌，以MgS04脫水乾燥及濃縮。使殘留物於矽膠上層析，以CH2C12 :己烷（3: 7)溶離，而得標題化合物（6.176 克，62%)。MS(DCI/NH3)m/z241，243 (M+l)+·A solution of 6-bromo small hydroxyisoquinoline (9.205 g, 41.0 mmol) in POCl3 (100 mL) was heated to 100 ° C for 4 hours. The reaction was concentrated to dryness. The residue was dissolved in ethyl acetate, and the organic layer was washed with 5% NaHC03, water, and brine, dried over MgS04, and concentrated. The residue was chromatographed on silica gel and dissolved in CH2C12: hexane (3: 7) to give the title compound (6.176 g, 62%). MS (DCI / NH3) m / z241,243 (M + l) + ·

實例90B 1-胺基臭基異峻g林將得自實例90A之氯化物（264毫克，1.09毫莫耳）、乙醯胺（1.3 克）及K2CO3(0.45克）之混合物，加熱至18〇°C，歷經5小時。於冷卻至室溫後，使混合物溶於醋酸乙酯中，將其以水、鹽水洗滌，以MgS04脫水乾燥及濃縮。使殘留物於矽膠上層析，以 CH2C12 : MeOH : NH4OH(100 : 5 ·· 0.5)溶離，而得標 -123- 200301122Example 90B 1-Aminylisoamylglycinate A mixture of the chloride (264 mg, 1.09 mmol), acetamide (1.3 g), and K2CO3 (0.45 g) from Example 90A was heated to 18 ° C ° C over 5 hours. After cooling to room temperature, the mixture was dissolved in ethyl acetate, which was washed with water and brine, dried over MgS04 and concentrated. The residue was chromatographed on silica gel and dissolved with CH2C12: MeOH: NH4OH (100: 5 · 0.5) to obtain the standard -123- 200301122

(116) 題化合物（159 毫克，65% )。MS(DCI/NH3)m/Z223,225 (M+l)+·(116) The title compound (159 mg, 65%). MS (DCI / NH3) m / Z223,225 (M + l) + ·

實例90CExample 90C

1-『(雙（第三-丁氧羰基胺基-6-溴某異，杏毗將實例 90B (616 亳克，2.76 亳莫耳）、B0C20 (1.81 克）、DMAP (67 毫克）及三乙胺（U5毫升）於乙腈（15毫升）中之溶液，在室溫下攪拌2小時。使反應物濃縮，並使殘留物於矽膠上層析，以AcOEt :己烷（3 : 7)溶離，而得標題化合物（U8克，71% ) 0 MS (DCI/NH3) m/z 423 (M+l)+·1-"(bis (tertiary-butoxycarbonylamino-6-bromo-iso-iso, apricots, Example 90B (616 g, 2.76 mol), B0C20 (1.81 g), DMAP (67 mg), and three A solution of ethylamine (U5 ml) in acetonitrile (15 ml) was stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was chromatographed on silica gel and dissolved in AcOEt: hexane (3: 7) To give the title compound (U8 g, 71%) 0 MS (DCI / NH3) m / z 423 (M + l) + ·

實例90D 1-胺基-6-{5-[X2S)-2-胺基丨噪-3-基）-丙氧基l-ΐ?比淀-3-基丨-異口奎啉三氟醋酸鹽Example 90D 1-Amino-6- {5- [X2S) -2-Amino-1-Nano-3-yl) -propoxyl-pyridine-3-yl 丨 -isoquinolline trifluoroacetic acid salt

標題化合物係經由以實例90C取代實例32中之6-溴基鄰苯二甲醯亞胺而製成。MS(DCI/NH3)m/z410(M+l)+; iHNMRpMSO-de， 300 MHz) 5 8.77 (s，1H)，8.55 (d，J=8.6 Hz，1H)，8.45 (d，J=2.5 Hz，1H)，8.20 (d，J= 1.5 Hz，1H)，8.05 (dd，J=1.8, 8.6 Hz，1H)，7.83 (dd，J=1.8, 2,5 Hz，1H)，7·61 (m，2H)， 7.38 (d，J=7.1 Hz，1H)，7.24 (s，1H)，7·12 (m，1H)，7·02 (m，1H)，4.44 (dd，J=3.1， 10·4 Hz，1H)，4.30 (dd，J=5.8, 10·4 Hz，1H)，4.01 (m，1H)，3·32 (m，2H). 實例91 6-{5-[(2S)-2-胺基吲哚-3-基）-丙氣某1-吡啶-3-基M-氯-異4啉三氟醋酸鹽標題化合物係經由以實例90A取代實例32中之6-溴基鄰苯二曱醯亞胺而製成。1^(£31)111/2429,431 (1^+1)+;111丽11(〇]\430- d6, 300 MHz) 5 11.03 (br s，1H)，8·75 (d，J=1.6 Hz，1H)，8.47 (d，JN1.6 Hz，1H)， 8.45 (d, J=5.6 Hz, 1H), 7.84 (m, 1H), 7.62 (d3 J=8.1 Hz, 1H), 7.39 (d5 J=8.1 Hz, 1H)? -124- 200301122The title compound was prepared by substituting 6-bromophthalimidine in Example 32 with Example 90C. MS (DCI / NH3) m / z410 (M + 1) +; iHNMRpMSO-de, 300 MHz) 5 8.77 (s, 1H), 8.55 (d, J = 8.6 Hz, 1H), 8.45 (d, J = 2.5 Hz, 1H), 8.20 (d, J = 1.5 Hz, 1H), 8.05 (dd, J = 1.8, 8.6 Hz, 1H), 7.83 (dd, J = 1.8, 2, 5 Hz, 1H), 7.61 (m, 2H), 7.38 (d, J = 7.1 Hz, 1H), 7.24 (s, 1H), 7.12 (m, 1H), 7.02 (m, 1H), 4.44 (dd, J = 3.1 , 10 · 4 Hz, 1H), 4.30 (dd, J = 5.8, 10 · 4 Hz, 1H), 4.01 (m, 1H), 3.32 (m, 2H). Example 91 6- {5-[( 2S) -2-Aminoindol-3-yl) -propanyl 1-pyridin-3-yl M-chloro-iso4line trifluoroacetate The title compound was prepared by substituting 6- Made from bromo-o-phthalimide. 1 ^ (£ 31) 111 / 2429,431 (1 ^ + 1) +; 111Li 11 (〇) \ 430- d6, 300 MHz) 5 11.03 (br s, 1H), 8.75 (d, J = 1.6 Hz, 1H), 8.47 (d, JN1.6 Hz, 1H), 8.45 (d, J = 5.6 Hz, 1H), 7.84 (m, 1H), 7.62 (d3 J = 8.1 Hz, 1H), 7.39 ( d5 J = 8.1 Hz, 1H)? -124- 200301122

(117) 7·31 (d，J=2.2 Hz，1H)，7.10 (m，1H)，7.01 (m，lH)，4.38 (dd，J=3.1，10.6 Hz，1H)， 4.22 (dd，J=6.2, 10.4 Hz，1H)，3.88 (m，1H)，3.18 (m，2H). 實例92 (2SV2-胺基-3-ΠΗ-吲哚-3-基VN45-(2-吡啶-4-基-乙烯基V吡啶-3-某1- 丙醯胺標題化合物係經由以Boc-色胺酸取代實例16中之Boc-高苯基丙胺酸而製成。MS(DCI/NH3)m/z384(M+l)+ ; iHNMRpMSO-dG，(117) 7.31 (d, J = 2.2 Hz, 1H), 7.10 (m, 1H), 7.01 (m, lH), 4.38 (dd, J = 3.1, 10.6 Hz, 1H), 4.22 (dd, J = 6.2, 10.4 Hz, 1H), 3.88 (m, 1H), 3.18 (m, 2H). Example 92 (2SV2-amino-3-Πfluorene-indol-3-yl VN45- (2-pyridine-4- -Vinyl-V-pyridine-3-a 1-propanamidinide The title compound was prepared by replacing Boc-homophenylalanine in Example 16 with Boc-tryptophan. MS (DCI / NH3) m / z384 (M + 1) +; iHNMRpMSO-dG,

300 MHz) δ 11.37 (s, 1Η), 11.05 (s, 1H), 8.88 (d5 J=6.44 Hz, 2H), 8.74 (m, 2H)? 8.42 (m，1H)，8.35 (s，1H)，8.22 (d，J=6.10 Hz，2H)，8.02 (d，J=16.61 Hz，1H)，7.71 (d，J= 7.80 Hz, 1H), 7.56 (d, J=16.27 Hz, 1H), 7.36 (d, J=7.80 Hz, 1H), 7.30 (m, 1H), 7.07 (m，1H)，6.95 (m，1H)，4·31 (m，1H)，3·36 (m，2H). 實例93 (2S)-2-胺基-3-(奈-1-基VN-f5-(2-p比淀-4-基-乙婦基）-p比淀-3_基V丙酿胺鹽酸鹽300 MHz) δ 11.37 (s, 1Η), 11.05 (s, 1H), 8.88 (d5 J = 6.44 Hz, 2H), 8.74 (m, 2H)? 8.42 (m, 1H), 8.35 (s, 1H), 8.22 (d, J = 6.10 Hz, 2H), 8.02 (d, J = 16.61 Hz, 1H), 7.71 (d, J = 7.80 Hz, 1H), 7.56 (d, J = 16.27 Hz, 1H), 7.36 ( d, J = 7.80 Hz, 1H), 7.30 (m, 1H), 7.07 (m, 1H), 6.95 (m, 1H), 4.31 (m, 1H), 3.36 (m, 2H). Examples 93 (2S) -2-amino-3- (naphthalen-1-yl VN-f5- (2-p ratio lake-4-yl-ethynyl) -p ratio lake-3_yl V-propylamine Acid salt

標題化合物係經由以Boo-3-(l-莕基）丙胺酸取代實例16中之 Boc-高苯基丙胺酸而製成。MS (DCI/NH3 )1^395 (1^+1)+)^^11 (DMSO-d63 500 MHz) δ 11.86 (s, 1H), 8.90 (d, J=6.86 Hz, 2H), 8.78 (m, 1H), 8.85 (m, 1H), 8.58 (m, 1H), 8.45 (m, 1H)? 8.26 (d, J=6.86 Hz, 2H), 8.04 (d, J=16.53 Hz, 1H)，7.89 (m，2H) 7.84 (m，1H)，7·60 (d，J=16.53 Hz，1H)，7·58 (m，1H)，7.49 (m，2H)， 4.53 (m, 1H)，3.49 (m，1H)，3·36 (m，1H). 實例94 (2SV2-胺基-3-苯基-N-[~5-(2-吡啶-4-基-乙烯基V吡啶各基1-丙醯胺鹽酸鹽標題化合物係經由以Boo-苯丙胺酸取代實例16中之Boc-高 -125- (118)The title compound was prepared by replacing Boc-homophenylalanine in Example 16 with Boo-3- (l-fluorenyl) alanine. MS (DCI / NH3) 1 ^ 395 (1 ^ + 1) +) ^^ 11 (DMSO-d63 500 MHz) δ 11.86 (s, 1H), 8.90 (d, J = 6.86 Hz, 2H), 8.78 (m , 1H), 8.85 (m, 1H), 8.58 (m, 1H), 8.45 (m, 1H)? 8.26 (d, J = 6.86 Hz, 2H), 8.04 (d, J = 16.53 Hz, 1H), 7.89 (m, 2H) 7.84 (m, 1H), 7.60 (d, J = 16.53 Hz, 1H), 7.58 (m, 1H), 7.49 (m, 2H), 4.53 (m, 1H), 3.49 (m, 1H), 3.36 (m, 1H). Example 94 (2SV2-amino-3-phenyl-N- [~ 5- (2-pyridin-4-yl-vinylVpyridine each 1 -Alanine hydrochloride The title compound was obtained by substituting Boo-Phenylalanine for Boc-High-125- in Example 16 (118)

苯基丙胺酸而製成。MS (DCI/NH3) m/z 345 (M+l)+ ; 1 H NMR (DMS0-d6, 500 MHz) 5 11.85 (s，1H)，8.93 (m，2H) 8·53 (m，2H)，8·49 (m，1H)，8·29 (m，2H)， 8.07 (d，J=16.22 Hz，1H)，7.63 (d，JN16.53 Hz，1H) 7.32 (m，5H)，4.44 (m，1H)，3·24 (m, 2H) 實例95 S-2-脖基-3-(咪咬-4-基VN-「5-(2-?比咬-4-基-乙烯基）-p比淀-3-基1-丙醯胺鹽酸鹽標題化合物係經由以雙（Boc)-組胺酸取代實例16中之Boc-高苯基丙胺酸而製成。MS (DCI/NH3) m/z 335 (M+l) V H NMR (DMSO-D6， 300 MHz) 5 10.95 (s，1H)，9.04 (s，1H)，8·74 (m，1H)，8.70 (m，1H)，8.52 (m，2H) 8.32 (m，1H) 8.08 (m，2H)，7.93 (d，J=16.61 Hz，1H)，7.50 (m，2H)，4.50 (m，1H)， 3.33 (m，2H)· 實例96 (lR)-2-(lH-啕哚各基異崦啉-6-基吡啶·3-基）氣基1甲基丨乙胺標題化合物係經由以R-Boc-色胺酸取代實例27中之L-Boc-色胺酸，以三氟醋酸鹽製成。MS(ESI)m/e395 (M+H)+ ; bNMR (DMSO-D6,300 MHz) δ 11.02 (br s, 1H), 9.52 (s, 1H), 8.76 (d, J=3 Hz, 1H), 8.62 (d3 J=8 Hz, 1H), 8.44-8.46 (m, 2H), 8.38 (d, J-9 Hz, 1H), 8.11-8.20 (m, 3H), 8.04-8.08 (m，1H)，7·83-7·86 (m，1H)，7.62 (d，J=9 Hz，1H)，7.37-7.40 (m，1H)，7.31 (d， J=3 Hz，1H)，7.08-7.12 (m，1H)，6.99-7.03 (m，1H)，4.37-4.41 (m，1H)，4·18-4·23 (m， 1H)，3·86-3·91 (m，1H)，3.16-3.20 (m，2H);對 C25H22N40 · 2.65TFA 之分析計算值：C，52.24 ; Η，3·57 ; N，8.04 ;·實測值：C，52.26 ; Η，3·70 ; N, 7.42. 實例97 -126- (119) 200301122Made from phenylalanine. MS (DCI / NH3) m / z 345 (M + l) +; 1 H NMR (DMS0-d6, 500 MHz) 5 11.85 (s, 1H), 8.93 (m, 2H) 8.53 (m, 2H) , 8.49 (m, 1H), 8.29 (m, 2H), 8.07 (d, J = 16.22 Hz, 1H), 7.63 (d, JN16.53 Hz, 1H) 7.32 (m, 5H), 4.44 (m, 1H), 3.24 (m, 2H) Example 95 S-2-neckyl-3- (imid-4-yl VN- "5- (2-? The title compound was prepared by substituting Boc-homophenylalanine in Example 16 with bis (Boc) -histamine. MS (DCI / NH3) m / z 335 (M + 1) VH NMR (DMSO-D6, 300 MHz) 5 10.95 (s, 1H), 9.04 (s, 1H), 8.74 (m, 1H), 8.70 (m, 1H) ), 8.52 (m, 2H) 8.32 (m, 1H) 8.08 (m, 2H), 7.93 (d, J = 16.61 Hz, 1H), 7.50 (m, 2H), 4.50 (m, 1H), 3.33 (m , 2H) · Example 96 (lR) -2- (lH-pyridinyl isopyridin-6-ylpyridine · 3-yl) amino 1methyl 丨 ethylamine The title compound was prepared by R-Boc-color Amino acid replaced L-Boc-tryptophan acid in Example 27 and was made from trifluoroacetate. MS (ESI) m / e395 (M + H) +; bNMR (DMSO-D6,300 MHz) δ 11.02 (br s, 1H), 9.52 (s, 1H), 8.76 (d, J = 3 Hz, 1H), 8.6 2 (d3 J = 8 Hz, 1H), 8.44-8.46 (m, 2H), 8.38 (d, J-9 Hz, 1H), 8.11-8.20 (m, 3H), 8.04-8.08 (m, 1H), 7.83-7.86 (m, 1H), 7.62 (d, J = 9 Hz, 1H), 7.37-7.40 (m, 1H), 7.31 (d, J = 3 Hz, 1H), 7.08-7.12 ( m, 1H), 6.99-7.03 (m, 1H), 4.37-4.41 (m, 1H), 4.18-4 · 23 (m, 1H), 3.86-3 · 91 (m, 1H), 3.16 -3.20 (m, 2H); Analytical calculated value for C25H22N40 · 2.65TFA: C, 52.24; Η, 3.57; N, 8.04; · Found: C, 52.26; Η, 3.70; N, 7.42. Example 97 -126- (119) 200301122

基胺Amine

f 例 97A 基-5-(二^^錫燒某」^ 代實例27A中所要之產物係經由以5-溴基-2-氟基苯甲猜取之6- >臭基異峻琳而製成。f Example 97A group-5- (Di ^ sintered tin) ^^ The desired product in Example 27A was obtained via 6- > production.

實例97B ⑽:仰分氰基I氟苯幻兔支土基哚各某甲基 i基1-胺甲某醢竿二·二所要之產物係經由以實例97A取代實例2祀中之實例27A而製成。Example 97B ⑽: Yang cyano I fluorobenzyl rabbit branched soil indole each methyl i-l-amino methyl a certain pole two · two desired product was replaced by Example 97A Example 27A in Example 2 and production.

實例97C ag>.[2-丨5-(3_胺碁u峻·5·基）-说啶士羞某甲基）-乙基v胺甲基酸第三-丁所將實例97B (120毫克，0.25毫莫耳）與98%肼（5毫升）之混合物’加熱至回流5小時’傾倒於冰上，以鹽水稀釋，以醋酸乙酯萃取，以MgS〇4脫水乾燥，及濃縮。藉急驟式層析 _ 純化（7% MeOH/O^Cl2)，提供所要之產物（103毫克，84% )。Example 97C ag >. [2- 丨 5- (3-Amine 峻 · 5 · yl) -saidrimidine a methyl) -ethyl v amine methyl acid third-butyrate Example 97B (120 A mixture of milligrams, 0.25 millimoles) and 98% hydrazine (5 mL) was 'heated to reflux for 5 hours' and poured onto ice, diluted with brine, extracted with ethyl acetate, dried over MgS04, and concentrated. Purification by flash chromatography (7% MeOH / O ^ Cl2) provided the desired product (103 mg, 84%).

實例97D (lS)-5-{5-「2-胺基g朵-3-基)-丙氣基l-p比咬各基峻各基胺所要之產物係經由以實例97C取代實例27C中之實例27B，以三氟醋酸鹽製成。MS (ESI) m/e 399 (M+H)+ ; 1 H NMR (DMSO-D6， 300 MHz) 5 3.17 (d，：Κ7·12 Hz，2H) 3·84 (m，1H) 4.18 (dd，J=10.51，5·76 Hz，1H) -127,Example 97D (lS) -5- {5-``2-Aminogado-3-yl) -propanyl lp ratio The desired product was obtained by substituting Example 97C for Example 27C 27B, made of trifluoroacetate. MS (ESI) m / e 399 (M + H) +; 1 H NMR (DMSO-D6, 300 MHz) 5 3.17 (d ,: K7 · 12 Hz, 2H) 3 · 84 (m, 1H) 4.18 (dd, J = 10.51, 5.76 Hz, 1H) -127,

200301122 (120) 4·36 (m，1Η) 7· 12 (m，4H) 7.30 (d，J=2.37 Hz，1Η) 7·38 (m，m) 7.42 (s，1H) 7.63 (d， JN7.46 Hz，1H) 7.66 (s，1H) 8.18 (m，4H) 8.32 (d，J=2.71 Hz，1H) 8.57 (d，J=1.70 Hz， 1H) 11.04 (s，1H) 11.92 (bs，1H);對 C23H22N60 · 2.9TFA 之分析計算值 :C，47.44 ; H，3.44 ; N，11.53 ;.實測值·· C，47.87 ; Η，3·49 ; N，11.19· 實例98 (1SV6-丨542-胺基吲哚-3-基）-丙氧基1-吡啶-3-基}-1Η-吲唑-3- 基胺所要之產物係經由以4-溴基-2-氟基苯甲腈取代實例97中之 5-溴基-2-氟基苯曱腈，以三氟醋酸鹽製成。MS (ESI) m/e 399 (M+H)+ ; 1 H NMR (DMSO-D6，300 MHz) δ 3.16 (d，J=5.42 Hz，2H) 3·91 (d，J= 30.85 Hz，1H) 4.19 (s，1H) 4.35 (m，1H) 7.07 (m，2H) 7.34 (m，3H) 7.63 (m，2H) 7.71 (s3 1H) 7.88 (d, J=8.14 Hz, 1H) 8.17 (s, 4H) 8.37 (d, J=2.37 Hz, 1H) 8.60 (d, J= 1·36Ηζ，1H) 11.03 (s，1H) 11.93 (bs，1H);對 C23H22N60 · 3.5TFA 之分析計算值：C，45·18 ; H，3.22; N，10.54, F，25.01;實測值：C，44.83 ; Η，3·19 ;N，10.40, F，25.01. 實例99 2-肤基jvK(lS)-HlH_4l哚-3-墓甲基V2-(5·異4啉-6-基-外1:啶-3-基氣200301122 (120) 4.36 (m, 1Η) 7.12 (m, 4H) 7.30 (d, J = 2.37 Hz, 1Η) 7.38 (m, m) 7.42 (s, 1H) 7.63 (d, JN7 .46 Hz, 1H) 7.66 (s, 1H) 8.18 (m, 4H) 8.32 (d, J = 2.71 Hz, 1H) 8.57 (d, J = 1.70 Hz, 1H) 11.04 (s, 1H) 11.92 (bs, 1H); Analytical calculations for C23H22N60 · 2.9TFA: C, 47.44; H, 3.44; N, 11.53; measured values · C, 47.87; Η, 3.49; N, 11.19. Example 98 (1SV6- 丨542-Aminoindol-3-yl) -propoxyl-pyridin-3-yl} -1H-indazol-3-ylamine The desired product is via 4-bromo-2-fluorobenzyl Nitrile was substituted for 5-bromo-2-fluorobenzonitrile in Example 97, and was made from trifluoroacetate. MS (ESI) m / e 399 (M + H) +; 1 H NMR (DMSO-D6, 300 MHz) δ 3.16 (d, J = 5.42 Hz, 2H) 3.91 (d, J = 30.85 Hz, 1H ) 4.19 (s, 1H) 4.35 (m, 1H) 7.07 (m, 2H) 7.34 (m, 3H) 7.63 (m, 2H) 7.71 (s3 1H) 7.88 (d, J = 8.14 Hz, 1H) 8.17 (s , 4H) 8.37 (d, J = 2.37 Hz, 1H) 8.60 (d, J = 1.36Ηζ, 1H) 11.03 (s, 1H) 11.93 (bs, 1H); Analytical calculation for C23H22N60 · 3.5TFA: C , 45 · 18; H, 3.22; N, 10.54, F, 25.01; Found: C, 44.83; Η, 3.19; N, 10.40, F, 25.01. Example 99 2-Skin-based jvK (lS) -HlH_4l Indole-3-methylmethyl V2- (5.iso4-line-6-yl-exo 1: pyridin-3-yl gas

基V乙基V乙醯胺實例99A {[(ί?)ι1.:(1Η-吸?木-3-基甲基）-2-(5-異π套琳-6-基比症-3-基氧基V乙羞..肢甲查基1-甲基丨-胺甲某酸第三-丁酯將實例27C(175毫克，〇·35毫莫耳）、义B〇c-甘胺酸（91毫克， 0.52 毫莫耳）、EDC (1〇〇毫克）、ipr2EtN (0,30 毫升）及 DMAP (10 毫克）於CH2 C12 (7毫升）中之溶液，於室溫下攪捽過夜，以Et〇Ac 200301122Examples of methyl Vethyl V acetamidine 99A {[(ί?) Ι1.: ((1Η-sapium-3-ylmethyl) -2- (5-isoπtaolin-6-base ratio-3 -Yloxy V ethoxylate: acylchalcyl 1-methyl 丨 -carbamic acid tert-butyl ester Example 27C (175 mg, 0.35 mmol), Boc-glycine A solution of acid (91 mg, 0.52 mmol), EDC (100 mg), ipr2EtN (0,30 ml) and DMAP (10 mg) in CH2 C12 (7 ml) was stirred overnight at room temperature To Et〇Ac 200301122

(121) 稀釋，以水及鹽水洗滌，脫水乾燥（MgS〇4)，過濾及濃縮。使殘田物於矽膠上藉急驟式管柱層析純化，使用甲醇 / CH2C12 ’提供所要之產物（112亳克，58% )。實例99§ 1联_基基甲基}2-(5_異口杳，株各基比啶_3_篡i 基）-乙基]-乙醯脖所要之產物係經由以實例99A取代實例27C中之實例27B , 以二氟醋酸鹽製成。MS (ESI) m/e 452 (M+H)+ ; 1H NMR (DMSO-D6， 300 MHz) δ ppm 3.07 (m, 2H) 3.58 (m, 2H) 4.22 (m, 2H) 4.48 (m, 1H) 6.97 (t, J= 6·95 Hz，1H) 7.06 (t，J=6.95 Hz，1H) 7.21 (d，J=2.37 Hz，1H) 7.34 (d，J=8.14 Hz，1H) 7.64 (d, J=7.46 Hz, 1H) 7.86 (m, 1H) 7.99 (bs, 2H) 8.13 (d5 J=6.10 Hz, 1H) 8.19 (dd5 J=8.82, 1.70 Hz, 1H) 8.42 (m, 2H) 8.51 (s3 1H) 8.64 (d, J=6.10 Hz, 1H) 8.67 (d, J= 7·80Ηζ，lH)8.74(d，J=1.70Hz，1H)9.60(s，1H) 10.88(s，1H);對 C27H25N502 • 2.9TFA之分析計算值：C，50.37; Η，3·60; N，8.95;實測值：C，50.59 ;H，3.43 ; N，8·83· 實例100(121) Diluted, washed with water and brine, dried (MgS04), filtered and concentrated. The residue was purified by flash column chromatography on silica gel using methanol / CH2C12 'to provide the desired product (112 g, 58%). Example 99§ 1-Methylmethyl} 2- (5_isomethylpyridine, each bispyridinyl_3_methylidyl) -ethyl] -acetamidine The desired product was replaced by Example 99A Example 27B in 27C is made of difluoroacetate. MS (ESI) m / e 452 (M + H) +; 1H NMR (DMSO-D6, 300 MHz) δ ppm 3.07 (m, 2H) 3.58 (m, 2H) 4.22 (m, 2H) 4.48 (m, 1H ) 6.97 (t, J = 6.95 Hz, 1H) 7.06 (t, J = 6.95 Hz, 1H) 7.21 (d, J = 2.37 Hz, 1H) 7.34 (d, J = 8.14 Hz, 1H) 7.64 (d , J = 7.46 Hz, 1H) 7.86 (m, 1H) 7.99 (bs, 2H) 8.13 (d5 J = 6.10 Hz, 1H) 8.19 (dd5 J = 8.82, 1.70 Hz, 1H) 8.42 (m, 2H) 8.51 ( s3 1H) 8.64 (d, J = 6.10 Hz, 1H) 8.67 (d, J = 7.80Ηζ, lH) 8.74 (d, J = 1.70Hz, 1H) 9.60 (s, 1H) 10.88 (s, 1H); Analytical calculation for C27H25N502 • 2.9TFA: C, 50.37; Η, 3.60; N, 8.95; Found: C, 50.59; H, 3.43; N, 8.83. Example 100

(2S)-2-胺基-N-「(lSVl-(lH-4丨嗓-3-基曱基）-2-(5-異邊琳-6-基-p比淀-3· 基乳基）-乙基V丙酿胺所要之產物係經由以L-Boc-丙胺酸取代實例99中之N-Boc-甘胺酸而製成。MS(ESI)m/e466 (M+H)+ ; iHNME^DMSO-DyOOMHz) δ 1.36 (d, J=6.86 Hz, 3H) 3.09 (m, 2H) 3.88 (m, 1H) 4.35 (m, 2H) 4.46 (m, 1H) 6.97 (t，J=7.33 Hz，1H) 7.05 (t，J=7.33 Hz，1H) 7.29 (d，J=1.87 Hz，1H) 7·35 (d，J=8.11 Hz， 1H) 7.66 (d，J=7.80 Hz，1H) 8·30 (s，1H) 8.34 (bs，2H) 8.47 (dd，J=8.74, 1·56 Hz，1H) 8.53 (d，J=6.55 Hz，1H) 8·62 (d，J=1.87 Hz，1H) 8·70 (d，J=6.74, 1H) 8·75 (d，J=6.24, -129- (122)(2S) -2-Amino-N-"(lSVl- (lH-4 丨 Horan-3-ylfluorenyl) -2- (5-Isoporim-6-yl-p The desired product was obtained by substituting L-Boc-alanine for N-Boc-glycine in Example 99. MS (ESI) m / e466 (M + H) + ; iHNME ^ DMSO-DyOOMHz) δ 1.36 (d, J = 6.86 Hz, 3H) 3.09 (m, 2H) 3.88 (m, 1H) 4.35 (m, 2H) 4.46 (m, 1H) 6.97 (t, J = 7.33 Hz, 1H) 7.05 (t, J = 7.33 Hz, 1H) 7.29 (d, J = 1.87 Hz, 1H) 7.35 (d, J = 8.11 Hz, 1H) 7.66 (d, J = 7.80 Hz, 1H) 8.30 (s, 1H) 8.34 (bs, 2H) 8.47 (dd, J = 8.74, 1.556 Hz, 1H) 8.53 (d, J = 6.55 Hz, 1H) 8.62 (d, J = 1.87 Hz , 1H) 8.70 (d, J = 6.74, 1H) 8.75 (d, J = 6.24, -129- (122)

1H) 8·89 (s，1H) 8.93 (s，1H) 9.01 (d，J=8.11 Hz，1H) 9·99 (s，1H) 10·98 (s，1H) 實例101 2-二曱胺基-N-IY1SVH1H-吲哚-3-基甲基）-2-(5-異4啉-6-基-吡啶-3- 某氳基乙基1-乙醯胺所要之產物係經由以N，N-二甲基甘胺酸取代實例99A中之 N-Boc-甘胺酸而製成。MS (ESI) m/e 480 (M+H)+ ; 1H NMR (DMSO-D6， 500 MHz) 5 2.71 (s，3H) 2·77 (s，3H) 3·10 (m，2H) 3·95 (m，2H) 4.40 (m，2H) 4·52 (m，1H) 6.97 (t，J=7.33 Hz，1H) 7.05 (t，J=7.49 Hz，1H) 7·28 (s，1H) 7.34 (d，J=8.11 Hz，1H) 7.67 (d，J=7.80 Hz，1H) 8·38 (s，1H) 8.50 (d，J=8.73 Hz，1H) 8.55 (d，J=6.24 Hz，1H) 8.67 (d，J=1.87 Hz，1H) 8.71 (d，J=8.73 Hz，1H) 8.75 (d，J=6.55 Hz，1H) 8.92 (s, 1H) 8.98 (s, 1H) 9.34 (d, J=8.42 Hz, 1H) 10.00 (s, 1H) 1L02 (s, 1H). 實例102 吲嗓-3-基曱基）-2-「5-Γ3-甲基-1H-叻1也-5-基W比啶-3-基氣1H) 8.89 (s, 1H) 8.93 (s, 1H) 9.01 (d, J = 8.11 Hz, 1H) 9.99 (s, 1H) 10 · 98 (s, 1H) Example 101 2-Difluorenamine -N-IY1SVH1H-indol-3-ylmethyl) -2- (5-iso4-line-6-yl-pyridine-3- some fluorenylethyl 1-acetamido , N-dimethylglycine was substituted for N-Boc-glycine in Example 99A. MS (ESI) m / e 480 (M + H) +; 1H NMR (DMSO-D6, 500 MHz) 5 2.71 (s, 3H) 2.77 (s, 3H) 3 · 10 (m, 2H) 3.95 (m, 2H) 4.40 (m, 2H) 4.52 (m, 1H) 6.97 (t, J = 7.33 Hz, 1H) 7.05 (t, J = 7.49 Hz, 1H) 7 · 28 (s, 1H) 7.34 (d, J = 8.11 Hz, 1H) 7.67 (d, J = 7.80 Hz, 1H) 8 · 38 (s, 1H) 8.50 (d, J = 8.73 Hz, 1H) 8.55 (d, J = 6.24 Hz, 1H) 8.67 (d, J = 1.87 Hz, 1H) 8.71 (d, J = 8.73 Hz, 1H) 8.75 (d, J = 6.55 Hz, 1H) 8.92 (s, 1H) 8.98 (s, 1H) 9.34 (d, J = 8.42 Hz, 1H) 10.00 (s, 1H) 1L02 (s, 1H). Example 102 -3-ylfluorenyl) -2- "5-Γ3-methyl-1H-lat 1-5-yl W than pyridin-3-yl

基1-乙胺實例102A 將5-溴基-2-氟基苯曱醛（24·75克；i22毫莫耳）於％〇 (125毫升）中之溶液，在0°C下，以Et2〇中之3.0MMeMgBr(43毫升，129 毫莫耳）處理’攪拌30分鐘，小心以水稀釋，然後以10% HC1 ( 水洛液）酸化。將水溶液以％〇萃取，以1〇% HC1 (水溶液）、水及鹽水連續沖洗，脫水乾燥（MgS04)並蒸發，而得所要之產物（26·6克；99% )，具有足夠純度以繼續進行至下一步驟0 實例102Β 基-2-氟苯基乙酮 200301122Example 1-ethylamine 102A A solution of 5-bromo-2-fluorobenzaldehyde (24.75 g; i22 mmol) in% 0 (125 ml) at 0 ° C with Et2 3.0 MMeMgBr (43 ml, 129 mmol) was treated 'stirred for 30 minutes, carefully diluted with water, and then acidified with 10% HC1 (Hydraulic solution). The aqueous solution was extracted with% 0, and it was continuously washed with 10% HC1 (aqueous solution), water and brine, dehydrated and dried (MgS04) and evaporated to obtain the desired product (26 · 6 g; 99%), with sufficient purity to continue. Proceed to the next step 0 Example 102B-yl-2-fluorophenyl ethyl ketone 20031122

(123) 將實例1〇2Α(26·6克；lU毫莫耳）與氧化錳（IV)(53克；61〇毫莫耳）於對-二氧陸圜（500毫升）中之溶液，在回流下加熱4 小時，冷卻，經過Celite®過濾，蒸發並藉急驟式層析純化& 10% EkO/己烷），產生所要之產物，為幾乎無色油，其係於靜置時固化（20.5克；78% )。(123) a solution of Example 102A (26.6 grams; 1 U millimolar) and manganese (IV) oxide (53 grams; 610 millimoles) in p-dioxolane (500 ml), Heat under reflux for 4 hours, cool, filter through Celite®, evaporate and purify by flash chromatography & 10% EkO / hexane) to produce the desired product, which is an almost colorless oil that solidifies upon standing ( 20.5 g; 78%).

Ψ 102C 5-溪基-3-甲基丨峻將102Β(10克，46毫莫耳）與98%肼（25毫升）之混合物，加熱至回流，歷經9小時，並傾倒於冰上。收集沉澱物，並藉急驟式層析純化（1 : 1 Et〗Ο :己燒），而得所要之產物，為白色固體（5·8克，60% )。Ψ 102C 5-Cyclo-3-methyl. A mixture of 102B (10 g, 46 mmol) and 98% hydrazine (25 ml) was heated to reflux for 9 hours and poured onto ice. The precipitate was collected and purified by flash chromatography (1: 1 Et): hexane. The desired product was obtained as a white solid (5.8 g, 60%).

實例102D 3-甲基-5-三甲基錫烷^ 將實例l〇2C(10.08克，47·8毫莫耳）、六甲基·二_錫2(18克，55 當莫耳）及肆（三苯膦）免（5.5克’ 4·8亳莫耳）於甲苯（1〇〇毫升）中之混合物，在95°C下攪拌6小時。然後，蒸發混合物，並使殘留物溶入醋酸乙酯（300毫升）中，以飽和碳酸氫鈉（1〇〇毫升）、水（100毫升）及鹽水（100毫升）洗滌。蒸發醋酸乙酯 ’並使殘留物於碎膠上藉急驟式管柱層析純化，以1 : 4醋酸乙酯/己烷溶離，獲得11.2克所要之產物（8〇% )。MS : (ESI) m/z 409 (M+H)+ ·Example 102D 3-methyl-5-trimethylstannane ^ Example 10C (10.08 g, 47.8 millimoles), hexamethyl di-tin 2 (18 g, 55 moles), and (Triphenylphosphine) (5.5 g '4.8 g mole) in toluene (100 ml) was stirred at 95 ° C for 6 hours. The mixture was then evaporated and the residue was dissolved in ethyl acetate (300 ml) and washed with saturated sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml). Ethyl acetate was evaporated and the residue was purified by flash column chromatography on crushed gel, and then separated with 1: 4 ethyl acetate / hexane to obtain 11.2 g of the desired product (80%). MS: (ESI) m / z 409 (M + H) +

實例102E 弓1只朵-3-基甲基）-2彳5-(3-甲基-1H-巧1畔-5-某）-口比淀-3-基氧基1-乙基μ胺甲羞酸星 200301122Example 102E 1-bend-3-ylmethyl) -2 彳 5- (3-methyl-1H-Cl-1a-5-a) -Kipido-3-yloxy 1-ethyl μamine Methyl acid star 200301122

(124) 所要之產物係經由以實例102D·取代實例27B中之實例27A 而製成。(124) The desired product was prepared by replacing Example 27A in Example 27B with Example 102D.

f 例 102F (1SVH1H-W哚-3-某甲基V2-『5-(3-甲某-1H-蚓唑-5-基吡啶各基氧基1-乙胺所要之產物係經由以實例102E取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (ESI) m/e 398 (M+H)+; 1 H NMR (DMSO-D6，f Example 102F (1SVH1H-W indol-3-some methyl V2- "5- (3-methylsome-1H-earnazol-5-ylpyridyl yloxy 1-ethylamine The desired product is obtained by using Example 102E Replaced Example 27B in Example 27C with trifluoroacetate. MS (ESI) m / e 398 (M + H) +; 1 H NMR (DMSO-D6,

300 MHz) 5 2.55 (s，3H) 2.79 (dd，J=14.07, 7·29 Hz，1H) 2.99 (dd，J=14.07, 7·29, 1H) 3.32 (s? 2H) 3.40 (τη, 1H) 4.03 (m, 2H) 6.95 (t5 J=7.46 Hz, 1H) 7.05 (t5 J=6.95 Hz, 1H) 7.21 (d, J=2.37 Hz, 1H) 7.34 (d, J=7.80 Hz, 1H) 7.56 (m5 2H) 7.67 (m, 2H) 8.08 (s, 1H) 8.26 (d, J=2.37 Hz, 1H) 8.54 (d, J=2.03 Hz, 1H) 10.85 (s, 1H) 12.73 (s, 1H) :對 C24H23N50.2.25HC1之分析計算值：C，59.62 ; Η，5·31; N，14.60 ;·實測值·· C，59.62 ; Η，5·31; N，14.28. 實例103 (jg)土(1HW1嗓^^甲基）-2]5-「3-ΠΗ-吡咯-2-某V1H-啕唑净基1-吡300 MHz) 5 2.55 (s, 3H) 2.79 (dd, J = 14.07, 7.29 Hz, 1H) 2.99 (dd, J = 14.07, 7.29, 1H) 3.32 (s? 2H) 3.40 (τη, 1H ) 4.03 (m, 2H) 6.95 (t5 J = 7.46 Hz, 1H) 7.05 (t5 J = 6.95 Hz, 1H) 7.21 (d, J = 2.37 Hz, 1H) 7.34 (d, J = 7.80 Hz, 1H) 7.56 (m5 2H) 7.67 (m, 2H) 8.08 (s, 1H) 8.26 (d, J = 2.37 Hz, 1H) 8.54 (d, J = 2.03 Hz, 1H) 10.85 (s, 1H) 12.73 (s, 1H) : Analysis and calculation value for C24H23N50.2.25HC1: C, 59.62; Η, 5.31; N, 14.60; · Measured value · C, 59.62; Η, 5.31; N, 14.28. Example 103 (jg) soil (1HW1 ^^ methyl) -2] 5- "3-ΠΗ-pyrrole-2-V1H-oxazolyl 1-pyridine

咬-3·基氧基}乙胺實例103A 5->臭基-2-氣-笨甲酸將5-溴基-2-氟基苯曱醛（81〇毫克；《ο毫莫耳）、15% NaOH( 水落液)(3毫升）、Me〇H (5毫升）及3〇% h2〇2(5毫升）之混合物，於室溫下攪拌2小時，然後以10% HC1 (水溶液）酸化。收集所形成之白色固體，以水沖洗並乾燥，而得所要之產物 (670 毫克；77% )。Bite-3.yloxy} ethylamine Example 103A 5- > Stylo-2-yl-benzylcarboxylic acid 5-bromo-2-fluorobenzaldehyde (81 mg; <οmmole), A mixture of 15% NaOH (water fall) (3 ml), MeOH (5 ml) and 30% h202 (5 ml), stirred at room temperature for 2 hours, and then acidified with 10% HC1 (aqueous solution) . The white solid formed was collected, washed with water and dried to obtain the desired product (670 mg; 77%).

實例103B -132- (125)Example 103B -132- (125)

轰.化5-溴基-2-氟-笨甲j|_ 將二氯化亞硫醯（7毫升）中之實例1〇3Α (665毫克；3.0毫莫耳），於回流下加熱2小時，濃縮並與甲苯共沸，獲得無色油，將其繼續進行，未進一步純化。B. 5-Bromo-2-fluoro-benzyl j | _ Example 103A (665 mg; 3.0 mmol) in thionyl dichloride (7 ml) was heated under reflux for 2 hours , Concentrated and azeotroped with toluene to give a colorless oil, which was carried on without further purification.

實例103C (5-溴基-2-氟笨基M1H-毗咯-2-基V甲酮將103B (720亳克；3·0毫莫耳）與吡咯（203毫克；3.0毫莫耳）於1，2-二氯乙烷（10毫升）中之溶液，在〇°C下，以A1C13分次處理，攪拌過夜，同時慢慢溫熱至室溫，以冰與IN HC1處理，攪拌1.5小時，並以CH2C12萃取。將萃液以水與飽和NaHC03( 水溶液）沖洗，以Na2 S04脫水乾燥，濃縮，並藉急驟式層析 (10% EtOAc /己烷）分離，而得所要之產物，為紫色固體（252 毫克；31% )。Example 103C (5-bromo-2-fluorobenzyl M1H-pyrrole-2-yl V methyl ketone) 103B (720 μg; 3.0 mmol) with pyrrole (203 mg; 3.0 mmol) The solution in 1,2-dichloroethane (10 ml) was treated with A1C13 in portions at 0 ° C and stirred overnight, while slowly warming to room temperature, treated with ice and IN HC1, and stirred for 1.5 hours. And extracted with CH2C12. The extract was washed with water and saturated NaHC03 (aqueous solution), dried over Na2S04, concentrated, and separated by flash chromatography (10% EtOAc / hexane) to obtain the desired product, as Purple solid (252 mg; 31%).

實例103D 5-溴基-3-(1Η-吡咯_2-基V1H-蜊唑所要之產物係經由以實例103C取代實例102C中之實例102B 而製成。Example 103D 5-Bromo-3- (1'-pyrrole_2-yl V1H-clamazole The desired product was prepared by substituting Example 103C for Example 102B in Example 102C.

實例103E (ISVI-ΠΗ-吲嗓-3-基甲基）-2-{5-『3·ΠΗ-口比嘻-2-基MH-口弓1唆-5-基1-口比淀-3-基乳基}-乙胺所要之產物係經由以實例103D取代實例27中之6-溴基異喹啉，以三氟醋酸鹽製成。MS (ESI) m/e 449 (Μ+Η)+ ; 1 H NMR (DMS0-D6,300 MHz) δ 3.18 (m3 2Η) 3.87 (m, 1Η) 4.20 (dd5 J=10.513 5.76 Hz, 1H) 4·38 (m，1H) 6·21 (m，1H) 6.86 (m，2H) 7.01 (t，J=7.46 Hz，1H) 7.10 (t，J=7.46 Hz， (126)Example 103E (ISVI-ΠΗ-Inth-3-ylmethyl) -2- {5- 『3.ΠΗ-Hippy-2-yl MH-Hip bow 1 唆 -5-yl 1-Hippy lake- The desired product of 3-based lactyl} -ethylamine was prepared by replacing the 6-bromoisoquinoline in Example 27 with Example 103D and using trifluoroacetate. MS (ESI) m / e 449 (Μ + Η) +; 1 H NMR (DMS0-D6, 300 MHz) δ 3.18 (m3 2Η) 3.87 (m, 1Η) 4.20 (dd5 J = 10.513 5.76 Hz, 1H) 4 · 38 (m, 1H) 6.21 (m, 1H) 6.86 (m, 2H) 7.01 (t, J = 7.46 Hz, 1H) 7.10 (t, J = 7.46 Hz, (126)

1H) 7.30 (d，J=2.03 Hz，1H) 7.38 (d，J=8.14 Hz，1Η) 7·67 (m，4H) 8·15 (bs，2H) 8·26 (s，1H) 8.35 (d，J=2.37 Hz，1H) 8.68 (s，1H) 11.03 (s，1H) 11.38 (s，1H) 13.10 (bs，1H) ;，C27H24N60.2.5TFA之分析計算值：C，52.39 ; H，3·64; N，11.46 ;·實測值：C，52.26 ; H，3·67 ; N，11·39· 實例104 (lSVl-HH-吲口朵-3-基甲基）·2-「5-(3-笨基-1H-口弓1咬-5·基V口比啶-3-基氧基V乙胺所要之產物係經由以溴化苯基鎂取代實例102中之溴化甲基鎂，以三氟醋酸鹽製成。MS (ESI) m/e 460 (Μ+Η)+ ; 1 H NMR (300 MHz, DMSO-D6) δ ppm 3.17 (m5 2Η) 3.87 (m5 1H) 4.19 (dd, 1=10.51, 5.76 Hz, 1H) 4.38 (m，1H) 7.00 (t，J=7.46 Hz，1H) 7·09 (t，J=7.46 Hz，1H) 7.30 (d，J=2.37 Hz， 1H) 7.39 (m, 1H) 7.44 (d, J=7.12 Hz, 1H) 7.54 (m, J=7.46, 7.46 Hz, 2H) 7.62 (d, J= 7.46 Hz, 1H) 7.72 (s, 2H) 7.76 (m, 1H) 8.05 (s5 1H) 8.08 (s, 1H) 8.16 (τη, 2H) 830 (s, 1H) 8.36 (d，J=2.71 Hz，1H) 8.68 (d，J=1.70 Hz，1H) 11.03 (s，1H) 13.45 (bs，1H)；對 C27H24N60.3TFA.2H20之分析計算值：C，53.24; H，4.08; N，8.87 ;實測值：C，52·91 ; H，3·68 ; N, 8.80. 實例105 (lS)-2-『5-(3-環丙基-1H-吲唑-5-基）-吡啶-3-基氧基Η-ΠΗ-<哚-3-基甲基V乙胺所要之產物係經由以溴化環丙基鎂取代實例102中之溴化甲基鎂以三氟醋酸鹽製成。MS (ESI) m/e 424 (M+H)+ ; 1 H NMR (300 MHz，DMSO-D6) 5 ppm 1·02 (m，4H) 2·36 (m，1H) 3.15 (m，2H) 3·86 (m, 1H) 4.19 (dd，J=10.68, 5·93 Hz，1H) 4.37 (dd，J=10.68, 3.22 Hz，1H) 7.01 (t，J=7.46 Hz， 1H) 7.10 (t3 J=6.95 Hz, 1H) 7.30 (d, J=2.37 Hz, 1H) 7.38 (d, J=8.14 Hz, 1H) 7.56 (d, 200301122 (127) J=8.48 Hz, 1H) 7.65 (m, 2H) 7.73 (m, 1H) 8.12 (s, 1H) 8.19 (m, 2H) 8.33 (d? J=2.37 Hz，1H) 8.63 (d，JN1 ·36 Hz，1H) 11.03 (d，J=2.03 Hz，1H) 12.73 (m，1H); 對匸261125>15〇.2.6丁?八之分析計算值：€：，52.05;11，3.86;凡9.73;. 實測值：C，52.03 ; H，3·89 ; N，9.69. 實例106 (lS)-2-f5-(3-乙基-1H-吲唑-5-基V吡啶-3-墓氣基1-H1H-吲哚-3-基甲基）-乙胺1H) 7.30 (d, J = 2.03 Hz, 1H) 7.38 (d, J = 8.14 Hz, 1Η) 7.67 (m, 4H) 8.15 (bs, 2H) 8.26 (s, 1H) 8.35 ( d, J = 2.37 Hz, 1H) 8.68 (s, 1H) 11.03 (s, 1H) 11.38 (s, 1H) 13.10 (bs, 1H) ;, C27H24N60.2.5TFA analysis calculated value: C, 52.39; H, 3.64; N, 11.46; · Measured values: C, 52.26; H, 3.67; N, 11.39 · Example 104 (lSVl-HH-indole-3-ylmethyl) · 2- "5 -(3-benzyl-1H-oral arch 1 bite-5.yl V orbital pyridin-3-yloxy V ethylamine The desired product is obtained by replacing the methyl bromide in Example 102 with phenyl magnesium bromide Magnesium, made from trifluoroacetate. MS (ESI) m / e 460 (Μ + Η) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 3.17 (m5 2Η) 3.87 (m5 1H) 4.19 ( dd, 1 = 10.51, 5.76 Hz, 1H) 4.38 (m, 1H) 7.00 (t, J = 7.46 Hz, 1H) 7.09 (t, J = 7.46 Hz, 1H) 7.30 (d, J = 2.37 Hz, 1H) 7.39 (m, 1H) 7.44 (d, J = 7.12 Hz, 1H) 7.54 (m, J = 7.46, 7.46 Hz, 2H) 7.62 (d, J = 7.46 Hz, 1H) 7.72 (s, 2H) 7.76 (m, 1H) 8.05 (s5 1H) 8.08 (s, 1H) 8.16 (τη, 2H) 830 (s, 1H) 8.36 (d, J = 2.71 Hz, 1H) 8.68 (d, J = 1.70 Hz, 1H) 11.03 (s, 1H) 13.45 (bs , 1H); Analytical calculation for C27H24N60.3TFA.2H20: C, 53.24; H, 4.08; N, 8.87; Found: C, 52 · 91; H, 3.68; N, 8.80. Example 105 (1S ) -2- "5- (3-Cyclopropyl-1H-indazol-5-yl) -pyridin-3-yloxyΗ-ΠΗ- < indol-3-ylmethyl V ethylamine Made from trifluoroacetate by replacing the methyl magnesium bromide in Example 102 with cyclopropyl magnesium bromide. MS (ESI) m / e 424 (M + H) +; 1 H NMR (300 MHz, DMSO -D6) 5 ppm 1.02 (m, 4H) 2.36 (m, 1H) 3.15 (m, 2H) 3.86 (m, 1H) 4.19 (dd, J = 10.68, 5.93 Hz, 1H) 4.37 (dd, J = 10.68, 3.22 Hz, 1H) 7.01 (t, J = 7.46 Hz, 1H) 7.10 (t3 J = 6.95 Hz, 1H) 7.30 (d, J = 2.37 Hz, 1H) 7.38 (d, J = 8.14 Hz, 1H) 7.56 (d, 200301122 (127) J = 8.48 Hz, 1H) 7.65 (m, 2H) 7.73 (m, 1H) 8.12 (s, 1H) 8.19 (m, 2H) 8.33 (d? J = 2.37 Hz, 1H) 8.63 (d, JN1 · 36 Hz, 1H) 11.03 (d, J = 2.03 Hz, 1H) 12.73 (m, 1H); Analytical calculation of 匸 261125 > 15〇.2.6 : € :, 52.05; 11, 3.86; Where 9.73 ;. Found: C, 52.03; H, 3.89; N, 9.69. Example 106 (lS) -2-f5- (3-ethyl-1H-ind Azole-5- Tomb gas pyridin-3-yl V 1-H1H- methyl-indol-3-yl) - ethylamine

所要之產物係經由以溴化乙基鎂取代實例102中之溴化甲基鎂，以三氟醋酸鹽製成。MS(ESI)m/e412(M+H)+ ; iHNMR (300 MHz, DMSO-D6) δ ppm L35 (t, J=7.63 Hz, 3H) 2.99 (q5 J=7.57 Hz, 2H) 3.17 (m，2H) 3.86 (m，1H) 4.19 (dd，J=10.85, 6·10 Hz，1H) 4.37 (m，1H) 7.01 (t，J=7.46 Hz， 1H) 7.11 (t3 J=7.46 Hz, 1H) 7.30 (d, J=2.37 Hz, 1H) 7.38 (d, J=7.80 Hz, 1H) 7.63 (m, 3H) 7.72 (m, 1H) 8.08 (s, 1H) 8.16 (m, 2H) 8.33 (d, J=2.71 Hz, 1H) 8.63 (d, J=1.70 Hz，1H) 11.04(d，J=2.03Hz，1H) 12.80(m，1H)對 C25H25N50 · 2.7TFA 之分析計算值：C，50.76 ; Η，3·88; N，9.74; ·實測值：C，51.09; H，3.88 ;Ν，9·66·The desired product was prepared from trifluoroacetate by replacing ethyl magnesium bromide with methyl magnesium bromide in Example 102. MS (ESI) m / e412 (M + H) +; iHNMR (300 MHz, DMSO-D6) δ ppm L35 (t, J = 7.63 Hz, 3H) 2.99 (q5 J = 7.57 Hz, 2H) 3.17 (m, 2H) 3.86 (m, 1H) 4.19 (dd, J = 10.85, 6.10 Hz, 1H) 4.37 (m, 1H) 7.01 (t, J = 7.46 Hz, 1H) 7.11 (t3 J = 7.46 Hz, 1H) 7.30 (d, J = 2.37 Hz, 1H) 7.38 (d, J = 7.80 Hz, 1H) 7.63 (m, 3H) 7.72 (m, 1H) 8.08 (s, 1H) 8.16 (m, 2H) 8.33 (d, J = 2.71 Hz, 1H) 8.63 (d, J = 1.70 Hz, 1H) 11.04 (d, J = 2.03Hz, 1H) 12.80 (m, 1H) Analysis and calculation of C25H25N50 · 2.7TFA: C, 50.76;; , 3.88; N, 9.74; · Found: C, 51.09; H, 3.88; N, 9.66 ·

實例107 (lS)-l-nH-吲哚-3-基甲基）-2-{5-『3-(l-甲基-1H-咪唑-2-基V1H-吲唑-5- 基1·口比淀-3-基乳基}•乙胺所要之產物係經由以Ν-曱基-2-咪唑基氯化鋰取代實例102 中之溴化曱基鎂，以三氟醋酸鹽製成。MS(ESI)m/e464(M+H)+ ；1 H NMR (400 MHz, DMSO-D6) δ ppm 3.18 (m, 2H) 3.84 (s, 1H) 4.07 (s, 3H) 420 (dd，J=10.59, 5·98 Hz，1H) 4·36 (m，1H) 7.00 (t，J=7.36 Hz，1H) 7·09 (t，J=7.36 Hz，1H) 7.18 (s，1H) 7.31 (d，J=2· 15 Hz，1H) 7·37 (m，2H) 7.64 (m，2H) 7·72 (s，2H) -135- 200301122 (128)Example 107 (1S) -l-nH-Indol-3-ylmethyl) -2- {5- "3- (l-methyl-1H-imidazol-2-yl V1H-indazol-5-yl 1 · Hipido Lake-3-yllactyl} • The desired product of ethylamine was prepared by replacing the fluorenylmagnesium bromide in Example 102 with N-fluorenyl-2-imidazolyl lithium chloride and using trifluoroacetate. .MS (ESI) m / e464 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.18 (m, 2H) 3.84 (s, 1H) 4.07 (s, 3H) 420 (dd, J = 10.59, 5.98 Hz, 1H) 4.36 (m, 1H) 7.00 (t, J = 7.36 Hz, 1H) 7.09 (t, J = 7.36 Hz, 1H) 7.18 (s, 1H) 7.31 (d, J = 2.15 Hz, 1H) 7.37 (m, 2H) 7.64 (m, 2H) 7.72 (s, 2H) -135- 200301122 (128)

8·33 (m，3H) 8.56 (d，J=1.53 Hz，1Η) 8·63 (s，ίΗ) 11.06 (s，1Η) 13·56 (s，1H). 實例108 nS)-l-(lH-口I丨口朵-3-基甲基）-245-(3-口塞峻-2-基-1H-吲峻-5-基）-口比啶 j二基氣基Ί-乙胺所要之產物係經由以2-嘍唑氯化鋰取代實例102中之溴化曱基鎂，以三氟醋酸鹽製成。MS(ESI)m/e467(M+H)+; iHNMRpOO MHz，DMSO-D6) δ ppm 3.19 (d, J=7.18 Hz, 2H) 3.86 (m, 1H) 4.22 (dd5 J=10.29,8.33 (m, 3H) 8.56 (d, J = 1.53 Hz, 1Η) 8.63 (s, Η) 11.06 (s, 1Η) 13.56 (s, 1H). Example 108 nS) -l- ( lH-port I 丨 portol-3-ylmethyl) -245- (3-portin-2-yl-1H-injun-5-yl) -bipyridine jdiylaminofluorene-ethylamine The desired product was prepared by replacing the fluorenylmagnesium bromide in Example 102 with 2-oxazole lithium chloride and using trifluoroacetate. MS (ESI) m / e467 (M + H) +; iHNMRpOO MHz, DMSO-D6) δ ppm 3.19 (d, J = 7.18 Hz, 2H) 3.86 (m, 1H) 4.22 (dd5 J = 10.29,

5·93 Hz，1H) 4.38 (dd，J=10.45, 2·65 Hz，1H) 7.01 (t，J=7.49 Hz，1H) 7·09 (t，J=7.49 Hz，1H) 7.31 (d，J=1.56 Hz，1H) 7·38 (d，J=8.11 Hz，1H) 7.64 (d，J=7.80 Hz，1H) 7.73 (s，1H) 7.78 (s，2H) 7·79 (d，J=3.12 Hz，1H) 8·04 (d，J=3.43 Hz，1H) 8·28 (s，2H) 8.38 (d，J=2.18 Hz，1H) 8·60 (s，2H) 11.04 (s，1H) 13.74 (s，1H) 實例109 (lS)-2-{5-_[3-(lH-咪唑-2-某 V1H-钊唑-5-基 1-吡啶各某氫甚哚各基甲基V乙胺5.93 Hz, 1H) 4.38 (dd, J = 10.45, 2.65 Hz, 1H) 7.01 (t, J = 7.49 Hz, 1H) 7.09 (t, J = 7.49 Hz, 1H) 7.31 (d, J = 1.56 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.64 (d, J = 7.80 Hz, 1H) 7.73 (s, 1H) 7.78 (s, 2H) 7.79 (d, J = 3.12 Hz, 1H) 8.04 (d, J = 3.43 Hz, 1H) 8.28 (s, 2H) 8.38 (d, J = 2.18 Hz, 1H) 8.60 (s, 2H) 11.04 (s, 1H) 13.74 (s, 1H) Example 109 (lS) -2- {5 -_ [3- (lH-imidazole-2-some V1H-zazol-5-yl 1-pyridine each hydroxidyl each Vethylamine

實例109AExample 109A

(lS)-[l-(lH-g?| 口木-3-基甲基二曱基珍燒> 基基」-jjj:味唑基V1H-⑼唑-5-基}-吡啶-3-基氫某νΛ 酸第三-丁酯所要之產物係經由以Ν-[2-三甲基矽烷基）乙氧基]甲基）2咪嗤基氯化叙，取代實例1〇2中之溴化甲基鎂，盔愛 ”，、而進行最後步驟’以三氟醋酸鹽製成。實例109Β 生唑-2-基 ΗΗ-θ丨唑-5-基 1-吡啶-3-某哚各基甲基）·乙胺 -136- 200301122 (129) 將實例109A (40毫克；0.06毫莫耳）於MeOH (4毫升）中之溶液，以濃HC1 (1毫升）處理，並在回流下加熱6小時，濃縮，且於C18管柱上藉逆相HPLC純化，使用0-100% CH3CN/H2O/0.1% TFA，提供所要之產物，為三氟醋酸鹽。MS (ESI) m/e 450 (M+H)+(lS)-[l- (lH-g? | Homogol-3-ylmethyldifluorenyl stilbene > yl group ''-jjj: amizol V1H-oxazol-5-yl} -pyridine-3 -Hydroxyhydrogen νΛ acid tert-butyl ester The desired product is substituted with N- [2-trimethylsilyl) ethoxy] methyl) 2imidyl chloride in place of Example 102 Methylmagnesium bromide, helmet love ", and the final step is' made with trifluoroacetate. Example 109B Sulzo-2-ylfluorene-θ 丨 azole-5-yl 1-pyridine-3-some indole (Methyl))-ethylamine-136- 200301122 (129) A solution of Example 109A (40 mg; 0.06 mmol) in MeOH (4 ml) was treated with concentrated HC1 (1 ml) and heated under reflux 6 hours, concentrated, and purified by reverse-phase HPLC on a C18 column using 0-100% CH3CN / H2O / 0.1% TFA to provide the desired product as trifluoroacetate. MS (ESI) m / e 450 ( M + H) +

;1 H NMR (500 MHz，DMSO-D6) δ ppm 3.19 (d, J=7.17 Hz, 2H) 3.86 (s, 1H) 4.22 (dd，J=10.45, 5·77 Hz，1H) 4.37 (dd，J=10.45, 2·96 Hz，1H) 7.00 (t，J=7.49 Hz， 1H) 7.09 (t, J=7.49 Hz, 1H) 7.30 (d5 J=2.18 Hz, 1H) 7.38 (d, J=8.11 Hz, 1H) 7.63 (d3 J=8.11 Hz，1H) 7.76 (s，1H) 7.83 (s，1H) 7.86 (s，2H) 8.26 (bs，3H) 8·39 (d，J=2.50 Hz， 1H) 8.61 (s，1H) 8.72 (s，1H) 11.04 (s，1H) 14.36 (s，1H) 實例110 (l,S)-l-aH^l 哚-3-基甲基）-245-(3-嘧吩-2-基-1H^弓 1 唑-5-基）-吡啶-3- 基氧基1-乙胺所要之產物係經由以2-硫苯基氯化鋰取代實例102中之溴化曱基鎂而製成。MS (ESI) m/e 466 (M+H)+ ; 1 H NMR (400 MHz, DMSO-D6); 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.19 (d, J = 7.17 Hz, 2H) 3.86 (s, 1H) 4.22 (dd, J = 10.45, 5.77 Hz, 1H) 4.37 (dd, J = 10.45, 2.96 Hz, 1H) 7.00 (t, J = 7.49 Hz, 1H) 7.09 (t, J = 7.49 Hz, 1H) 7.30 (d5 J = 2.18 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.63 (d3 J = 8.11 Hz, 1H) 7.76 (s, 1H) 7.83 (s, 1H) 7.86 (s, 2H) 8.26 (bs, 3H) 8.39 (d, J = 2.50 Hz, 1H ) 8.61 (s, 1H) 8.72 (s, 1H) 11.04 (s, 1H) 14.36 (s, 1H) Example 110 (l, S) -1-aH ^ l indol-3-ylmethyl) -245- ( 3-Pyridin-2-yl-1H ^ 1 azol-5-yl) -pyridin-3-yloxy 1-ethylamine The desired product was obtained by substituting 2-thiophenyllithium chloride in Example 102. Made of fluorenyl magnesium bromide. MS (ESI) m / e 466 (M + H) +; 1 H NMR (400 MHz, DMSO-D6)

5 ppm 3.21 (d, J=7.06 Hz, 2H) 3.86 (bs, 1H) 4.23 (dd, J=10.43, 5.83 Hz, 1H) 4.38 (m, 1H) 7.00 (t，J=7.52 Hz，1H) 7.10 (t，J=7.06 Hz，1H) 7·23 (dd，J=5.22, 3.68 Hz，1H) 7.31 (d，J=2.15 Hz, 1H) 7.39 (d，J=7.98 Hz，1H) 7·59 (d，J=6.14 Hz，1H) 7.64 (d，J= 7.98 Hz, 1H) 7.73 (m? 3H) 7.91 (d, J=2.76 Hz, 1H) 8.34 (m, 4H) 8.67 (s, 1H) 11.06 (s, 1H) 13.39 (s，1H) 實例111 (1SV1-(1H-口弓1 口朵-3-基曱基嗎福琳-4-基-1H-口弓1峻-5-基）-口比咬-5 ppm 3.21 (d, J = 7.06 Hz, 2H) 3.86 (bs, 1H) 4.23 (dd, J = 10.43, 5.83 Hz, 1H) 4.38 (m, 1H) 7.00 (t, J = 7.52 Hz, 1H) 7.10 (t, J = 7.06 Hz, 1H) 7.23 (dd, J = 5.22, 3.68 Hz, 1H) 7.31 (d, J = 2.15 Hz, 1H) 7.39 (d, J = 7.98 Hz, 1H) 7.59 (d, J = 6.14 Hz, 1H) 7.64 (d, J = 7.98 Hz, 1H) 7.73 (m? 3H) 7.91 (d, J = 2.76 Hz, 1H) 8.34 (m, 4H) 8.67 (s, 1H) 11.06 (s, 1H) 13.39 (s, 1H) Example 111 (1SV1- (1H-Mouth Bow 1 Mouth-3-ylpyrimidin Molyfolin-4-yl-1H-Mouth Bow 1 Jun-5-M) -Mouth bite-

3-基氧基1-乙胺實例111A 5-溴基-3-嗎福啉-4-基-1H-W唑 -137-3-yloxy 1-ethylamine Example 111A 5-Bromo-3-morpholin-4-yl-1H-Wazole -137-

200301122 (130) 於實例35A與嗎福琳間之反應，係根據U· Wrzeciono, Κ· Majewska， J. Dudzinska-Usarewicz，Μ· Bemas，Pharmzie，1986, 41，472-474 中所述之程序進行。200301122 (130) The reaction between Example 35A and Morphine was performed according to the procedures described in U. Wrzeciono, K. Majewska, J. Dudzinska-Usarewicz, M. Bemas, Pharmzie, 1986, 41, 472-474 .

實例111B (1SV1-(1H-W 哚-3-基甲基）-2-「5-(3-嗎福啉-4-基-1H-W 唑-5-基）-吡啶- 3-基氣基1-乙胺Example 111B (1SV1- (1H-W indol-3-ylmethyl) -2- "5- (3-morpholine-4-yl-1H-Wazole-5-yl) -pyridine-3-yl 1-ethylamine

所要之產物係經由以實例111A取代實例27中之6-溴基異喹啉而製成。MS (ESI) m/e 469 (M+H)+ ; 1 H NMR (300 MHz，DMSO-D6) 5 ppm 3·16 (d，J=7.12 Hz，2H) 3.35 (m，4H) 3.81 (m，4H) 3·88 (m，1H) 4·19 (dd，J= 10·68, 5·93 Hz，1H) 4.35 (m，1H) 7·01 (t，J=7.46 Hz，1H) 7.10 (t，J=7.46 Hz，1H) 7.30 (d5 J=2.37 Hz, 1H) 7.38 (d5 J=7.80 Hz, 1H) 7.48 (d5 J=8.82 Hz, 1H) 7.62 (m, 2H) 7.72 (m，1H) 8.09 (s，1H) 8.17 (m，2H) 8.33 (d，J=2.71 Hz，1H) 8·65 (d，J=1 ·70 Hz，1H) 11.03 (s，lH) 12.21 (s，lH);對 C27H28N60.3.4TFA之分析計算值·· C， 47.41; Η，3·70; N，9.82; ·實測值：C，47·10 ; Η，3·86; Ν，9·95· 實例112 (i_S>2-[5-(l，3-二甲基-1Η-吲唑-5-基V吡啶-3-基氣基啕哚-3-基The desired product was prepared by substituting Example 111A for 6-bromoisoquinoline in Example 27. MS (ESI) m / e 469 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 3.16 (d, J = 7.12 Hz, 2H) 3.35 (m, 4H) 3.81 (m , 4H) 3.88 (m, 1H) 4.19 (dd, J = 10 · 68, 5.93 Hz, 1H) 4.35 (m, 1H) 7.01 (t, J = 7.46 Hz, 1H) 7.10 (t, J = 7.46 Hz, 1H) 7.30 (d5 J = 2.37 Hz, 1H) 7.38 (d5 J = 7.80 Hz, 1H) 7.48 (d5 J = 8.82 Hz, 1H) 7.62 (m, 2H) 7.72 (m, 1H) 8.09 (s, 1H) 8.17 (m, 2H) 8.33 (d, J = 2.71 Hz, 1H) 8.65 (d, J = 1.70 Hz, 1H) 11.03 (s, lH) 12.21 (s, lH); Analytical calculated value for C27H28N60.3.4TFA ·· C, 47.41; Η, 3.70; N, 9.82; · Measured value: C, 47 · 10; Η, 3.86; Ν, 9.95 · Example 112 (i_S > 2- [5- (l, 3-Dimethyl-1fluorene-indazol-5-yl Vpyridin-3-ylaminopyridin-3-yl

i基）乙胺i group) Ethylamine

實例112A 5-溴基-1,3-二甲基唑將實例102C (500毫克；2.37毫莫耳）添加至60% NaH(115毫克，2.84宅莫耳）於DMF⑼毫升）中之混合物内。15分鐘後，於室溫下添加碘甲烷（456毫克；321毫莫耳），將反應物攪拌2 小時，然後以水稀釋，並以Et〇Ac萃取。將萃液以水及鹽水沖洗’脫水乾燥（MgS〇4)，蒸發，並藉急驟式層析（1: 1恥〇 > 138- 200301122Example 112A 5-Bromo-1,3-dimethylazole Example 102C (500 mg; 2.37 mmol) was added to a mixture of 60% NaH (115 mg, 2.84 μmol) in DMF (ml). After 15 minutes, methyl iodide (456 mg; 321 mmol) was added at room temperature, and the reaction was stirred for 2 hours, then diluted with water and extracted with EtoAc. The extract was washed with water and salt water ’and dried (MgS〇4), evaporated, and subjected to flash chromatography (1: 1). 138-200301122

(131) :己烷）分離，而得所要之產物（360毫克；67% )。(131): hexane) to obtain the desired product (360 mg; 67%).

實例112B 所要之產物係經由以實例112A取代實例27中之實例6-溴基異喹啉，以三氟醋酸鹽製成。MS(ESI)m/e412(M+H)+ ; iHNMR (300 MHz，DMSO-D6) δ ppm 2.54 (s，3Η) 3·18 (m，2Η) 3.86 (s，1Η) 4.00 (s，3Η)The desired product of Example 112B was prepared by substituting Example 112A for Example 6-bromoisoquinoline in Example 27 with trifluoroacetate. MS (ESI) m / e412 (M + H) +; iHNMR (300 MHz, DMSO-D6) δ ppm 2.54 (s, 3Η) 3.18 (m, 2Η) 3.86 (s, 1Η) 4.00 (s, 3Η )

4.20 (dd，J=10.51，6·10 Hz，1H) 4.37 (m，1H) 7.01 (t，J=7.46 Hz, 1H) 7.10 (t，J=7.12 Hz，1H) 7.30 (d，J=2.37 Hz，1H) 7.39 (d，J=7.80 Hz，1H) 7.63 (d，J=7.80 Hz，1H) 7.73 (m, 2H) 8.08 (s, 1H) 8.18 (m5 3H) 8.34 (d3 J=2.71 Hz3 1H) 8.66 (d, J=1.70 Hz, 111)11.04(5，1印；對（：251125>15〇.2.8丁?八之分析計算值：（：，50.29; H，3·83 ; N，9·58 ;·實測值·· C，50·36 ; H，3·84 ; N，9.60. 實例1134.20 (dd, J = 10.51, 6.10 Hz, 1H) 4.37 (m, 1H) 7.01 (t, J = 7.46 Hz, 1H) 7.10 (t, J = 7.12 Hz, 1H) 7.30 (d, J = 2.37 Hz, 1H) 7.39 (d, J = 7.80 Hz, 1H) 7.63 (d, J = 7.80 Hz, 1H) 7.73 (m, 2H) 8.08 (s, 1H) 8.18 (m5 3H) 8.34 (d3 J = 2.71 Hz3 1H) 8.66 (d, J = 1.70 Hz, 111) 11.04 (5, 1 print; analysis and calculation of (: 251125 > 15〇.2.8 d? 8: (:, 50.29; H, 3.83; N, 9 · 58; · Measured value · C, 50 · 36; H, 3.84; N, 9.60. Example 113

qSM-(lH-4l哚-3-基甲基）-243-(3-甲基-1H-钊唑-5-基V笨氣基1-乙胺所要之產物係經由以3-溴酚取代實例102中之3-溴基-5-羥基吡啶，以三氟醋酸鹽製成。MS (ESI) m/e 397 (M+H)+ ; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.54 (s, 3H) 3.17 (m3 2H) 3.81 (m3 1H) 4.09 (dd3 J= 10.51，5.76 Hz，1H) 4.25 (dd，J=10.51，3.05 Hz，1H) 6.93 (m，1H) 7.01 (t，J=7.46 Hz， 1H) 7.10 (t, J=7.46 Hz, 1H) 7.28 (m5 2H) 7.37 (m, 3H) 7.52 (d3 J=8.48 Hz, 1H) 7.61 (m, 2H) 7.93 (s, 1H) 8.15 (bs, 2H) 11.03 (s, 1H) 12.62 (bs3 1H) 實例114 嗲-3-基甲基甲基-六氫吡畊-1-基）-1H-W唑-t基P比咬-3-基氣某卜乙胺qSM- (lH-4l indol-3-ylmethyl) -243- (3-methyl-1H-zazol-5-yl V benzyl 1-ethylamine The desired product is substituted by 3-bromophenol 3-Bromo-5-hydroxypyridine in Example 102, made from trifluoroacetate. MS (ESI) m / e 397 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.54 (s, 3H) 3.17 (m3 2H) 3.81 (m3 1H) 4.09 (dd3 J = 10.51, 5.76 Hz, 1H) 4.25 (dd, J = 10.51, 3.05 Hz, 1H) 6.93 (m, 1H) 7.01 (t , J = 7.46 Hz, 1H) 7.10 (t, J = 7.46 Hz, 1H) 7.28 (m5 2H) 7.37 (m, 3H) 7.52 (d3 J = 8.48 Hz, 1H) 7.61 (m, 2H) 7.93 (s, 1H) 8.15 (bs, 2H) 11.03 (s, 1H) 12.62 (bs3 1H) Example 114 fluoren-3-ylmethylmethyl-hexahydropyrine-1-yl) -1H-Wazole-tyl P ratio Bite-3-yl gas

實例114A 臭基-3·(4_甲基-六氫p比口井-1-基）-1Η-Η丨峻於實例35A與N-甲基六氫p比呼間之反應，係根據u. Wrzeciono, -139· 2〇〇3〇i (132)Example 114A Sinyl-3 · (4-methyl-hexahydro p ratio Koukai-1-yl) -1Η-Η 丨 Compared to the reaction between Example 35A and N-methyl hexahydro p ratio, based on u Wrzeciono, -139 · 2〇〇〇〇 (132)

κ· Majewska，J· Dudzinska-Usarewicz，Μ· Bertias，Pharmzie，1986, 41，472-474 中所述之程序進行。κ Majewska, J Dudzinska-Usarewicz, M Bertias, Pharmzie, 1986, 41, 472-474.

實例114B (lSH-αΗ-吲哚-3-基曱基V2-{5-「3-(4-甲基-六氫吡畊-1-基HH-巧唑- 5-基"I-吡啶-3-基氧基丨-乙胺Example 114B (lSH-αΗ-Indol-3-ylfluorenyl group V2- {5-``3- (4-methyl-hexahydropyridin-1-yl HH-conazole- 5-yl) " I-pyridine -3-yloxy 丨 -ethylamine

所要之產物係經由以實例114A取代實例27中之6-溴基異喹啉而製成。MS (ESI) m/e 482 (M+H)+ ; 1 H NMR (300 MHz，DMS0-D6) δ ppm 2.54 (s, 3H) 2.90 (m, 2H) 3.21 (m, 4H) 3.54 (m, 2H) 3.83 (m, 1H) 4.06 (m, 2H) 4.19 (dd, J=10.68, 5.93 Hz? 1H) 4.35 (dd, J=10.51, 2.71 Hz, 1H) 7.01 (t, J=6.95 Hz，1H) 7.10 (t，J=7.12 Hz，1H) 7·30 (d，J=2.03 Hz，1H) 7.38 (d，J=8.14 Hz，1H) 7·51 (d, J=8.82 Hz, 1H) 7.65 (m, 3H) 8.15 (s, 1H) 8.21 (m, 2H) 8.33 (d, J=2.71 Hz, 1H) 8.66 (d, J=1.70 Hz, 1H) 11.04 (s, 1H) 12.36 (s, 1H)；對 C2 8 H3 i N7 O · 4.45TFA 之分析計算值：C，44.81; H，3·61; N，9.91 ;·實測值：C，44.83 ; H，3.53 ;Ν，9·97· 實例115 qSM5]5-[2-胺基-3-ΠΗ-吲哚-3-基丙氧基1-吡啶-3-基ΜΗ-吲唑-3- 基V二甲基-胺實例115Α (5-溴基-1H-W唑各基）·二甲某-胺於實例35Α與二甲胺間之反應，係根據U. Wrzeciono, K. Majewska， J. Dudzinska-Usarewicz，Μ· Bemas，Pharmzie，1986, 41，472-474 中所述之程序進行。The desired product was prepared by substituting Example 114A for 6-bromoisoquinoline in Example 27. MS (ESI) m / e 482 (M + H) +; 1 H NMR (300 MHz, DMS0-D6) δ ppm 2.54 (s, 3H) 2.90 (m, 2H) 3.21 (m, 4H) 3.54 (m, 2H) 3.83 (m, 1H) 4.06 (m, 2H) 4.19 (dd, J = 10.68, 5.93 Hz? 1H) 4.35 (dd, J = 10.51, 2.71 Hz, 1H) 7.01 (t, J = 6.95 Hz, 1H ) 7.10 (t, J = 7.12 Hz, 1H) 7.30 (d, J = 2.03 Hz, 1H) 7.38 (d, J = 8.14 Hz, 1H) 7.51 (d, J = 8.82 Hz, 1H) 7.65 (m, 3H) 8.15 (s, 1H) 8.21 (m, 2H) 8.33 (d, J = 2.71 Hz, 1H) 8.66 (d, J = 1.70 Hz, 1H) 11.04 (s, 1H) 12.36 (s, 1H ); Analytical calculated value for C2 8 H3 i N7 O · 4.45TFA: C, 44.81; H, 3.61; N, 9.91; · Found: C, 44.83; H, 3.53; N, 9.97 · Example 115 qSM5] 5- [2-Amino-3-ΠΗ-indol-3-ylpropoxy 1-pyridin-3-yl MΗ-indazol-3-yl V dimethyl-amine Example 115A (5- Bromo-1H-Wazole groups). The reaction of dimethyl-amine between Example 35A and dimethylamine is based on U. Wrzeciono, K. Majewska, J. Dudzinska-Usarewicz, M. Bemas, Pharmzie, 1986 , 41, 472-474.

實例115B aSW5]5-「2-胺某哚各基丙氧基1-吡啶-3-基卜1H-啕唑-3- (133) 基二甲基-胺所要之產物係經由以實例115A取代實例27中之6-溴基異喹啉而製成。MS (ESI) m/e 427 (M+H)+ ; 1H NMR (300 MHz，DMS0-D6) 5 ppm 3·04 (s，6H) 3.16 (m，2H) 3·86 (s，1H) 4.19 (m，1H) 4·36 (m，1H) 7.01 (t，J= 6·95 Hz，1H) 7.10 (t，J=7.12 Hz，1H) 7.30 (d，J=2.37 Hz，1H) 7·38 (d，J=8.14 Hz，1H) 7.45 (d, J=8.82 Hz, 1H) 7.61 (m, 2H) 7.73 (s, 1H) 8.07 (s, 1H) 8.17 (m, 2H) 8.33 (d, J=2.37 Hz, 1H) 8.62 (d, J=1.36 Hz, 1H) 11.03 (s, 1H) 12.04 (s, 1H)；對匸251126乂〇.3.5丁?八之分析計算值：（：，46.55;11，3.60;凡10.18 ;實測值：C，46.71 ; H，3.65 ; N，10.02. 實例116 (lS)-(4-(5-(2-胺基-3-(lH-吲哚各基丙氧基V吡啶-3-基V芊基笨基-胺Example 115B aSW5] 5- "2-Amino-indolylpropoxyl-pyridin-3-ylbu 1H-oxazole-3- (133) yldimethyl-amine The desired product was substituted by Example 115A Prepared from 6-bromoisoquinoline in Example 27. MS (ESI) m / e 427 (M + H) +; 1H NMR (300 MHz, DMS0-D6) 5 ppm 3.04 (s, 6H) 3.16 (m, 2H) 3.86 (s, 1H) 4.19 (m, 1H) 4.36 (m, 1H) 7.01 (t, J = 6.95 Hz, 1H) 7.10 (t, J = 7.12 Hz, 1H) 7.30 (d, J = 2.37 Hz, 1H) 7.38 (d, J = 8.84 Hz, 1H) 7.45 (d, J = 8.82 Hz, 1H) 7.61 (m, 2H) 7.73 (s, 1H) 8.07 (s, 1H) 8.17 (m, 2H) 8.33 (d, J = 2.37 Hz, 1H) 8.62 (d, J = 1.36 Hz, 1H) 11.03 (s, 1H) 12.04 (s, 1H); 匸 251126 乂〇.3.5 Calculated value of analysis of Ding Yao: (:, 46.55; 11, 3.60; Where 10.18; Found: C, 46.71; H, 3.65; N, 10.02. Example 116 (lS)-(4- (5- (2-Amino-3- (lH-indolyl propoxy Vpyridin-3-yl V fluorenylbenzyl-amine

實例116A (1SHMM4-甲醯基苯某吡啶-3-基氧基1-H1H-吲哚各基甲基乙基1-胺甲基酸第三-丁酯所要之產物係經由以4-甲醯基苯基二羥基硼烷取代實例 22中之4-氰基苯基二羥基硼烷而製成。ms : (ESI) m/z 472 (M+H)+ ·Example 116A (1SHMM4-formylbenzylpyridin-3-yloxy 1-H1H-indole each methylmethylethyl 1-aminomethyl acid tert-butyl ester The desired product is obtained via 4-formamidine Was prepared by substituting 4-cyanophenyldihydroxyborane in Example 22. ms: (ESI) m / z 472 (M + H) + ·

實例116B 嘴曱基V2-『5-(4-笨基胺某甲基·笨基V吡啶-3-基蓋乙基卜胺甲基酸第三-丁酯使實例116A (0.03克，〇·〇6毫莫耳）於2毫升MeOH中之溶液，冷卻至0 C，然後以苯胺（0 018克〇 2毫莫耳）、NaBH3CN(〇〇〇4 克’ 0·06愛莫耳）及Ac〇H (丨毫升）處理。使混合物溫熱至室溫過夜。將混合物以醋酸乙g旨（2〇毫升）稀釋，以水（1〇毫升）及鹽水（10毫升）洗滌。蒸發醋酸乙酯，並使用此殘留物， 200301122 (134) 無需進一步純化。Example 116B Methylpyridyl V2- "5- (4-benzylamine, a methyl · benzyl Vpyridin-3-ylgathylethylamine amino acid tertiary-butyl ester, Example 116A (0.03 g, 〇 · 〇6mmol) in 2 ml of MeOH, cooled to 0 C, and then with aniline (0 018 grams 〇02mmol), NaBH3CN (〇04 gram '0. 06 Emole) and Ac OH (丨 ml). The mixture was allowed to warm to room temperature overnight. The mixture was diluted with ethyl acetate (20 ml), washed with water (10 ml) and brine (10 ml). Ethyl acetate was evaporated. And using this residue, 200301122 (134) without further purification.

實例116C (lSV(4-(5-(2-胺基-3-(1Η-吲哚；基丙氣基V吡啶各基芊基V茉某-fe 所要之產物係經由以實例116B取代實例27C中之實例27B 而製成。MS: (ESI) (M+H)+m/z = 449. 1H NMR (500 MHz，DMSO-D6) 5 ppmExample 116C (1SV (4- (5- (2-Amino-3- (1'-indole; propylpropanyl, pyridyl, fluorenyl, hydrazone, vamo--fe) The desired product was obtained by replacing Example 27C with Example 116B 27B in MS. (ESI) (M + H) + m / z = 449.1 1H NMR (500 MHz, DMSO-D6) 5 ppm

3.82 (m, 7H) 4.18 (m, 1H) 4.32 (d? J=4.06 Hz, 2H) 6.55 (d, J=32.76 Hz, 1H) 6.59 (d, J=7.49 Hz，1H) 6·89 (d，J=7.49 Hz，1H) 7.04 (m，3H) 7·18 (m，1H) 7·29 (d，J=2.50 Hz， 1H) 7.37 (d，J=7.80 Hz，1H) 7·48 (d，J=8.11 Hz，1H) 7.62 (m，3H) 8.31 (bs，3H) 8.52 (d, J=1.56 Hz, 1H) 11.04 (d, J=1.87 Hz, 1H) 實例117 (lSM4-(5-(2-胺基-3-(lH-啕哚-3-基V丙氣基V吡啶-3-基V笨某V甲薛3.82 (m, 7H) 4.18 (m, 1H) 4.32 (d? J = 4.06 Hz, 2H) 6.55 (d, J = 32.76 Hz, 1H) 6.59 (d, J = 7.49 Hz, 1H) 6.89 (d , J = 7.49 Hz, 1H) 7.04 (m, 3H) 7 · 18 (m, 1H) 7 · 29 (d, J = 2.50 Hz, 1H) 7.37 (d, J = 7.80 Hz, 1H) 7.48 ( d, J = 8.11 Hz, 1H) 7.62 (m, 3H) 8.31 (bs, 3H) 8.52 (d, J = 1.56 Hz, 1H) 11.04 (d, J = 1.87 Hz, 1H) Example 117 (lSM4- (5 -(2-amino-3- (lH-pyridin-3-yl) V propanyl Vpyridin-3-yl V

實例117A (lSM2-f5-(4-羥甲基-苯基吡啶-3-基氣基1-1-笨基-乙基μ胺甲某酸第三-丁酯Example 117A (1SM2-f5- (4-Hydroxymethyl-phenylpyridin-3-ylamino) 1-benzyl-ethyl μ carbamic acid tert-butyl ester

使實例116Α (0.03克，0.06毫莫耳）溶於2毫升MeOH中，並冷卻至0°C，然後以NaBH4 (0.003克，0.08毫莫耳）處理。使混合物溫熱至室溫，歷經2小時。將混合物以醋酸乙酯（20毫升）稀釋，以水（10毫升）及鹽水（10毫升）洗滌。蒸發醋酸乙酯，並使用此殘留物，無需進一步純化。Example 116A (0.03 g, 0.06 mmol) was dissolved in 2 ml of MeOH, cooled to 0 ° C, and then treated with NaBH4 (0.003 g, 0.08 mmol). The mixture was allowed to warm to room temperature over 2 hours. The mixture was diluted with ethyl acetate (20 ml) and washed with water (10 ml) and brine (10 ml). Ethyl acetate was evaporated and the residue was used without further purification.

實例117B (lSV(4-(5-(2-胺基哚各基V丙氧基V吡啶各基笨某V甲薛所要之產物係經由以實例117A取代實例27C中之實例27B 而製成。MS: (ESI)m/z374(M+H)+; iHNMRpOOMHADMSCM^) 5ppm 3.15 (m，4H) 3·72 (m，1H) 4·16 (dd，J=10.29, 5·93 Hz，1H) 4·29 (m，1H) 4.55 (s，2H) -142- (135) 5·29 (s，1H) 6·99 (t，>7·02 Hz，1H) 7·09 (t，J=7.02 Hz，1H) 7.28 (d，J=2.18 Hz，1H) 7·37 (d，J=8.11 Hz，1H) 7.43 (d，J=8.42 Hz，2H) 7.59 (m，1H) 7.64 (dd，J=10.61，8.42 Hz，3H) 8·30 (d，J=2.81 Hz，1H) 8.51 (d，J=1.56 Hz，1H) 11.03 (s，1H) 實例118 〇SV2-(5-(4-氟笨基）-吡啶-3-基氧基Vl-ΠΗ-吲哚！基甲基）-乙胺所要之產物係經由以4-氟苯基二羥基硼烷取代實例22中之4-氰基苯基二羥基硼烷而製成。MS: (ESI) m/z 362 (M+H)+ ; 1 H NMR (500 MHz，DMSO-D6) 5 ppm 3.09 (m，2H) 3.17 (d，J=4.68 Hz，1H) 3.71 (s? 1H) 4.12 (dd? J=10.295 6.24 Hz3 1H) 4.26 (dd5 J=10.29, 3.43 Hz, 1H) 6.99 (t, J= 7·49Ήζ，1H) 7.09 (m，1H) 7·26 (d，J=2.18 Hz，1H) 7.34 (m，3H) 7.59 (m，2H) 7.74 (m? 2H) 8.32 (d, J=2.50 Hz, 1H) 8.50 (d, J=L87 Hz, 1H) 10.97 (s, 1H). 實例119 (lS)-4-(5-(2-胺基-3-(111-41嗓-3-基V丙氧基Vp比咬-3-基）-苯甲酸所要之產物係經由以4-羥羰基苯基二羥基硼烷取代實例 22中之4-氰基苯基二羥基硼烷而製成。MS (ESI) m/z 388 (M+H)+ ；1H NMR (500 MHz, DMSO-D6) δ ppm 3.17 (m5 1H) 3.84 (m3 1H) 4.20 (m? 1H) 4.35 (m，1H) 7.00 (t，J=6.86 Hz，1H) 7.10 (t，J=7.02 Hz，1H) 7.30 (d，J=2· 18 Hz，1H) 7.38 (d，J=8.11 Hz，1H) 7·63 (d，J=7.49 Hz，1H) 7.68 (m，1H) 7·83 (d，J=8.42 Hz，1H) 8.04 (m3 2H) 8.26 (s3 3H) 8.38 (d5 J=2.50 Hz, 1H) 8.59 (d, J=1.87 Hz, 1H) 11.02 (d, J=1.87 Hz, 1H) 實例120 (lS)-2-(3->臭基-5-異峻琳-6-基-笨氣基氣基丨嗓-3-基甲基）- 乙胺步騾1. -143- (136) 實例120Α ί^Η1-(3,5-=^ -苯氣墓甲基）_2_(1Η-啕哚基1-胺甲基_ 第三-丁酯將3,5-二溴.（1克，4.1毫莫耳）、（2-#里基小苯基-乙基）-胺曱基酸第三-丁酯（1·2克，4·1毫莫耳）及三笨膦（1.6克，2毫莫耳）於THF (30亳升）中之溶液，在〇它下攪掉3〇分鐘。於混合物中，添加疊氮基二羧酸二-第三-丁酯（1·45克，9.2毫莫耳）在 5毫升THF中之溶液。使混合物溫熱至室溫，然後於室溫下攪拌20小時。蒸發THF，並使殘留物溶入醋酸乙酯（75毫升）中’以飽和碳酸氫鈉（50毫升）、水（50亳升）及鹽水（50毫升）洗滌《蒸發醋酸乙酯，並使殘留物於矽膠上藉急騾式管柱層析純化，以1 : 4至1 : 1醋酸乙酯/己烷之溶劑梯度液溶離。回收1.33克產物（64% )。Example 117B (1SV (4- (5- (2-Aminoindolyl, propionyl, Vpyridinyl, phenylmethyl, methanophenone, methanoxyl) The desired product was prepared by replacing Example 27B in Example 27C with Example 117A. MS: (ESI) m / z374 (M + H) +; iHNMRpOOMHADMSCM ^) 5ppm 3.15 (m, 4H) 3.72 (m, 1H) 4.16 (dd, J = 10.29, 5.93 Hz, 1H) 4 · 29 (m, 1H) 4.55 (s, 2H) -142- (135) 5 · 29 (s, 1H) 6 · 99 (t, > 7.02 Hz, 1H) 7 · 09 (t, J = 7.02 Hz, 1H) 7.28 (d, J = 2.18 Hz, 1H) 7.37 (d, J = 8.11 Hz, 1H) 7.43 (d, J = 8.42 Hz, 2H) 7.59 (m, 1H) 7.64 (dd , J = 10.61, 8.42 Hz, 3H) 8.30 (d, J = 2.81 Hz, 1H) 8.51 (d, J = 1.56 Hz, 1H) 11.03 (s, 1H) Example 118 〇SV2- (5- (4 -Fluorobenzyl) -pyridin-3-yloxy Vl-ΠΗ-indole! Ylmethyl) -ethanamine The desired product was obtained by substituting 4-cyanocyanine in Example 22 with 4-fluorophenyldihydroxyborane Phenyl dihydroxyborane. MS: (ESI) m / z 362 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 3.09 (m, 2H) 3.17 (d, J = 4.68 Hz, 1H) 3.71 (s? 1H) 4.12 (dd? J = 10.295 6.24 Hz3 1H) 4.26 (dd5 J = 10.29, 3.43 Hz, 1H) 6.99 (t, J = 7.49Ήζ, 1H) 7.09 ( m, 1 H) 7.26 (d, J = 2.18 Hz, 1H) 7.34 (m, 3H) 7.59 (m, 2H) 7.74 (m? 2H) 8.32 (d, J = 2.50 Hz, 1H) 8.50 (d, J = L87 Hz, 1H) 10.97 (s, 1H). Example 119 (lS) -4- (5- (2-Amino-3- (111-41H-3--3-yl-V-propoxy-Vp-ratio-3- ) -Benzoic acid The desired product was prepared by replacing 4-cyanophenyldihydroxyborane in Example 22 with 4-hydroxycarbonylphenyldihydroxyborane. MS (ESI) m / z 388 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 3.17 (m5 1H) 3.84 (m3 1H) 4.20 (m? 1H) 4.35 (m, 1H) 7.00 (t, J = 6.86 Hz, 1H) 7.10 (t, J = 7.02 Hz, 1H) 7.30 (d, J = 2.18 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.63 (d, J = 7.49 Hz, 1H) 7.68 ( m, 1H) 7.83 (d, J = 8.42 Hz, 1H) 8.04 (m3 2H) 8.26 (s3 3H) 8.38 (d5 J = 2.50 Hz, 1H) 8.59 (d, J = 1.87 Hz, 1H) 11.02 ( d, J = 1.87 Hz, 1H) Example 120 (lS) -2- (3- > Alkyl-5-isojunline-6-yl-benzylyloxy-1-phenyl-3-ylmethyl)- Ethylamine Step 1.-143- (136) Example 120Α ί ^ 1- (3,5-= ^-Benzenemethyl) _2_ (1Η-fluorinyl1-aminemethyl_ tertiary-butyl ester Add 3,5-dibromo. (1 g, 4.1 mmol), (2- # Lilyl-phenyl-ethyl )-A solution of tertiary-butyl amino acid (1.2 g, 4.1 mmol) and tribenzylphosphine (1.6 g, 2 mmol) in THF (30 ml). Stir down for 30 minutes. To the mixture was added a solution of di-third-butyl azidedicarboxylic acid (1.45 g, 9.2 mmol) in 5 ml of THF. The mixture was allowed to warm to room temperature and then stirred at room temperature for 20 hours. Evaporate THF and dissolve the residue in ethyl acetate (75 ml). Wash with saturated sodium bicarbonate (50 ml), water (50 ml) and brine (50 ml). Evaporate the ethyl acetate and make the residue The material was purified on a silica gel by flash column chromatography, and then separated with a solvent gradient of 1: 4 to 1: 1 ethyl acetate / hexane. Recovered 1.33 g of product (64%).

實例120B (2S)-[,L：(3-鱼^異喹啉-6-基-苯氧基甲基V2-rm-啕哚-3-基V乙基 1-胺甲基酸第三-丁酯將上述實例120Α (0·6克，0U毫莫耳）與孓三曱基錫烷基_異口奎淋（〇·26克，；[毫莫耳）於5毫升DMF中之溶液，以pd2(dba)3(〇] 克’ 〇·1亳莫耳）、P(〇-t〇l)3(0.07克，〇·2毫莫耳）及丁ΕΑ(〇·3毫升，2.3毫莫耳）處理。將反應物加熱至95艺，歷經6.5小時，然後冷卻，並以醋酸乙酯（75毫升）稀釋，以飽和碳酸氫鈉（50 毫升）、水（50毫升）及鹽水（50毫升）洗滌。蒸發醋酸乙酯，並使殘留物於矽膠上藉急驟式管柱層析純化，以1 : 4至i ·· 1醋酸乙酯/己烷之溶劑梯度液溶離。〇·2克產物（3〇% )。 200301122 (137) MS (ESI) m/z 572 (M+H)+.Example 120B (2S)-[, L: (3-fish ^ isoquinolin-6-yl-phenoxymethyl V2-rm-pyridin-3-yl Vethyl 1-aminomethyl acid third- Butyl ester The solution of the above Example 120A (0.6 g, 0 U millimolar) and stilbenetrisyltinyl-isokourine (0.26 g; [mmol) in 5 ml of DMF, Pd2 (dba) 3 (〇) g '〇 · 1 亳 Mor), P (〇-t〇l) 3 (0.07 g, 0.2 mM) and Ding EA (0.3 ml, 2.3 mM) Mol) treatment. The reaction was heated to 95 ° C for 6.5 hours, then cooled and diluted with ethyl acetate (75 ml), saturated with sodium bicarbonate (50 ml), water (50 ml) and brine (50 Ml). The ethyl acetate was evaporated, and the residue was purified by flash column chromatography on silica gel, and the solvent was separated by a gradient of 1: 4 to i ·· 1 ethyl acetate / hexane. 0.2 g Product (30%). 200301122 (137) MS (ESI) m / z 572 (M + H) +.

實例120C (lS)-2-(3-溪基-5-異口查口林-6-基-苯氣基乳基-口弓j 口果-3-基甲基乙胺Example 120C (lS) -2- (3-Cryl-5-Isochachaline-6-yl-benzene-air-based milk-based-orophylline j Oral-3-ylmethyl ethylamine

所要之產物係經由以實例120B取代實例27C中之實例27B 而製成。MS (ESI) m/z 472 (M+H)+ ; 1 H NMR (500 MHz，DMSO-D6) 5 ppm 2.87 (d，J=6.55 Hz，1H) 3.00 (d，J=6.55 Hz，1H) 3.47 (m，2H) 3.99 (dd，J二9.67, 6.24 Hz，1H) 4.07 (d，J=4.37 Hz，1H) 6·96 (t，J=7.02 Hz，1H) 7.06 (t，J=7.02 Hz，1H) 7.22 (d，J=2.18 Hz，1H) 7.24 (m，1H) 7.35 (d，J=8.11 Hz，1H) 7·41 (m，1H) 7.58 (d，J二 7.80 Hz3 1H) 7.62 (s, 1H) 7.89 (d, J=5.93 Hz, 1H) 8.00 (dd5 J=8.42, 1.87 Hz? 1H) 8.21 (d，J=8.73 Hz，1H) 8.32 (s，1H) 8.54 (d, J=5.62 Hz，1H) 9.35 (s，1H) 10.87 (s， 1H) 實例121 N4-(3-(5-(2-胺基-3-OH-啕哚-3-基）-丙氧基V吡啶各基V苽某嘧啶-The desired product was prepared by replacing Example 27B in Example 27C with Example 120B. MS (ESI) m / z 472 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 2.87 (d, J = 6.55 Hz, 1H) 3.00 (d, J = 6.55 Hz, 1H) 3.47 (m, 2H) 3.99 (dd, J = 9.67, 6.24 Hz, 1H) 4.07 (d, J = 4.37 Hz, 1H) 6.96 (t, J = 7.02 Hz, 1H) 7.06 (t, J = 7.02 Hz, 1H) 7.22 (d, J = 2.18 Hz, 1H) 7.24 (m, 1H) 7.35 (d, J = 8.11 Hz, 1H) 7.41 (m, 1H) 7.58 (d, J = 7.80 Hz3 1H) 7.62 (s, 1H) 7.89 (d, J = 5.93 Hz, 1H) 8.00 (dd5 J = 8.42, 1.87 Hz? 1H) 8.21 (d, J = 8.73 Hz, 1H) 8.32 (s, 1H) 8.54 (d, J = 5.62 Hz, 1H) 9.35 (s, 1H) 10.87 (s, 1H) Example 121 N4- (3- (5- (2-amino-3-OH-pyridin-3-yl) -propoxy Vpyridine

2,4-二胺實例121A2,4-diamine Example 121A

(lSM2-「5-(3-胺基-笨基V吡啶_3-基氣基1-H1H-蜊哚各某甲基V乙墓1-胺甲基酸第三-丁酯所要之產物係經由以3-胺基苯基二羥基硼烷取代實例22 中之4-氰基苯基二羥基删烷而製成。(1SM2-``5- (3-Amino-benzyl Vpyridin-3-ylamino 1-H1H-cyl indole each methyl V ethyl 1-aminomethyl acid third-butyl ester is the desired product It was prepared by replacing 4-cyanophenyldihydroxyalkane in Example 22 with 3-aminophenyldihydroxyborane.

實例121B (lSM2]5-『3-(2-胺基-嘧啶-4-某胺基V笨某1-吡啶-3-某氫基吲哚-3-基甲某V乙基1-胺甲基酸第三-丁酯使實例121A (0.07克，0.153毫莫耳）與4-氯基2-嘧啶基胺（0.021 -145- 200301122Example 121B (lSM2) 5- [3- (2-Amino-pyrimidine-4-aminyl group V stupid 1-pyridine-3-a hydroindol-3-ylmethyl group V ethyl 1-aminomethyl group Tertiary-butyl carboxylic acid Example 121A (0.07 g, 0.153 mmol) with 4-chloro 2-pyrimidinylamine (0.021 -145- 200301122)

(138) 克，0.163毫莫耳）之混合物溶於EtOH (1毫升）中。將混合物加熱至80°c過夜，然後冷卻並蒸發。使用此產物，無需進一步純化。(138) g, 0.163 mmol) was dissolved in EtOH (1 ml). The mixture was heated to 80 ° C overnight, then cooled and evaporated. This product was used without further purification.

實例121C nS)-『2-『5-(3-胺基-苯基）-p比咬-3-基乳基丨噪-3-基曱基V乙基1-胺甲基酸第三-丁酿Example 121C nS)-"2-" 5- (3-Amino-phenyl) -p-ratio-3-yllactyl 丨 no-3-ylfluorenyl Vethyl 1-aminomethyl acid third- Ding

所要之產物係經由以實例121B取代實例27C中之實例27BThe desired product was obtained by replacing Example 27B in Example 27C with Example 121B.

而製成。MS (ESI) m/z 452 (M+H)+ · 1 H NMR (500 MHz，DMSO-D6) 5 ppm 3.17 (m，2H) 3.85 (m，1H) 3·97 (s，1H) 4.19 (m，1H) 4·35 (m，1H) 6·35 (d，J=6.86 Hz， 1H) 7.00 (t5 J=7.49 Hz, 1H) 7.10 (m5 1H) 7.29 (d5 J=2.18 Hz, 1H) 7.38 (d, J=8.11 Hz, 1H) 7.52 (m5 J=7.80 Hz, 2H) 7.62 (d5 J=7.80 Hz, 1H) 7.66 (m, 1H) 7.88 (d, J=7.18 Hz, 1H) 8.25 (d，J=4.37 Hz，2H) 8.38 (d，J=2.50 Hz，1H) 8.58 (d，J=1.56 Hz，1H) 10.73 (s， 1H) 11.02 (d，J=l.87 Hz，1H). 實例122 胺基啕哚-3-基V丙氣某ϋ異，杳嗾_6_甚-节胺While made. MS (ESI) m / z 452 (M + H) + · 1 H NMR (500 MHz, DMSO-D6) 5 ppm 3.17 (m, 2H) 3.85 (m, 1H) 3.97 (s, 1H) 4.19 ( m, 1H) 4.35 (m, 1H) 6.35 (d, J = 6.86 Hz, 1H) 7.00 (t5 J = 7.49 Hz, 1H) 7.10 (m5 1H) 7.29 (d5 J = 2.18 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.52 (m5 J = 7.80 Hz, 2H) 7.62 (d5 J = 7.80 Hz, 1H) 7.66 (m, 1H) 7.88 (d, J = 7.18 Hz, 1H) 8.25 ( d, J = 4.37 Hz, 2H) 8.38 (d, J = 2.50 Hz, 1H) 8.58 (d, J = 1.56 Hz, 1H) 10.73 (s, 1H) 11.02 (d, J = l.87 Hz, 1H) Example 122 Aminopyridin-3-yl V-propane is different, 杳嗾 _6_even-benzylamine

實例122A 二苯亞甲基-胺基）-5-異喳啉冬基-茉氳甚i-wmw卜朵-3· 基甲基）-乙基]-胺曱基酸第三-丁酷將實例120Β(0·165克，0.29毫莫耳）與二苯甲酮亞胺（〇1毫升 ’ 〇·6毫莫耳）於5毫升甲苯中之溶液，以Pd2dba3(〇〇26克，〇〇28 毫莫耳）、BINAP (0.036克，0.058毫莫耳）及第三.丁醇鈉（〇〇42 克’ 0.44毫莫耳）處理。將反應物加熱至8〇它過夜，然後至％ C，歷經24小時。使混合物冷卻，並經過矽藻土過濾。使殘留物於矽膠上藉急驟式管柱層析純化，以n 1醋酸乙酉旨 -146- 200301122 (139) / 己烷溶離。回收 0.175 克產物（90% )。MS (ESI) m/z 673 (M+H)+ ·Example 122A Diphenylmethylene-amino group) -5-Isomorpholinoyl-molybdenum i-wmw budol-3.ylmethyl) -ethyl] -aminophosphonic acid tertiary-butanol Example 120B (0.165 g, 0.29 mmol) and a solution of benzophenone imide (0.1 ml '0.6 mmol) in 5 ml toluene, Pd2dba3 (〇26 g, 0.000) 28 millimoles), BINAP (0.036 grams, 0.058 millimoles) and tertiary sodium butoxide (0402 grams' 0.44 millimoles). The reaction was heated to 80 ° C. overnight and then to% C over 24 hours. The mixture was allowed to cool and was filtered through celite. The residue was purified by flash column chromatography on silica gel and dissolved with n 1 ethyl acetate -146- 200301122 (139) / hexane. Recovered 0.175 g of product (90%). MS (ESI) m / z 673 (M + H) +

實例122B (lSV3-(2-胺基-3-(1Η-Ή丨嘴-3-基）-丙乳基V5-異邊？林-6-基-笨胺使實例122A (0.175克，0.26毫莫耳）於2亳升THF中之溶液，冷卻至0X：，然後以1毫升3N HC1處理。將混合物在〇°C下攪掉15分鐘，接著於室溫下4小時。蒸發混合物，並使殘留Example 122B (1SV3- (2-Amino-3- (1Η-fluorene-3-yl) -propanoyl V5-isoside? Lin-6-yl-benzylamine) Example 122A (0.175 g, 0.26 mmol Mol) in 2 liters of THF, cooled to 0X: and then treated with 1 ml of 3N HC1. The mixture was stirred at 0 ° C for 15 minutes, and then at room temperature for 4 hours. The mixture was evaporated and allowed to Residue

物於矽膠上藉急騾式管柱層析純化，以二氯曱燒中之10% 甲醇溶離。回收〇·〇29 克產物（23% )。MS(ESI)m/z408 (M+H)+ ; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.20 (m, 2H) 3.77 (m, 1H) 4.12 (d, J=5.62 Hz，1H) 4.21 (d，J=3.43 Hz，1H) 6.58 (s，1H) 6.86 (m，1H) 6·95 (s，1H) 7.01 (m，1H) 7.08 (d, J=7.18 Hz, 1H) 7.29 (d, J=2.18 Hz, 1H) 7.37 (d, J=8.11 Hz, 1H) 7.66 (d, J= 7.80 Hz，1H) 8.13 (d，J=8.73 Hz，1H) 8·38 (d，J=6.24 Hz，1H) 8·43 (s，1H) 8·52 (m， 3H) 8·65 (d，J二6.24 Hz，1H) 9.78 (s，1H) 11.06 (d，J=1.87 Hz，1H) 實例123 4-(5-異4淋-6-基比咬-3-基）-六惫，？比呼-1-致酸第三-丁酷The material was purified on silica gel by flash column chromatography and dissolved in 10% methanol in dichloromethane. 0.029 g of product was recovered (23%). MS (ESI) m / z408 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.20 (m, 2H) 3.77 (m, 1H) 4.12 (d, J = 5.62 Hz, 1H) 4.21 (d, J = 3.43 Hz, 1H) 6.58 (s, 1H) 6.86 (m, 1H) 6.95 (s, 1H) 7.01 (m, 1H) 7.08 (d, J = 7.18 Hz, 1H) 7.29 ( d, J = 2.18 Hz, 1H) 7.37 (d, J = 8.11 Hz, 1H) 7.66 (d, J = 7.80 Hz, 1H) 8.13 (d, J = 8.73 Hz, 1H) 8.38 (d, J = 6.24 Hz, 1H) 8.43 (s, 1H) 8.52 (m, 3H) 8.65 (d, J = 6.24 Hz, 1H) 9.78 (s, 1H) 11.06 (d, J = 1.87 Hz, 1H ) Example 123 4- (5-Iso4-Lin-6-base than Bite-3-yl) -hexa exhaustion? Thirty-one acid

實例123A 4-(5-溴-p比咬-3-基）-六j. p比喷-1-致酸第三-丁醋將3,5-二溴-P比啶（12.8克，68.8毫莫耳）與六氫吡畊小羧酸第三丁酯（10克，42.4毫莫耳）於200毫升二氧陸圜中之溶液，以PdHdba)#克，5.5毫莫耳）、2-(二-第三-丁基-膦基）聯苯基（4 克’ 13,4毫莫耳）及第二-丁醇鋼（7.2克，75毫莫耳）處理。將反應物加熱至95°C ’歷經8小時，然後冷卻及經過矽藻土過濾。蒸發混合物，並使殘留物於矽膠上藉急驟式管柱層析純化，以1 : 4醋酸乙酯/己烷至100%醋酸乙酯之溶劑梯度 -147- 200301122 (140) 液溶離。回收 2·9 克產物（20% )。MS (ESI) m/z 344 (M+H)+ ·Example 123A 4- (5-Bromo-p-ratio-3-yl) -hexaj. P-ratio-1-acid tertiary-butyric acid 3,5-dibromo-Pridine (12.8 g, 68.8 Millimolar) and hexahydropyridine tricarboxylic acid third butyl ester (10 g, 42.4 millimolar) in 200 ml of dioxolane, PdHdba) #g, 5.5 millimolar), 2- (Di-tertiary-butyl-phosphino) biphenyl (4 g '13, 4 mmol) and second-butanol steel (7.2 g, 75 mmol) were treated. The reaction was heated to 95 ° C 'for 8 hours, then cooled and filtered through celite. The mixture was evaporated and the residue was purified by flash column chromatography on silica gel with a solvent gradient of 1: 4 ethyl acetate / hexane to 100% ethyl acetate -147- 200301122 (140). 2.9 g of product was recovered (20%). MS (ESI) m / z 344 (M + H) +

實例123BExample 123B

4-(5-異p奎琳-6-基-p比咬-3-基）-六氣？比p井-1-複酸第三-丁酉旨— 所要之產物係經由以實例123Α取代實例IBB中之實例27八而製成。MS (ESI) m/z 408 (Μ+Η)+ ; 1 H NMR (500 ΜΗζ，氯仿-D) (5 ppm 1·50 (m，9Η) 3·29 (m，4Η) 3·65 (m，4Η) 7·46 (m，1Η) 7·72 (d，JN5.62 Ηζ，1Η) 7·83 (d， J=1.87 Hz, 1H) 7.99 (s, 1H) 8.09 (d5 J=8.74 Hz, 1H) 8.37 (d, J=2.81 Hz, 1H) 8.46 (d, J=1.87 Hz, 1H) 8.59 (d5 J=5.93 Hz, 1H) 9.31 (s, 1H). 實例124 6-(5-六氫p比喷-1-基比症-3-基）-異嗅琳所要之產物係經由以實例123取代實例27C中之實例27B而製成。MS (ESI) m/z 291 (M+H)4* ; 1H NMR (500 MHz,溶劑）5 ppm 3.47 (m， 4H) 3·79 (m，4H) 8·30 (m，1H) 8.39 (dd，J=8.58, 1.72 Hz，1H) 8.49 (d，J=6.55 Hz，1H) 8.57 (d，J=2.50 Hz，1H) 8.63 (m，2H) 8.70 (m，2H) 9.78 (s，1H)· 實例125 ((2SV2-胺基各(5-(2-胺基-3-ΠΗ-Θ丨哚-3-基）-丙氧基V吡啶-3-基V苯基4- (5-Iso-p-quelin-6-yl-p than bite-3-yl) -hexaki? Bi-Phi-1-Flavic Acid Tertiary-Butyric Acid-The desired product was prepared by replacing Example 27A in Example IBB with Example 123A. MS (ESI) m / z 408 (Μ + Η) +; 1 H NMR (500 ΜΗζ, chloroform-D) (5 ppm 1.50 (m, 9Η) 3.29 (m, 4Η) 3.65 (m , 4Η) 7.46 (m, 1Η) 7.72 (d, JN5.62 Ηζ, 1 ，) 7.83 (d, J = 1.87 Hz, 1H) 7.99 (s, 1H) 8.09 (d5 J = 8.74 Hz , 1H) 8.37 (d, J = 2.81 Hz, 1H) 8.46 (d, J = 1.87 Hz, 1H) 8.59 (d5 J = 5.93 Hz, 1H) 9.31 (s, 1H). Example 124 6- (5-Six Hydrogen p-Phenyl-1-ylpyridin-3-yl) -Isothelin The desired product was prepared by replacing Example 27B in Example 27C with Example 123. MS (ESI) m / z 291 (M + H ) 4 *; 1H NMR (500 MHz, solvent) 5 ppm 3.47 (m, 4H) 3.79 (m, 4H) 8.30 (m, 1H) 8.39 (dd, J = 8.58, 1.72 Hz, 1H) 8.49 (d, J = 6.55 Hz, 1H) 8.57 (d, J = 2.50 Hz, 1H) 8.63 (m, 2H) 8.70 (m, 2H) 9.78 (s, 1H) · Example 125 ((2SV2-amino groups ( 5- (2-Amino-3-ΠΗ-Θ 丨 indol-3-yl) -propoxy Vpyridin-3-yl Vphenyl

-(3-氪笨基-甲酮）標題化合物係經由以2-胺基-5-碘基-3’-氯基二苯甲酮取代實例 32 中之實例 32A 而製成。MS(ESI)m/z291 (M+H)+ ; ^NMR (500 MHz, DMSO-D6) δ ppm 3.15 (m5 2H) 3.81 (m, 1H) 4.11 (m, 1H) 4.26 (m, 1H) 7.00 (m, 2H) 7.09 (m, 1H) 7.27 (τη, 1H) 7.39 (m, 2H) 7.60 (m, 4H) 8.21 (m, 1H) 8.32 (m，3H) 11.07 (m，1H). 實例126 (lS)-N6-(3-(5-(2-胺基哚-3-基）-丙氣基 V吡啶-3-基 V笨基 V9H- -148- 200301122-(3-fluorenyl-methanone) The title compound was prepared by substituting Example 32A in Example 32 with 2-amino-5-iodo-3'-chlorobenzophenone. MS (ESI) m / z291 (M + H) +; ^ NMR (500 MHz, DMSO-D6) δ ppm 3.15 (m5 2H) 3.81 (m, 1H) 4.11 (m, 1H) 4.26 (m, 1H) 7.00 (m, 2H) 7.09 (m, 1H) 7.27 (τη, 1H) 7.39 (m, 2H) 7.60 (m, 4H) 8.21 (m, 1H) 8.32 (m, 3H) 11.07 (m, 1H). Example 126 (1S) -N6- (3- (5- (2-Aminoindol-3-yl) -propanyl Vpyridin-3-yl V benzyl V9H- -148- 200301122

(141) 嘌呤-2,6-立胺標題化合物係經由以6-氯基-9H-嘌呤-2-基胺取代實例121中之 4-氯基-2-嘧啶基胺而製成。MS (ESI) m/z 492 (M+H)+ ; 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.18 (d, J=8.29 Hz, 2H) 3.83 (m5 1H) 4.01 (m, 1H) 4.19 (m5 1H) 4.36 (m3 1H) 7.01 (m, 2H) 7.09 (t, J=7.06 Hz, 1H) 7.16 (s5 1H) 7.30 (m, 2H) 7.38 (d3 J=8.29 Hz5 1H) 7.63 (m, 2H) 8.18 (s, 2H) 8.30 (m, 2H) 8.35 (d, J=2.45 Hz, 1H) 8.56 (d5 J=1.84 Hz, 1H) 11.02 (s, 1H).(141) Purine-2,6-triamine The title compound was prepared by replacing 4-chloro-2-pyrimidinylamine in Example 121 with 6-chloro-9H-purin-2-ylamine. MS (ESI) m / z 492 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.18 (d, J = 8.29 Hz, 2H) 3.83 (m5 1H) 4.01 (m, 1H) 4.19 (m5 1H) 4.36 (m3 1H) 7.01 (m, 2H) 7.09 (t, J = 7.06 Hz, 1H) 7.16 (s5 1H) 7.30 (m, 2H) 7.38 (d3 J = 8.29 Hz5 1H) 7.63 (m , 2H) 8.18 (s, 2H) 8.30 (m, 2H) 8.35 (d, J = 2.45 Hz, 1H) 8.56 (d5 J = 1.84 Hz, 1H) 11.02 (s, 1H).

實例127 (3-(5-((2SV2-胺基丨哚-3-基V丙氧基）-吡啶各基茉某V嘧啶- 2-基-胺Example 127 (3- (5-((2SV2-Amino-indol-3-yl-V-propoxy) -pyridinyl molybdenum V-pyrimidin- 2-yl-amine

標題化合物係經由以2-氯基嘧啶取代實例121中之4-氯基-2-嘧啶基胺而製成。MS(ESI)m/z437(M+H)+ ; iHNMR^OOMHz， DMSO-D6) δ ppm 3.17 (d5 J=5.30 Hz, 1H) 4.06 (q, J=5.30 Hz, 5H) 6.86 (t3 J=4.84 Hz，2H) 6.96 (d，J=7.18 Hz，1H) 7.05 (s，1H) 7·26 (m，1H) 7.34 (d，J=8.11 Hz，1H) 7.40 (t，J=7.96 Hz，1H) 7.54 (m，1H) 7·55 (s，1H) 7.85 (m，2H) 8.07 (t，J=1 ·72 Hz，1H) 8.30 (d，J=2.50 Hz，1H) 8.44 (d，J=l.87 Hz，1H) 8·50 (d，J=4.68 Hz，2H) 9.68 (s，1H) 10.85 (s，1H). 實例128 (3-(5-((2SV2-胺基啕哚-3-基V丙氧基V吡啶各基）-苯基）-嘍唑- 2-基-胺標題化合物係經由以2-氯基噻唑取代實例121中之4-氯基-2-嘧啶基胺而製成。MS(ESI)m/z442(M+H)+ ; iHNMR^OOMHz， DMSO-D6) δ ppm 3.16 (m, 3H) 4.16 (m5 1H) 4.34 (m, 1H) 6.94 (d5 J=3.74 Hz, 1H) 7·01 (m，1H) 7.10 (m，1H) 7.22 (m，1H) 7.28 (dd，J=7.96, 2·96 Hz，2H) 7.38 (d，J= -149- (142) 8.42 Hz，1H) 7.42 (d，>7·80 Hz，1H) 7.57 (m，lH) 7·62 (d，J=8.11 Hz，1H) 8·02 (s， 1H) 8.14 (s, 2H) 8.35 (d, J=2.50 Hz, 1H) 8.48 (d5 J=1.87 Hz, 1H) 10.31 (s, 1H) 11.01 (s，1H)· 實例129 N-(3-(5-((2S)-2-胺基-3-(1沁钊哚-3-基丙氣基V吡啶-3-基）-笨基）-乙醯胺The title compound was prepared by replacing 4-chloro-2-pyrimidinylamine in Example 121 with 2-chloropyrimidine. MS (ESI) m / z437 (M + H) +; iHNMR ^ OOMHz, DMSO-D6) δ ppm 3.17 (d5 J = 5.30 Hz, 1H) 4.06 (q, J = 5.30 Hz, 5H) 6.86 (t3 J = 4.84 Hz, 2H) 6.96 (d, J = 7.18 Hz, 1H) 7.05 (s, 1H) 7.26 (m, 1H) 7.34 (d, J = 8.11 Hz, 1H) 7.40 (t, J = 7.96 Hz, 1H) 7.54 (m, 1H) 7.55 (s, 1H) 7.85 (m, 2H) 8.07 (t, J = 1.72 Hz, 1H) 8.30 (d, J = 2.50 Hz, 1H) 8.44 (d, J = l.87 Hz, 1H) 8.50 (d, J = 4.68 Hz, 2H) 9.68 (s, 1H) 10.85 (s, 1H). Example 128 (3- (5-((2SV2-aminopyrene) Indole-3-yl V-propoxy V pyridyl) -phenyl) -oxazole-2-yl-amine The title compound was prepared by substituting 4-chloro-2-pyrimidine in Example 121 with 2-chlorothiazole. Based on amine. MS (ESI) m / z442 (M + H) +; iHNMR ^ OOMHz, DMSO-D6) δ ppm 3.16 (m, 3H) 4.16 (m5 1H) 4.34 (m, 1H) 6.94 (d5 J = 3.74 Hz, 1H) 7.01 (m, 1H) 7.10 (m, 1H) 7.22 (m, 1H) 7.28 (dd, J = 7.96, 2.96 Hz, 2H) 7.38 (d, J = -149 -(142) 8.42 Hz, 1H) 7.42 (d, > 7.80 Hz, 1H) 7.57 (m, lH) 7.62 (d, J = 8.11 Hz, 1H) 8.02 (s, 1H) 8.14 (s, 2H) 8.35 (d, J = 2.50 Hz, 1H) 8.48 (d5 J = 1.87 Hz, 1H) 10.31 (s, 1H) 1 1.01 (s, 1H) · Example 129 N- (3- (5-((2S) -2-Amino-3- (1qindol-3-ylpropanyl Vpyridin-3-yl) -benzyl ) -Acetylamine

實例129A nSM2-「5-(3-乙醯胺基-苯基）-吡啶：基氣基1-H1H-㈣哚-3-基甲基 V乙基1-胺甲基酸第三-丁酯使實例121A (0.05克，0.11毫莫耳）溶於二氯甲烷（1.5毫升）中，並以醋酸酐（〇·2毫升，2.1毫莫耳）與三乙胺（0.1毫升，0.77 毫莫耳）處理。將混合物於室溫下攪拌過夜，然後以二氯甲烷（25毫升）稀釋，並以水（15毫升）及鹽水（15毫升）洗滌。蒸發混合物，並使用之而無需進一步純化。實例129Β N-(3-(5-((2SV2-胺基-3-(1Η-吲哚各基）-丙氧基V吡啶各基）-苯基V乙醯胺所要之產物係經由以實例129A取代實例27C中之實例27B 而製成。MS(ESI)m/z401(M+H)+ ; iHNMRGOOMHADMSO-DS) 5ppm 2.07 (m，3H) 3·16 (m，3H) 4.16 (m，1H) 4·33 (m，1H) 7.01 (m，1H) 7.10 (m，1H) 7·29 (m，1H) 7.38 (m，3H) 7·55 (m，2H) 7.62 (m，1H) 7.99 (m，1H) 8.14 (m，2H) 8.35 (m， 1H) 8.48 (m，1H) 10.06 (m，1H) 11.01 (m，1H)· 實例130 丨嗓-3-基甲基）-穴复p比呼-1-基）-p比症-3-基）-異峻琳 (143)Example 129A nSM2- "5- (3-Ethylamido-phenyl) -pyridine: ylamino 1-H1H-pyridin-3-ylmethyl Vethyl 1-aminomethyl acid tert-butyl ester Example 121A (0.05 g, 0.11 mmol) was dissolved in dichloromethane (1.5 ml) and acetic anhydride (0.2 ml, 2.1 mmol) and triethylamine (0.1 ml, 0.77 mmol) were dissolved. ). The mixture was stirred at room temperature overnight, then diluted with dichloromethane (25 ml) and washed with water (15 ml) and brine (15 ml). The mixture was evaporated and used without further purification. Examples 129B N- (3- (5-((2SV2-Amino-3- (1H-indolyl) -propoxyVpyridyl))-phenyl Vacetamide The desired product was obtained by using Example 129A Made by replacing Example 27B in Example 27C. MS (ESI) m / z401 (M + H) +; iHNMRGOOMHADMSO-DS) 5ppm 2.07 (m, 3H) 3.16 (m, 3H) 4.16 (m, 1H) 4.33 (m, 1H) 7.01 (m, 1H) 7.10 (m, 1H) 7.29 (m, 1H) 7.38 (m, 3H) 7.55 (m, 2H) 7.62 (m, 1H) 7.99 ( m, 1H) 8.14 (m, 2H) 8.35 (m, 1H) 8.48 (m, 1H) 10.06 (m, 1H) 11.01 (m, 1H) · Example 130 丨 Homo-3-ylmethyl)- Call complex than p-1-yl) -p disease than 3-yl) - iso Jun Lin (143)

標題化合物係經由以實例124取代苯胺，並以3-甲醯基啕哚取代實例116B中之實例116A而製成。MS(ESI)(m/z420M + H)+ ；1 H NMR (400 MHz, DMSO-D6) δ ppm 1.89 (s, 2H) 2.50 (m, 4H) 2.60 (m, 4H) 7.02 (m, 2H) 7.27 (d, ]=2A6 Hz, 1H) 7.36 (d, J=7.98 Hz? 1H) 7.68 (m, 2H) 7.87 (d3 J=5.83 Hz，1H) 8.05 (dd，J=8.59, 1 ·53 Hz，1H) 8.22 (d，J=8_90 Hz，1H) 8·34 (m，2H) 8.44 (d，J=1 ·84 Hz，1H) 8.54 (d，J=5.83 Hz，1H) 9.35 (s，1H) 10.93 (s，1H). 實例131 3-((2S)-2-胺基-3-(1Η·Ήΐ嗓-3-基）-丙氧基）-5-異邊g林-6-基-苯曱酸The title compound was prepared by replacing aniline with Example 124 and substituting Example 116A of Example 116B with 3-methylfluorenyl indole. MS (ESI) (m / z420M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 1.89 (s, 2H) 2.50 (m, 4H) 2.60 (m, 4H) 7.02 (m, 2H) 7.27 (d,] = 2A6 Hz, 1H) 7.36 (d, J = 7.98 Hz? 1H) 7.68 (m, 2H) 7.87 (d3 J = 5.83 Hz, 1H) 8.05 (dd, J = 8.59, 1 · 53 Hz , 1H) 8.22 (d, J = 8_90 Hz, 1H) 8.34 (m, 2H) 8.44 (d, J = 1 · 84 Hz, 1H) 8.54 (d, J = 5.83 Hz, 1H) 9.35 (s, 1H) 10.93 (s, 1H). Example 131 3-((2S) -2-amino-3- (1Η · Ήΐ-3-yl) -propoxy) -5-isoside g-lin-6- Phenyl-benzoic acid

實例131A 3-「(2SV2-第三-丁氣羰基胺基-3-(1Η-吲哚-3-某V丙氧基1-5-異4啉- 6-基-表甲酸將實例120 (0·2克，0.3毫莫耳）在6毫升DMF中之溶液，以 Pd(dppf)2Cl2 (0.039 克，0·07 毫莫耳）、Pd(OAc)2 (0.016 克，0·07 毫莫耳）、氫氧化銨（0.15毫升）及三乙胺（0.5毫升，3.9毫莫耳）處理。將反應物加熱至80°C，然後使CO起泡經過30分鐘。將混合物加熱至80°C過夜，然後冷卻，以HC1中和，並以醋酸乙酯洗滌。蒸發水而得產物。MS (ESI) m/z 53·8 (M+H)+ ·Example 131A 3-"(2SV2-Third-butanecarbonylamino-3- (1H-indole-3-V-propoxy1-5-iso4-line-6-yl-epicarboxylic acid) Example 120 ( 0.2 g, 0.3 mmol) in 6 ml of DMF with Pd (dppf) 2Cl2 (0.039 g, 0.007 mmol), Pd (OAc) 2 (0.016 g, 0.007 mmol) Ear), ammonium hydroxide (0.15 ml) and triethylamine (0.5 ml, 3.9 mmol). The reaction was heated to 80 ° C and then the CO was bubbled over 30 minutes. The mixture was heated to 80 ° C Overnight, then cooled, neutralized with HC1, and washed with ethyl acetate. The product was evaporated by evaporation. MS (ESI) m / z 53 · 8 (M + H) + ·

實例131B 3-((2S)-2-胺基各(1H-吲哚-3-基V丙氧基V5-異4啉各基-苯甲酸所要之產物係經由以實例131A取代實例27C中之實例27B 而製成。MS(ESI)m/z438 (M+H)+ ; iHNMRpOOMHADMSO-De) 5ppm 3·14 (m，3H) 4·20 (m，1H) 4·35 (d，J=2.81 Hz，1H) 7·02 (m，1H) 7.09 (d，J=8.11 Hz， 1H) 7.30 (d, J=2.50 Hz, 1H) 7.38 (d5 J=8.11 Hz, 1H) 7.63 (m, 2H) 7.68 (s5 1H) 8.04 (s, 1H) 8.11 (m，2H) 8.18 (s，3H) 8.36 (d，J=8.73 Hz，1H) 8.42 (s，1H) 8.61 (d，J=5.93 Hz， 200301122 (144) 1H) 9·53 (s，1H) 11.02 (d，J=1.56 Hz，1H)·Example 131B 3-((2S) -2-amino group (1H-indole-3-yl Vpropoxy V5-iso4line group-benzoic acid) The desired product was obtained by replacing Example 27C with Example 131A Example 27B. MS (ESI) m / z438 (M + H) +; iHNMRpOOMHADMSO-De) 5ppm 3 · 14 (m, 3H) 4 · 20 (m, 1H) 4 · 35 (d, J = 2.81 Hz, 1H) 7.02 (m, 1H) 7.09 (d, J = 8.11 Hz, 1H) 7.30 (d, J = 2.50 Hz, 1H) 7.38 (d5 J = 8.11 Hz, 1H) 7.63 (m, 2H) 7.68 (s5 1H) 8.04 (s, 1H) 8.11 (m, 2H) 8.18 (s, 3H) 8.36 (d, J = 8.73 Hz, 1H) 8.42 (s, 1H) 8.61 (d, J = 5.93 Hz, 200301122 (144) 1H) 9 · 53 (s, 1H) 11.02 (d, J = 1.56 Hz, 1H) ·

實例132Example 132

4-(5-((2S)-2-胺基各(1H-吲哚-3-基丙氧基）-吡啶-3-基V笨胺所要之產物係經由以4-胺基苯基二羥基硼烷取代實例22 中之4-氰基苯基二羥基硼烷而製成。MS (ESI) m/z 359 (M+H)+ ; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.16 (τη, 2H) 3.90 (d, J=6333 Hz, 3H) 4.16 (dd，J=10.61，6·24 Hz，1H) 4.33 (m，1H) 6·77 (d，J=8.42 Hz，1H) 7.01 (m，1H) 7.11 (s， 1H) 7.29 (d, J=2.18 Hz, 1H) 738 (d, J=8.11 Hz, 1H) 7.47 (d, J=8.42 Hz, 1H) 7.61 (m, 2H) 8.17 (s, 2H) 8.24 (d? J=2.50 Hz, 1H) 8.50 (d, J=1.56 Hz, 1H) 11.02 (s, 1H). 實例1334- (5-((2S) -2-amino group (1H-indol-3-ylpropoxy) -pyridin-3-yl V benzylamine The desired product is via 4-aminophenyldi Hydroxyborane was prepared in place of 4-cyanophenyldihydroxyborane in Example 22. MS (ESI) m / z 359 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.16 (τη, 2H) 3.90 (d, J = 6333 Hz, 3H) 4.16 (dd, J = 10.61, 6.24 Hz, 1H) 4.33 (m, 1H) 6.77 (d, J = 8.42 Hz, 1H ) 7.01 (m, 1H) 7.11 (s, 1H) 7.29 (d, J = 2.18 Hz, 1H) 738 (d, J = 8.11 Hz, 1H) 7.47 (d, J = 8.42 Hz, 1H) 7.61 (m, 2H) 8.17 (s, 2H) 8.24 (d? J = 2.50 Hz, 1H) 8.50 (d, J = 1.56 Hz, 1H) 11.02 (s, 1H). Example 133

醯胺所要之產物係經由以實例132取代實例129中之實例121A而製成。MS (ESI) m/z 401 (M+H)+ ; 1 H NMR (500 MHz，DMSO-D6) (5 ppm 3·17 (d，J=6.86 Hz，5H) 4·18 (d，J=5.93 Hz，1H) 4.32 (d，J=3.12 Hz，1H) 7·01 (m，1H) 7.09 (d，J=7.18 Hz，1H) 7·29 (d，>2·18 Hz，1H) 7·38 (d，J=8.11 Hz，1H) 7·58 (d，J= 2.18 Hz，1H) 7.65 (m，4H) 8.28 (m，4H) 8.51 (d，J=1.25 Hz，1H) 10.10 (s，1H) 11.03 (d，J=1.25 Hz，1H). 實例134 -152- (145)Amidine The desired product was prepared by substituting Example 132 for Example 121A in Example 129. MS (ESI) m / z 401 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) (5 ppm 3.17 (d, J = 6.86 Hz, 5H) 4 · 18 (d, J = 5.93 Hz, 1H) 4.32 (d, J = 3.12 Hz, 1H) 7.01 (m, 1H) 7.09 (d, J = 7.18 Hz, 1H) 7.29 (d, > 2.18 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.58 (d, J = 2.18 Hz, 1H) 7.65 (m, 4H) 8.28 (m, 4H) 8.51 (d, J = 1.25 Hz, 1H) 10.10 (s, 1H) 11.03 (d, J = 1.25 Hz, 1H). Example 134 -152- (145)

N6-(4-(5-((2S)-2-胺基-3-(1Η-口?I 嗓-3-基）-丙乳基 V口比咬-3-基）-笨基）-9H- 嘌呤-2,6-二胺標題化合物係經由以實例132取代實例U6中之實例121A而製成。MS (ESI) m/z 492 (M+H)+ ; 1 H NMR (500 MHz，DMS0-D6) 5 ppm 2.51 (m，3H) 3·16 (t，J=7.49 Hz，1H) 3.91 (d，J=53.97 Hz，2H) 4·19 (dd，J=10.76, 6.08 Hz， 1H) 4.35 (dd，J=10.76, 2·96 Hz，1H) 7.01 (t，J=7.18 Hz，1H) 7.11 (t，JM7.02 Hz，1H) 7.30 (d，JN2.18 Hz，1H) 7.39 (d，J=8.11 Hz，1H) 7.64 (m，2H) 7.74 (d，J=8.73 Hz，1H) 8.02 (d，】=8·42 Hz，1H) 8.20 (d，J=3.74 Hz，2H) 8,26 (s，1H) 8.34 (d，J=2.50 Hz, 1H) 8.58 (d，J=l.56 Hz，1H) 10.52 (s，1H) 11.03 (d，J=1 ·87 Hz，1H)· 實例135 N4-(4-(5-((2S)-2-胺某吲哚-3-基V丙氣基）-吡啶-3-基苯基V嘧啶-2,4-二胺標題化合物係經由以實例132取代實例121中之實例121A而製成。MS (ESI) m/z 452 (M+H)+ ; 1H NMR (500 MHz，DMSO-D6) 5 ppm 3.16 (d, J=7.18 Hz, 2H) 3.86 (m, 2H) 4.18 (m, 1H) 4.33 (d, J=3.12 Hz, 1H) 635 (d, J= 7·18 Hz，1H) 7·01 (t，J=7.33 Hz，1H) 7.10 (t，J=7.02 Hz，1H) 7.29 (d，JN2.18 Hz，1H) 7.39 (d, J=8.11 Hz, 1H) 7.62 (dd, J=4.52, 2.03 Hz, 2H) 7.73 (d, J=8.73 Hz, 2H) 7.88 (d，J=7.49 Hz，2H) 8·20 (s，3H) 8.34 (d，>2,81 Hz，1H) 8.56 (d，J=l ·87 Hz，1H) 10.69 (s, 1H) 11.02 (d, J=1.87 Hz, 1H). 實例136 (4-(5-((2SV2-胺基各ΠΗ-⑻哚-3-基丙氣基）-吡啶-3-基）-笨基V嘧啶- 2备胺標題化合物係經由以實例132取代實例U7中之實例121A而製成。MS (ESI) m/z 437 (M+H)+ ; 1 H NMR (500 MHz，DMSO-D6) (5 ppm 2.94 200301122 (146) (d，J=6.55 Hz，1H) 3·04 (m，1H) 3.17 (d，J=3.74 Hz，1H) 3·55 (m，1H) 4·04 (dd，J= 9.83, 6.40 Hz，1H) 4.16 (dd，J=9.98, 4.06 Hz，1H) 6.88 (t，J=4.84 Hz，1H) 6.98 (t，J= 7.49 Hz, 1H) 7.08 (t, J=7.64 Hz, 1H) 7.24 (d, J=2.18 Hz, 1H) 7.36 (d, J=8.11 Hz, 1H) 7.55 (m，1H) 7·59 (d，JN7.80 Hz, 1H) 7.64 (d，J=8.73 Hz，2H) 7.90 (d，JN9.05 Hz，2H) 8.25 (d，J=2.81 Hz，1H) 8.49 (d，J=1.56 Hz，1H) 8.52 (d，J=4.99 Hz，2H) 9.78 (s，1H). 實例137 K(2S)-2-胺基嗓-3-基丙氧基）-5-異g奎琳-6-基-笨甲月青N6- (4- (5-((2S) -2-Amino-3- (1H-O-I? -3-yl) -Prolactyl-V-I-By-3-yl) -benzyl)- The 9H-purine-2,6-diamine title compound was prepared by replacing Example 121A in Example U6 with Example 132. MS (ESI) m / z 492 (M + H) +; 1 H NMR (500 MHz, DMS0-D6) 5 ppm 2.51 (m, 3H) 3.16 (t, J = 7.49 Hz, 1H) 3.91 (d, J = 53.97 Hz, 2H) 4.19 (dd, J = 10.76, 6.08 Hz, 1H ) 4.35 (dd, J = 10.76, 2.96 Hz, 1H) 7.01 (t, J = 7.18 Hz, 1H) 7.11 (t, JM7.02 Hz, 1H) 7.30 (d, JN2.18 Hz, 1H) 7.39 (d, J = 8.11 Hz, 1H) 7.64 (m, 2H) 7.74 (d, J = 8.73 Hz, 1H) 8.02 (d,] = 8.42 Hz, 1H) 8.20 (d, J = 3.74 Hz, 2H ) 8,26 (s, 1H) 8.34 (d, J = 2.50 Hz, 1H) 8.58 (d, J = 1.56 Hz, 1H) 10.52 (s, 1H) 11.03 (d, J = 1.87 Hz, 1H) · Example 135 N4- (4- (5-((2S) -2-amine indole-3-yl V propanyl) -pyridin-3-ylphenyl V pyrimidine-2,4-diamine The title compound was prepared by replacing Example 121A in Example 121 with Example 132. MS (ESI) m / z 452 (M + H) +; 1H NMR (500 MHz, DMSO-D6) 5 ppm 3.16 (d, J = 7.18 Hz, 2H) 3.86 (m, 2H) 4.18 (m, 1H) 4.33 (d, J = 3.1 2 Hz, 1H) 635 (d, J = 7.18 Hz, 1H) 7.01 (t, J = 7.33 Hz, 1H) 7.10 (t, J = 7.02 Hz, 1H) 7.29 (d, JN2.18 Hz , 1H) 7.39 (d, J = 8.11 Hz, 1H) 7.62 (dd, J = 4.52, 2.03 Hz, 2H) 7.73 (d, J = 8.73 Hz, 2H) 7.88 (d, J = 7.49 Hz, 2H) 8 · 20 (s, 3H) 8.34 (d, > 2,81 Hz, 1H) 8.56 (d, J = l · 87 Hz, 1H) 10.69 (s, 1H) 11.02 (d, J = 1.87 Hz, 1H) Example 136 (4- (5-((2SV2-amino group ΠΗ-pyridin-3-ylpropanyl) -pyridin-3-yl) -benzyl V-pyrimidine-2 preparative amine The title compound is given by way of example 132 was prepared in place of Example 121A in Example U7. MS (ESI) m / z 437 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) (5 ppm 2.94 200301122 (146) (d, J = 6.55 Hz, 1H) 3.04 (m, 1H) 3.17 (d, J = 3.74 Hz, 1H) 3.55 (m, 1H) 4.04 (dd, J = 9.83, 6.40 Hz, 1H) 4.16 (dd, J = 9.98, 4.06 Hz, 1H) 6.88 (t, J = 4.84 Hz, 1H) 6.98 (t, J = 7.49 Hz, 1H) 7.08 (t, J = 7.64 Hz, 1H) 7.24 (d, J = 2.18 Hz, 1H) 7.36 (d, J = 8.11 Hz, 1H) 7.55 (m, 1H) 7.59 (d, JN7.80 Hz, 1H) 7.64 (d, J = 8.73 Hz, 2H) 7.90 (d, JN9.05 Hz, 2H) 8.25 (d, J = 2.81 Hz, 1H) 8.49 (d, J = 1.56 Hz, 1H) 8.52 (d, J = 4.99 Hz, 2H) 9.78 (s, 1H). Example 137 K (2S) -2-amino group-3- Propylpropoxy) -5-isog-quelin-6-yl-benzylazine

(lS)-[2-(3-氰基-5-異喳啉-6-基-茉氫基Vl-ΠΗ-吲哚-3-基甲某乙基 V胺甲某酸第三-丁酯(lS)-[2- (3-Cyano-5-isophosphon-6-yl-jamohydrol Vl-ΠΗ-indole-3-ylmethyl ethyl ethyl V-amino acid tert-butyl ester

將實例120 (0.15克，0.3亳莫耳）在3毫升二氧陸圜與1毫升 DMF中之溶液，以Pd(PPh3)4(0.030克，0.026毫莫耳）與氰化鋅 (0.037克’ 0·3毫莫耳）處理。將反應物加熱至95°C，歷經3天。將混合物以醋酸乙酯（25毫升）稀釋，並以水（15毫升）及鹽水（15毫升）洗滌。蒸發混合物，並使殘留物於矽膠上藉急驟式管柱層析純化，以1 : 1醋酸乙酯/己烷溶離。回收〇·1〇8 克產物（79% )。MS(ESI)m/z519(M+H)+·A solution of Example 120 (0.15 g, 0.3 mol) in 3 ml of dioxolane and 1 ml of DMF was prepared with Pd (PPh3) 4 (0.030 g, 0.026 mmol) and zinc cyanide (0.037 g ' 0.3 millimoles). The reaction was heated to 95 ° C over 3 days. The mixture was diluted with ethyl acetate (25 ml) and washed with water (15 ml) and brine (15 ml). The mixture was evaporated, and the residue was purified by flash column chromatography on silica gel and eluted with 1: 1 ethyl acetate / hexane. 0.18 g of product was recovered (79%). MS (ESI) m / z519 (M + H) + ·

實例137BExample 137B

3-((2g)-2-胺基吲哚-3-某V丙氫基V5-異喹啉-6-基-茉甲腈所要之產物係經由以實例137A取代實例27C中之實例27B -154- (147)3-((2g) -2-Aminoindole-3-a certain propane group V5-isoquinolin-6-yl-jasonitrile The desired product is obtained by replacing Example 27B in Example 27C with Example 137A- 154- (147)

而製成。MS(ESI)m/z419(M+H)+ ; iHNMRpOOMHADMSCH^) 5ppm 2.95 (d，J=6.55 Hz，1H) 3.05 (dd，J=14.35, 7·18 Hz，1H) 3·57 (m，1H) 4.07 (m，1H) 4·16 (d，J=4.06 Hz，1H) 6.96 (t，J=7.18 Hz，1H) 7.06 (t，J=7.18 Hz，1H) 7.23 (d，J= 2·18 Hz，1H) 7.34 (d，J=8.11 Hz，1H) 7·50 (s，1H) 7.58 (d，J=7.80 Hz，1H) 7.73 (s，1H) 7.87 (d, J=5.93 Hz, 1H) 7.93 (s, 1H) 8.04 (dd, J=8.58, 1.72 Hz, 1H) 8.23 (d3 J=8.42 Hz, 1H) 8.36 (s, 1H) 8.55 (d, J=5.62 Hz, 1H) 9.36 (s, 1H) 10.91 (s, 1H). 實例138While made. MS (ESI) m / z419 (M + H) +; iHNMRpOOMHADMSCH ^) 5ppm 2.95 (d, J = 6.55 Hz, 1H) 3.05 (dd, J = 14.35, 7.18 Hz, 1H) 3.57 (m, 1H) 4.07 (m, 1H) 4.16 (d, J = 4.06 Hz, 1H) 6.96 (t, J = 7.18 Hz, 1H) 7.06 (t, J = 7.18 Hz, 1H) 7.23 (d, J = 2 18 Hz, 1H) 7.34 (d, J = 8.11 Hz, 1H) 7.50 (s, 1H) 7.58 (d, J = 7.80 Hz, 1H) 7.73 (s, 1H) 7.87 (d, J = 5.93 Hz , 1H) 7.93 (s, 1H) 8.04 (dd, J = 8.58, 1.72 Hz, 1H) 8.23 (d3 J = 8.42 Hz, 1H) 8.36 (s, 1H) 8.55 (d, J = 5.62 Hz, 1H) 9.36 (s, 1H) 10.91 (s, 1H). Example 138

5’-芊氣基-5-異4啉-6-基-(3,3’)聯吡啶實例138A 6-(5->臭-口比淀-3-基）-異口查口林標題化合物係經由以3,5_二溴基吡啶取代實例27B中之實例2A而製成。Example of 5'-fluorenyl-5-iso4line-6-yl- (3,3 ') bipyridine 138A 6- (5- > odorous-Kyobido-3-yl) -iso-chachaline The title compound was prepared by replacing Example 2A in Example 27B with 3,5-dibromopyridine.

實例138B 3-芊氧基-5-三甲基錫烷基-吡啶標題化合物係經由以3-苄氧基-5-溴基吡啶取代實例27A中之6-溴基異p奎啦而製成。Example 138B 3-Methoxy-5-trimethylstannyl-pyridine The title compound was prepared by substituting 6-bromoisopropylquinone in Example 27A with 3-benzyloxy-5-bromopyridine. .

實例138C 5’-芊氧基_5_異4啉-6-基-(3,3’)聯吡啶標題化合物係經由以實例138A取代實例27B中之實例2A，實例138B取代實例27B中之實例27A而製成。MS(ESI)m/z390 (M+H)+ ； 1 H NMR (400 MHz, DMS0-D6) δ ppm 5.35 (s5 2H) 738 (d5 J=7.36 Hz, 1H) 7.44 (t, J=7.21 Hz, 2H) 7.53 (d, J=6.75 Hz, 2H) 8.11 (m3 1H) 8.32 (d, J=6.14 Hz, 1H) 8.50 (m3 2H) 8.57 (m5 1H) 8.70 (d3 J=6.14 Hz, 1H) 8.74 (t, J=2.15 Hz, 1H) 8.79 (m5 2H) 9.14 (d, J=2.15 Hz5 1H) 9.22 (d? J=1.84 Hz, 1H) 9.76 (s, 1H). -155- 200301122 (148) 實例142 (7-(5-((2S)-2-胺某-3-ΠΗ-钊哚-3-基）-丙羞^基 >吡啶-3-基）-吡啶并（2>d) ζϋ斗基）篆蓋A ψ Μ 140Α 士腹基-6-氯-兹^鱼於200psi下，將2,6-二氯-於驗酸（17·77克，92.6毫莫耳）在濃氨水（173毫升）中之混合物加熱至130°C，歷經24小時。蒸發混合物，並使殘留物溶入水（200毫升）中，且以濃HC1中和 φ ，然後萃取於醚（200毫升）中。蒸發醚，產生12克產物（75% ) 。MS (DCI/NH3) m/z 173 (M+1). ·Example 138C The 5'-fluorenyloxy-5_iso4line-6-yl- (3,3 ') bipyridine title compound was prepared by replacing Example 2A in Example 27B with Example 138A, and replacing Example 138B with Example 138B 27A. MS (ESI) m / z390 (M + H) +; 1 H NMR (400 MHz, DMS0-D6) δ ppm 5.35 (s5 2H) 738 (d5 J = 7.36 Hz, 1H) 7.44 (t, J = 7.21 Hz , 2H) 7.53 (d, J = 6.75 Hz, 2H) 8.11 (m3 1H) 8.32 (d, J = 6.14 Hz, 1H) 8.50 (m3 2H) 8.57 (m5 1H) 8.70 (d3 J = 6.14 Hz, 1H) 8.74 (t, J = 2.15 Hz, 1H) 8.79 (m5 2H) 9.14 (d, J = 2.15 Hz5 1H) 9.22 (d? J = 1.84 Hz, 1H) 9.76 (s, 1H). -155- 200301122 (148 ) Example 142 (7- (5-((2S) -2-Amine-3-ΠΗ-zhaodol-3-yl) -propylamyl > pyridin-3-yl) -pyrido (2 &d; d ) ϋ ϋ 基篆) cover A ψ M 140 Α Shibuji-6-chloro-z ^ fish at 200psi, 2,6-dichloro-yu acid (17.77 g, 92.6 mmol) in concentrated The mixture in aqueous ammonia (173 ml) was heated to 130 ° C for 24 hours. The mixture was evaporated and the residue was dissolved in water (200 ml), and φ was neutralized with concentrated HC1, and then extracted into ether (200 ml). Evaporation of the ether produced 12 g of product (75%). MS (DCI / NH3) m / z 173 (M + 1).

實例140B 2-胺基-6-氯-If驗酸胺於實例140A (11.9克，69.2毫莫耳）在1，2-二氯乙烷（100毫升）中之混合物内，添加二氯化亞硫醯（30毫升，411毫莫耳）與 DMF (觸媒）。使混合物回流4小時，然後蒸發。使殘留物溶於醚（200毫升）中，並使氨起泡經過15分鐘。將混合物於室溫下攪拌過夜，然後以水（100毫升）及鹽水（100毫升）洗滌。 ® 蒸發醚，產生 9·2 克產物（78% )。MS(DCI/NH3)m/Z172(M+l)+·Example 140B 2-Amino-6-chloro-If acid amine was added to a mixture of Example 140A (11.9 g, 69.2 mmol) in 1,2-dichloroethane (100 ml), and dichlorodichloride was added. Thiosulfan (30 ml, 411 mmol) with DMF (catalyst). The mixture was refluxed for 4 hours and then evaporated. The residue was dissolved in ether (200 ml) and ammonia was allowed to foam for 15 minutes. The mixture was stirred at room temperature overnight and then washed with water (100 ml) and brine (100 ml). ® Evaporates the ether to produce 9.2 g of product (78%). MS (DCI / NH3) m / Z172 (M + l) + ·

OHOH

t 140C 7-氯-吨J定并[2,3:^1嘧途-4-醇使實例140B (1克，5·8毫莫耳）於原甲酸三乙酯（30毫升）中 -156- 20030Π22 20030Π22t 140C 7-Chloro-tonine Benzene [2,3: ^ 1 Pyridino-4-ol Make Example 140B (1 g, 5.8 mmol) in triethyl orthoformate (30 ml) -156 -20030Π22 20030Π22

(149) 之混合物，回流6小時，然後冷卻。添加己烷（15〇毫升），並將所形成之固體過遽’且以水及己烷洗滌，而得〇·27克產物（26% )。MS : (DCI/NH3)m/z=182(M+l) C1tx>(149) mixture, refluxed for 6 hours, and then cooled. Hexane (150 ml) was added, and the formed solid was washed with water and hexane to obtain 0.27 g of the product (26%). MS: (DCI / NH3) m / z = 182 (M + l) C1tx >

ClCl

實例140D 4,7-二氯-吡啶并使實例140C (1克，5·5毫莫耳）於氯化磷醯（4〇毫升）中之混合物回流2小時，然後冷卻並蒸發。使殘留物溶於醋酸乙酯（75毫升）中，以飽和碳酸氫鈉（5〇毫升）、水（5〇毫升）及鹽水（50毫升）洗滌。蒸發醋酸乙酯，產生〇·8克產物（73% )。Example 140D 4,7-dichloro-pyridine and a mixture of Example 140C (1 g, 5.5 mmol) in phosphonium chloride (40 ml) was refluxed for 2 hours, then cooled and evaporated. The residue was dissolved in ethyl acetate (75 ml) and washed with saturated sodium bicarbonate (50 ml), water (50 ml) and brine (50 ml). Evaporation of ethyl acetate gave 0.8 g of product (73%).

CI ΗΝCI ΗΝ

實例140Ε (7-氯-吡啶并「2,3-dl嘧啶-4-基V笨基-胺將實例140D (0.5克，2.5毫莫耳）與苯胺（0.23毫升，2.5毫莫耳）於THF (25毫升）與2-丙醇（2.5毫升）中之溶液，在0°C下攪拌1小時，然後在室溫下2天。蒸發THF，並使殘留物溶於醋酸乙酯（75毫升）中，以水（50毫升）及鹽水（50毫升）洗滌。蒸發醋酸乙酯，並使殘留物於矽膠上藉急驟式管柱層析純化，以1 : 1醋酸乙酯/己烷溶離。回收0.15克產物（23% )。 -157- 200301122 (150) MS (ESI) m/z 390 (M+H)+ ·Example 140E (7-chloro-pyrido "2,3-dlpyrimidin-4-yl Vbenzyl-amine. Example 140D (0.5 g, 2.5 mmol) with aniline (0.23 ml, 2.5 mmol) in THF (25 ml) and 2-propanol (2.5 ml) were stirred at 0 ° C for 1 hour and then at room temperature for 2 days. The THF was evaporated and the residue was dissolved in ethyl acetate (75 ml) It was washed with water (50 ml) and brine (50 ml). Ethyl acetate was evaporated, and the residue was purified by flash column chromatography on silica gel, and was separated by 1: 1 ethyl acetate / hexane. Recovery 0.15 g of product (23%). -157- 200301122 (150) MS (ESI) m / z 390 (M + H) + ·

實例140F (7-(5-((2S)-2-胺基-3-(lH-Hl 嗓-3-基 V丙氧基）-p比咬-3-基比淀并（2,3-d) 盘啶-4-基苯基-胺標題化合物係經由以實例140E取代實例27中之6-溴基異 4 啉而製成。MS (ESI) m/z 257 (M+H)+ ; 1H NMR (500 MHz, DMSO-D6) δ ppm 3.15 (m, 3H) 3.38 (s? 4H) 4.06 (dd, J=10.295 5.93 Hz, 4H) 4.21 (dd, 1=10.45, 2·96 Hz，1H) 6·99 (t，J=7.18 Hz，1H) 7·09 (t，J=7.18 Hz，1H) 7.26 (d，J=2.18 Hz，1H) 7.35 (m，4H) 8·21 (d，J=4.37 Hz，3H) 11.02 (s，1H)Example 140F (7- (5-((2S) -2-amino-3- (lH-Hl-l-3-yl-V-propoxy) -p-r--3-yl-r- (2,3- d) the title compound of panidin-4-ylphenyl-amine was prepared by substituting 6-bromoisotetraline in Example 27 with Example 140E. MS (ESI) m / z 257 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 3.15 (m, 3H) 3.38 (s? 4H) 4.06 (dd, J = 10.295 5.93 Hz, 4H) 4.21 (dd, 1 = 10.45, 2.96 Hz, 1H ) 6.99 (t, J = 7.18 Hz, 1H) 7.09 (t, J = 7.18 Hz, 1H) 7.26 (d, J = 2.18 Hz, 1H) 7.35 (m, 4H) 8.21 (d, J = 4.37 Hz, 3H) 11.02 (s, 1H)

A-565462.6 實例141 (7-(5-((2S)-2-胺基-3-ΠΗ-咱哚各基V丙氧基V吡啶各基）:吨—唉并（2?3_d) 峰途-4-基V乙基-胺 -158- 200301122A-565462.6 Example 141 (7- (5-((2S) -2-Amino-3-ΠΗ-oxindole groups V propoxy V pyridine groups): ton-pyrene (2? 3_d) peak path -4-yl Vethyl-amine-158- 200301122

(151) 標題化合物係經由以乙胺取代實例140中之苯胺而製成。 MS (ESI) m/z 440 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) 5 ppm 130 (m5 3H) 3.19 (m, 2H) 3.78 (m? 2H) 4.05 (s, 2H) 4.21 (dd, J=10.45, 5.77 Hz, 1H) 4.38 (dd5 J= 10.45, 2.96 Hz，1H) 7.00 (t，J=7.49 Hz，1H) 7.09 (t，J=7.49 Hz，1H) 7.30 (d，JN2.18 Hz, 1H) 7.38 (d, J=7.80 Hz, 1H) 7.61 (d, J=7.80 Hz, 1H) 8.15 (s, 1H) 8.24 (d, J=4.06 Hz，2H) 8·51 (d，J=8.42 Hz，1H) 8·56 (d，J=1.56 Hz，1H) 8.96 (s，1H) 9.01 (d，J=8.74 Hz, 1H) 9.12 (s, 1H) 11.03 (d? J=1.56 Hz, 1H).(151) The title compound was prepared by replacing the aniline in Example 140 with ethylamine. MS (ESI) m / z 440 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 130 (m5 3H) 3.19 (m, 2H) 3.78 (m? 2H) 4.05 (s, 2H ) 4.21 (dd, J = 10.45, 5.77 Hz, 1H) 4.38 (dd5 J = 10.45, 2.96 Hz, 1H) 7.00 (t, J = 7.49 Hz, 1H) 7.09 (t, J = 7.49 Hz, 1H) 7.30 ( d, JN2.18 Hz, 1H) 7.38 (d, J = 7.80 Hz, 1H) 7.61 (d, J = 7.80 Hz, 1H) 8.15 (s, 1H) 8.24 (d, J = 4.06 Hz, 2H) 8 · 51 (d, J = 8.42 Hz, 1H) 8.56 (d, J = 1.56 Hz, 1H) 8.96 (s, 1H) 9.01 (d, J = 8.74 Hz, 1H) 9.12 (s, 1H) 11.03 (d J = 1.56 Hz, 1H).

A-622026.6 實例142 (7-(5-((2SV2-胺基-3-ΠΗ-吲哚各基V丙氧基V吡啶各基V吡啶并（2,3-d)A-622026.6 Example 142 (7- (5-((2SV2-Amino-3-Πfluorene-indole each group V propoxy V pyridine each group V pyrido (2,3-d)

口密咬-4-基）_宇基-胺標題化合物係經由以芊胺取代實例140中之苯胺而製成。 MS (ESI) m/z 502 (M+H)+. 1H NMR (400 MHz, DMSO-D6) δ ppm 3.19 (m,J= 6.60, 6.60 Hz，2H) 3.89 (m，1H) 4.22 (dd，J=10.43, 5.52 Hz，1H) 4.38 (m，1H) 5.00 (d， J=5.52 Hz，2H) 7.00 (m，1H) 7.09 (m，1H) 7.34 (m，5H) 7·45 (m，1H) 7.62 (d，J=7,98 Hz, 1H) 8.17 (m5 1H) 8.31 (d5 J=3.68 Hz, 2H) 8.54 (m, 2H) 8.97 (s, 1H) 9.07 (d5 J= 8.90 Hz, 1H) 9.12 (d, J=1.84 Hz, 1H) 10.81 (s5 1H) 11.05 (d, J=2.15 Hz, 1H). -159- 200301122 (152)Mouth octyl-4-yl) _Uki-amine The title compound was prepared by replacing the aniline in Example 140 with amidine. MS (ESI) m / z 502 (M + H) +. 1H NMR (400 MHz, DMSO-D6) δ ppm 3.19 (m, J = 6.60, 6.60 Hz, 2H) 3.89 (m, 1H) 4.22 (dd, J = 10.43, 5.52 Hz, 1H) 4.38 (m, 1H) 5.00 (d, J = 5.52 Hz, 2H) 7.00 (m, 1H) 7.09 (m, 1H) 7.34 (m, 5H) 7.45 (m, 1H) 7.62 (d, J = 7,98 Hz, 1H) 8.17 (m5 1H) 8.31 (d5 J = 3.68 Hz, 2H) 8.54 (m, 2H) 8.97 (s, 1H) 9.07 (d5 J = 8.90 Hz, 1H) 9.12 (d, J = 1.84 Hz, 1H) 10.81 (s5 1H) 11.05 (d, J = 2.15 Hz, 1H). -159- 200301122 (152)

實例143 基甲美νΆ豈邊说-6-某-毗畊-2-基氣基）-乙胺標題化合物係經由以6-氯4畊-2-醇取代實例27中之3-溴基 -5-羥基吡啶而製成。MS(ESI)m/z396(M+H)+ ; iHNMRGOOMHz， DMSO-D6) δ ppm 3.20 (m5 1H) 3.95 (m, 1H) 4.52 (m5 J=7.36 Hz, 1H) 4.76 (m, 1H) 7.02 (m? J=7.06 Hz, 1H) 7.11 (m3 J=7.98 Hz, 1H) 7.34 (d? J=2.15 Hz? 1H) 7.41 (d, J= 8.29 Hz, 1H)7.65 (d5 J=7.98 Hz, 1H) 7.99 (d5 J=5.83 Hz, 1H) 8.17 (s, 3H) 8.28 (m, 2H) 8.41 (s, 1H) 8.62 (m, 1H) 8.72 (s, 1H) 9.10 (s, 1H) 11.05 (s, 1H).Example 143 Chromametyl -6-a certain-pyridin-2-ylamino group) -ethylamine The title compound was prepared by replacing the 3-bromo group in Example 27 with 6-chloro-4-pent-2-ol- 5-hydroxypyridine. MS (ESI) m / z396 (M + H) +; iHNMRGOOMHz, DMSO-D6) δ ppm 3.20 (m5 1H) 3.95 (m, 1H) 4.52 (m5 J = 7.36 Hz, 1H) 4.76 (m, 1H) 7.02 (m? J = 7.06 Hz, 1H) 7.11 (m3 J = 7.98 Hz, 1H) 7.34 (d? J = 2.15 Hz? 1H) 7.41 (d, J = 8.29 Hz, 1H) 7.65 (d5 J = 7.98 Hz, 1H) 7.99 (d5 J = 5.83 Hz, 1H) 8.17 (s, 3H) 8.28 (m, 2H) 8.41 (s, 1H) 8.62 (m, 1H) 8.72 (s, 1H) 9.10 (s, 1H) 11.05 ( s, 1H).

〇〇

實例144 (lSV2-(5-異4啉-6-基-吡啶-3-基氳某VI-笨基-乙胺 bA^o 克 HBocExample 144 (1SV2- (5-Iso-4-line-6-yl-pyridin-3-yl) a VI-benzyl-ethylamine bA ^ o g HBoc

實例144A -160-Example 144A -160-

(153) 溴4比咬-3_i氧基）小苯基·-乙基1-胺甲基酸第三-丁酯將5-溴4咬-3-醇（〇.3克，1/7毫莫耳）、（2-羥基小苯基·乙基> 接甲基酸第三-丁酯（0.41克L7毫莫耳）及三苯膦（0.52克，2亳莫耳）於THF (15毫升）中之溶液，在〇°c下攪拌3〇分鐘。於混合物中，添加疊氮基二羧酸二-第三-丁酯（〇 46克，2毫莫耳）在5毫升THF中之溶液。使混合物溫熱至室溫，然後於室溫下攪拌20小時。蒸發THF，並使殘留物溶入醋酸乙酯（75亳升）中，以飽和碳酸氫鈉（5〇毫升）、水（50毫升）及鹽水（50毫升）洗滌。蒸發醋酸乙酯，並使殘留物於矽膠上藉急驟式警柱層析純化，以1 : 4至1 : 2醋酸乙酯/己烷之溶劑梯度硬溶離。回收0.82克產物與疊氮基二羧酸二-第三-丁酯之混合物。MS (ESI) m/z 395 (M+H)+.(153) Bromine 4 is less than 3 -i-oxy) small phenyl-ethyl 1-aminomethyl acid tert-butyl ester 5-bromo 4 -3 -ol (0.3 g, 1/7 milligrams) Mol), (2-Hydroxyphenyl · ethyl), and tert-butyl methyl acid (0.41 g L7 mmol) and triphenylphosphine (0.52 g, 2 mol) in THF (15 Ml), and stirred at 0 ° C for 30 minutes. To the mixture, add bis-di-azido dicarboxylic acid di-tertiary-butyl ester (0 46 g, 2 mmol) in 5 ml of THF. Solution. Warm the mixture to room temperature, then stir at room temperature for 20 hours. Evaporate THF and dissolve the residue in ethyl acetate (75 ml). (50 ml) and brine (50 ml). Ethyl acetate was evaporated and the residue was purified by flash column chromatography on silica gel with a solvent gradient of 1: 4 to 1: 2 ethyl acetate / hexane. Hard dissociation. A mixture of 0.82 g of the product and the di-third-butyl azide dicarboxylic acid was recovered. MS (ESI) m / z 395 (M + H) +.

實例144B (lSV2-(5-異4啉各基-吡啶-3-基氣基VI-苯基-乙胺標題化合物係經由以實例144A取代實例27中之實例2A而製成。MS (ESI) m/z 342 (M+H)+ ; 1 H NMR (500 MHz，DMSO-D6) 5 ppm 4.51 (m，JN8.74 Hz，1H) 4·57 (m，1H) 4·87 (m，1H) 7.49 (m，3H) 7·63 (d，J=7.18 Hz，2H) 7.90 (d，J=5.62 Hz, 1H) 7.93 (m，1H) 8.10 (dd，J=8.73, 1.56 Hz，1H) 8.26 (d，J=8.73 Hz, 1H) 8.39 (s, 1H) 8.45 (d, J=2.50 Hz, 1H) 8.56 (d, J=5.62 Hz, 1H) 8.69 (m, 2H) -161 - 200301122 (154) 8·74 (d，J=1.56 Hz，1Η) 9·39 (s，1H)·Example 144B (1SV2- (5-Iso-4lineyl-pyridin-3-ylamino) VI-phenyl-ethylamine The title compound was prepared by replacing Example 2A in Example 27 with Example 144A. MS (ESI) m / z 342 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 4.51 (m, JN8.74 Hz, 1H) 4 · 57 (m, 1H) 4 · 87 (m, 1H ) 7.49 (m, 3H) 7.63 (d, J = 7.18 Hz, 2H) 7.90 (d, J = 5.62 Hz, 1H) 7.93 (m, 1H) 8.10 (dd, J = 8.73, 1.56 Hz, 1H) 8.26 (d, J = 8.73 Hz, 1H) 8.39 (s, 1H) 8.45 (d, J = 2.50 Hz, 1H) 8.56 (d, J = 5.62 Hz, 1H) 8.69 (m, 2H) -161-200301122 ( 154) 8 · 74 (d, J = 1.56 Hz, 1Η) 9 · 39 (s, 1H) ·

實例145Example 145

(lS)-l-(lH-吲哚-3-基甲基）-2-(6-(3-甲基-1H-吲唑-5-基）-吡畊-2-基氧基乙胺標題化合物係經由以102C取代實例143中之6-溴基異喳啉而製成。MS (ESI) m/z 399 (M+H)+ ; 1 H NMR (400 MHz，DMSO-D6) 6 ppm 2.54 (s3 3H) 3.18 (m, 2H) 3.92 (m? 1H) 4.47 (d, J=7.06 Hz, 1H) 4.70 (m? 1H) 7.02 (d5 J=7.06 Hz，1H) 7·10 (m，1H) 7.32 (d，J=2.15 Hz，1H) 7·39 (d，J=8.29 Hz，1H) 7.49 (d， J=8.59 Hz, 1H) 7.64 (d, J=8.29 Hz, 1H) 7.92 (dd, J-8.75, 1.69 Hz? 1H) 8.15 (m5 2H) 8·24 (s，1H) 8.46 (s，1H) 8.95 (s，1H) 11.04 (d，J=1.53 Hz，1H)·(lS) -l- (lH-indol-3-ylmethyl) -2- (6- (3-methyl-1H-indazol-5-yl) -pyroxy-2-yloxyethylamine The title compound was prepared by substituting 102C for 6-bromoisoxoline in Example 143. MS (ESI) m / z 399 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) 6 ppm 2.54 (s3 3H) 3.18 (m, 2H) 3.92 (m? 1H) 4.47 (d, J = 7.06 Hz, 1H) 4.70 (m? 1H) 7.02 (d5 J = 7.06 Hz, 1H) 7.10 (m, 1H) 7.32 (d, J = 2.15 Hz, 1H) 7.39 (d, J = 8.29 Hz, 1H) 7.49 (d, J = 8.59 Hz, 1H) 7.64 (d, J = 8.29 Hz, 1H) 7.92 ( dd, J-8.75, 1.69 Hz? 1H) 8.15 (m5 2H) 8.24 (s, 1H) 8.46 (s, 1H) 8.95 (s, 1H) 11.04 (d, J = 1.53 Hz, 1H) ·

下列化合物係根據使用於實例27或102中之程序，使用適當Boc保護之N-Boc-胺基乙醇製成〇The following compounds were prepared according to the procedure used in Examples 27 or 102 using N-Boc-aminoethanol, which is appropriately Boc protected.

實例146 (1SV1-環己基甲基-2-(5-異喹啉-6-基-吡啶-3-基氣基乙胺 -162- 200301122Example 146 (1SV1-cyclohexylmethyl-2- (5-isoquinolin-6-yl-pyridin-3-ylaminoethylamine -162- 200301122

(155) MS (ESI) m/z 362 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) 5 ppm 0.92 (s, 2H) 1.24 (m，3H) 1.64 (m，6H) 3·52 (s，2H) 4·23 (dd，J=10.61，6·55 Hz，1H) 4·40 (dd，J= 10.61，3.12 Hz，1H) 7·91 (m，1H) 7.96 (d，J=5.93 Hz，1H) 8.13 (dd，J=8.58, 1.72 Hz， 4H) 8.32 (d，J=8.73 Hz，1H) 8.43 (m，2H) 8.59 (m，J=5.62 Hz，1H) 8·74 (d，J=1.56 Hz， 1H) 9.44 (s，1H).(155) MS (ESI) m / z 362 (M + H) +; 1H NMR (500 MHz, DMSO-D6) 5 ppm 0.92 (s, 2H) 1.24 (m, 3H) 1.64 (m, 6H) 3. · 52 (s, 2H) 4 · 23 (dd, J = 10.61, 6.55 Hz, 1H) 4 · 40 (dd, J = 10.61, 3.12 Hz, 1H) 7.91 (m, 1H) 7.96 (d, J = 5.93 Hz, 1H) 8.13 (dd, J = 8.58, 1.72 Hz, 4H) 8.32 (d, J = 8.73 Hz, 1H) 8.43 (m, 2H) 8.59 (m, J = 5.62 Hz, 1H) 8 · 74 (d, J = 1.56 Hz, 1H) 9.44 (s, 1H).

H A-674563.7H A-674563.7

音例147Example 147

芊基-2-(5-(3-甲基-1H-W唑-5-基）-吡啶各基氧基V乙胺 MS (ESI) m/z 359 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (m, 3H) 3.05 (m5 1H) 3.38 (m, 1H) 3.87 (m, 1H) 4.12 (dd5 J=10.76, 5.77 Hz, 1H) 4.28 (dd, J= 10.76, 2.96 Hz, 1H) 7.33 (m, 4H) 7.57 (d, J=8.73 Hz, 1H) 7.67 (m? 2H) 8.06 (s, 1H) 8.21 (s5 2H) 8.31 (d, J-1.56 Hz, 1H) 8.61 (s? 1H) 12.74 (s5 1H).Fluorenyl-2- (5- (3-methyl-1H-Wazole-5-yl) -pyridinyloxy Vethylamine MS (ESI) m / z 359 (M + H) +; 1H NMR ( 500 MHz, DMSO-D6) δ ppm 2.55 (m, 3H) 3.05 (m5 1H) 3.38 (m, 1H) 3.87 (m, 1H) 4.12 (dd5 J = 10.76, 5.77 Hz, 1H) 4.28 (dd, J = 10.76, 2.96 Hz, 1H) 7.33 (m, 4H) 7.57 (d, J = 8.73 Hz, 1H) 7.67 (m? 2H) 8.06 (s, 1H) 8.21 (s5 2H) 8.31 (d, J-1.56 Hz, 1H) 8.61 (s? 1H) 12.74 (s5 1H).

H A-679219.7 實例148 (lSV2-(5-(3-甲基-1H-H丨吨-5-基）-吡啶-3-基氧基）-1-苯基-乙胺 -163- 200301122 (156) MS (ESI) m/z 345 (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) 5 ppm 2.55 (m, 3H) 4.01 (s，1H) 4.31 (m，1H) 4.39 (m，1H) 4.57 (m，1H) 7.36 (m，1H) 7.43 (t，J=7.36 Hz， 2H) 7.55 (t，J=7.67 Hz，4H) 7.70 (m，1H) 8.08 (s，1H) 8.29 (d，J二2·76 Hz，1H) 8.57 (d， J=1.84Hz，1H) 12.72 (s，1H).H A-679219.7 Example 148 (1SV2- (5- (3-methyl-1H-H Ton-5-yl) -pyridin-3-yloxy) -1-phenyl-ethylamine-163- 200301122 ( 156) MS (ESI) m / z 345 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) 5 ppm 2.55 (m, 3H) 4.01 (s, 1H) 4.31 (m, 1H) 4.39 ( m, 1H) 4.57 (m, 1H) 7.36 (m, 1H) 7.43 (t, J = 7.36 Hz, 2H) 7.55 (t, J = 7.67 Hz, 4H) 7.70 (m, 1H) 8.08 (s, 1H) 8.29 (d, J = 2.76 Hz, 1H) 8.57 (d, J = 1.84Hz, 1H) 12.72 (s, 1H).

實例149 (lS)-2-(5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基VI-苯基-乙胺 MS (ESI) m/z 365 (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) 5 ppm 0.90 (d5 J= 14.12 Hz，2H) 1.16 (m，3H) 1·44 (m，3H) 1.69 (m，3H) 2.55 (d，J=5.22 Hz，3H) 3.37 (m3 3H) 4.03 (m5 1H) 4.17 (dd, J=9.97, 4.14 Hz? 1H) 7.56 (d? J=8.59 Hz, 1H) 7.71 (m5 2H) 8.08 (s，1H) 8·28 (d，J=2.76 Hz，1H) 8.57 (d，J=1 ·53 Hz，1H) 12.73 (s，1H).Example 149 (1S) -2- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy VI-phenyl-ethylamine MS (ESI) m / z 365 ( M + H) +; 1 H NMR (400 MHz, DMSO-D6) 5 ppm 0.90 (d5 J = 14.12 Hz, 2H) 1.16 (m, 3H) 1.44 (m, 3H) 1.69 (m, 3H) 2.55 (d, J = 5.22 Hz, 3H) 3.37 (m3 3H) 4.03 (m5 1H) 4.17 (dd, J = 9.97, 4.14 Hz? 1H) 7.56 (d? J = 8.59 Hz, 1H) 7.71 (m5 2H) 8.08 (s, 1H) 8 · 28 (d, J = 2.76 Hz, 1H) 8.57 (d, J = 1 · 53 Hz, 1H) 12.73 (s, 1H).

A-697376.7 實例150 4-((2SV2-胺基-3-(5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基）丙基V苯曱腈 MS (ESI) m/z 384 (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) δ ppm 2.55 (s5 3H) -164- 200301122 (157) 3.14 (d，J=7.06 Hz，2H) 3·94 (m，1H) 4.15 (dd，J=10.74, 5·52 Hz，1H) 4.32 (dd，J= 10.74, 3.07 Hz, 1H) 7.57 (t, J=8.13 Hz, 2H) 7.69 (m5 1H) 7.73 (t, J=1.99 Hz, 1H) 7.85 (d，J=7.98 Hz，2H) 8.07 (s，1H) 8.24 (m，2H) 8.32 (d，J=2.45 Hz，1H) 8.64 (d，J= 1.53 Hz, 1H).A-697376.7 Example 150 4-((2SV2-amino-3- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) propyl V benzonitrile MS (ESI) m / z 384 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 2.55 (s5 3H) -164- 200301122 (157) 3.14 (d, J = 7.06 Hz, 2H) 3.94 (m, 1H) 4.15 (dd, J = 10.74, 5.52 Hz, 1H) 4.32 (dd, J = 10.74, 3.07 Hz, 1H) 7.57 (t, J = 8.13 Hz, 2H) 7.69 (m5 1H) 7.73 (t, J = 1.99 Hz, 1H) 7.85 (d, J = 7.98 Hz, 2H) 8.07 (s, 1H) 8.24 (m, 2H) 8.32 (d, J = 2.45 Hz, 1H) 8.64 (d , J = 1.53 Hz, 1H).

‘ 實例151 (lS)-2_(5_(3_甲基峻-5-基）-p比咬-3-基氣基）-1-奈-2-基甲基-乙胺 MS： (ESI) m/z 409 (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) δ ppm 2.54 (s, 3H) 3.23 (d，J=7.06 Hz，2H) 4.00 (s，1H) 4·21 (dd，J=10.74, 5·52 Hz，1H) 4·37 (dd，J= 10.74, 3.07 Hz, 1H) 7.51 (m, 3H) 7.56 (d, J=8.29 Hz, 1H) 7.67 (dd, J=8.59, 1.84 Hz, 1H) 7.78 (m, 1H) 7.86 (m5 2H) 7.91 (m, 2H) 8.07 (s, 1H) 8.26 (m, 2H) 836 (d3 J= 2.76 Hz，1H) 8.65 (d，J=1 ·84 Hz，1H).'' Example 151 (1S) -2_ (5_ (3-Methylammon-5-yl) -p-ratio-3-ylamino) -1-naphth-2-ylmethyl-ethylamine MS: (ESI) m / z 409 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 2.54 (s, 3H) 3.23 (d, J = 7.06 Hz, 2H) 4.00 (s, 1H) 4.21 (dd, J = 10.74, 5.52 Hz, 1H) 4.37 (dd, J = 10.74, 3.07 Hz, 1H) 7.51 (m, 3H) 7.56 (d, J = 8.29 Hz, 1H) 7.67 (dd, J = 8.59, 1.84 Hz, 1H) 7.78 (m, 1H) 7.86 (m5 2H) 7.91 (m, 2H) 8.07 (s, 1H) 8.26 (m, 2H) 836 (d3 J = 2.76 Hz, 1H) 8.65 ( d, J = 1 · 84 Hz, 1H).

實例152 4-((2S)-2-胺基-3-(5-異4啉-6-基-吡啶各基氧基-丙基V苯甲腈 MS (ESI) m/z 381 (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.16 (m, 2H) 3.97 (s，1H) 4·26 (m，2H) 7.56 (d，J=8.29 Hz，2H) 7.84 (d，J=8.29 Hz，2H) 7.90 (m， -165- 200301122 (158) 1Η) 8·24 (m，2H) 8.33 (m，2H) 8.48 (m，2H) 8·55 (s，1H) 8.67 (d，J=6.14 Hz，1H) 8.79 (d，J=1.84 Hz，1H) 9.67 (s，1H).Example 152 4-((2S) -2-amino-3- (5-iso4-line-6-yl-pyridyloxy-propyl V benzonitrile MS (ESI) m / z 381 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.16 (m, 2H) 3.97 (s, 1H) 4.26 (m, 2H) 7.56 (d, J = 8.29 Hz, 2H) 7.84 ( d, J = 8.29 Hz, 2H) 7.90 (m, -165- 200301122 (158) 1Η) 8.24 (m, 2H) 8.33 (m, 2H) 8.48 (m, 2H) 8.55 (s, 1H) 8.67 (d, J = 6.14 Hz, 1H) 8.79 (d, J = 1.84 Hz, 1H) 9.67 (s, 1H).

實例153 (lS)-2-(5-異p奎琳-6-基比症-3-基氧基）-1-蕃-2-基甲基V乙胺 MS ： (ESI) m/z 406 (M+H)+ ； 1H NMR (400 MHz, DMSO-D6) δ ppm 3.24 (m5 2H) 4.03 (s, 1H) 4.31 (m, 2H) 7.50 (m, 3H) 7.89 (m5 5H) 8.22 (m, 2H) 8.33 (s5 3H) 8.48 (m3 2H) 8.54 (s, 1H) 8.66 (m5 J=6.14 Hz, 1H) 8.78 (d, J=1.84 Hz, 1H).Example 153 (lS) -2- (5-Isoquinine-6-ylpyridin-3-yloxy) -1-fan-2-ylmethyl Vethylamine MS: (ESI) m / z 406 (M + H) +; 1H NMR (400 MHz, DMSO-D6) δ ppm 3.24 (m5 2H) 4.03 (s, 1H) 4.31 (m, 2H) 7.50 (m, 3H) 7.89 (m5 5H) 8.22 (m , 2H) 8.33 (s5 3H) 8.48 (m3 2H) 8.54 (s, 1H) 8.66 (m5 J = 6.14 Hz, 1H) 8.78 (d, J = 1.84 Hz, 1H).

實例154 (lSVl-芊基-2-(5-異4啉-6-基-吡啶-3-基氧基）-乙胺 MS (ESI) m/z 356 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 3.05 (m3 2H) 3·88 (s，1H) 4.16 (dd，J=10.61，5.62 Hz，1H) 4.32 (dd，J=10.76, 2·96 Hz，1H) 7.29 (m， 1H) 7·35 (m，3H) 7.85 (m，1H) 7.99 (d，J=5.62 Hz，1H) 8.12 (dd，J=8.58, 1.72 Hz，1H) 8.27 (m，3H) 8.33 (d，J=8.74 Hz，1H) 8.43 (m，2H) 8·60 (d，JM5.93 Hz，1H) 8·75 (d， J=1.87Hz，lH)9.47(s，1H). -166 - 200301122Example 154 (1SVl-fluorenyl-2- (5-iso4-line-6-yl-pyridin-3-yloxy) -ethylamine MS (ESI) m / z 356 (M + H) +; 1H NMR ( 500 MHz, DMSO-D6) δ ppm 3.05 (m3 2H) 3.88 (s, 1H) 4.16 (dd, J = 10.61, 5.62 Hz, 1H) 4.32 (dd, J = 10.76, 2.96 Hz, 1H) 7.29 (m, 1H) 7.35 (m, 3H) 7.85 (m, 1H) 7.99 (d, J = 5.62 Hz, 1H) 8.12 (dd, J = 8.58, 1.72 Hz, 1H) 8.27 (m, 3H) 8.33 (d, J = 8.74 Hz, 1H) 8.43 (m, 2H) 8.60 (d, JM5.93 Hz, 1H) 8.75 (d, J = 1.87Hz, lH) 9.47 (s, 1H). -166-200301122

(159)(159)

(lS)-l-(4-乳-卞基）-2-(5-(3-甲基-ΙΗ-βΙ峻-5-基V卩比淀-3-基乳基）-乙胺 MS (ESI) m/z 377 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s? 3H)(lS) -l- (4-lacto-fluorenyl) -2- (5- (3-methyl-l-l-β-l-5-yl-pyridine-3-yllactyl) -ethylamine MS ( ESI) m / z 377 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s? 3H)

3.04 (d, J=7.18 Hz, 2H) 3.85 (m, 1H) 4.14 (dd, J=10.76, 5.77 Hz, 1H) 4.30 (m, 1H) 7.19 (m，J=8.89, 8·89 Hz，2H) 7.37 (dd，J=8.58, 5·46 Hz，2H) 7.58 (d，J=8.73 Hz，1H) 7.69 (dd，J=8.74, 1.56 Hz，1H) 7.75 (s，1H) 8.08 (s，1H) 8.23 (s，3H) 8·34 (s，1H) 8.65 (s，1H)3.04 (d, J = 7.18 Hz, 2H) 3.85 (m, 1H) 4.14 (dd, J = 10.76, 5.77 Hz, 1H) 4.30 (m, 1H) 7.19 (m, J = 8.89, 8.89 Hz, 2H ) 7.37 (dd, J = 8.58, 5.46 Hz, 2H) 7.58 (d, J = 8.73 Hz, 1H) 7.69 (dd, J = 8.74, 1.56 Hz, 1H) 7.75 (s, 1H) 8.08 (s, 1H) 8.23 (s, 3H) 8.34 (s, 1H) 8.65 (s, 1H)

實例156Example 156

(18)-1-(4-^ -卞基）-2-(5-異口奎这林-6-基-p比症-3-基乳基）·乙胺 MS (ESI) m/z 374 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.05 (m, 2H) 3.88 (s，1H) 4.17 (dd，J二 10.92, 5·62 Hz，1H) 4·34 (dd，J=10.76, 2.96 Hz，1H) 7.18 (m， 2H) 7.38 (dd，J=8.58, 5.46 Hz，2H) 7.90 (m，1H) 8·24 (m，5H) 8.47 (d，J=8.73 Hz，2H) 8.53 (d，J=9.98 Hz，1H) 8.79 (s，1H) 9·67 (s，1H)·(18) -1- (4-^-fluorenyl) -2- (5-isokouquelin-6-yl-p ratio syndrome-3-yllactyl) · Ethylamine MS (ESI) m / z 374 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.05 (m, 2H) 3.88 (s, 1H) 4.17 (dd, J 2 10.92, 5.62 Hz, 1H) 4 · 34 (dd, J = 10.76, 2.96 Hz, 1H) 7.18 (m, 2H) 7.38 (dd, J = 8.58, 5.46 Hz, 2H) 7.90 (m, 1H) 8.24 (m, 5H) 8.47 (d, J = 8.73 Hz, 2H) 8.53 (d, J = 9.98 Hz, 1H) 8.79 (s, 1H) 9 · 67 (s, 1H) ·

CNCN

H 167- 200301122 (160) A-733910.7 實例157 2-((2SV2-胺基-3-(5-(3-甲基-1Η-Θ丨唑-5-基V吡啶-3-基氧基）-丙基V笨甲腈 MS (ESI) m/z 384 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.54 (d5 J= 4.06 Hz，3H) 3.34 (m，2H) 4.03 (m，1H) 4.11 (dd，J=10.61，4.99 Hz，1H) 4.33 (dd，J= 10.92, 3.12 Hz，1H) 7.50 (t，J=7.64 Hz，1H) 7.65 (m，7H) 7·85 (d，J=7.80 Hz，1H) 8.06 (s，1H) 8.37 (s，2H) 8.65 (s，1H).H 167- 200301122 (160) A-733910.7 Example 157 2-((2SV2-amino-3- (5- (3-methyl-1Η-Θ 丨 azole-5-ylVpyridin-3-yloxy)) -Propyl V Benzonitrile MS (ESI) m / z 384 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.54 (d5 J = 4.06 Hz, 3H) 3.34 (m, 2H ) 4.03 (m, 1H) 4.11 (dd, J = 10.61, 4.99 Hz, 1H) 4.33 (dd, J = 10.92, 3.12 Hz, 1H) 7.50 (t, J = 7.64 Hz, 1H) 7.65 (m, 7H) 7.85 (d, J = 7.80 Hz, 1H) 8.06 (s, 1H) 8.37 (s, 2H) 8.65 (s, 1H).

A-734322.2 實例158 2-((2SV2-胺基各(5-異喹啉-6-基）-吡啶-3-基氧基）-丙基）-苯甲腈 MS (ESI) m/z 381 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) 5 ppm 3.32 (m, 2H) 4.04 (m，1H) 4.16 (m，1H) 4.37 (dd，J=10.76, 3·28 Hz，1H) 7.50 (t，J=7.64 Hz，1H) 7.64 (d，J=7.49 Hz，1H) 7 (d，J=7.49 Hz，1H) 7·84 (m，2H) 8.00 (d，J=5.62 Hz，1H) 8.12 (dd, J=8.73, 1.87 Hz, 1H) 8.34 (d, J=8.73 Hz, 1H) 8.40 (m, 2H) 8.54 (s, 2H) 8.60 (d，J=5.61 Hz，1H) 8·74 (d，J=1.56 Hz，1H) 9.48 (s，1H)·A-734322.2 Example 158 2-((2SV2-amino (5-isoquinolin-6-yl) -pyridin-3-yloxy) -propyl) -benzonitrile MS (ESI) m / z 381 (M + H) +; 1H NMR (500 MHz, DMSO-D6) 5 ppm 3.32 (m, 2H) 4.04 (m, 1H) 4.16 (m, 1H) 4.37 (dd, J = 10.76, 3.28 Hz, 1H) 7.50 (t, J = 7.64 Hz, 1H) 7.64 (d, J = 7.49 Hz, 1H) 7 (d, J = 7.49 Hz, 1H) 7.84 (m, 2H) 8.00 (d, J = 5.62 Hz, 1H) 8.12 (dd, J = 8.73, 1.87 Hz, 1H) 8.34 (d, J = 8.73 Hz, 1H) 8.40 (m, 2H) 8.54 (s, 2H) 8.60 (d, J = 5.61 Hz, 1H ) 8 · 74 (d, J = 1.56 Hz, 1H) 9.48 (s, 1H) ·

Ν' Η A-738508.7 200301122 (161) 實例159 (1SV2-5彳3-甲基-1H-㈣唑-5-基V吡啶-3-基氣基VI-吡啶-4-基甲墓-乙胺 MS (ESI) m/z 360 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.50 (s5 3H) 3.24 (d，J=6.86 Hz，2H) 4.05 (m，1H) 4·12 (m，1H) 4.25 (m，J=3.43 Hz，1H) 7.49 (m， J=4.68 Hz，2H) 7.53 (d，J=1 ·87 Hz，1H) 7.59 (m，1H) 7·71 (m，1H) 7.80 (m，3H) 8.09 (s，1H) 8.30 (d，J=4.06 Hz，1H) 8·40 (s，2H) 8·78 (m，J=499 Hz，1H)·Ν 'Η A-738508.7 200301122 (161) Example 159 (1SV2-5 彳 3-methyl-1H-oxazol-5-yl Vpyridin-3-ylamino VI-pyridin-4-ylmethylpyridine-ethylamine MS (ESI) m / z 360 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.50 (s5 3H) 3.24 (d, J = 6.86 Hz, 2H) 4.05 (m, 1H) 4 · 12 (m, 1H) 4.25 (m, J = 3.43 Hz, 1H) 7.49 (m, J = 4.68 Hz, 2H) 7.53 (d, J = 1 · 87 Hz, 1H) 7.59 (m, 1H) 7 71 (m, 1H) 7.80 (m, 3H) 8.09 (s, 1H) 8.30 (d, J = 4.06 Hz, 1H) 8.40 (s, 2H) 8.78 (m, J = 499 Hz, 1H ) ·

實例160Example 160

(lS)-2-(5-異口奎口林-6-基-卩比症-3-基乳基）-1-口比淀·4-基甲基-乙胺 MS (ESI) m/z 357 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.24 (d? J= 7·17 Hz，1H) 3·28 (d，J=7.18 Hz，1H) 4.04 (m，1H) 4.26 (m，1H) 4.40 (d，J=3.43 Hz， 1H) 7.83 (dd, J=14.66, 6.24 Hz, 3H) 7.93 (m5 1H) 8.26 (m, 2H) 8.38 (m? 1H) 8.47 (d5 J=2.81 Hz，2H) 8.51 (d，J=8.42 Hz，1H) 8.58 (s，1H) 8·68 (d，J=6.24 Hz，1H) 8.80 (m， 2H) 9.71 (s，1H)·(lS) -2- (5-Isoquinone-6-yl-pyridine-3-yllactyl) -1-ylpyridine4-ylmethyl-ethylamine MS (ESI) m / z 357 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.24 (d? J = 7.17 Hz, 1H) 3.28 (d, J = 7.18 Hz, 1H) 4.04 ( m, 1H) 4.26 (m, 1H) 4.40 (d, J = 3.43 Hz, 1H) 7.83 (dd, J = 14.66, 6.24 Hz, 3H) 7.93 (m5 1H) 8.26 (m, 2H) 8.38 (m? 1H ) 8.47 (d5 J = 2.81 Hz, 2H) 8.51 (d, J = 8.42 Hz, 1H) 8.58 (s, 1H) 8.68 (d, J = 6.24 Hz, 1H) 8.80 (m, 2H) 9.71 (s , 1H) ·

A-740051.7 實例161 -169- 200301122 (162) (1SVH4-甲基-芊基）-2-(5-(3-甲某-1HW[唑·5-基V吡啶-3-基氣基V乙胺 MS (ESI) m/z 373 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.28 (m, 3H) 2·55 (s，3H) 2.98 (m，2H) 3.81 (s，1H) 4·11 (dd，J=10.45, 6.08 Hz，1H) 4.27 (dd，J二 10.76, 2·96 Hz，1H) 7·16 (m，3H) 7·21 (m，1H) 7.57 (d，J= 8·73 Hz，1H) 7.69 (m，2H) 8.07 (s, 1H) 8.21 (m, 3H) 8.31 (d, J=2.18 Hz, 1H) 8.62 (s, 1H).A-740051.7 Example 161 -169- 200301122 (162) (1SVH4-methyl-fluorenyl) -2- (5- (3-methyl-1HW Amine MS (ESI) m / z 373 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.28 (m, 3H) 2.55 (s, 3H) 2.98 (m, 2H) 3.81 (s, 1H) 4 · 11 (dd, J = 10.45, 6.08 Hz, 1H) 4.27 (dd, J = 10.76, 2.96 Hz, 1H) 7 · 16 (m, 3H) 7 · 21 (m, 1H ) 7.57 (d, J = 8.73 Hz, 1H) 7.69 (m, 2H) 8.07 (s, 1H) 8.21 (m, 3H) 8.31 (d, J = 2.18 Hz, 1H) 8.62 (s, 1H).

實例162 (lS)-2-(5-異喳啉-6-基-吡啶-3-基氧基Vl-(4-甲基-芊基）-乙胺 MS (ESI) m/z 370 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.28 (m, 3H) 3.01 (m，2H) 3.83 (s，1H) 4·14 (dd，J=10.76, 5·77 Hz，1H) 4.30 (m，1H) 7·18 (m，6H) 7.84 (m，1H) 7.97 (d，J=5.93 Hz，1H) 8.10 (dd，J=8.58, L72 Hz，·1Η) 8.24 (m，2H) 8.31 (d，J=8.74 Hz，1H) 8.59 (d，J=5.93 Hz，1H) 8.74 (d，J=1.87 Hz，1H) 9.45 (s，1H)Example 162 (lS) -2- (5-Isophosphon-6-yl-pyridin-3-yloxy Vl- (4-methyl-fluorenyl) -ethylamine MS (ESI) m / z 370 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.28 (m, 3H) 3.01 (m, 2H) 3.83 (s, 1H) 4.14 (dd, J = 10.76, 5.77 Hz , 1H) 4.30 (m, 1H) 7.18 (m, 6H) 7.84 (m, 1H) 7.97 (d, J = 5.93 Hz, 1H) 8.10 (dd, J = 8.58, L72 Hz, · 1Η) 8.24 ( m, 2H) 8.31 (d, J = 8.74 Hz, 1H) 8.59 (d, J = 5.93 Hz, 1H) 8.74 (d, J = 1.87 Hz, 1H) 9.45 (s, 1H)

H A-741302.7 實例163 (lS)-2-(5-(3-甲基-1H-啕唑-5-基V吡啶-3-基氧基VP奎啉-3-基甲基- 乙胺 MS (ESI) m/z 410 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.56 (m3 3H) -170- 200301122H A-741302.7 Example 163 (1S) -2- (5- (3-methyl-1H-oxazol-5-yl Vpyridin-3-yloxyVP quinolin-3-ylmethyl-ethylamine MS (ESI) m / z 410 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.56 (m3 3H) -170- 200301122

(163) 3·29 (m, 2H) 4.12 (m，1H) 4.29 (m，1H) 4.42 (dd，J=10.76, 3.28 Hz，1Η) 7·56 (d，J= 8·73 Hz，1H) 7·66 (m，2H) 7.78 (m，2H) 7.97 (t，J=7· 18 Hz，2H) 8.05 (m，2H) 8.36 (m， 4H) 8.91 (m，2H)(163) 3.29 (m, 2H) 4.12 (m, 1H) 4.29 (m, 1H) 4.42 (dd, J = 10.76, 3.28 Hz, 1Η) 7.56 (d, J = 8.73 Hz, 1H ) 7.66 (m, 2H) 7.78 (m, 2H) 7.97 (t, J = 7.18 Hz, 2H) 8.05 (m, 2H) 8.36 (m, 4H) 8.91 (m, 2H)

(lS)-2-(5-異喳啉-6-基-吡啶-3-基氣基）小喹啉-3-基甲基-乙胺 MS (ESI) m/z 407 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.27 (m, 2H) 4.09 (d, J=5.62 Hz, 1H) 4.27 (dd5 J=10.92, 5.62 Hz, 1H) 4.43 (dd, J=10.61, 3.43 Hz, 1H) 5.75 (s，1H) 7.62 (m，1H) 7.76 (m，1H) 7·86 (m，1H) 7.94 (m，2H) 8.06 (m，1H) 8.30 (m, 5H) 8.46 (d, J=2.81 Hz, 1H) 8.59 (d, J=5.93 Hz, 1H) 8.74 (m, J=1.87 Hz, 1H) 8.89 (dd，J=20.28, 2.18 Hz，1H) 9.43 (s，lH)·(lS) -2- (5-Isophosphon-6-yl-pyridin-3-ylamino) quinolin-3-ylmethyl-ethylamine MS (ESI) m / z 407 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.27 (m, 2H) 4.09 (d, J = 5.62 Hz, 1H) 4.27 (dd5 J = 10.92, 5.62 Hz, 1H) 4.43 (dd, J = 10.61, 3.43 Hz, 1H) 5.75 (s, 1H) 7.62 (m, 1H) 7.76 (m, 1H) 7.86 (m, 1H) 7.94 (m, 2H) 8.06 (m, 1H) 8.30 (m, 5H ) 8.46 (d, J = 2.81 Hz, 1H) 8.59 (d, J = 5.93 Hz, 1H) 8.74 (m, J = 1.87 Hz, 1H) 8.89 (dd, J = 20.28, 2.18 Hz, 1H) 9.43 (s , LH) ·

H A-742710.7 實例165 卞基一2-(5-(3-甲基-1H-v^\ 基外匕 < 一3-基 ι 基）一乙胺 MS (ESI) m/z 358 (Μ+Η)+ ; 1 H NMR (500 MHz，DMSO-D6) 5 ppm 2.49 (s，3Η) 2.99 (m, 2Η) 3.79 (s, 1Η) 4.07 (dd3 J=10.61, 5.93 Hz? 1H) 4.23 (dd, J=10.76, 2.96 Hz, 1H) 7.22 (m, 2H) 7.29 (m, 3H) 7.51 (d, J=8.73 Hz, 1H) 7.62 (dd5 J=8.73? 1.56 Hz, 1H) -171- 200301122 (164) 7·64 (m，1H) 8·00 (s，1H) 8·19 (s，3H) 8·26 (m，1H) 8.56 (s，1H).H A-742710.7 Example 165 Fluorenyl-2- (5- (3-methyl-1H-v ^ \ exoyl < 3-3-yl) -ethylamine MS (ESI) m / z 358 (Μ + Η) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 2.49 (s, 3Η) 2.99 (m, 2Η) 3.79 (s, 1Η) 4.07 (dd3 J = 10.61, 5.93 Hz? 1H) 4.23 ( dd, J = 10.76, 2.96 Hz, 1H) 7.22 (m, 2H) 7.29 (m, 3H) 7.51 (d, J = 8.73 Hz, 1H) 7.62 (dd5 J = 8.73? 1.56 Hz, 1H) -171- 200301122 (164) 7.64 (m, 1H) 8.00 (s, 1H) 8.19 (s, 3H) 8.26 (m, 1H) 8.56 (s, 1H).

實例166Example 166

(1R)_1-卞基-2-(5-異口奎口林-6_基比途-3-基氧基）-乙胺 MS (ESI m/z 356)(M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.86 (m, 1H) 2.95 (m5 1H) 3.58 (m3 1H) 4.08 (m, 1H) 4.18 (m, 1H) 7.28 (m, 5H) 7.81 (m, 1H) 7.88 (m，1H) 8.06 (m，1H) 8.25 (m，1H) 8.36 (m，1H) 8.39 (m，1H) 8.55 (m，1H) 8.69 (m， 1H) 9.37 (m, 1H)(1R) _1-fluorenyl-2- (5-isokouquiline-6-ylbito-3-yloxy) -ethylamine MS (ESI m / z 356) (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.86 (m, 1H) 2.95 (m5 1H) 3.58 (m3 1H) 4.08 (m, 1H) 4.18 (m, 1H) 7.28 (m, 5H) 7.81 (m, 1H) 7.88 (m, 1H) 8.06 (m, 1H) 8.25 (m, 1H) 8.36 (m, 1H) 8.39 (m, 1H) 8.55 (m, 1H) 8.69 (m, 1H) 9.37 (m, 1H)

實例167 4-((2S)-2-胺基-3-(5-(3-甲基-1H-W唑-5-基V吡啶-3-基氧基V丙基V酚 MS (ESI) m/z 374 (M+H)+ ； 1H NMR (400 MHz, DMSO-D6) δ ppm 2.55 (s5 3H) 3,50 (m，8H) 6.73 (dd，J=8.44, 2.92 Hz，1H) 7.09 (m，1H) 7·59 (m，2H) 7.69 (m，2H) 7.87 (s, 1H) 8.14 (m5 2H) 8.23 (d, J=1.84 Hz, 1H) 8.62 (s5 1H).Example 167 4-((2S) -2-Amino-3- (5- (3-methyl-1H-Wazole-5-yl Vpyridin-3-yloxy Vpropyl V phenol MS (ESI) m / z 374 (M + H) +; 1H NMR (400 MHz, DMSO-D6) δ ppm 2.55 (s5 3H) 3,50 (m, 8H) 6.73 (dd, J = 8.44, 2.92 Hz, 1H) 7.09 (m, 1H) 7.59 (m, 2H) 7.69 (m, 2H) 7.87 (s, 1H) 8.14 (m5 2H) 8.23 (d, J = 1.84 Hz, 1H) 8.62 (s5 1H).

-172· 200301122 (165) 實例168-1722003200122 (165) Example 168

(lSM-(4-芊氣基-芊基V2-(5-(3-曱基-1H-啕唑-5-基）-吡啶各基氣基V 乙胺 MS m/z 465 (ESI) (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) 5 ppm 2.55 (s, 3H)(lSM- (4-fluorenylamino-fluorenyl V2- (5- (3-fluorenyl-1H-oxazol-5-yl) -pyridinyl radical Vethylamine MS m / z 465 (ESI) ( M + H) +; 1 H NMR (400 MHz, DMSO-D6) 5 ppm 2.55 (s, 3H)

2.97 (m, 2H) 3.82 (m, 1H) 4.13 (m5 1H) 4.28 (m, 1H) 5.07 (s, 2H) 6.99 (d, J=8.59 Hz, 3H) 7.24 (d，J=8.59 Hz，2H) 7·32 (m，J=7.06 Hz，1H) 7.40 (m，4H) 7.69 (dd，J=8.75， 1.69 Hz, 1H) 7.73 (m, 1H) 8.08 (s5 1H) 8.19 (m5 3H) 8.33 (m, J=2.46 Hz, 1H) 8.64 (d3 J=1.53 Hz, 1H).2.97 (m, 2H) 3.82 (m, 1H) 4.13 (m5 1H) 4.28 (m, 1H) 5.07 (s, 2H) 6.99 (d, J = 8.59 Hz, 3H) 7.24 (d, J = 8.59 Hz, 2H ) 7.32 (m, J = 7.06 Hz, 1H) 7.40 (m, 4H) 7.69 (dd, J = 8.75, 1.69 Hz, 1H) 7.73 (m, 1H) 8.08 (s5 1H) 8.19 (m5 3H) 8.33 (m, J = 2.46 Hz, 1H) 8.64 (d3 J = 1.53 Hz, 1H).

H A-751256.7 實例169H A-751256.7 Example 169

(lS)-l-(3-甲基-芊基）-2-(5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氧基）-乙胺 MS (ESI) m/z 373 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) 6 ppm 2.28 (s, 3H) 2.56 (s, 3H) 3.01 (m, 2H) 4.15 (dd, J=10.92, 5.62 Hz, 1H) 4.30 (m, J=2.81 Hz, 1H) 7.11 (m, J=17.00,7.64 Hz, 3H) 7.23 (m? J=7.49 Hz, 1H) 7.58 (d, J=8.73 Hz, 1H) 7.70 (dd5 J=8.73, 1.56 Hz, 1H) 7.80 (m, 1H) 8.10 (s, 1H) 8.26 (s3 3H) 8.35 (d5 J= 2.81 Hz, 1H) 8.67 (d, J=1.56 Hz, 1H).(lS) -l- (3-methyl-fluorenyl) -2- (5- (3-methyl-1H-indazol-5-ylVpyridin-3-yloxy) -ethylamine MS (ESI ) m / z 373 (M + H) +; 1H NMR (500 MHz, DMSO-D6) 6 ppm 2.28 (s, 3H) 2.56 (s, 3H) 3.01 (m, 2H) 4.15 (dd, J = 10.92, 5.62 Hz, 1H) 4.30 (m, J = 2.81 Hz, 1H) 7.11 (m, J = 17.00,7.64 Hz, 3H) 7.23 (m? J = 7.49 Hz, 1H) 7.58 (d, J = 8.73 Hz, 1H ) 7.70 (dd5 J = 8.73, 1.56 Hz, 1H) 7.80 (m, 1H) 8.10 (s, 1H) 8.26 (s3 3H) 8.35 (d5 J = 2.81 Hz, 1H) 8.67 (d, J = 1.56 Hz, 1H ).

H A-751278.7 -173- 200301122 (166) 實例no (lS)-l-(2-甲基-卞基）-2-(5-(3-甲基丨峻-5-基）-p比咬-3-基乳基）-乙胺 MS (ESI) m/z 373 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) 5 ppm 2.30 (d, J= 7.80 Hz，1H) 2.33 (s，3H) 2·56 (m，3H) 3.07 (d，J=7.80 Hz，1H) 3.80 (s，1H) 4·12 (dd， J= 10.76, 4.84 Hz，1H) 4·26 (dd，J=10.61，2.81 Hz，1H) 7·19 (m，4H) 7·57 (d，J二8·73 Hz，1H) 7.68 (dd，11.07, 2.03 Hz，2H) 8·06 (s，1H) 8.31 (s，3H) 8·62 (s，1H).H A-751278.7 -173- 200301122 (166) Example no (lS) -l- (2-methyl-fluorenyl) -2- (5- (3-methyl 丨 -5-yl) -p specific bite -3-yl milk group) -ethylamine MS (ESI) m / z 373 (M + H) +; 1H NMR (500 MHz, DMSO-D6) 5 ppm 2.30 (d, J = 7.80 Hz, 1H) 2.33 ( s, 3H) 2.56 (m, 3H) 3.07 (d, J = 7.80 Hz, 1H) 3.80 (s, 1H) 4 · 12 (dd, J = 10.76, 4.84 Hz, 1H) 4 · 26 (dd, J = 10.61, 2.81 Hz, 1H) 7.19 (m, 4H) 7.57 (d, J 2 8.73 Hz, 1H) 7.68 (dd, 11.07, 2.03 Hz, 2H) 8.06 (s, 1H ) 8.31 (s, 3H) 8.62 (s, 1H).

實例171Example 171

(lS)-2-(5-(3-甲基丨峻-5-基比咬-3-基氧基）-1-(4-確基-字基）-乙胺 MS (ESI) m/z 404 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.19 (m, 2H) 3.97 (s5 1H) 4.18 (dd, J=10.92, 5.62 Hz, 1H) 4.34 (dd, J=10.76, 3.28 Hz, 1H) 7.57 (d, J=8.74 Hz, 1H) 7.64 (m? J=8.73 Hz, 2H) 7.69 (dd, J-8.58, 1.72 Hz, 1H) 7.77 (m, 1H) 8.08 (s, 1H) 8.23 (d, J=8.73 Hz, 2H) 8.29 (m, 2H) 8.34 (d3 J=2.50 Hz, 1H) 8.66 (d, J=1.25 Hz, 1H).(lS) -2- (5- (3-Methyl-5-Anayl-5-yl than N--3-yloxy) -1- (4-Amino-Branyl) -Ethylamine MS (ESI) m / z 404 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.19 (m, 2H) 3.97 (s5 1H) 4.18 (dd, J = 10.92, 5.62 Hz, 1H ) 4.34 (dd, J = 10.76, 3.28 Hz, 1H) 7.57 (d, J = 8.74 Hz, 1H) 7.64 (m? J = 8.73 Hz, 2H) 7.69 (dd, J-8.58, 1.72 Hz, 1H) 7.77 (m, 1H) 8.08 (s, 1H) 8.23 (d, J = 8.73 Hz, 2H) 8.29 (m, 2H) 8.34 (d3 J = 2.50 Hz, 1H) 8.66 (d, J = 1.25 Hz, 1H).

H A-755097.7 實例172 -174- 200301122H A-755097.7 Example 172 -174- 200301122

(167) (1SVU4-甲氧基-芊基V2-(5-(3-甲基-1H-吲唑-5-基V吡啶各基氧基）- 乙胺 MS (ESI) m/z 389 (M+H)+ ; 1H NMR (500 MHz，DMSO-D6) 5 ppm 2·56 (s，3H) 2.98 (dd，J=15.13, 6·08 Hz，2H) 3·73 (m，3H) 3.80 (m，1H) 4·16 (dd，J=10.76, 5·77 Hz， 1H) 4.32 (dd, J=10.61, 3.12 Hz, 1H) 6.91 (m? 2H) 7.21 (dd3 J=8.58, 2.65 Hz, 1H) 7.25 (d，J=8.73 Hz，2H) 7.59 (d，J=8.73 Hz，1H) 7.71 (dd，J=873, 1·87 Hz，1H) 7·84 (m， 1H) 8.11 (s，1H) 8.28 (m，2H) 8·37 (d，J=2.81 Hz，1H) 8.69 (d，J=1.56 Hz，1H)·(167) (1SVU4-methoxy-fluorenyl V2- (5- (3-methyl-1H-indazol-5-yl V pyridyloxy) -ethylamine MS (ESI) m / z 389 ( M + H) +; 1H NMR (500 MHz, DMSO-D6) 5 ppm 2.56 (s, 3H) 2.98 (dd, J = 15.13, 6.08 Hz, 2H) 3.73 (m, 3H) 3.80 (m, 1H) 4 · 16 (dd, J = 10.76, 5.77 Hz, 1H) 4.32 (dd, J = 10.61, 3.12 Hz, 1H) 6.91 (m? 2H) 7.21 (dd3 J = 8.58, 2.65 Hz , 1H) 7.25 (d, J = 8.73 Hz, 2H) 7.59 (d, J = 8.73 Hz, 1H) 7.71 (dd, J = 873, 1.87 Hz, 1H) 7.84 (m, 1H) 8.11 ( s, 1H) 8.28 (m, 2H) 8.37 (d, J = 2.81 Hz, 1H) 8.69 (d, J = 1.56 Hz, 1H) ·

A-757584.7 實例173A-757584.7 Example 173

(1SV1-聯苯-4-基甲基-2-(5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氣基V 乙胺(1SV1-biphenyl-4-ylmethyl-2- (5- (3-methyl-1H-indazol-5-yl Vpyridin-3-ylamino Vethylamine

MS (ESI) m/z 435 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) 5 ppm 2.55 (s5 3H) 3.10 (m, 2H) 3.92 (s, 1H) 4.21 (dd, J=10.92, 5.62 Hz, 1H) 4.36 (dd, J=10.76, 2.96 Hz, 1H) 7.36 (t, J=7.49 Hz, 1H) 7.44 (m5 4H) 7.57 (d, J=8.73 Hz, 1H) 7.65 (dd, J=10.29, 7.80 Hz，4H) 7.70 (dd，J=8.73, 1.56 Hz，1H) 7.82 (s，1H) 8.10 (s，1H) 8.30 (d，J=2.81 Hz，3H) 8.37 (d，J=2.50 Hz，1H) 8.67 (d，J=1.25 Hz，1H).MS (ESI) m / z 435 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 2.55 (s5 3H) 3.10 (m, 2H) 3.92 (s, 1H) 4.21 (dd, J = 10.92, 5.62 Hz, 1H) 4.36 (dd, J = 10.76, 2.96 Hz, 1H) 7.36 (t, J = 7.49 Hz, 1H) 7.44 (m5 4H) 7.57 (d, J = 8.73 Hz, 1H) 7.65 ( dd, J = 10.29, 7.80 Hz, 4H) 7.70 (dd, J = 8.73, 1.56 Hz, 1H) 7.82 (s, 1H) 8.10 (s, 1H) 8.30 (d, J = 2.81 Hz, 3H) 8.37 (d , J = 2.50 Hz, 1H) 8.67 (d, J = 1.25 Hz, 1H).

H A-757602.7 -175- (168)H A-757602.7 -175- (168)

實例174 (lS)-2-(5-(3-甲基-1H-钊唑-5-基V吡啶-3-基氧基VI-苯小基甲基-乙胺 MS (ESI) m/z 409 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.44 (dd，JN14.04, 6·86 Hz，2H) 3.93 (s，1H) 4.17 (dd，J=10.61，4·99 Hz，1H) 4.32 (m， 1H) 7·48 (m，2H) 7.59 (m，3H) 7.66 (dd，J=8.58，l ·72 Hz，1H) 7.69 (m，1H) 7·89 (dd， J=6.24, 3.12 Hz, 1H) 7.98 (d? J=8.11 Hz, 1H) 8.05 (s, 1H) 8.21 (d? J=8.42 Hz, 1H) 8.2 9 (m, 2H) 8.32 (d? J=2.81 Hz, 1H) 8.63 (d? J=1.56 Hz, 1H).Example 174 (1S) -2- (5- (3-Methyl-1H-zazol-5-yl) V-pyridin-3-yloxy VI-phenyl small methyl-ethylamine MS (ESI) m / z 409 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.44 (dd, JN14.04, 6.86 Hz, 2H) 3.93 (s, 1H) 4.17 ( dd, J = 10.61, 4.99 Hz, 1H) 4.32 (m, 1H) 7.48 (m, 2H) 7.59 (m, 3H) 7.66 (dd, J = 8.58, 1.72 Hz, 1H) 7.69 ( m, 1H) 7.89 (dd, J = 6.24, 3.12 Hz, 1H) 7.98 (d? J = 8.11 Hz, 1H) 8.05 (s, 1H) 8.21 (d? J = 8.42 Hz, 1H) 8.2 9 ( m, 2H) 8.32 (d? J = 2.81 Hz, 1H) 8.63 (d? J = 1.56 Hz, 1H).

Ν' H A-763516.7 實例175 (lS)-l-(3-氯-芊基）-2-(5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氧基V乙胺 MS (ESI) m/z 393 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.06 (d，J=7.49 Hz, 2H) 3.92 (m，1H) 4.16 (m，1H) 4.33 (dd，J=10.92, 3.12 Hz，1H) 7.31 (d5 J=7.49 Hz, 1H) 7.37 (m, J=14.51, 7.02 Hz, 2H) 7.45 (s3 1H) 7.58 (d, J=8.73 Hz, 1H) 7.70 (dd, J=8.73, 1.56 Hz, 1H) 7.77 (s? 1H) 8.08 (s5 1H) 8.23 (s, 3H) 8.34 (d3 J=2.50 Hz, 1H) 8.65 (s5 1H).Ν 'H A-763516.7 Example 175 (1S) -1- (3-chloro-fluorenyl) -2- (5- (3-methyl-1H-indazol-5-yl Vpyridin-3-yloxy V Ethylamine MS (ESI) m / z 393 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.06 (d, J = 7.49 Hz, 2H) 3.92 (m , 1H) 4.16 (m, 1H) 4.33 (dd, J = 10.92, 3.12 Hz, 1H) 7.31 (d5 J = 7.49 Hz, 1H) 7.37 (m, J = 14.51, 7.02 Hz, 2H) 7.45 (s3 1H) 7.58 (d, J = 8.73 Hz, 1H) 7.70 (dd, J = 8.73, 1.56 Hz, 1H) 7.77 (s? 1H) 8.08 (s5 1H) 8.23 (s, 3H) 8.34 (d3 J = 2.50 Hz, 1H ) 8.65 (s5 1H).

Ν· Η A-763977.7 (169)Ν · Η A-763977.7 (169)

實例176 3-((2SV2-胺基-3-(5-(3-甲基-1H-蜊唑-5-基V吡啶各某氣基）·丙基）-笨甲腈 MS (ESI) mix 384 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s? 3H) 3.12 (d，J=7.49 Hz，2H) 3.96 (s，1H) 4·17 (dd5 J=10.76, 5.77 Hz，1H) 4.33 (m，1H) 7·57 (dd，J=8.11，6·55 Hz，2H) 7.69 (dd，J=8.42, 1.56 Hz，2H) 7.76 (m，2H) 7.84 (s， 1H) 8.08 (s，1H) 8.23 (s，3H) 8.33 (d，J=2.81 Hz，1H) 8·64 (d，JN1.56 Hz，1H).Example 176 3-((2SV2-Amino-3- (5- (3-methyl-1H-clamazol-5-yl Vpyridine), propyl) -benzonitrile MS (ESI) mix 384 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s? 3H) 3.12 (d, J = 7.49 Hz, 2H) 3.96 (s, 1H) 4.17 (dd5 J = 10.76, 5.77 Hz, 1H) 4.33 (m, 1H) 7.57 (dd, J = 8.11, 6.55 Hz, 2H) 7.69 (dd, J = 8.42, 1.56 Hz, 2H) 7.76 (m, 2H) 7.84 (s, 1H) 8.08 (s, 1H) 8.23 (s, 3H) 8.33 (d, J = 2.81 Hz, 1H) 8.64 (d, JN1.56 Hz, 1H).

H A-764024.7H A-764024.7

F F 實例177F F Example 177

二氟-芊基）-2-(5-(3-甲基-1H-吲唑-5-墓）-吡啶-3-基氧基V 乙胺 MS (ESI) m/z 395 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.56 (s, 3H) 3.05 (d, J=7.18 Hz, 2H) 3.90 (m, 1H) 4.17 (dd, J=10.92, 5.93 Hz, 1H) 4.34 (dd, J= 10.61, 3.12 Hz, 1H) 7.19 (m, J=2.18 Hz, 1H) 7.44 (m, 2H) 7.58 (d, J=8.73 Hz, 1H) 7.70 (dd5 J=8.73, 1.56 Hz, 1H) 7.77 (d, J=2.50 Hz, 1H) 8.08 (s, 1H) 8.23 (s, 3H) 8.34 (d? J=2.50 Hz, 1H) 8.65 (d, J=1.56 Hz, 1H).Difluoro-fluorenyl) -2- (5- (3-methyl-1H-indazole-5-tomb) -pyridin-3-yloxy V ethylamine MS (ESI) m / z 395 (M + H ) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 2.56 (s, 3H) 3.05 (d, J = 7.18 Hz, 2H) 3.90 (m, 1H) 4.17 (dd, J = 10.92, 5.93 Hz, 1H ) 4.34 (dd, J = 10.61, 3.12 Hz, 1H) 7.19 (m, J = 2.18 Hz, 1H) 7.44 (m, 2H) 7.58 (d, J = 8.73 Hz, 1H) 7.70 (dd5 J = 8.73, 1.56 Hz, 1H) 7.77 (d, J = 2.50 Hz, 1H) 8.08 (s, 1H) 8.23 (s, 3H) 8.34 (d? J = 2.50 Hz, 1H) 8.65 (d, J = 1.56 Hz, 1H).

H A-768008.7 200301122 (170) 實例178 (lS)-l-(3,4-二甲氧基-芊基）-2-(5-(3-甲基-1H-吲唑-5-墓）-吡啶-3-基氣基V乙胺 MS (ESI) m/z 419 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 2.98 (m, 2H) 3.70 (s, 3H) 3.71 (s, 3H) 3.82 (s, 1H) 4.14 (dd, J=10.61, 5.62 Hz, 1H) 431 (dd, J=10.76, 2.96 Hz, 1H) 6.82 (d5 J=8.11 Hz, 1H) 6.91 (m5 2H) 7.57 (d5 J=8.42 Hz，1H) 7.68 (m，1H) 7.71 (s，1H) 8.07 (s，1H) 8·28 (s，3H) 8,32 (s，1H) 8.62 (s，1H).H A-768008.7 200301122 (170) Example 178 (lS) -l- (3,4-dimethoxy-fluorenyl) -2- (5- (3-methyl-1H-indazole-5-tomb) -Pyridin-3-ylamino Vethylamine MS (ESI) m / z 419 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 2.98 (m, 2H) 3.70 (s, 3H) 3.71 (s, 3H) 3.82 (s, 1H) 4.14 (dd, J = 10.61, 5.62 Hz, 1H) 431 (dd, J = 10.76, 2.96 Hz, 1H) 6.82 (d5 J = 8.11 Hz, 1H) 6.91 (m5 2H) 7.57 (d5 J = 8.42 Hz, 1H) 7.68 (m, 1H) 7.71 (s, 1H) 8.07 (s, 1H) 8.28 (s, 3H) 8,32 (s , 1H) 8.62 (s, 1H).

H A-768009.7 實例179 (lS)-l-(3-就-卞基）-2-(5-(3-甲基-ΙΗ-β丨也-5-基）-p比症-3-基氧基）-乙胺H A-768009.7 Example 179 (lS) -l- (3-Zoo-fluorenyl) -2- (5- (3-methyl-lΗ-β 丨 also-5-yl) -p ratio syndrome-3-yl (Oxy) -ethylamine

MS (ESI) m/z 377 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.08 (m，2H) 3·91 (s，1H) 4.15 (dd，J=10.61，5.93 Hz，1H) 4.32 (dd，J=10.61，3.12 Hz， 1H) 7·12 (m，1H) 7·20 (m，2H) 7.40 (m，1H) 7.57 (d，J=8.73 Hz，1H) 7·69 (dd，J=8.42, 1·56 Hz，1H) 7·71 (d，J=1.87 Hz，1H) 8.07 (s，1H) 8.29 (s，3H) 8·31 (d，J=2.81 Hz，1H) 8.62 (s, 1H).MS (ESI) m / z 377 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.08 (m, 2H) 3.91 (s, 1H) 4.15 ( dd, J = 10.61, 5.93 Hz, 1H) 4.32 (dd, J = 10.61, 3.12 Hz, 1H) 7.12 (m, 1H) 7.20 (m, 2H) 7.40 (m, 1H) 7.57 (d, J = 8.73 Hz, 1H) 7.69 (dd, J = 8.42, 1.556 Hz, 1H) 7.71 (d, J = 1.87 Hz, 1H) 8.07 (s, 1H) 8.29 (s, 3H) 8 · 31 (d, J = 2.81 Hz, 1H) 8.62 (s, 1H).

H A-770247.7 -178- (171)H A-770247.7 -178- (171)

實例180 (lS)-2-(5-(3-甲基-1H-吲唑-5-基W比啶-3-基氣基VH3-三氟甲基-芊基V乙胺 MS (ESI) m/z 427. (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.16 (dd5 J=7.335 2.34 Hz, 2H) 3.97 (s, 1H) 4.16 (dd, J=10.61, 5.62 Hz, 1H) 434 (dd, J=10.76, 3.28 Hz, 1H) 7.58 (d, J=8.42 Hz, 1H) 7.61 (d? J=7.49 Hz, 1H) 7.65 (s, 1H) 7.66 (s, 1H) 7.69 (dd, J=8.74, L56 Hz, 1H) 7.73 (s, 1H) 7.75 (m, 1H) 8.07 (s, 1H) 8.22 (s, 3H) 833 (d, J=2.50 Hz, 1H) 8.64 (d, J=1.56 Hz, 1H).Example 180 (lS) -2- (5- (3-Methyl-1H-indazol-5-yl) W than pyridin-3-ylamino VH3-trifluoromethyl-fluorenyl Vethylamine MS (ESI) m / z 427. (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.16 (dd5 J = 7.335 2.34 Hz, 2H) 3.97 (s, 1H) 4.16 ( dd, J = 10.61, 5.62 Hz, 1H) 434 (dd, J = 10.76, 3.28 Hz, 1H) 7.58 (d, J = 8.42 Hz, 1H) 7.61 (d? J = 7.49 Hz, 1H) 7.65 (s, 1H) 7.66 (s, 1H) 7.69 (dd, J = 8.74, L56 Hz, 1H) 7.73 (s, 1H) 7.75 (m, 1H) 8.07 (s, 1H) 8.22 (s, 3H) 833 (d, J = 2.50 Hz, 1H) 8.64 (d, J = 1.56 Hz, 1H).

H A-770248.7 實例181 (lS)-l-(4-乙氣基芊基V2-『5-(3-甲基-1H·巧唑-5-基吡啶-3_基氧基1- 乙胺 MS (ESI) m/z 403 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm L30 (t? J= 7.02 Hz, 3H) 2.55 (s3 3H) 2.97 (m, 2H) 3.79 (s3 1H) 3.98 (q, J=6.86 Hz, 2H) 4.13 (dd, J=10.76, 5.77 Hz，1H) 4.29 (dd，J= 10.76, 2.96 Hz，1H) 6.89 (d，J=8.42 Hz，1H) 7.22 (d5 J=8.42 Hz, 1H) 7.57 (d5 J=8.42 Hz, 2H) 7.61 (m, J=11.85 Hz, 1H) 7.69 (dd, J=8.73, 1.56 Hz，1H) 7.75 (s，1H) 8.08 (s，1H) 8.18 (s，3H) 8·33 (d，J=2.50 Hz，1H) 8.65 (d， J=1.56Hz，1H)· (172)H A-770248.7 Example 181 (lS) -l- (4-Ethylaminofluorenyl group V2- "5- (3-methyl-1H.Cizol-5-ylpyridin-3-yloxy1-ethylamine MS (ESI) m / z 403 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm L30 (t? J = 7.02 Hz, 3H) 2.55 (s3 3H) 2.97 (m, 2H) 3.79 (s3 1H) 3.98 (q, J = 6.86 Hz, 2H) 4.13 (dd, J = 10.76, 5.77 Hz, 1H) 4.29 (dd, J = 10.76, 2.96 Hz, 1H) 6.89 (d, J = 8.42 Hz, 1H) 7.22 (d5 J = 8.42 Hz, 1H) 7.57 (d5 J = 8.42 Hz, 2H) 7.61 (m, J = 11.85 Hz, 1H) 7.69 (dd, J = 8.73, 1.56 Hz, 1H) 7.75 (s, 1H) 8.08 (s, 1H) 8.18 (s, 3H) 8.33 (d, J = 2.50 Hz, 1H) 8.65 (d, J = 1.56Hz, 1H) · (172)

Η A-771648.7 實例182 (lSVl-(4-第三-丁基-芊某）-2-(5-(3-甲某-1H-W唑-5-基）·吡啶-3-基氣基乙胺 MS (ESI) m/z 415 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) 6 ppm 1.26 (m, 9H) 2.55 (s, 3H) 2.80 (dd, J=13.73, 6.86 Hz, 1H) 2.92 (m, 1H) 3.55 (m, 1H) 4.06 (dd, J= 9.98, 5.93 Hz, 1H) 4.15 (m5 1H) 7.21 (d, J=8.11 Hz, 2H) 7.34 (d, J=8.42 Hz, 2H) 7.56 (d, J=8.42 Hz, 1H) 7.69 (m, 2H) 8.08 (s, 1H) 8.28 (d, J=2.50 Hz? 1H) 8.57 (d, J= 1.56 Hz，1H) 12.73 (s，1H)·Η A-771648.7 Example 182 (1SVl- (4-third-butyl-fluorene) -2- (5- (3-methyl-1H-Wazole-5-yl) · pyridin-3-ylamino Ethylamine MS (ESI) m / z 415 (M + H) +; 1H NMR (500 MHz, DMSO-D6) 6 ppm 1.26 (m, 9H) 2.55 (s, 3H) 2.80 (dd, J = 13.73, 6.86 Hz, 1H) 2.92 (m, 1H) 3.55 (m, 1H) 4.06 (dd, J = 9.98, 5.93 Hz, 1H) 4.15 (m5 1H) 7.21 (d, J = 8.11 Hz, 2H) 7.34 (d, J = 8.42 Hz, 2H) 7.56 (d, J = 8.42 Hz, 1H) 7.69 (m, 2H) 8.08 (s, 1H) 8.28 (d, J = 2.50 Hz? 1H) 8.57 (d, J = 1.56 Hz, 1H ) 12.73 (s, 1H) ·

Ν' Η Α-772078.7 實例183 (1SVM4-甲氣基-3-甲基-芊基V2-(5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基）乙胺 MS (ESI) m/z 403 (Μ+Η)+ ; 1 H NMR (500 MHz，DMSO-D6) 5 ppm 2·11 (s，3Η) 2.55 (s, 3Η) 2.71 (m, 1Η) 2.83 (dd, J=13.73, 6.86 Hz, 1H) 3.17 (d, J=3.74 Hz, 2H) 3.47 (m，1H) 3·74 (m，3H) 4.07 (m，2H) 6·86 (d，J=8.11 Hz，1H) 7.05 (m，2H) 7·56 (m， (173)Ν ′ Η A-772078.7 Example 183 (1SVM4-methylamino-3-methyl-fluorenyl V2- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy ) Ethylamine MS (ESI) m / z 403 (Μ + Η) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 2.11 (s, 3Η) 2.55 (s, 3Η) 2.71 (m, 1Η ) 2.83 (dd, J = 13.73, 6.86 Hz, 1H) 3.17 (d, J = 3.74 Hz, 2H) 3.47 (m, 1H) 3.74 (m, 3H) 4.07 (m, 2H) 6.86 (d , J = 8.11 Hz, 1H) 7.05 (m, 2H) 7.56 (m, (173)

J=8.73 Hz，1H) 7.67 (m，2H) 8.07 (s，1H) 8.27 (d，J=2.81 Hz，1H) 8·57 (d，J=1.56 Hz， 1H) 12.72 (s, 1H).J = 8.73 Hz, 1H) 7.67 (m, 2H) 8.07 (s, 1H) 8.27 (d, J = 2.81 Hz, 1H) 8.57 (d, J = 1.56 Hz, 1H) 12.72 (s, 1H).

H A-772635.7 實例184 2-((2S)-2-胺基·3-(5-(3-甲基-1HWI唑-5-基）-吡啶-3-基氣基丙基M- 甲基-酚 MS (ESI) m/z 403 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 2.18 (s, 3H) 2·55 (s，3H) 2.98 (d，J=7.49 Hz，2H) 3.73 (d，J=3.74 Hz，3H) 3.79 (m，1H) 4.12 (dd， J=10.61, 5.62 Hz, 1H) 4.27 (dd, J=10.61, 3.12 Hz, 1H) 6.90 (d, J=8.11 Hz, 1H) 7.02 (s5 1H) 7.07 (d, J=8.42 Hz, 1H) 7.57 (d, J=8.73 Hz, 1H) 7.68 (dd, J=8.73, 1.56 Hz, 1H) 7J1 (s，1H) 8.07 (s，1H) 8·17 (s，3H) 8.31 (d，J=2.50 Hz，1H) 8·64 (d，J=L56 Hz， 1H).H A-772635.7 Example 184 2-((2S) -2-amino group 3- (5- (3-methyl-1HWIazole-5-yl) -pyridin-3-ylaminopropyl M-methyl -Phenol MS (ESI) m / z 403 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 2.18 (s, 3H) 2.55 (s, 3H) 2.98 (d, J = 7.49 Hz, 2H) 3.73 (d, J = 3.74 Hz, 3H) 3.79 (m, 1H) 4.12 (dd, J = 10.61, 5.62 Hz, 1H) 4.27 (dd, J = 10.61, 3.12 Hz, 1H) 6.90 (d , J = 8.11 Hz, 1H) 7.02 (s5 1H) 7.07 (d, J = 8.42 Hz, 1H) 7.57 (d, J = 8.73 Hz, 1H) 7.68 (dd, J = 8.73, 1.56 Hz, 1H) 7J1 ( s, 1H) 8.07 (s, 1H) 8.17 (s, 3H) 8.31 (d, J = 2.50 Hz, 1H) 8.64 (d, J = L56 Hz, 1H).

(A-755387) 實例185 (ISM-甲基-2-『5-(3-甲基-1H-蚓唑-5-基V吡啶各基氣基1-乙胺 MS (ESI) m/e 283 (M+H)+ ； 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.32 (d5 J= 200301122(A-755387) Example 185 (ISM-methyl-2-'5- (3-methyl-1H-earmazol-5-yl Vpyridine each ylamino 1-ethylamine MS (ESI) m / e 283 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.32 (d5 J = 200301122

(174) 6·78 Hz，3H) 2·56 (s，3H) 3·66 (m，1Η)4·16 (dd，J=10.51，7·12 Hz，1H) 4.35 (dd，J= 10.51，3.73 Hz，1H) 7.57 (d，JN8.81 Hz，1H) 7·72 (m，1H) 7·78 (m，1H) 8.01 (m，2H) 8.10 (m，1H) 8.33 (d，J=2.71 Hz，1H) 8.63 (d，J=1.70 Hz，1H) 12.70 (bs，1H);對 Ci6H18N40.2.2TFA之分析計算值：C，45.95; Η，3·82; N，10.51 ; · 實測值：C，46.11; Η，3·76; Ν，10·55·(174) 6.78 Hz, 3H) 2.56 (s, 3H) 3.66 (m, 1Η) 4.16 (dd, J = 10.51, 7.12 Hz, 1H) 4.35 (dd, J = 10.51 , 3.73 Hz, 1H) 7.57 (d, JN8.81 Hz, 1H) 7.72 (m, 1H) 7.78 (m, 1H) 8.01 (m, 2H) 8.10 (m, 1H) 8.33 (d, J = 2.71 Hz, 1H) 8.63 (d, J = 1.70 Hz, 1H) 12.70 (bs, 1H); Analysis and calculation of Ci6H18N40.2.2TFA: C, 45.95; 95, 3.82; N, 10.51; Value: C, 46.11; Η, 3.76; Ν, 10 · 55 ·

(A-444277) 實例186 (士 Μ-(1Η-苯并咪唑冬基甲基V2-(5-異4啉-6-基-ρ比啶-3-基氣基）- 乙胺 MS (ESI) m/e 396 (M+H)+ ； 1H NMR (500 MHz, DMSO-D6) δ ppm 3.51 (m? 2H) 4·32 (m，1H) 4.44 (m，1H) 4.55 (m，1H) 7·36 (dd，J=6.24, 3·12 Hz，2H) 7.68 (dd，J= 5.93, 3.12 Hz, 2H) 7.88 (d5 J=2.18 Hz, 1H) 8.12 (d, J=6.24 Hz, 1H) 8.19 (dd, J=8.58, 1.40 Hz，1H) 8.42 (m，2H) 8·49 (s，1H) 8·64 (d，J=5.93 Hz，1H) 8.77 (d，J=L56 Hz， 1H) 9.60 (s，1H).(A-444277) Example 186 (MS- (1H-benzimidazolylmethyl V2- (5-iso4-line-6-yl-p-pyridin-3-ylamino))-ethylamine MS (ESI ) m / e 396 (M + H) +; 1H NMR (500 MHz, DMSO-D6) δ ppm 3.51 (m? 2H) 4.32 (m, 1H) 4.44 (m, 1H) 4.55 (m, 1H) 7.36 (dd, J = 6.24, 3.12 Hz, 2H) 7.68 (dd, J = 5.93, 3.12 Hz, 2H) 7.88 (d5 J = 2.18 Hz, 1H) 8.12 (d, J = 6.24 Hz, 1H ) 8.19 (dd, J = 8.58, 1.40 Hz, 1H) 8.42 (m, 2H) 8.49 (s, 1H) 8.64 (d, J = 5.93 Hz, 1H) 8.77 (d, J = L56 Hz, 1H) 9.60 (s, 1H).

(A-475104) (175) 實例1打 (± )-1-ΠΗ-<唑-3-墓甲基）-2-(5-異4啉-6-基-外I:啶-3-基氧基）-乙胺 MS (ESI) m/e 396 (M+H)+ ； 1 H NMR (400 MHz? DMSO-D6) δ ppm 3.21 (m, 2H) 3.84 (m，1H) 4.21 (dd，J=9.97, 5·98 Hz，1H) 4.31 (dd，J=9.97, 5·98 Hz，1H) 7.08 (t，J= 7.21 Hz，1H) 7.33 (t，J=7.21 Hz，1H) 7·49 (d，J=8.59 Hz，1H) 7.80 (m，2H) 7.89 (d，J= 5.83 Hz，1H) 8.06 (dd，J=8.59, 1.84 Hz，1H) 8.25 (d，J=8.59 Hz，1H) 8.36 (s，1H) 8·39 (d，J=2.76 Hz，1H) 8.56 (d，J=5.83 Hz，1H) 8·69 (d，J=1.84 Hz，1H) 9·37 (s，1H) 12.87 (s，1H).(A-475104) (175) Example 1 dozen (±) -1-ΠΗ- < azole-3-methylmethyl) -2- (5-iso4-line-6-yl-exo I: pyridin-3- (Oxy) -ethylamine MS (ESI) m / e 396 (M + H) +; 1 H NMR (400 MHz? DMSO-D6) δ ppm 3.21 (m, 2H) 3.84 (m, 1H) 4.21 (dd , J = 9.97, 5.98 Hz, 1H) 4.31 (dd, J = 9.97, 5.98 Hz, 1H) 7.08 (t, J = 7.21 Hz, 1H) 7.33 (t, J = 7.21 Hz, 1H) 7 49 (d, J = 8.59 Hz, 1H) 7.80 (m, 2H) 7.89 (d, J = 5.83 Hz, 1H) 8.06 (dd, J = 8.59, 1.84 Hz, 1H) 8.25 (d, J = 8.59 Hz , 1H) 8.36 (s, 1H) 8.39 (d, J = 2.76 Hz, 1H) 8.56 (d, J = 5.83 Hz, 1H) 8.69 (d, J = 1.84 Hz, 1H) 9.37 ( s, 1H) 12.87 (s, 1H).

(A-757590) 實例188 (lSM-(2-氟-芊基）-245-(3-甲某-1H-吲唑-5-基V吡啶各基氧基1-乙胺 MS (ESI) m/e 377 (M+H)+ ； 1H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.11 (d，J=7.12 Hz，2H) 3·86 (m，1H) 4.15 (m，1H) 4.31 (dd，J=10.85, 3·39 Hz，1H) 7.20 (m，2H) 7.37 (m，2H) 7·57 (d，J=9.49 Hz，1H) 7.71 (m，2H) 8.08 (s，1H) 8.29 (s， 2H) 8.31 (d，J=2.71 Hz，1H) 8.64 (d，J=1.69 Hz，1H) 12.74 (bs，1H)·(A-757590) Example 188 (lSM- (2-fluoro-fluorenyl) -245- (3-methyl-1H-indazol-5-yl Vpyridyloxy 1-ethylamine MS (ESI) m / e 377 (M + H) +; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.11 (d, J = 7.12 Hz, 2H) 3.86 (m, 1H) 4.15 (m , 1H) 4.31 (dd, J = 10.85, 3.39 Hz, 1H) 7.20 (m, 2H) 7.37 (m, 2H) 7.57 (d, J = 9.49 Hz, 1H) 7.71 (m, 2H) 8.08 (s, 1H) 8.29 (s, 2H) 8.31 (d, J = 2.71 Hz, 1H) 8.64 (d, J = 1.69 Hz, 1H) 12.74 (bs, 1H) ·

(A-760116) 200301122(A-760116) 200301122

(176) * 實例189 氯-芊基V2-「5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1-乙胺 MS (ESI) m/e 393 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.55 (s5 3H) 3.22 (m，2H) 3.89 (m，1H) 4·15 (m，1H) 4.31 (m，1H) 7·35 (m，2H) 7.48 (m，3H) 7.58 (d，J=8.82 Hz，1H) 7.70 (m，2H) 8.08 (s，1H) 8·31 (d，J=2.71 Hz，2H) 8.64 (d，J=1.70 Hz, 1H) 12.84 (bs? 1H).(176) * Example 189 Chloro-fluorenyl V2- "5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1-ethylamine MS (ESI) m / e 393 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.55 (s5 3H) 3.22 (m, 2H) 3.89 (m, 1H) 4.15 (m, 1H) 4.31 (m, 1H ) 7.35 (m, 2H) 7.48 (m, 3H) 7.58 (d, J = 8.82 Hz, 1H) 7.70 (m, 2H) 8.08 (s, 1H) 8.31 (d, J = 2.71 Hz, 2H ) 8.64 (d, J = 1.70 Hz, 1H) 12.84 (bs? 1H).

(A-760117) 實例190 (lS)-2-「5-(3-甲基-1H、1唑-5-基）-吡啶-3-基氣基1-1-嘧吩-2-基甲基- 乙胺(A-760117) Example 190 (1S) -2- "5- (3-methyl-1H, 1zol-5-yl) -pyridin-3-ylamino 1-pyrimidin-2-ylmethyl -Ethylamine

MS (ESI) m/e 365 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.28 (m，2H) 3·90 (m，1H) 4·20 (m，1H) 4.35 (m，1H) 7.03 (m，2H) 7·46 (m，1H) 7.58 (d，J=8.82 Hz，1H) 7·70 (m，1H) 7.75 (m，1H) 8·09 (s，1H) 8·26 (m，2H) 8,33 (d，J= 2.71 Hz，1H) 8.64 (d，J=1.70 Hz，1H) 12.53 (bs，1H)·MS (ESI) m / e 365 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.28 (m, 2H) 3.90 (m, 1H) 4 · 20 (m, 1H) 4.35 (m, 1H) 7.03 (m, 2H) 7.46 (m, 1H) 7.58 (d, J = 8.82 Hz, 1H) 7.70 (m, 1H) 7.75 (m, 1H ) 8 · 09 (s, 1H) 8.26 (m, 2H) 8,33 (d, J = 2.71 Hz, 1H) 8.64 (d, J = 1.70 Hz, 1H) 12.53 (bs, 1H) ·

實例191 (1RVU1H-啕哚-3-基甲基）-245-(3-甲基-1H-㈣唑-5-基V吡啶-3-基氧 -184- 200301122 (177) 基1-乙胺 MS (ESI) m/e 398 (M+H)+ ； 1H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.16 (m, 2H) 3.86 (d? J=1.70 Hz? 1H)4.19 (dd, J=10.51, 6.10 Hz, 1H) 436 (dd, J=10.8 5, 3·39 Hz，1H) 7.01 (t，J=7.46 Hz，1H) 7.10 (t，J=6.95 Hz，1H) 7.30 (d，J=2.37 Hz， 1H) 7·38 (d，J=8.14 Hz，1H) 7·65 (m，5H) 8.07 (s，1H) 8.16 (s，2H) 8.33 (d，J=2.71 Hz， lH)8.63(d，J=1.70Hz，lH)11.04(bs，lH);對（：241123化0.2.9丁?八之分析計算值：C，49.16 ; Η，3·59 ; Ν，9·62 ;·實測值：C，49.36 ; Η，3·66 ; N，9·78·Example 191 (1RVU1H-pyridin-3-ylmethyl) -245- (3-methyl-1H-oxazol-5-yl Vpyridin-3-yloxy-184- 200301122 (177) yl 1-ethylamine MS (ESI) m / e 398 (M + H) +; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 3.16 (m, 2H) 3.86 (d? J = 1.70 Hz? 1H) 4.19 (dd, J = 10.51, 6.10 Hz, 1H) 436 (dd, J = 10.8 5, 3.39 Hz, 1H) 7.01 (t, J = 7.46 Hz, 1H) 7.10 (t, J = 6.95 Hz, 1H ) 7.30 (d, J = 2.37 Hz, 1H) 7.38 (d, J = 8.14 Hz, 1H) 7.65 (m, 5H) 8.07 (s, 1H) 8.16 (s, 2H) 8.33 (d, J = 2.71 Hz, lH) 8.63 (d, J = 1.70Hz, lH) 11.04 (bs, lH); Analytical calculated value for (: 241123, 0.2.9, but 8): C, 49.16; Η, 3.59 Ν, 9.62; · Measured value: C, 49.36; Η, 3.66; N, 9.78 ·

實例192 -卞基甲基 -5—基) 口比 < 一3-基 1 基 V乙胺 MS (ESI) m/e 393 (M+l)+ ; 1 H NMR (300 MHz，溶劑）5 ppm 2·63 (s，3H) 3.16 (m，2H) 3.98 (m，1H) 4.29 (m，1H) 4·44 (m，1H) 7·34 (m，2H) 7.39 (m，2H) 7.63 (d， J=8.82 Hz，1H) 7.74 (dd，J=8.82, 1.70 Hz，1H) 8.09 (m，1H) 8·11 (m，1H) 8.42 (寬廣 s，1H) 8·73 (寬廣 s，1H).Example 192 -Methenylmethyl-5-yl) Mouth ratio < -3-Methyl-1yl Vethylamine MS (ESI) m / e 393 (M + l) +; 1 H NMR (300 MHz, solvent) 5 ppm 2 · 63 (s, 3H) 3.16 (m, 2H) 3.98 (m, 1H) 4.29 (m, 1H) 4.44 (m, 1H) 7.34 (m, 2H) 7.39 (m, 2H) 7.63 (d , J = 8.82 Hz, 1H) 7.74 (dd, J = 8.82, 1.70 Hz, 1H) 8.09 (m, 1H) 8.11 (m, 1H) 8.42 (wide s, 1H) 8.73 (wide s, 1H ).

A-768094.0 200301122 (178) 實例193 (lS)-2-「5-(3-曱某-1H-吲唑-5-基）-吡啶-3-基氳基1-H4-吡咯小某-芏基）-乙胺 MS (ESI) m/e 424 (M+1)4*; 1H NMR (300 MHz，溶劑）5 ppm 2.61 (m，3H) 3·19 (m? 2H) 4.10 (m, 1H) 4.30 (m? 1H) 4.44 (m5 1H) 6.27 (t5 J=2.03 Hz5 2H) 7.16 (t, J= 2.03 Hz，2H) 7·41 (d，J=8.48 Hz，1H) 7.49 (d，JM8.48 Hz，2H) 7.59 (d，>8·48 Hz，1H) 7.70 (m，1H) 7.94 (m，1H) 8.07 (m，1H) 8.38 (寬廣 s，1H) 8.66 (寬廣 s，1H)·A-768094.0 200301122 (178) Example 193 (1S) -2- "5- (3-fluorene-1H-indazol-5-yl) -pyridin-3-ylfluorenyl 1-H4-pyrrole Based) -Ethylamine MS (ESI) m / e 424 (M + 1) 4 *; 1H NMR (300 MHz, solvent) 5 ppm 2.61 (m, 3H) 3.19 (m? 2H) 4.10 (m, 1H ) 4.30 (m? 1H) 4.44 (m5 1H) 6.27 (t5 J = 2.03 Hz5 2H) 7.16 (t, J = 2.03 Hz, 2H) 7.41 (d, J = 8.48 Hz, 1H) 7.49 (d, JM8 .48 Hz, 2H) 7.59 (d, > 8.48 Hz, 1H) 7.70 (m, 1H) 7.94 (m, 1H) 8.07 (m, 1H) 8.38 (broad s, 1H) 8.66 (broad s, 1H ) ·

A-770737.7A-770737.7

實例194 甲基-芊基硫基甲基甲基-1H-啕唑-5-基）-吡啶-3- 基氧基1-乙胺Example 194 Methyl-fluorenylthiomethylmethyl-1H-oxazol-5-yl) -pyridin-3-yloxy 1-ethylamine

MS (ESI) m/e 419 (M+l). ； 1 H NMR (300 MHz, MeOH) δ ppm 2.26 (s5 3H) 2.62 (s，3H) 2.88 (m，2H) 3.67 (m，1H) 3.82 (s，2H) 4·38 (m，2H) 7.18 (m，6H) 7.62 (d，J= 8·81 Hz，1H) 7.72 (dd，J二8.81，1.70 Hz, 1H) 7.85 (dd，J=2.71，1.70 Hz，1H) 8.06 (m， 1H) 830 (d, J=2.71 Hz, 1H) 8.62 (d5 J=1.70 Hz, 1H). cf3MS (ESI) m / e 419 (M + 1).; 1 H NMR (300 MHz, MeOH) δ ppm 2.26 (s5 3H) 2.62 (s, 3H) 2.88 (m, 2H) 3.67 (m, 1H) 3.82 (s, 2H) 4.38 (m, 2H) 7.18 (m, 6H) 7.62 (d, J = 8.81 Hz, 1H) 7.72 (dd, J 2 8.81, 1.70 Hz, 1H) 7.85 (dd, J = 2.71, 1.70 Hz, 1H) 8.06 (m, 1H) 830 (d, J = 2.71 Hz, 1H) 8.62 (d5 J = 1.70 Hz, 1H). Cf3

A-750982.3 實例195 -186 - 200301122A-750982.3 Example 195 -186-200301122

(179) (lS)-2-[5-(3-甲基-1H-啕唑-5-基V吡途-3-基氣基1-H2-三氟甲基-宇基V乙胺 MS m/z 427 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.57 (s? 3H) 3.30 (m，2H) 3·93 (s，1H) 4·32 (dd，J=10.85, 5.42 Hz，1H) 4.45 (m，1H) 7·53 (td，J=8.22, 3.90 Hz，1H) 7.61 (dd，J=8.82, 0.68 Hz，1H) 7.68 (m，2H) 7·77 (m，2H) 8.14 (s，1H) 8.23 (d，J=0.68 Hz，1H) 8.46 (d，J=2.03 Hz，1H) 8.65 (s，3H) 8.83 (s，1H).(179) (1S) -2- [5- (3-methyl-1H-oxazol-5-yl Vpyridin-3-ylamino 1-H2-trifluoromethyl-uryl V ethylamine MS m / z 427 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.57 (s? 3H) 3.30 (m, 2H) 3.93 (s, 1H) 4 · 32 (dd, J = 10.85, 5.42 Hz, 1H) 4.45 (m, 1H) 7.53 (td, J = 8.22, 3.90 Hz, 1H) 7.61 (dd, J = 8.82, 0.68 Hz, 1H) 7.68 (m, 2H) 7 77 (m, 2H) 8.14 (s, 1H) 8.23 (d, J = 0.68 Hz, 1H) 8.46 (d, J = 2.03 Hz, 1H) 8.65 (s, 3H) 8.83 (s, 1H).

實例196 卞基-3-『5-(3-甲基-1H-口弓1也-5-基）-口比咬-3-基乳基1-丙胺 MS m/z 373 (M+H)+ ； 1H NMR (300 MHz, DMSO-D6) δ ppm 2.05 (m, 2H) 2.57 (s5 3H) 2.91 (dd, J=13.73, 8.65 Hz, 1H) 3.11 (m, 1H) 3.63 (m, 1H) 4.41 (m5 2H) 7.25 (m，1H) 7·33 (m，4H) 7.61 (dd，J=8.81，0.68 Hz，1H) 7.81 (dd，J=8.81，1·70 Hz，1H) 8.21 (s，1H) 8·28 (s，2H) 8·47 (d，J二2.37 Hz，1H) 8.82 (s，1H)·Example 196 fluorenyl-3- "5- (3-methyl-1H-orbyl-1-5-yl) -orbital-3-yllactyl 1-propylamine MS m / z 373 (M + H) +; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.05 (m, 2H) 2.57 (s5 3H) 2.91 (dd, J = 13.73, 8.65 Hz, 1H) 3.11 (m, 1H) 3.63 (m, 1H) 4.41 (m5 2H) 7.25 (m, 1H) 7.33 (m, 4H) 7.61 (dd, J = 8.81, 0.68 Hz, 1H) 7.81 (dd, J = 8.81, 1.70 Hz, 1H) 8.21 (s , 1H) 8 · 28 (s, 2H) 8 · 47 (d, J 2 2.37 Hz, 1H) 8.82 (s, 1H) ·

實例197 (1RV1-芊基·4-『5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氣基1-丁胺 MS m/z 387 (M+H)+ ; 1 H NMR (300 MHz，DMSO-D6) 5 ppm 1.70 (q，J=7.23 Hz，2H) 1·91 (m，2H) 2·57 (s，3H) 2.82 (dd，J=13.56, 8·48 Hz，1H) 3·06 (dd，J=13.73, -187- (180) 5.26 Hz，1H) 3.47 (s，1H) 4·27 (m，2H) 7·27 (m，5H) 7·61 (d，J=8.48 Hz，1H) 7.84 (dd， J=8.81，1.70 Hz，1H) 8·29 (s，2H) 8·33 (s，1H) 8.49 (d，J=2.37 Hz，1H) 8.87 (s，1H)· (180)Example 197 (1RV1-fluorenyl · 4- "5- (3-methyl-1H-indazol-5-yl) -pyridin-3-ylamino1-butylamine MS m / z 387 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 1.70 (q, J = 7.23 Hz, 2H) 1.91 (m, 2H) 2.57 (s, 3H) 2.82 (dd, J = 13.56, 8 · 48 Hz, 1H) 3 · 06 (dd, J = 13.73, -187- (180) 5.26 Hz, 1H) 3.47 (s, 1H) 4 · 27 (m, 2H) 7 · 27 (m, 5H) 7.61 (d, J = 8.48 Hz, 1H) 7.84 (dd, J = 8.81, 1.70 Hz, 1H) 8.29 (s, 2H) 8.33 (s, 1H) 8.49 (d, J = 2.37 Hz , 1H) 8.87 (s, 1H) · (180)

A-7616133 實例198 (lS)-H5-(3-甲基-1H-吲唑-5-基）-吡啶·3-基氣基甲基1-3-笨基-丙胺 MS m/z 373 (Μ+Η)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.04 (m5 2H) 2.57 (s，3H) 2.80 (m，2H) 3.57 (m，1H) 4.44 (dd，J=10.68, 6·61 Hz，1H) 4·59 (m，1H) 7·24 (m, 5H) 7.62 (d5 J=8.82 Hz, 1H) 7.82 (dd, J=8.65, 1.53 Hz, 1H) 8.27 (s, 2H) 8.50 (s, 2H) 8.54 (d3 J=2.71 Hz, 1H) 8.86 (s, 1H).A-7616133 Example 198 (1S) -H5- (3-methyl-1H-indazol-5-yl) -pyridine · 3-ylaminomethyl 1-3-benzyl-propylamine MS m / z 373 ( Μ + Η) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.04 (m5 2H) 2.57 (s, 3H) 2.80 (m, 2H) 3.57 (m, 1H) 4.44 (dd, J = 10.68, 6.61 Hz, 1H) 4.59 (m, 1H) 7.24 (m, 5H) 7.62 (d5 J = 8.82 Hz, 1H) 7.82 (dd, J = 8.65, 1.53 Hz, 1H) 8.27 (s, 2H) 8.50 (s, 2H) 8.54 (d3 J = 2.71 Hz, 1H) 8.86 (s, 1H).

N A-431070.6 實例199 (lS)-2-(5-異口查淋-6-基-口比咬-3-基乳基）-1-(1-甲基-lH-H丨嗓·3-基甲基 )-乙胺三氟醋酸鹽 MS (DCI/NH3) m/z 409 (M+l)+ ； 1 H NMR (500 MHz, MeOD) 5 ppm 3.28 (m, 1H) 3.33 (m，1H) 3.77 (s，3H) 4·00 (m，1H) 4.33 (dd，J=10.61，5·93 Hz，1H) 4·46 (dd，J= 10.61, 3.12 Hz, 1H) 7.04 (m, 1H) 7.17 (m5 1H) 7.17 (s, 1H) 7.36 (d, J=8.42 Hz? 1H) 7.59 (d, J=7.80 Hz, 1H) 7.93 (m5 1H) 8.28 (dd, J=8.73, 1.87 Hz5 1H) 8.49 (m, 2H) 8.59 (m，3H) 8·76 (s，1H) 9.77 (s，1H). 200301122 (181)N A-431070.6 Example 199 (lS) -2- (5-Iso-chazal-6-yl-lipid-3-yllactyl) -1- (1-methyl-lH-H 丨 throat · 3 -Methyl) -Ethylamine trifluoroacetate MS (DCI / NH3) m / z 409 (M + 1) +; 1 H NMR (500 MHz, MeOD) 5 ppm 3.28 (m, 1H) 3.33 (m, 1H) 3.77 (s, 3H) 4.00 (m, 1H) 4.33 (dd, J = 10.61, 5.93 Hz, 1H) 4.46 (dd, J = 10.61, 3.12 Hz, 1H) 7.04 (m, 1H) 7.17 (m5 1H) 7.17 (s, 1H) 7.36 (d, J = 8.42 Hz? 1H) 7.59 (d, J = 7.80 Hz, 1H) 7.93 (m5 1H) 8.28 (dd, J = 8.73, 1.87 Hz5 1H) 8.49 (m, 2H) 8.59 (m, 3H) 8.76 (s, 1H) 9.77 (s, 1H). 200301122 (181)

實例199Example 199

實例200Example 200

(1SV1-苯并fbl嘧吩-3-基甲基-245-(3-甲基-1H-W唑-5-基）-吡啶-3-基氣基1-乙胺 MS (DCI/NH3) m/z 415 (M+l) ； 1 2 H NMR (400 MHz, MeOD) 5 ppm 2.62 (s3 3H) 3.41 (dd5 J=14.73, 6.75 Hz, 1H) 3.50 (dd, J=14.42, 8.59 Hz, 1H) 4.12 (m, 1H) 4.32 (dd, 1=10.43, 5.22 Hz, 1H) 4.45 (dd, J=10.74, 3.07 Hz, 1H) 7.40 (m5 2H) 7.55 (m5 1H) 7.61 (d, J=8.90 Hz, 1H) 7.68 (dd, J=8.59, 1.53 Hz, 1H) 7.91 (m5 3H) 8.03 (s, 1H) 8.35 (s，1H) 8.64(s，1H)· -189- 1 吲口朵-3-基甲基KM5-異口奎琳-6-基-p比咬-3-基氣基）-乙基 1-二甲基-胺 2 H NMR (400 MHz, MeOD) δ ppm 3.16 (s3 6H) 3.44 (m, 2H) 4.11 (m5 1H) 4.46 (m5 1H) 4.55 (m，1H) 7.00 (m，1H) 7.09 (m，1H) 7.26 (m，1H) 7.35 (d，J=8.29 Hz，1H) 7.60 (d5 J=7.98 Hz, 1H) 7.81 (m, 1H) 8.22 (dd5 J=8.59, 1.53 Hz, 1H) 8.42 (m5 2H) 8.50 (m，1H) 8.55 (d，J=8.90 Hz，1H) 8.61 (m，1H) 8.72 (m，1H) 9.73 (s，1H) 200301122(1SV1-benzofbl pyrimiphen-3-ylmethyl-245- (3-methyl-1H-Wazole-5-yl) -pyridin-3-ylamino 1-ethylamine MS (DCI / NH3) m / z 415 (M + l); 1 2 H NMR (400 MHz, MeOD) 5 ppm 2.62 (s3 3H) 3.41 (dd5 J = 14.73, 6.75 Hz, 1H) 3.50 (dd, J = 14.42, 8.59 Hz, 1H) 4.12 (m, 1H) 4.32 (dd, 1 = 10.43, 5.22 Hz, 1H) 4.45 (dd, J = 10.74, 3.07 Hz, 1H) 7.40 (m5 2H) 7.55 (m5 1H) 7.61 (d, J = 8.90 Hz, 1H) 7.68 (dd, J = 8.59, 1.53 Hz, 1H) 7.91 (m5 3H) 8.03 (s, 1H) 8.35 (s, 1H) 8.64 (s, 1H) · -189- 1 3-Methylmethyl KM5-Isoquinine-6-yl-p-ratio-3-ylamino) -ethyl 1-dimethyl-amine 2 H NMR (400 MHz, MeOD) δ ppm 3.16 (s3 6H) 3.44 (m, 2H) 4.11 (m5 1H) 4.46 (m5 1H) 4.55 (m, 1H) 7.00 (m, 1H) 7.09 (m, 1H) 7.26 (m, 1H) 7.35 (d, J = 8.29 Hz , 1H) 7.60 (d5 J = 7.98 Hz, 1H) 7.81 (m, 1H) 8.22 (dd5 J = 8.59, 1.53 Hz, 1H) 8.42 (m5 2H) 8.50 (m, 1H) 8.55 (d, J = 8.90 Hz , 1H) 8.61 (m, 1H) 8.72 (m, 1H) 9.73 (s, 1H) 200301122

(182) Η(182) Η

實例201 (lS)-2-「5-(3-甲基丨峻-5-基）-ρ比症-3-基氧某塞吩-3-基甲基- 乙胺Example 201 (lS) -2- "5- (3-Methyl, 5--5-yl) -rhobiazine-3-yloxy, a certain phenphen-3-ylmethyl-ethylamine

MS (DCI/NH3) m/z 365 (M+l)+ ； 1 H NMR (500 MHz, MeOD) δ ppm 2.63 (s, 3H) 3,43 (m，2H) 3·98 (m，1H) 4.40 (dd5 J=10.61，5.62 Hz，3H) 4·52 (dd，J=10.61，3.12 Hz， 1H) 7.03 (dd，J=8.42, 3·43 Hz，1H) 7.06 (m，1H) 7.36 (dd，J=4.99, 1·25 Hz，1H) 7.64 (d，J=8.73 Hz，1H) 7.75 (dd，J=8.73, 1.87 Hz，1H) 8.14 (s，1H) 8.21 (m，1H) 8·47 (br s， 1H) 8.77 (s，1H).MS (DCI / NH3) m / z 365 (M + l) +; 1 H NMR (500 MHz, MeOD) δ ppm 2.63 (s, 3H) 3,43 (m, 2H) 3.98 (m, 1H) 4.40 (dd5 J = 10.61, 5.62 Hz, 3H) 4.52 (dd, J = 10.61, 3.12 Hz, 1H) 7.03 (dd, J = 8.42, 3.43 Hz, 1H) 7.06 (m, 1H) 7.36 ( dd, J = 4.99, 1.25 Hz, 1H) 7.64 (d, J = 8.73 Hz, 1H) 7.75 (dd, J = 8.73, 1.87 Hz, 1H) 8.14 (s, 1H) 8.21 (m, 1H) 8 47 (br s, 1H) 8.77 (s, 1H).

nh2 A-713679.21nh2 A-713679.21

實例202 芊氧基甲基-2-(5-異4:啉-6-某w比啶-3-基氣基V乙胺 ^HBocExample 202 Ethyloxymethyl-2- (5-iso4: line-6-one)

實例202A (1SM1-芊氧基甲基-2-(5-溴-吡啶各某氫基乙基1-胺甲基酸第三 -丁酉& -190- 200301122 (183)Example 202A (1SM1-Methoxymethyl-2- (5-bromo-pyridine, each hydroxyethyl 1-aminomethyl acid tertiary-butyrene & -190- 200301122 (183)

產物係經由以Boc-絲胺醇（Bn)取代實例2A中之Boc-色胺酸而製成。MS m/z 437, 439 (M+H)+ ; 1 H NMR (300 MHz，DMSO-D6) 5 ppm 1·37 (s，9H) 3.50 (d，J=6.10 Hz，2H) 3.97 (m，1H) 4·11 (m，2H) 4·50 (s，2H) 6·99 (d， J=7.80 Hz, 1H) 7.29 (m, 5H) 7.70 (m, 1H) 8.28 (dd5 J=4.75? 2.37 Hz, 2H).The product was prepared by replacing Boc-tryptophan acid in Example 2A with Boc-serine (Bn). MS m / z 437, 439 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 1.37 (s, 9H) 3.50 (d, J = 6.10 Hz, 2H) 3.97 (m, 1H) 4 · 11 (m, 2H) 4 · 50 (s, 2H) 6 · 99 (d, J = 7.80 Hz, 1H) 7.29 (m, 5H) 7.70 (m, 1H) 8.28 (dd5 J = 4.75? 2.37 Hz, 2H).

實例202BExample 202B

(1SM1-芊氣基甲基-2-(5-異4啉各基-说啶-3-某氣基）-乙基1-胺甲基酸第三丁酯所要之產物係經由以2〇2A取代實例27B中之實例2A而製成。1 H NMR (300 MHz，DMSO-D6) 5 ppm L38 (s，9H) 3.56 (d，J=6.10 Hz，2H) 4.04 (m，1H) 4.22 (d，JN5.43 Hz，2H) 4.52 (s，2H) 7.05 (d，J=8.14 Hz，1H) 7·28 (m， 5H) 7.87 (m，2H) 8·10 (dd，J=8.65, 1·53 Hz，1H) 8·25 (d，J=8.82 Hz，1H) 8·35 (d，J= 2.71 Hz，1H) 8·40 (s，1H) 8·56 (d，J=5.76 Hz，1H) 8.68 (d，J=1.70 Hz，1H) 9·37 (s，The desired product of (1SM1-fluorenylmethyl-2- (5-iso4-morpholine-s-pyridin-3-ceryl) -ethyl-1-aminomethyl acid tert-butyl ester is 2A was prepared in place of Example 2A in Example 27B. 1 H NMR (300 MHz, DMSO-D6) 5 ppm L38 (s, 9H) 3.56 (d, J = 6.10 Hz, 2H) 4.04 (m, 1H) 4.22 ( d, JN5.43 Hz, 2H) 4.52 (s, 2H) 7.05 (d, J = 8.14 Hz, 1H) 7.28 (m, 5H) 7.87 (m, 2H) 8.10 (dd, J = 8.65, 1 · 53 Hz, 1H) 8 · 25 (d, J = 8.82 Hz, 1H) 8 · 35 (d, J = 2.71 Hz, 1H) 8 · 40 (s, 1H) 8 · 56 (d, J = 5.76 Hz, 1H) 8.68 (d, J = 1.70 Hz, 1H) 9.37 (s,

(ISH-y氧基曱基-2-(5-異喹啉-6-某-P比啶各其氧基）·乙胺所要之產物係經由以實例202B取代實例27C中之實例27A而製成。MSm/z386 (M+l)+; iHNMRpOOMHADMSCM^Sppn^/ZGCm， -191- 200301122(ISH-yoxyfluorenyl-2- (5-isoquinoline-6-a-P-pyridine each has its oxy group). The desired product of ethylamine was prepared by substituting Example 202B for Example 27A in Example 27C. MSm / z386 (M + 1) +; iHNMRpOOMHADMSCM ^ Sppn ^ / ZGCm, -191- 200301122

(184) 3H) 3.97 (s，2H) 4.44 (m，2H) 4.60 (s，2H) 7.35 (m，5H) 8.00 (m，1H) 8.33 (m，2H) 8.48 (d，J=2.71 Hz，1H) 8·54 (d，J=8.81 Hz，1H) 8.66 (s，1H) 8.68 (d，J=6.10 Hz，1H) 8.81 (d，J=1.70 Hz，1H) 9.75 (s，lH).(184) 3H) 3.97 (s, 2H) 4.44 (m, 2H) 4.60 (s, 2H) 7.35 (m, 5H) 8.00 (m, 1H) 8.33 (m, 2H) 8.48 (d, J = 2.71 Hz, 1H) 8.54 (d, J = 8.81 Hz, 1H) 8.66 (s, 1H) 8.68 (d, J = 6.10 Hz, 1H) 8.81 (d, J = 1.70 Hz, 1H) 9.75 (s, lH).

A-750983.3 實例203 (1SH-芊氣某甲基-2-[5-(3-甲基-1H-W唑-5-基）-吡啶-3-某氮甚1-λA-750983.3 Example 203 (1SH-tritium methyl-2- [5- (3-methyl-1H-Wazole-5-yl) -pyridine-3-some nitrogen even 1-λ

實例203A 5-溴基-3-甲基4唑小羧酸第三-丁酯將實例102C (1·0克；4.7毫莫耳）、TEA (526毫克；5.2毫莫耳）、DMAP (200毫克；1.6毫莫耳）及二碳酸二-第三-丁酯（U克； 5.0毫莫耳）於CI^CN (15毫升）中之溶液，在室溫下攪拌3小 · 時，蒸發，並藉急騾式層析（30% EbO /己烷）分離，而得所要之產物，為白色固體（1.4克；95% )。Example 203A Tertiary-butyl 5-bromo-3-methyl4azole small carboxylic acid Example 102C (1.0 g; 4.7 mmol), TEA (526 mg; 5.2 mmol), DMAP (200 Mg; 1.6 millimoles) and a solution of di-tertiary-butyl dicarbonate (Ug; 5.0 millimoles) in CI ^ CN (15 ml), stirred at room temperature for 3 hours, evaporated, It was separated by flash chromatography (30% EbO / hexane) to obtain the desired product as a white solid (1.4 g; 95%).

實例203B 3-甲某-5-三甲基錫烷某^唑小羧酸第三-丁酯 -192- (185) 200301122 將實例2〇3Α(1·35克；4.3毫莫耳）、六曱基二錫（1·56克；4·8 毫莫耳）及Pd(PPh3 )4(250毫克，0.22毫莫耳）於甲苯（15毫升）中之溶液，在85°C下攪掉過夜，蒸發並藉急騾式層析純化（20 % Et20/己烷），提供所要之產物（1.32克；77% )。Example 203B 3-methyl-5-trimethylstannane triazole small carboxylic acid tert-butyl ester-192- (185) 200301122 Example 203A (1.35 g; 4.3 mmol), six A solution of fluorenyl ditin (1.56 g; 4.8 mmol) and Pd (PPh3) 4 (250 mg, 0.22 mmol) in toluene (15 ml) was stirred overnight at 85 ° C. , Evaporated and purified by flash chromatography (20% Et20 / hexane) to provide the desired product (1.32 g; 77%).

實例203C (2S)-5-[5-(3-芊氣基-2-第三-丁氧羰某胺某-丙氫基V吡啶-3-基甲基唑小羧酸第三-丁酯所要之產物係經由以203B取代實例202B中之實例27A而製成。MSm/z 589 (M+H)+ ; iHNMRpOOMHiDMSODe) (5ppml.38(s，9H) 1·66 (s，9H) 2.59 (s，3H) 3.32 (m，1H) 3·56 (d,】=6·10 Hz，2H) 4·20 (d，J= 5·76 Hz， 2H) 4.52 (s? 2H) 7.03 (d, J=8.14 Hz, 1H) 121 (m, 1H) 732 (m, 4H) 7.78 (s, 1H) 8.00 (dd，J=8.82, 1.70 Hz，1H) 8.12 (m，1H) 8.26 (d，J=1.02 Hz，1H) 8·29 (d，J=2.71 Hz， 1H) 8.61 (d5 J=1.7〇 Hz, 1H).Example 203C (2S) -5- [5- (3-Hydroxy-2-yl-tertiary-butoxycarbonylamine amine-propanyl-V-pyridin-3-ylmethylazole small carboxylic acid tertiary-butyl ester The desired product was prepared by replacing Example 27A in Example 202B with 203B. MSm / z 589 (M + H) +; iHNMRpOOMHiDMSODe) (5ppm 1.38 (s, 9H) 1.66 (s, 9H) 2.59 ( s, 3H) 3.32 (m, 1H) 3.56 (d,) = 6.10 Hz, 2H) 4.20 (d, J = 5.76 Hz, 2H) 4.52 (s? 2H) 7.03 (d, J = 8.14 Hz, 1H) 121 (m, 1H) 732 (m, 4H) 7.78 (s, 1H) 8.00 (dd, J = 8.82, 1.70 Hz, 1H) 8.12 (m, 1H) 8.26 (d, J = 1.02 Hz, 1H) 8.29 (d, J = 2.71 Hz, 1H) 8.61 (d5 J = 1.7〇Hz, 1H).

HH

實例203D (1S)-1:主..氧基甲基冬「5-(3-甲基-1H-吲唑-5-基吡啶各基氣某1-乙胺所要之產物係經由以2(BC取代實例27C中之實例27B而製成。MS m/z 389 (M+H)+ ; 1H NMR (300 MHz，DMSO-D6) 6 ppm 2.57 (s，3H) -193- 200301122 (186) 3.79 (m，3H) 4.51 (m，2H) 4.60 (s，2H) 4.90 (br s，2H) 7.34 (m，5H) 7.61 (d，J=8.81 Hz? 1H) 7.80 (dd, J=8.81, 1.70 Hz, 1H) 8.23 (s, 1H) 8.27 (s? 1H) 8.52 (m5 2H) 8.85 (d, J=1.70 Hz, 1H).Example 203D (1S) -1: Main: oxymethyl dong, 5- (3-methyl-1H-indazol-5-ylpyridine, each radical, the desired product of 1-ethylamine is BC was prepared in place of Example 27B in Example 27C. MS m / z 389 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 6 ppm 2.57 (s, 3H) -193- 200301122 (186) 3.79 (m, 3H) 4.51 (m, 2H) 4.60 (s, 2H) 4.90 (br s, 2H) 7.34 (m, 5H) 7.61 (d, J = 8.81 Hz? 1H) 7.80 (dd, J = 8.81, 1.70 Hz, 1H) 8.23 (s, 1H) 8.27 (s? 1H) 8.52 (m5 2H) 8.85 (d, J = 1.70 Hz, 1H).

實例204 (lSV2-(5-異4啉-6-基·吡啶-3-基氧基M-(篇-2-基氧基甲基）-乙良Example 204 (1SV2- (5-Iso-4-line-6-yl · pyridin-3-yloxyM- (Phy-2-yloxymethyl) -Ethyl

實例204AExample 204A

(1SM1-羥甲基-2-(5-異4啉-6-基-吡啶-3-基氣基）·乙基l·胺甲基霞第三丁酯於實例202B (290毫克，0.60毫莫耳）中，相繼地添加：甲酸銨（377毫克，5·97毫莫耳）、MeOH (潮濕）(15毫升）及1〇% Pd/C (320 毫克）。使所形成之黑色反應混合物溫熱至7〇°C ’歷經6天，然後冷卻至室溫，並經過矽藻土過濾。添加K2 C〇3 (50毫克）與矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（2-3-5-7% MeOH/CH2Cl2)，獲得40毫克（14% )回收之起始物質與89毫克（38% )無色蠟狀固體。1^0.32(10% MeOH/CH2Cl2) -194- (187) ;1H NMR (300 MHz，DMS0-D6) (5 ppm 1.38 (s，9H) 3.51 (td，JN5.76, 2.71 Hz， 2H) 3.84 (m5 1H) 4.19 (m, 2H) 4.84 (t, J=5.76 Hz, 1H) 6.82 (d? J=8.14 Hz, 1H) 7.89 (m，2H) 8.11 (dd，J=8.65, 1.53 Hz，1H) 8·25 (d，J=8.82 Hz，1H) 8.36 (d，J= 2.71 Hz， 1H) 8.41 (s，1H) 8·56 (d，J=5.76 Hz，1H) 8·68 (d，J=1 ·70 Hz，1H) 9.37 (s，1H).(1SM1-Hydroxymethyl-2- (5-iso4-line-6-yl-pyridin-3-ylamino). Ethyl l. Amine methyl tertiary butyl ester in Example 202B (290 mg, 0.60 mmol Mol), ammonium formate (377 mg, 5.97 mmol), MeOH (wet) (15 ml), and 10% Pd / C (320 mg) were added successively. The resulting black reaction mixture was allowed to form. Warm to 70 ° C for 6 days, then cool to room temperature and filter through diatomaceous earth. Add K2CO3 (50 mg) and silica gel and remove volatiles on a rotary evaporator. Flash chromatography (2-3-5-7% MeOH / CH2Cl2) gave 40 mg (14%) of recovered starting material and 89 mg (38%) of a colorless waxy solid. 1 ^ 0.32 (10% MeOH / CH2Cl2) -194- (187); 1H NMR (300 MHz, DMS0-D6) (5 ppm 1.38 (s, 9H) 3.51 (td, JN5.76, 2.71 Hz, 2H) 3.84 (m5 1H) 4.19 (m, 2H) 4.84 (t, J = 5.76 Hz, 1H) 6.82 (d? J = 8.14 Hz, 1H) 7.89 (m, 2H) 8.11 (dd, J = 8.65, 1.53 Hz, 1H) 8.25 (d, J = 8.82 Hz, 1H) 8.36 (d, J = 2.71 Hz, 1H) 8.41 (s, 1H) 8.56 (d, J = 5.76 Hz, 1H) 8.68 (d, J = 70 Hz, 1H ) 9.37 (s, 1H).

實例204B 異喹啉·6-基-吡啶-3-基氣基）-1-(¾ -2-某氣基甲基V乙某 V胺甲基酸第三-丁酉旨將2-莕酚（15毫克，101微莫耳）、實例204Α (20毫克，51微莫耳）、DBAD (17毫克，76微莫耳）及PPh3-聚合體（3毫莫耳/ 克）(34毫克，101微莫耳）合併於10毫升圓底燒瓶中。添加THF (2毫升），並將反應混合物於23°C下攪拌2天，然後以矽膠旋轉蒸發。急驟式層析（2-3-5-10% MeOH/CH2Cl2)，獲得19毫克（73 %)，為無色蠟狀固體。Rf=〇.47(10% MeOH/CH2Cl2); 4刪11(300 MHz, DMS0-D6) δ ppm 1.41 (s, 9H) 4.24 (m, 3H) 4.37 (m, 2H) 7.19 (dd, J= 8.82, 2.71 Hz, 1H) 7.34 (m, 3H) 7.45 (td3 J=7.54, 1.19 Hz, 1H) 7.78 (s, 1H) 7.81 (s, 1H) 7.84 (s, 1H) 7.88 (d, J=5.76 Hz, 1H) 7.92 (s, 1H) 8.10 (dd5 J=8.48? 1.70 Hz, 1H) 8.24 (d, J=8.48 Hz, 1H) 8.40 (m, 2H) 8.56 (d, J=5.76 Hz, 1H) 8.69 (d3 J=1.70 Hz, 1H) 9,37 (s，1H)· (188)Example 204B Isoquinoline · 6-yl-pyridin-3-ylamino group) -1- (¾-2-A certain methyl group V ethyl certain V amine methyl acid 15 mg, 101 μmol), Example 204A (20 mg, 51 μmol), DBAD (17 mg, 76 μmol), and PPh3-polymer (3 mmol / g) (34 mg, 101 μmol) Mol) was combined in a 10 ml round-bottomed flask. THF (2 ml) was added, and the reaction mixture was stirred at 23 ° C for 2 days, followed by rotary evaporation with silica gel. Flash chromatography (2-3-5-10 % MeOH / CH2Cl2) to obtain 19 mg (73%) as a colorless waxy solid. Rf = 0.47 (10% MeOH / CH2Cl2); 4 delete 11 (300 MHz, DMS0-D6) δ ppm 1.41 (s, 9H) 4.24 (m, 3H) 4.37 (m, 2H) 7.19 (dd, J = 8.82, 2.71 Hz, 1H) 7.34 (m, 3H) 7.45 (td3 J = 7.54, 1.19 Hz, 1H) 7.78 (s, 1H ) 7.81 (s, 1H) 7.84 (s, 1H) 7.88 (d, J = 5.76 Hz, 1H) 7.92 (s, 1H) 8.10 (dd5 J = 8.48? 1.70 Hz, 1H) 8.24 (d, J = 8.48 Hz , 1H) 8.40 (m, 2H) 8.56 (d, J = 5.76 Hz, 1H) 8.69 (d3 J = 1.70 Hz, 1H) 9,37 (s, 1H) · (188)

(lS)-2-(5-異峻淋-6-基比咬-3-基氧基）-1-(客-2-基氧基甲基）-乙胺所要之產物係經由以實例204B取代實例27C中之實例27B 而製成。LCMSm/z422(M+l)+; iHNMRpOOMHsDMSG-DG) (5ppm3.54 (dt，J=11.44, 5·64 Hz，1H) 4·23 (m，4H) 7·20 (dd，J=8.98, 2·54 Hz，1H) 7.34 (m，2H) 7.45 (ddd，J=8.05, 6.87, 1·36 Hz，1H) 7.81 (m，3H) 7.88 (m，2H) 8.09 (m，1H) 8.24 (d， J=8.48 Hz, 1H) 8.38 (s, 1H) 8.42 (d, J=2.71 Hz, 1H) 8.55 (d, J=5.76 Hz, 1H) 8.67 (d, J=1.70 Hz, 1H) 9.37 (s, 1H). 實例205 (lS)-2-(5-異邊p林-6-基比淀-3-基氧基比咬-3-基氧基曱基）-乙胺所要之產物係經由以3-羥基吡啶取代實例204中之2-莕酚，以三-TFA 鹽製成。MS m/z 373 (M+l)+ ; 1H NMR (300 MHz, DMS0-D6) 5ppm 4.10 (m, 1H) 4.48 (m, 4H) 7.44 (dd, J=8.65, 4.92 Hz, 1H) 7.54 (m, 1H) 7.96 (t5 J=2.03 Hz，1H) 8·09 (d，J=6.78 Hz，1H) 8.21 (dd，J=8.65, 1·53 Hz，1H) 8.27 (d，J= 4.75 Hz, 1H) 8.41 (m, 2H) 8.49 (m, 4H) 8.63 (d? J=5.76 Hz, 1H) 8.79 (d, J=1.70 Hz, 1H) 9·56 (s，1H)· 實例206 (lS)-2-(5-異4啉-6-基—比啶-3-基氣基M-(喹啉-7-基氧基甲基）-乙胺所要之產物係經由以7-羥基喹啉取代實例204中之2-莕酚，以三氟醋酸鹽製成。1H NMR (300 MHz, DMS0-D6) δ ppm 4·24 (m， 4H) 7·45 (m，3H) 7.90 (m，3H) 8·09 (dd，J=8.48, 1.70 Hz，1H) 8.23 (s，1H) 8.25 (s， 1H) 8.39 (s, 1H) 8.42 (d, J=2.71 Hz, 1H) 8.56 (d5 J=5.43 Hz, 1H) 8.67 (d, J=1.70 Hz, 200301122 (189) 1H) 8.73 (dd, J=4.41, 1.70 Hz, 1H) 9.37 (s, 1H). 實例207 (2SV442-胺基-3-(5-異喹啉-6-基-咄唉-3-基氧某v丙氫某1-笨曱腈所要之產物係經由以4-氰基酚取代實例204中之2-莕酚，以三氟醋酸鹽製成。4 NMR (300 MHz，DMSO-D6) 5 ppm 2.27 (br s，2H) 3.49 (m, 1H) 4.18 (m5 4H) 7.16 (m, 2H) 7.76 (m, 2H) 7.86 (dd, J=2.71, 2.03 Hz, 1H) 7.89 (d，J=5.76 Hz，1H) 8.09 (dd，J二8.65, 1·86 Hz，1H) 8.25 (d，J=8.82 Hz，1H) 8.39 (m，2H) 8.56 (d，J=5.76 Hz，1H) 8.68 (d，J=1 ·69 Hz，1H) 9·37 (s，1H)· φ 實例208 (◎)-N，-(5-(3-甲基-1H-W唑-5-基）-吡啶-3m赛基-丙烷-U-二胺The desired product of (lS) -2- (5-Isotrien-6-yl than -3-benzyloxy) -1- (guest-2-yloxymethyl) -ethylamine was obtained using Example 204B. This was prepared in place of Example 27B in Example 27C. LCMSm / z422 (M + l) +; iHNMRpOOMHsDMSG-DG) (5ppm3.54 (dt, J = 11.44, 5.64 Hz, 1H) 4.23 (m, 4H) 7.20 (dd, J = 8.98, 2.54 Hz, 1H) 7.34 (m, 2H) 7.45 (ddd, J = 8.05, 6.87, 1.36 Hz, 1H) 7.81 (m, 3H) 7.88 (m, 2H) 8.09 (m, 1H) 8.24 ( d, J = 8.48 Hz, 1H) 8.38 (s, 1H) 8.42 (d, J = 2.71 Hz, 1H) 8.55 (d, J = 5.76 Hz, 1H) 8.67 (d, J = 1.70 Hz, 1H) 9.37 ( s, 1H). Example 205 (lS) -2- (5-Iso-p-lin-6-ylpyridine-3-yloxy than bit-3-yloxyfluorenyl) -ethylamine Made by substituting 2-hydroxyphenol in Example 204 with 3-hydroxypyridine and tri-TFA salt. MS m / z 373 (M + 1) +; 1H NMR (300 MHz, DMS0-D6) 5ppm 4.10 (m , 1H) 4.48 (m, 4H) 7.44 (dd, J = 8.65, 4.92 Hz, 1H) 7.54 (m, 1H) 7.96 (t5 J = 2.03 Hz, 1H) 8.09 (d, J = 6.78 Hz, 1H ) 8.21 (dd, J = 8.65, 1.53 Hz, 1H) 8.27 (d, J = 4.75 Hz, 1H) 8.41 (m, 2H) 8.49 (m, 4H) 8.63 (d? J = 5.76 Hz, 1H) 8.79 (d, J = 1.70 Hz, 1H) 9.56 (s, 1H) · Example 206 (1S) -2- (5-iso4-line-6-yl-pyridin-3-ylamino group M- ( Quinoline-7-yloxymethyl) -ethylamine The desired product is substituted by 7-hydroxyquinoline 2-Phenol in Example 204, made from trifluoroacetate. 1H NMR (300 MHz, DMS0-D6) δ ppm 4 · 24 (m, 4H) 7 · 45 (m, 3H) 7.90 (m, 3H ) 8 · 09 (dd, J = 8.48, 1.70 Hz, 1H) 8.23 (s, 1H) 8.25 (s, 1H) 8.39 (s, 1H) 8.42 (d, J = 2.71 Hz, 1H) 8.56 (d5 J = 5.43 Hz, 1H) 8.67 (d, J = 1.70 Hz, 200301122 (189) 1H) 8.73 (dd, J = 4.41, 1.70 Hz, 1H) 9.37 (s, 1H). Example 207 (2SV442-amino-3- (5-Isoquinoline-6-yl-fluoren-3-yloxy v propyl hydrogen v 1-benzonitrile The desired product was obtained by substituting 2-cyanol in Example 204 with 4-cyanophenol to Made from trifluoroacetate. 4 NMR (300 MHz, DMSO-D6) 5 ppm 2.27 (br s, 2H) 3.49 (m, 1H) 4.18 (m5 4H) 7.16 (m, 2H) 7.76 (m, 2H) 7.86 (dd, J = 2.71, 2.03 Hz, 1H) 7.89 (d, J = 5.76 Hz, 1H) 8.09 (dd, J = 8.65, 1.86 Hz, 1H) 8.25 (d, J = 8.82 Hz, 1H) 8.39 (m, 2H) 8.56 ( d, J = 5.76 Hz, 1H) 8.68 (d, J = 1 · 69 Hz, 1H) 9 · 37 (s, 1H) · φ Example 208 (◎) -N,-(5- (3-methyl- 1H-Wazole-5-yl) -pyridine-3m syl-propane-U-diamine

實例208A (亞溴-峨嚏各基胺基）-甲基]-2-苯某-乙基丨-胺甲基酸第三 -丁酯將實例23Β (0.4克，2.3毫莫耳）、（1-甲醯基-2-苯基-乙基）-胺曱基酸第三丁酯（0.7克，2.8毫莫耳）及Ti(iPrO)4(10毫升）於 CH2Cl2(15毫升）中之溶液，在室溫下攪拌2小時。蒸發溶劑，並使殘留物溶於15毫升EtOH中。將溶液以NaBH3CN(0.5克修 ’ 4.9毫莫耳）處理，然後於室溫下攪拌過夜。將混合物以醋酸乙酯（50毫升）稀釋，以水（25毫升）及鹽水（25毫升）洗滌。蒸發醋酸乙酯，並使殘留物於矽膠上藉急驟式管柱層析純化’以1 : 4至1 ··丨醋酸乙酯/己烷之溶劑梯度液溶離，獲得 0·28 克產物（30% )。MS : (ESI)m/z408 (Μ+Η)+· 實例208Β 第^丁氫羰某胺基各苯基_丙胺基）·吡兔_3·基ι·3·甲 -197- (190) 基θΐ唑-l-義酸第三-丁酯所要之產物係經由以實例2〇8Α取代實例203C中之實例202Α 而製成。Example 208A (Bromo-Ethylamino) -methyl] -2-benzene-ethyl-ethyl-aminomethyl acid third-butyl ester Example 23B (0.4 g, 2.3 mmol), ( 1-methylamido-2-phenyl-ethyl) -aminoammonium tert-butyl ester (0.7 g, 2.8 mmol) and Ti (iPrO) 4 (10 ml) in CH2Cl2 (15 ml) The solution was stirred at room temperature for 2 hours. The solvent was evaporated and the residue was dissolved in 15 ml of EtOH. The solution was treated with NaBH3CN (0.5 g of repair 4.9 mmol) and then stirred at room temperature overnight. The mixture was diluted with ethyl acetate (50 ml) and washed with water (25 ml) and brine (25 ml). Ethyl acetate was evaporated, and the residue was purified by flash column chromatography on silica gel with a solvent gradient of 1: 4 to 1 ·· 丨 ethyl acetate / hexane to obtain 0. 28 g of product (30 %). MS: (ESI) m / z408 (M + Η) + Example 208B ^ Butyl hydrocarbyl amine each phenyl_propylamino) · Pyridyl_ 3 · yl · 3 · methyl-197- (190) The desired product of the base θ-oxazole-l-sense acid third-butyl ester was prepared by substituting Example 202A in Example 203C with Example 208A.

實例208CExample 208C

(2S)：Ei(M3-甲基-1Η-啕唑-5-基吡啶-3-某V3-笨基-丙烷-1,2-二胺所要之產物係經由以實例208B取代實例27C中之實例27B 而製成。MS: (ESI)m/z358 (M+H)+; iHNMRpOOMHz’DMSO-DG) 5ppm 2.56 (d，J=3.74 Hz，3H) 3.00 (m，2H) 3.42 (d，J= 5·30 Hz，3H) 6.89 (m，1H) 7.27 (m， 2H) 7.35 (m，3H) 7.57 (s，1H) 7.62 (d，JM.06 Hz，2H) 8.01 (s，1H) 8.07 (m，1H) 8.13 (s，2H) 8.38 (s，1H)· 實例209 (2S)-N-(2-胺基-3-苯基-丙基）·Ν-「5-(3-甲基-lH-Kl 也-5-基比症-3-基曱烷磺醯胺於吡啶（8毫升）中之實例208B (500毫克，0.90毫莫耳）内，在冰浴中，逐滴添加氯化甲基磺醯（308毫克，2.7毫莫耳）。使反應混合物溫熱至室溫，並攪捽12小時。經由使氮起泡至反應燒瓶中，移除溶劑。使殘留物於矽膠上層析，以EtOAc 溶離，獲得Boc保護之產物，根據實例27C中所述之程序，將其去除保護，而得標題化合物，為三氟醋酸鹽（21.2毫克，4% )。MS (DCI/NH3) m/z 436 (M+l)+ ; 1H NMR (500 MHz，MeOD) 5 ppm 2.62 (s, 3H) 2.89 (dd, J=14.35, 9.36 Hz, 1H) 3.03 (s, 3H) 3.05 (dd, J=14.35, 5.62 Hz, 1H) 3.59 (m，1H) 4.06 (d，J=5.93 Hz，2H) 7.07 (s，1H) 7.09 (s，1H) 7·18 (d，J=7.18 Hz， 1H) 7.24 (m，2H) 7.60 (s，1H) 7.60 (s，1H) 7.95 (s，1H) 8.10 (t，J=1.87 Hz，1H) 8.59 (s，1H) 8·87 (s，1H). (191) 實例2ί0 (2S)-N-(2-胺基-3-苯基-丙基）-N-「5-(3-甲某-1Η-吲唑-5-基）-吡啶-3-基1- 笨磺醯胺所要之產物係經由以氯化苯磺醯取代實例209中之氯化甲烷磺醯，以三氟醋酸鹽製成。MS(DCI/NH)m/z498 (M+l)+; hNMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 2.84 (dd5 J=14.04, 8.42 Hz, 1H) 2.97 (dd5 J=14.04, 5·62 Hz，1H) 3.45 (m，1H) 3.78 (m，2H) 7.17 (s，1H) 7.19 (s，1H) 7.24 (d，J= 7·18 Hz，1H) 7·30 (m，2H) 7.43 (s，1H) 7·44 (d，J=0.62 Hz，1H) 7.50 (dd，J=8.73， 1.56 Hz, 1H) 7.57 (d, J=8.42 Hz, 1H) 7.62 (m, 3H) 7.78 (t, J=7.49 Hz, 1H) 7.82 (s, 1H) 8.11 (s, 3H) 8.25 (d, J=2.18 Hz, 1H) 8.92 (d, J=1.87 Hz, 1H). 實例211 (2S)-N-(2-胺基-3-笨基-丙基甲基-1H-W唑-5-基）-吡啶-3-基1- 苯甲醯胺所要之產物係經由以氯化苯甲醯取代實例209中之氯化甲烷磺醯，以三氟醋酸鹽製成。MS(DCI/NH3)m/z462(M+l)+ ; 1 H NMR (500 MHz，DMSO-D6) 5 ppm 2.54 (s，3H) 2·90 (dd，J=14.04, 9.05 Hz，1H) 3.03 (dd，J=14.04, 5·30 Hz，1H) 3·65 (m，1H) 4.09 (dd，J=14.97, 4.06 Hz，1H) 4.28 (dd，JN14.97, 8.42 Hz，1H) 7.19 (m，3H) 7,27 (m，4H) 7·33 (m，2H) 7.44 (dd，J=8.73， 1.56 Hz，1H) 7.54 (d，J=8.73 Hz，1H) 7·75 (s，1H) 7.86 (m，1H) 8·09 (s，3H) 8.22 (d， J=2.18 Hz, 1H) 8.69 (d, J=1.87 Hz, 1H). 實例212 (2S)-N-(2-胺基-3-笨基-丙基VN-『5-(3-甲基-1H-W唑-5-基）-吡啶-3-基1- 乙醯胺所要之產物係經由以氯化乙醯取代實例209中之氯化甲烷 -199- (192)(2S): Ei (M3-methyl-1fluoren-oxazol-5-ylpyridine-3-V3-benzyl-propane-1,2-diamine The desired product was obtained by replacing Example 27C with Example 208B Example 27B. MS: (ESI) m / z358 (M + H) +; iHNMRpOOMHz'DMSO-DG) 5ppm 2.56 (d, J = 3.74 Hz, 3H) 3.00 (m, 2H) 3.42 (d, J = 5.30 Hz, 3H) 6.89 (m, 1H) 7.27 (m, 2H) 7.35 (m, 3H) 7.57 (s, 1H) 7.62 (d, JM.06 Hz, 2H) 8.01 (s, 1H) 8.07 (m, 1H) 8.13 (s, 2H) 8.38 (s, 1H) · Example 209 (2S) -N- (2-amino-3-phenyl-propyl) · N- "5- (3-methyl -LH-Kl Also Example of -5-ylpyridin-3-ylsulfanilidinesulfonamide in pyridine (8 ml) 208B (500 mg, 0.90 mmol), add dropwise in an ice bath Methanesulfonium chloride (308 mg, 2.7 mmol). The reaction mixture was warmed to room temperature and stirred for 12 hours. The solvent was removed by bubbling nitrogen into the reaction flask. The residue was allowed to pass through silicone Chromatography and dissociation with EtOAc gave the Boc protected product, which was removed and protected according to the procedure described in Example 27C to give the title compound as trifluoroacetate (21.2 mg, 4%). MS (DCI / NH3) m / z 436 (M + l) +; 1H NMR (500 MHz, MeOD) 5 ppm 2.62 (s, 3H) 2.89 (dd, J = 14.35, 9.36 Hz, 1H) 3.03 (s, 3H) 3.05 ( dd, J = 14.35, 5.62 Hz, 1H) 3.59 (m, 1H) 4.06 (d, J = 5.93 Hz, 2H) 7.07 (s, 1H) 7.09 (s, 1H) 7.18 (d, J = 7.18 Hz , 1H) 7.24 (m, 2H) 7.60 (s, 1H) 7.60 (s, 1H) 7.95 (s, 1H) 8.10 (t, J = 1.87 Hz, 1H) 8.59 (s, 1H) 8.87 (s, 1H). (191) Example 2 (0) (2S) -N- (2-amino-3-phenyl-propyl) -N- "5- (3-methyl-1-1-indazol-5-yl)- The desired product of pyridin-3-yl 1-benzylamidine was prepared by substituting benzenesulfonium chloride for methanesulfonium chloride in Example 209 and trifluoroacetate. MS (DCI / NH) m / z498 (M + l) +; hNMR (500 MHz, DMSO-D6) δ ppm 2.55 (s, 3H) 2.84 (dd5 J = 14.04, 8.42 Hz, 1H) 2.97 (dd5 J = 14.04, 5.62 Hz, 1H) 3.45 (m, 1H) 3.78 (m, 2H) 7.17 (s, 1H) 7.19 (s, 1H) 7.24 (d, J = 7 · 18 Hz, 1H) 7.30 (m, 2H) 7.43 (s, 1H ) 7.44 (d, J = 0.62 Hz, 1H) 7.50 (dd, J = 8.73, 1.56 Hz, 1H) 7.57 (d, J = 8.42 Hz, 1H) 7.62 (m, 3H) 7.78 (t, J = 7.49 Hz, 1H) 7.82 (s, 1H) 8.11 (s, 3H) 8.25 (d, J = 2.18 Hz, 1H) 8.92 (d, J = 1.87 Hz, 1H). Example 211 (2S) -N- (2-amino-3-benzyl-propylmethyl-1H-Wazole-5-yl) -pyridine-3- The desired product of the 1-benzamide was prepared by replacing the sulfonium chloride methanesulfonium chloride in Example 209 with benzamidine chloride and trifluoroacetate. MS (DCI / NH3) m / z462 (M + l) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 2.54 (s, 3H) 2.90 (dd, J = 14.04, 9.05 Hz, 1H) 3.03 (dd, J = 14.04, 5.30 Hz, 1H) 3.65 (m, 1H) 4.09 (dd, J = 14.97, 4.06 Hz, 1H) 4.28 (dd, JN14.97, 8.42 Hz, 1H) 7.19 (m, 3H) 7,27 (m, 4H) 7.33 (m, 2H) 7.44 (dd, J = 8.73, 1.56 Hz, 1H) 7.54 (d, J = 8.73 Hz, 1H) 7.75 (s , 1H) 7.86 (m, 1H) 8.09 (s, 3H) 8.22 (d, J = 2.18 Hz, 1H) 8.69 (d, J = 1.87 Hz, 1H). Example 212 (2S) -N- (2 -Amino-3-benzyl-propyl VN- "5- (3-methyl-1H-Wazole-5-yl) -pyridin-3-yl1-acetamidamine Acetylamine replaces methane chloride-199- (192) in Example 209

磺醯，以三氟醋酸鹽製成。MS(DCI/NH3)m/z400(M+l)+ ; iHNMR (400 MHz, MeOD) δ ppm 1.98 (s, 3H) 2.63 (s, 3H) 2.90 (dd5 J=14.12, 8.90 Hz, 1H) 3·02 (dd，J=13.81，5·83 Hz，1H) 3.68 (m，1H) 3·76 (dd，J=15.04, 2.46 Hz，1H) 4.31 (dd，J=15.04, 7.98 Hz, 1H) 7.25-7.11 (m，6H) 7.64 (m，2H) 8.00 (s，1H) 8.03 (s，1H) 8.46 (s, 1H) 8.93 (s, 1H) 實例213 (2S)-3-f2-胺基-3~(1H-vV[ 口朵-3-基）-亞丙基 V5-異口奎淋-6-基-1,3-二乳哚-2-酮所要之產物係經由以5-溴基氧化吲嗓取代實例44中之5-溴基-7-氮-氧化啕哚，以三氟醋酸鹽製成。MS(DCI/NH3)m/z431 (M+l)+ ； 1H NMR (500 MHz, MeOD) δ ppm 3.26 (dd, J=14.35, 9.67 Hz, 1H) 3.57 (dd, J=14.66, 4.06 Hz, 1H) 5.05 (dt, J=19.34, 4.06 Hz, 1H) 6.71 (m, 1H) 6.83 (d, J= 9.98 Hz, 1H) 6.85 (m, 1H) 6.98 (d, J=8.42 Hz, 1H) 7.03 (m5 1H) 7.06 (d5 J=8.11 Hz, 1H) 7.14 (d，J=1.56 Hz，1H) 7.55 (dd，J=8.73, 1.87 Hz，1H) 7.64 (dd，J=8.11，1.56 Hz， 1H) 7.69 (d，J=8.11 Hz，1H) 7.94 (s，1H) 8·18 (d，J=6.24 Hz，1H) 8.31 (d，J=8.73 Hz， 1H) 8.52 (s，1H) 9.55 (s，1H). 實例214 (lSV2-(5-異♦啉-6-基-吡啶-3-基氧基VH1-甲基-1H-蚓哚-3-基甲基 )-乙胺標題化合物係經由以5-溴基-7-氮啕哚（D. Mazeas等人，雜環 1990, 50, 1065)，取代實例32中之6-溴基鄰苯二曱醯亞胺，以三氟醋酸鹽製成。MS(DCI/NH3)m/z384(M+l)+ ; iHNMR^OOMHz， MeOD) δ ppm 3.29 (m, 1H) 3.33 (dd, J=8.11, 2.81 Hz, 1H) 4.03 (m, 1H) 4.36 (dd, J=10.61, 5.62 Hz, 1H) 4.49 (dd, J=10.61, 3.12 Hz, 1H) 6.69 (d3 J=3.12 Hz, 1H) 7.02 200301122 (193) (m，1H) 7·10 (t，J=7.49 Hz，1H) 7.25 (s，1H) 7.36 (d，J=8.11 Hz，1H) 7.57 (m，2H) 8.08 (s，1H) 8.45 (s，2H) 8·58 (s，1H) 8.80 (s，1H)· 實例215 (1SH-(1H-啕哚-3-基甲基）-2-「5-(1Η-吡咯并|~2,3-bl吡啶-5-基）-吡啶-3- 基氧基1-乙脖Sulfonium, made from trifluoroacetate. MS (DCI / NH3) m / z400 (M + l) +; iHNMR (400 MHz, MeOD) δ ppm 1.98 (s, 3H) 2.63 (s, 3H) 2.90 (dd5 J = 14.12, 8.90 Hz, 1H) 3 · 02 (dd, J = 13.81, 5.83 Hz, 1H) 3.68 (m, 1H) 3.76 (dd, J = 15.04, 2.46 Hz, 1H) 4.31 (dd, J = 15.04, 7.98 Hz, 1H) 7.25-7.11 (m, 6H) 7.64 (m, 2H) 8.00 (s, 1H) 8.03 (s, 1H) 8.46 (s, 1H) 8.93 (s, 1H) Example 213 (2S) -3-f2-amino -3 ~ (1H-vV [口朵 -3-yl) -propylene group V5-Isoquinone-6-yl-1,3-dilactol-2-one The desired product is via 5-bromo The indoxy group was substituted with 5-bromo-7-nitro-oxo-indole in Example 44 and was made of trifluoroacetate. MS (DCI / NH3) m / z431 (M + l) +; 1H NMR (500 MHz, MeOD) δ ppm 3.26 (dd, J = 14.35, 9.67 Hz, 1H) 3.57 (dd, J = 14.66, 4.06 Hz, 1H) 5.05 (dt, J = 19.34, 4.06 Hz, 1H) 6.71 (m, 1H) 6.83 (d, J = 9.98 Hz, 1H) 6.85 (m, 1H) 6.98 (d, J = 8.42 Hz, 1H) 7.03 (m5 1H) 7.06 (d5 J = 8.11 Hz, 1H) 7.14 (d, J = 1.56 Hz, 1H) 7.55 (dd, J = 8.73, 1.87 Hz, 1H) 7.64 (dd, J = 8.11, 1.56 Hz, 1H ) 7.69 (d, J = 8.11 Hz, 1H) 7.94 (s, 1H) 8.18 (d, J = 6.24 Hz, 1H) 8.31 (d, J = 8.73 Hz, 1H) 8.52 (s, 1H) 9.55 ( s, 1H). Example 214 (lSV2- (5-Isoline-6-yl-pyridin-3-yloxyVH1-methyl-1H-earmdol-3-ylmethyl) -ethylamine title compound system By substituting 5-bromo-7-azepine (D. Mazeas et al., Heterocyclic 1990, 50, 1065), replacing the 6-bromo-o-phthalimide of Example 32 with trifluoroacetate Made of. MS (DCI / NH3) m / z384 (M + 1) +; iHNMR ^ OOMHz, MeOD) δ ppm 3.29 (m, 1H) 3.33 (dd, J = 8.11, 2.81 Hz, 1H) 4.03 (m, 1H) 4.36 (dd, J = 10.61, 5.62 Hz, 1H) 4.49 (dd, J = 10.61, 3.12 Hz, 1H) 6.69 (d3 J = 3.12 Hz, 1H) 7.02 200301122 (193) (m, 1H) 7 · 10 (t, J = 7.49 H z, 1H) 7.25 (s, 1H) 7.36 (d, J = 8.11 Hz, 1H) 7.57 (m, 2H) 8.08 (s, 1H) 8.45 (s, 2H) 8.58 (s, 1H) 8.80 (s , 1H) · Example 215 (1SH- (1H-pyridin-3-ylmethyl) -2- "5- (1Η-pyrrolo | ~ 2,3-blpyridin-5-yl) -pyridine-3- 1-ethoxy

實例215A 哚，3-基甲基）-2-(5-異♦呲-6-基-吡啶-3-基氧基）-乙基1-2-硝基本鴻·酿胺於實例27 (400毫克，1·〇1毫莫耳）與mEA (丨〇6毫升，6 〇6毫莫耳）在THF (30毫升）中，於冰浴冷卻之溶液内，添加氯化2_ 硝基芊基磺醯（896毫克，4.04毫莫耳）。使反應物溫熱至室溫，歷經12小時。使反應混合物濃縮，並使所形成之粗製油藉急驟式管柱層析純化，以Et0Ac/己烷（丨：丨）、Et〇Ac及 EtOAc/MeOH (20 : 1)溶離，而得標題化合物（267毫克，46% )。 MS (DCI/NH3) m/z 580 (M+l)+.Example 215A Indole, 3-ylmethyl) -2- (5-Isopyridin-6-yl-pyridin-3-yloxy) -ethyl1-2-nitrobenhon. Brewing amine in Example 27 (400 Mg, 1.01 mmol) and mEA (0.6 ml, 6.0 mmol) in THF (30 ml) in a solution cooled in ice bath, 2-nitronitrosulfonyl chloride was added Thorium (896 mg, 4.04 mmol). The reaction was allowed to warm to room temperature over 12 hours. The reaction mixture was concentrated and the resulting crude oil was purified by flash column chromatography and dissolved in EtoAc / hexane (丨: 丨), EtoAc and EtOAc / MeOH (20: 1) to give the title compound. (267 mg, 46%). MS (DCI / NH3) m / z 580 (M + l) +.

實例215B 卜朵-3-1甲基）-2-(5-1 4啉各某4啶各基氣某VA 羞JL-N-甲基-2-硝基-笨碏醯胺於實例215A(260毫克，〇·45毫莫耳）、Me0H(16微升，45毫莫耳）及Ph3P (591亳克，2.25亳莫耳）在THF (10毫升）中之溶液内，於冰浴中，逐滴添加DEAD (392毫克，2.25毫莫耳）。使反應溫熱至室溫’歷經12小時。使反應混合物濃縮，並使所形成之粗製油藉急驟式管柱層析純化，以Et〇Ac與Et〇Ac/ MeOH(40 : 3)溶離，而得標題化合物（47毫克，18% )。 -201 - 200301122Example 215B BUDO-3-1 Methyl) -2- (5-1 4-Porphyrin, 4 Pyridine, 4 Pyridine, 4 Molecules, 1 VA Substitute JL-N-methyl-2-nitro-benzylamine 260 mg, 0.45 mmol), Me0H (16 μl, 45 mmol) and Ph3P (591 μg, 2.25 μmol) in THF (10 mL) in an ice bath, DEAD (392 mg, 2.25 mmol) was added dropwise. The reaction was allowed to warm to room temperature 'over 12 hours. The reaction mixture was concentrated and the resulting crude oil was purified by flash column chromatography to Et. Ac was dissolved with EtoAc / MeOH (40: 3) to give the title compound (47 mg, 18%). -201-200301122

(194) MS (DCI/NH3) m/z 594 (M+l)+.(194) MS (DCI / NH3) m / z 594 (M + l) +.

實例215C 吲哚-3-基甲基V2-f5-(lH-吡咯并「2,3-bl吡啶-5羞V,比症各基氧基1-乙胺將實例21兕（4?亳克，0.08毫莫耳）、PhSH (9·7微升，〇.095毫莫耳）及K2C〇3(33毫克，0.237毫莫耳）於DMF(5毫升）中之混合Example 215C Indole-3-ylmethyl V2-f5- (lH-pyrrolo "2,3-blpyridin-5V, specific oxy 1-ethylamine Example 21 (4? G) , 0.08 mmoles), PhSH (9.7 μl, 0.095 mmoles) and K2CO3 (33 mg, 0.237 mmoles) in DMF (5 ml)

物，在室溫下攪拌2小時。使反應物濃縮至乾涸。使所形成之殘留物於C18 HPLC上純化，而得標題化合物（34.2毫克， 58% )。MS(DCI/NH3)m/z409 (M+l)+ ; iHNMRpOOMHz^MeOD) δ ppm 2.91 (s，3Η) 2·99 (br s，1Η) 3·37 (dd，J=14.66, 9.36 Ηζ，1Η) 3·43 (dd，J=14.66， 5·93 Hz，1H) 3.96 (m，1H) 4·38 (dd，J=10.92, 4.37 Hz，·1Η) 4.52 (dd，J=10.92, 2.81 Hz, 1H) 6.99 (dt5 J=8.11, 0.94 Hz, 1H) 7.10 (dt, J=8.11, 0.94 Hz, 1H) 7.25 (s, 1H) 7.36 (d，J=8.11 Hz，1H) 7.58 (d，J=8.11 Hz，1H) 7.92 (m，1H) 8.29 (dd，J=8.73, 1.87 Hz，1H) 8.49 (d，J二6.55 Hz，1H) 8.50 (s，1H) 8·56 (s，1H) 8.60 (d，J=8.73 Hz，1H) 8.63 (d5 J=6.55 Hz, 1H) 8.77 (s, 1H) 9.78 (s, 1H). 實例216The mixture was stirred at room temperature for 2 hours. The reaction was concentrated to dryness. The resulting residue was purified on C18 HPLC to give the title compound (34.2 mg, 58%). MS (DCI / NH3) m / z409 (M + l) +; iHNMRpOOMHz ^ MeOD) δ ppm 2.91 (s, 3Η) 2.99 (br s, 1Η) 3.37 (dd, J = 14.66, 9.36 Ηζ, 1Η) 3.43 (dd, J = 14.66, 5.93 Hz, 1H) 3.96 (m, 1H) 4.38 (dd, J = 10.92, 4.37 Hz, · 1Η) 4.52 (dd, J = 10.92, 2.81 Hz, 1H) 6.99 (dt5 J = 8.11, 0.94 Hz, 1H) 7.10 (dt, J = 8.11, 0.94 Hz, 1H) 7.25 (s, 1H) 7.36 (d, J = 8.11 Hz, 1H) 7.58 (d, J = 8.11 Hz, 1H) 7.92 (m, 1H) 8.29 (dd, J = 8.73, 1.87 Hz, 1H) 8.49 (d, J = 6.55 Hz, 1H) 8.50 (s, 1H) 8.56 (s, 1H ) 8.60 (d, J = 8.73 Hz, 1H) 8.63 (d5 J = 6.55 Hz, 1H) 8.77 (s, 1H) 9.78 (s, 1H). Example 216

丨5-『2-(2-氣-p比淀-4-基）-乙婦基Ι-p比咬-3-基氧基丨p朵-3-丨 5- 『2- (2-Gas-p ratio Yodo-4-yl) -ethynyl 1-p ratio -3-yloxy 丨 p-do-3-

基甲基乙胺實例216A 2-乱基-4-乙缔基ρ比症將2-氣基-4-換基p比淀（2·23克’ 10·0愛莫耳）、三丁基乙婦基錫（3.8克，12毫莫耳）及Pd2Cl2(PPh3)2(703毫克，1.0毫莫耳）於二氧陸圜（20毫升）中之混合物，在氮氣及80°C下加熱過夜。於冷卻後，將醋酸乙酯（40毫升）與飽和KF水溶液添加至反 -202- (195)Example of methylmethylethylamine 216A 2-Phenyl-4-ethenyl p ratio disease 2-Phenyl-4-replacement p ratio (2.23 g '10. 0 Emole), tributyl A mixture of ethynyl tin (3.8 g, 12 mmol) and Pd2Cl2 (PPh3) 2 (703 mg, 1.0 mmol) in dioxolane (20 ml), heated under nitrogen at 80 ° C overnight . After cooling, add ethyl acetate (40 mL) and saturated KF aqueous solution to trans-202- (195)

應混合物中。將混合物攪拌30分鐘。分離有機層，並以水洗滌，脫水乾燥（MgS04)及濃縮。使所形成之殘留物藉急騾式管柱層析純化，以己烷/醋酸乙酯（2〇 : 1)溶離，提供標題化合物（463 毫克，38% )。1H NMR (500 MHz，CDC13) 5 ppm 5·55 (d， J=10.92 Hz, 1H) 5.99 (d, J=17.47 Hz, 1H) 6.67 (dd5 J=17.47, 10.61 Hz, 1H) 6.88 (m, 1H) 7.17 (dt，J=5.30, 1.56 Hz，1H) 8.16 (d，J=5.30 Hz，1H)·Should be in the mixture. The mixture was stirred for 30 minutes. The organic layer was separated, washed with water, dried (MgS04) and concentrated. The resulting residue was purified by flash column chromatography and dissolved in hexane / ethyl acetate (20: 1) to provide the title compound (463 mg, 38%). 1H NMR (500 MHz, CDC13) 5 ppm 5.55 (d, J = 10.92 Hz, 1H) 5.99 (d, J = 17.47 Hz, 1H) 6.67 (dd5 J = 17.47, 10.61 Hz, 1H) 6.88 (m, 1H) 7.17 (dt, J = 5.30, 1.56 Hz, 1H) 8.16 (d, J = 5.30 Hz, 1H) ·

實例216B (lSH2-{5-[2-(2-氟-P比咬-4-基V乙烯基Ι-p比咬-3-基氧基丨嗓-3-基甲基）乙基1-胺甲基酸第三-丁酯所要之產物係經由以實例216A取代實例2中之4-乙烯基吡啶，以三氟醋酸鹽製成（1.067克，84% )。MS(DCI/NH3)m/z489 (M+l)+ ； 1 H NMR (400 MHz, MeOD) δ ppm 1.42 (m5 9H) 2.98 (m, 1H) 3.04 (m3 1H) 3.14 (m，1H) 4.09 (m，2H) 4.25 (m，1H) 6.96 (t，J=7.36 Hz，1H) 7·07 (t，J=7.07 Hz, 1H) 7.09 (m，1H) 7.20 (m，1H) 7.29 (m，2H) 7.45 (m，2H) 7·59 (m，2H) 8.16 (d， J=5.52 Hz, 1H) 8.19 (s, 1H) 8.32 (s, 1H). 實例217 R处1:迎:’!丨」果！基.甲基氧-p比攻·4_基）·乙締基ι·吡啶 -3-基氧基卜a脸實例 (LS」-iRl--Mj哚-3:基甲基）-2-(5-政曱氣某_吡咗_4_某）·乙嫌甚生焚-3-基氧基卜乙基）-胺甲其醢竿三_丁酯 -203 - 200301-22 (196) 使實例 216B(100 毫克，〇·2 毫莫耳）、NaOMe(25%，於 MeOH 中）(1毫升）在MeOH (10毫升）中之混合物回流8小時。使混合物濃縮，獲得粗產物。Example 216B (lSH2- {5- [2- (2-fluoro-P-ratio-4-yl V vinyl 1-p-ratio-3-yloxy 丨 thr-3-ylmethyl) ethyl 1- The desired product of the tertiary butyl methanoate was prepared from trifluoroacetate (1.067 g, 84%) by replacing 4-vinylpyridine in Example 2 with Example 216A. MS (DCI / NH3) m / z489 (M + l) +; 1 H NMR (400 MHz, MeOD) δ ppm 1.42 (m5 9H) 2.98 (m, 1H) 3.04 (m3 1H) 3.14 (m, 1H) 4.09 (m, 2H) 4.25 ( m, 1H) 6.96 (t, J = 7.36 Hz, 1H) 7.07 (t, J = 7.07 Hz, 1H) 7.09 (m, 1H) 7.20 (m, 1H) 7.29 (m, 2H) 7.45 (m, 2H) 7.59 (m, 2H) 8.16 (d, J = 5.52 Hz, 1H) 8.19 (s, 1H) 8.32 (s, 1H). Example 217 R 1: Welcome: '! 丨' 'Fruit! Methyloxy-p specific group 4-yl group) Ethylene group Pyridin-3-yloxy group (LS "-iRl--Mj indole-3: ylmethyl) -2- (5 -Political qi _Pyridoxine _4_) · Ethyl acetazol-3-yloxybuethyl) -Aminomethyl its tris-butyl ester-203-200301-22 (196) Make Example 216B ( A mixture of 100 mg, 0.2 mmoles, NaOMe (25% in MeOH) (1 mL) in MeOH (10 mL) was refluxed for 8 hours. The mixture was concentrated to obtain a crude product.

實例217B j2SVl-(lH-蚓哚-3-基甲基）-2-丨542-(2-甲氣基-吡啶-4-基乙嬌某1-毗啶-3-基氣基丨-乙胺Example 217B j2SVl- (lH-earthin-3-ylmethyl) -2- 丨 542- (2-methylamino-pyridin-4-ylethoxyl 1-pyridin-3-yloxyl-ethyl amine

將實例217A於室溫下以TFA (1毫升）處理10分鐘。在移除 TFA後，使粗產物於C18 HPLC上純化，而得標題化合物（101.8 毫克，69%)。MS(DCI/NH3)m/z401(M+l)+ ; iHNMRGOOMHiMeOD) 5 ppm 3·31 (m，2H) 3·99 (s，3H) 4.00 (m，1H) 4·29 (dd，J=10.43, 5.52 Hz，1H) 4·41 (dd, J=10.43, 3.07 Hz, 1H) 7.03 (m3 1H) 7.06 (s, 1H) 7.13 (m, 1H) 7.24 (s, 1H) 7.27 (dd, J=5.52, 1.23 Hz, 1H) 7.34 (d, 1=1626 Hz, 1H) 7.39 (d, J=8.29 Hz, 1H) 7.48 (d, J=16.57 Hz, 1H) 7.59 (d, J=7.98 Hz, 1H) 7.87 (s, 1H) 8.16 (d5 J=5.22 Hz, 1H) 8.40 (brs，lH)8.57(brs，1H). 實例218 (ISM-ΠΗ-口弓1哚-3-基甲墓）·2-{5·『2-(2-笨氧基-吡啶-4-基）-乙烯基V吡Example 217A was treated with TFA (1 mL) at room temperature for 10 minutes. After removing TFA, the crude product was purified on C18 HPLC to give the title compound (101.8 mg, 69%). MS (DCI / NH3) m / z401 (M + l) +; iHNMRGOOMHiMeOD) 5 ppm 3.31 (m, 2H) 3.99 (s, 3H) 4.00 (m, 1H) 4.29 (dd, J = 10.43, 5.52 Hz, 1H) 4.41 (dd, J = 10.43, 3.07 Hz, 1H) 7.03 (m3 1H) 7.06 (s, 1H) 7.13 (m, 1H) 7.24 (s, 1H) 7.27 (dd, J = 5.52, 1.23 Hz, 1H) 7.34 (d, 1 = 1626 Hz, 1H) 7.39 (d, J = 8.29 Hz, 1H) 7.48 (d, J = 16.57 Hz, 1H) 7.59 (d, J = 7.98 Hz, 1H) 7.87 (s, 1H) 8.16 (d5 J = 5.22 Hz, 1H) 8.40 (brs, lH) 8.57 (brs, 1H). Example 218 (ISM-ΠΗ- 口弓 1 丁 -3- 基甲墓墓) · 2- {5 · "2- (2-Benzyloxy-pyridin-4-yl) -vinyl Vpy

淀-3-基乳基}-乙胺將實例216Β (50毫克，0.1毫莫耳）、酚（94毫克，1.0毫莫耳）及KOH (1L2毫克，0·2毫莫耳）之混合物，於140°C下，在密封瓶中加熱2小時。使混合物濃縮至乾涸。然後，將殘留物於室溫下以TFA (1毫升）處理10分鐘。在移除TFA後，使粗產物於C18 HPLC上純化，而得標題化合物（4.3毫克，5.3% )。 MS(DCI/NH3)m/z463 (M+l)+ ; 1H NMR (400 MHz, MeOD) δ ppm 330 (m, 1H) 3.48 (dd，J=13.81，7·06 Hz，1H) 4.00 (m，1H) 4·27 (dd，J=10.43, 5·83 Hz，1H) -204- 200301122Ethyl-3-yllactyl} -ethylamine is a mixture of Example 216B (50 mg, 0.1 mmol), phenol (94 mg, 1.0 mmol) and KOH (1 L2 mg, 0.2 mmol), Heat in a sealed bottle at 140 ° C for 2 hours. The mixture was concentrated to dryness. Then, the residue was treated with TFA (1 ml) at room temperature for 10 minutes. After removing TFA, the crude product was purified on C18 HPLC to give the title compound (4.3 mg, 5.3%). MS (DCI / NH3) m / z463 (M + l) +; 1H NMR (400 MHz, MeOD) δ ppm 330 (m, 1H) 3.48 (dd, J = 13.81, 7.06 Hz, 1H) 4.00 (m , 1H) 4 · 27 (dd, J = 10.43, 5.83 Hz, 1H) -204- 200301122

(197) 4·40 (dd，J=10.43, 3·07 Hz，1H) 7.15-7.01 (m，5H) 7.26-7.23 (m，2H) 7.48-7.32 (m， 6H) 7.59 (d, J= 7.98 Hz, 1H) 7.87 (m, 1H) 8.16 (d5 J=5.52 Hz, 1H) 8.35 (s3 1H) 8.53 (s，1H). 實例219 (lS)-2-{5-「2-(2-卞基硫基比症-4-基）-乙婦基l-ϊ?比度-3-基氣基啕哚-3-基甲基V乙胺(197) 4.40 (dd, J = 10.43, 3.07 Hz, 1H) 7.15-7.01 (m, 5H) 7.26-7.23 (m, 2H) 7.48-7.32 (m, 6H) 7.59 (d, J = 7.98 Hz, 1H) 7.87 (m, 1H) 8.16 (d5 J = 5.52 Hz, 1H) 8.35 (s3 1H) 8.53 (s, 1H). Example 219 (lS) -2- {5- 「2- (2- Fluorenylsulfanyl-4-methyl) -ethynyl l-fluorenyl-3-pyridyl-3-ylaminoindol-3-ylmethyl V ethylamine

標題化合物係經由以芊基硫醇取代實例218中之酚，以三氟醋酸鹽製成。MS (DCI/NH3) m/z 493 (M+l)+; 1 H NMR (500 MHz，MeOD) δ ppm 3.31 (m, 1H) 3.35 (m, 1H) 4.00 (m, 1H) 4.26 (dd, J=10.61, 5.62 Hz, 1H) 4.39 (dd，J=10.61，3·43 Hz，1H) 4.48 (m，2H) 7.03 (m，1H) 7.13 (m，1H) 7.27 (m，6H) 7.40 (m, 4H) 7.47 (d, J=16.53 Hz, 1H) 7.52 (m, 1H) 7.59 (d, J= 7.80 Hz, 1H) 7.78 (s, 1H) 8.43 (d3 J=5.30 Hz, 1H) 8.56 (s, 1H). 實例220The title compound was prepared from trifluoroacetate by replacing the phenol in Example 218 with fluorenyl mercaptan. MS (DCI / NH3) m / z 493 (M + l) +; 1 H NMR (500 MHz, MeOD) δ ppm 3.31 (m, 1H) 3.35 (m, 1H) 4.00 (m, 1H) 4.26 (dd, J = 10.61, 5.62 Hz, 1H) 4.39 (dd, J = 10.61, 3.43 Hz, 1H) 4.48 (m, 2H) 7.03 (m, 1H) 7.13 (m, 1H) 7.27 (m, 6H) 7.40 ( m, 4H) 7.47 (d, J = 16.53 Hz, 1H) 7.52 (m, 1H) 7.59 (d, J = 7.80 Hz, 1H) 7.78 (s, 1H) 8.43 (d3 J = 5.30 Hz, 1H) 8.56 ( s, 1H). Example 220

[4-(2-丨5-f(2S)-2-胺基-3-ΠΗ-峭哚-3-基V丙氣基1-吡啶-3-基丨-乙烯基V 外匕咬-2-基1¾丙基-胺[4- (2- 丨 5-f (2S) -2-Amino-3-ΠΗ-Aquidin-3-yl V propanyl 1-pyridin-3-yl 丨 -vinyl V outer bite-2 -Yl 12-propyl-amine

將實例216 (100毫克，0.2毫莫耳）與環丙基胺（1·5毫升）之混合物在125°C下加熱36小時。使混合物濃縮至乾涸。然後，將殘留物於室溫下，以TFA (1毫升）處理10分鐘。移除TFA ，使粗產物於C18 HPLC上純化，而得標題化合物（4.1毫克，3 % ) 〇 MS (DCI/NH3) m/z 426 (M+1); 1 H NMR (500 MHz，MeOD) 5 ppm 0.74 (m, 2H) 1.03 (m, 2H) 2.71 (m, 1H) 3.29 (m, 1H) 3.34 (m, 1H) 4.00 (m, 1H) 4.27 (dd, J=10.61，5·62 Hz，（H) 4.39 (dd，J=10.61，3·43 Hz，1H) 7.03 (m，J=15.91 Hz，1H) 7·10 (s，1H) 7.13 (m，1H) 7.23 (s，1H) 7.26 (dd，J=6.86, 1.56 Hz，1H) 7.39-7.34 (m，2H) 7.58 (d，J=5.30 Hz，1H) 7.60 (d，J=3.12 Hz，1H) 7.83 (m，1H) 7.87 (d，J=6.86 Hz，1H) -205- (198) 8.37 (s，1H) 8·52 (s，1H)· 實例221A mixture of Example 216 (100 mg, 0.2 mmol) and cyclopropylamine (1.5 ml) was heated at 125 ° C for 36 hours. The mixture was concentrated to dryness. Then, the residue was treated with TFA (1 ml) at room temperature for 10 minutes. The TFA was removed and the crude product was purified on C18 HPLC to give the title compound (4.1 mg, 3%). MS (DCI / NH3) m / z 426 (M + 1); 1 H NMR (500 MHz, MeOD) 5 ppm 0.74 (m, 2H) 1.03 (m, 2H) 2.71 (m, 1H) 3.29 (m, 1H) 3.34 (m, 1H) 4.00 (m, 1H) 4.27 (dd, J = 10.61, 5.62 Hz (H) 4.39 (dd, J = 10.61, 3.43 Hz, 1H) 7.03 (m, J = 15.91 Hz, 1H) 7.10 (s, 1H) 7.13 (m, 1H) 7.23 (s, 1H) 7.26 (dd, J = 6.86, 1.56 Hz, 1H) 7.39-7.34 (m, 2H) 7.58 (d, J = 5.30 Hz, 1H) 7.60 (d, J = 3.12 Hz, 1H) 7.83 (m, 1H) 7.87 (d, J = 6.86 Hz, 1H) -205- (198) 8.37 (s, 1H) 8.52 (s, 1H) · Example 221

「4-(2-{54(2SV2-胺某吲哚-3-基丙氧基V吡啶-3-基μ乙烯基V 对匕啶-2-某1-芊基-胺標題化合物係經由以芊胺取代實例220中之環丙基胺，以三氟醋酸鹽製成（38.2 毫克，23% )。MS(DCI/NH3)m/z476(M+l)+ ；1 H NMR (500 MHz, MeOD) δ ppm 3.30 (m3 1H) 3.34 (m, 1H) 3.99 (m, 1H) 4.24 (dd，J=10.61，5.62 Hz，1H) 4·37 (dd，J=10.61，3.12 Hz，1H) 4.63 (s，2H) 7.02 (m，1H) 7.10 (m5 1H) 7.12 (m5 1H) 7.22 (m5 2H) 7.41 (m? 3H) 7.39-7.29 (m5 4H) 7.57 (d, J= 9.05 Hz? 1H) 7.59 (m? 1H) 7.73 (s? 1H) 7.82 (d? J=6.86 Hz, 1H) 8.37 (s, 1H) 8.52 (s, 1H)· 實例222 『4-(2]5-『(2SV2-胺某-3-ΠΗ-㈣哚-3-基）-丙氧基1-吡啶-3-基丨-乙烯基）- 口比淀_2_基乙胺標題化合物係經由以乙胺取代實例220中之環丙基胺，以三氟醋酸鹽製成（16 毫克，15% )。MS(DCI/NH)m/z414(M+l)+ ; 1 H NMR (400 MHz, MeOD) δ ppm 1.36 (t, J=7.06 Hz, 3H) 3.98 (m5 4H) 4.24 (dd, J=10.43, 5.52 Hz, 1H) 4.37 (dd，J=10.74, 3.38 Hz，1H) 7.02 (m，2H) 7.12 (d，J=8.29 Hz, 1H) 7.18 (d, J=8.29 Hz, 1H) 7.23 (s, 1H) 7.30 (d, J=16.26 Hz, 1H) 7.38 (d3 J= 8.90 Hz, 1H) 7.56 (d, J=11.97 Hz, 1H) 7.59 (d, J=3.68 Hz, 1H) 7.72 (s, 1H) 7.77 (d, J=7.06 Hz，1H) 7.87 (m，2H) 8.33 (s，1H) 8.48 (s，1H). 實例223 『4-(2-(5-f(2S)-2-胺基-3-ΠΗ-峭哚-3-基）-丙氧基1-吡啶-3-墓卜乙烯基）· 口比咬·2-基甲基-胺 200301122`` 4- (2- {54 (2SV2-Amine indol-3-ylpropoxy Vpyridin-3-yl μvinyl V p-pyridin-2-one 1-fluorenyl-amine titled via Amidine replaced the cyclopropylamine in Example 220 and was made from trifluoroacetate (38.2 mg, 23%). MS (DCI / NH3) m / z476 (M + 1) +; 1 H NMR (500 MHz, MeOD) δ ppm 3.30 (m3 1H) 3.34 (m, 1H) 3.99 (m, 1H) 4.24 (dd, J = 10.61, 5.62 Hz, 1H) 4.37 (dd, J = 10.61, 3.12 Hz, 1H) 4.63 (s, 2H) 7.02 (m, 1H) 7.10 (m5 1H) 7.12 (m5 1H) 7.22 (m5 2H) 7.41 (m? 3H) 7.39-7.29 (m5 4H) 7.57 (d, J = 9.05 Hz? 1H) 7.59 (m? 1H) 7.73 (s? 1H) 7.82 (d? J = 6.86 Hz, 1H) 8.37 (s, 1H) 8.52 (s, 1H) Example 222 『4- (2) 5-『 (2SV2- Amine-3-ΠΗ-pyridin-3-yl) -propoxy 1-pyridin-3-yl 丨 -vinyl) -Kipido_2_ylethylamine The title compound was substituted by ethylamine Example 220 Cyclopropylamine, made from trifluoroacetate (16 mg, 15%). MS (DCI / NH) m / z414 (M + l) +; 1 H NMR (400 MHz, MeOD) δ ppm 1.36 (t, J = 7.06 Hz, 3H) 3.98 (m5 4H) 4.24 (dd, J = 10.43, 5.52 Hz, 1H) 4.37 (dd, J = 10.74, 3.38 Hz, 1H) 7.02 (m, 2H) 7. 12 (d, J = 8.29 Hz, 1H) 7.18 (d, J = 8.29 Hz, 1H) 7.23 (s, 1H) 7.30 (d, J = 16.26 Hz, 1H) 7.38 (d3 J = 8.90 Hz, 1H) 7.56 (d, J = 11.97 Hz, 1H) 7.59 (d, J = 3.68 Hz, 1H) 7.72 (s, 1H) 7.77 (d, J = 7.06 Hz, 1H) 7.87 (m, 2H) 8.33 (s, 1H) 8.48 (s, 1H). Example 223 "4- (2- (5-f (2S) -2-Amino-3-ΠΗ-adol-3-yl) -propoxy 1-pyridine-3- Bu vinyl) · mouth bite · 2-ylmethyl-amine 200301122

(199) 標題化合物係經由以甲胺取代實例220中之環丙基胺，以三氟醋酸鹽製成（11.9 毫克，8% )。MS(DCI/NH3) : m/z400(M+l)+ ;1 H NMR (400 MHz，MeOD) 5 ppm ppm 3·05 (s，3H) 3.32 (m，2H) 3.99 (m，1H) 4.24 (dd，J=10.43, 5·52 Hz，1H) 4.37 (dd，J=10.74, 3·38 Hz，1H) 7.03 (m，1H) 7.05 (m， 1H) 7.13 (m，1H) 7·19 (d，J=7.06 Hz，1H) 7.23 (m，1H) 7.31 (d，J=16.57 Hz，1H) 7.39 (d，J=7.36 Hz，1H) 7·57 (d，J=7.06 Hz，1H) 7.60 (m，1H) 7.74 (s，1H) 7.80 (d，J= 7.06 Hz, 1H) 8.41 (brs，1H) 8.57 (brs，1H). 實例224 (ISM-ΠΗ-吲哚-3-某甲基哚-1-基-吡啶-4-基）-乙烯基1- 吡啶-3-基氣基丨-乙胺將實例216 (100毫克，0.2毫莫耳）、吲哚（48毫克，0.4毫莫耳）及NaH (60% )(29毫克，0.72毫莫耳）於DMF (5毫升）中之混合物，在125°C下加熱1.5小時。將混合物濃縮至乾涸。然後，將殘留物於室溫下，以TFA (1毫升）處理10分鐘。移除TFA ，使粗產物於C18 HPLC上純化，而得標題化合物（8·1毫克，5 % )。MS (DCI/NH3) m/z 486 (M+l)+ ; 1 H NMR (500 MHz，MeOD) 5 ppm 3.29 (m5 1Η) 3.35 (m，1Η) 4·00 (m，1Η) 4·26 (dd，J=10.61，5·93 Ηζ，1Η) 4.39 (dd，J=10.29, 3.12 Hz, 1H) 6.73 (d, J=3.43 Hz, 1H) 7.05 (m, 1H) 7.11-7.18 (m, 2H) 7.24 (s, 1H) 7.26 (m, 1H) 7.63-7.38 (m, 6H) 7.75 (m, 1H) 7.80 (m3 1H) 7.84 (d? J=3.43 Hz, 1H) 8.22 (dd, J=8.42, 0.62 Hz, 1H) 8.32 (s5 1H) 8.52 (s, 1H) 8.53 (s, 1H). 實例225 (± )-2-「5-(3-甲基-1H-W唑-5-基）-吡啶-3-基氧基1-1-(2-甲基-1H-吲哚-(199) The title compound was prepared by replacing the cyclopropylamine in Example 220 with methylamine and using trifluoroacetate (11.9 mg, 8%). MS (DCI / NH3): m / z400 (M + 1) +; 1 H NMR (400 MHz, MeOD) 5 ppm ppm 3.05 (s, 3H) 3.32 (m, 2H) 3.99 (m, 1H) 4.24 (dd, J = 10.43, 5.52 Hz, 1H) 4.37 (dd, J = 10.74, 3.38 Hz, 1H) 7.03 (m, 1H) 7.05 (m, 1H) 7.13 (m, 1H) 7.19 (d, J = 7.06 Hz, 1H) 7.23 (m, 1H) 7.31 (d, J = 16.57 Hz, 1H) 7.39 (d, J = 7.36 Hz, 1H) 7.57 (d, J = 7.06 Hz, 1H ) 7.60 (m, 1H) 7.74 (s, 1H) 7.80 (d, J = 7.06 Hz, 1H) 8.41 (brs, 1H) 8.57 (brs, 1H). Example 224 (ISM-ΠΗ-indole-3-some Methyl indole-1-yl-pyridin-4-yl) -vinyl 1-pyridin-3-ylamino-1-ethylamine Example 216 (100 mg, 0.2 mmol), indole (48 mg, 0.4 A mixture of mM) and NaH (60%) (29 mg, 0.72 mol) in DMF (5 ml) was heated at 125 ° C for 1.5 hours. The mixture was concentrated to dryness. Then, the residue was treated with TFA (1 ml) at room temperature for 10 minutes. The TFA was removed and the crude product was purified on C18 HPLC to give the title compound (8.1 mg, 5%). MS (DCI / NH3) m / z 486 (M + l) +; 1 H NMR (500 MHz, MeOD) 5 ppm 3.29 (m5 1Η) 3.35 (m, 1Η) 4.00 (m, 1Η) 4 · 26 (dd, J = 10.61, 5.93 Ηζ, 1Η) 4.39 (dd, J = 10.29, 3.12 Hz, 1H) 6.73 (d, J = 3.43 Hz, 1H) 7.05 (m, 1H) 7.11-7.18 (m, 2H) 7.24 (s, 1H) 7.26 (m, 1H) 7.63-7.38 (m, 6H) 7.75 (m, 1H) 7.80 (m3 1H) 7.84 (d? J = 3.43 Hz, 1H) 8.22 (dd, J = 8.42, 0.62 Hz, 1H) 8.32 (s5 1H) 8.52 (s, 1H) 8.53 (s, 1H). Example 225 (±) -2-``5- (3-methyl-1H-Wazole-5-yl ) -Pyridin-3-yloxy1-1- (2-methyl-1H-indole-

3-基甲基乙胺實例225A -207- 2003011223-ylmethylethylamine Example 225A -207- 200301122

(200) 3-溴基-2-#垔亞胺墓-丙酸乙酯將溴丙酮酸乙酯（5.0毫升，39.8毫莫耳）添加至h2〇(1〇毫升）與CHC〗3 (10毫升）中之幾胺鹽酸鹽（2.52克，36.2毫莫耳）内。將反應混合物加罩蓋，並於23°C下攪拌過夜，此時添加Ch2C12 與H2〇，分離液層，以Na2S04使有機物質脫水乾燥，並於迴轉式蒸發器上移除揮發性物質，而得7·58克（100% )，為白色固體。1 H NMR (300 MHz，DMSO-D6) 5 ppm 1·26 (t，J=7.12Hz，3Η) 4.20 (s，2H) 4·24 (m，2H) 13.19 (s，1H).(200) 3-Bromo-2- # fluorenimide-ethyl propionate Ethyl bromopyruvate (5.0 ml, 39.8 mmol) was added to h20 (10 ml) and CHC 3 (10 Ml) of chloramine hydrochloride (2.52 g, 36.2 mmol). Cover the reaction mixture and stir overnight at 23 ° C. At this time, add Ch2C12 and H2O, separate the liquid layer, dehydrate and dry the organic matter with Na2S04, and remove the volatile matter on the rotary evaporator. 7.58 g (100%) was obtained as a white solid. 1 H NMR (300 MHz, DMSO-D6) 5 ppm 1.26 (t, J = 7.12Hz, 3Η) 4.20 (s, 2H) 4.24 (m, 2H) 13.19 (s, 1H).

實例225B 2-¾亞胺基-3-(2-甲基-ΙΗ-Θ丨嗓-3-基）-丙酸乙酉旨所要之化合物係藉由參考方法製成（J. Chem. Soc. Chem. Comm 1979, 1089)。於CH2C12中之2-甲基W哚（1·28克，9·76毫莫耳）與 Na2C04(1.24 克，11.7 毫莫耳）内，添加實例 225Α(2·05 克，9.76 毫莫耳）。將所形成之反應混合物於23°C下攪拌過夜，此時添加H2 0，分離液層，並以Na2 S04使有機物質脫水乾燥。急驟式層析（20-30-50-70% EtOAc/己燒），獲得1.41克（56% )，為綠色固體。Rf=0.30(50% EtOAc/ 己烷）；MSm/z261 (M+H)+; iHNMR (300 MHz, DMSO-D6) (5 ppm 1·13 (t，J=7.12 Hz，3H) 2.35 (s，3H) 3.84 (s，2H) 4.08 (q，J=7.12 Hz，2H) 6.92 (m，2H) 7.19 (d，J=7.80 Hz，1H) 7.44 (d，J=7.46 Hz，1H) 10.74 (s, 1H) 12.34 (s, 1H).Example 225B 2-¾imino-3- (2-methyl-lΗ-Θ 丨 hex-3-yl) -acetic acid propionate The desired compound was prepared by reference method (J. Chem. Soc. Chem Comm 1979, 1089). In CH2C12, 2-methylWindole (1.28 g, 9.76 mmol) and Na2C04 (1.24 g, 11.7 mmol) were added Example 225A (2.05 g, 9.76 mmol) . The resulting reaction mixture was stirred at 23 ° C. overnight, at which time H 2 0 was added, the liquid layer was separated, and the organic matter was dehydrated and dried with Na 2 S 04. Flash chromatography (20-30-50-70% EtOAc / hexane) gave 1.41 g (56%) as a green solid. Rf = 0.30 (50% EtOAc / hexane); MSm / z261 (M + H) +; iHNMR (300 MHz, DMSO-D6) (5 ppm 1.13 (t, J = 7.12 Hz, 3H) 2.35 (s , 3H) 3.84 (s, 2H) 4.08 (q, J = 7.12 Hz, 2H) 6.92 (m, 2H) 7.19 (d, J = 7.80 Hz, 1H) 7.44 (d, J = 7.46 Hz, 1H) 10.74 ( s, 1H) 12.34 (s, 1H).

實例225C (± V2-第三-丁氧羰基胺基-3-(2-甲某-1H-W哚！基V丙酸乙酉旨所要之化合物係藉由參考方法製成（Angew· Chem· Int· Ed· Engl· 1979, 78 與 Tet· Lett· 1988,第 447 頁）。將鋁箔（1.18 克，43.8 毫莫耳） •208- 200301122Example 225C (± V2-Third-butoxycarbonylamino-3- (2-methyl-1H-W indol! Yl V propionate) The desired compound was prepared by reference method (Angew · Chem · Int · Ed · Engl · 1979, 78 and Tet · Lett · 1988, p. 447). Aluminum foil (1.18 g, 43.8 mmol) • 208- 200301122

(201) 切成長薄（1公分）片條，然後浸泡在2% HgCl2水溶液（各片條 3〇秒）中。將各片條立即連續以％〇、Me〇H，然後以與〇洗滌接著’乂即將各片條切成小片塊（〜1 X 0.5公分），置於貝例225B (1.14克，4.38亳莫耳）於THF (6〇毫升）與H2〇 (6亳升）中又溶液内，以水浴使其保持在室溫下。將混合物於23。〇下激烈攪拌。在短時間後，微細黑色固體開始形成，且發現許多氣泡。將反應混合物攪拌3小時，然後經過矽藻土過濾，並將濾餅以Eb 0洗滌。於迴轉式蒸發器上移除所有 · 揮發性物質。添加MeOH (50亳升），接著是Na2c〇3 (〇·5ΐ克，4.82 晕莫耳）與BoqO (1·00克，4.60毫莫耳）。將所形成之反應混合物於23°C下攪拌30分鐘，然後添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（1〇-3〇-4〇-5〇% EtOAc /己垸），獲得1.33克（88% )，為灰白色固體。Rf=0 68 (70% Et〇Ac/ 己烷）；MS m/z 345 (M-H)+ ; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 1.02 (t5 J=7.12 Hz，3H) 1.33 (s，9H) 2.28 (s，3H) 3.00 (m，2H) 3.97 (q，J=7.12 Hz，2H) 4·10 (m5 1H) 6.94 (m, 2H) 7.14 (d, J=8.14 Hz, 1H) 7.21 (d, J=7.12 Hz, 1H) 7.38 (d5 J= 7.12 Hz，lH) 10.73 (S，1H).(201) Cut into thin (1 cm) strips and soak in 2% HgCl2 aqueous solution (30 seconds for each strip). Each strip was immediately and continuously washed with% 〇, Me〇H, and then washed with 〇 and then '乂 Each slice was cut into small pieces (~ 1 X 0.5 cm), placed in the shellfish 225B (1.14 g, 4.38 mm) Ear) in THF (60 mL) and H2O (6 liters), and kept at room temperature in a water bath. Mix the mixture at 23. 〇 Stir vigorously. After a short time, a fine black solid began to form, and many air bubbles were found. The reaction mixture was stirred for 3 hours, then filtered through celite, and the filter cake was washed with Eb 0. Remove all · Volatile substances on a rotary evaporator. MeOH (50 liters) was added, followed by Na2co3 (0.5 gram, 4.82 hamol) and BoqO (1.00 g, 4.60 millimolar). The resulting reaction mixture was stirred at 23 ° C for 30 minutes, then silicone was added, and volatile materials were removed on a rotary evaporator. Flash chromatography (10-30-40-50% EtOAc / hexane) gave 1.33 g (88%) as an off-white solid. Rf = 0 68 (70% Et〇Ac / hexane); MS m / z 345 (MH) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 1.02 (t5 J = 7.12 Hz, 3H) 1.33 ( s, 9H) 2.28 (s, 3H) 3.00 (m, 2H) 3.97 (q, J = 7.12 Hz, 2H) 4.10 (m5 1H) 6.94 (m, 2H) 7.14 (d, J = 8.14 Hz, 1H ) 7.21 (d, J = 7.12 Hz, 1H) 7.38 (d5 J = 7.12 Hz, lH) 10.73 (S, 1H).

實例225D (土）-『2-羥基小(2-甲基-1沁巧哚-3-基甲基）-乙基1-胺曱基酸第三- 丁酯於裝有攪拌棒之500毫升圓底燒瓶中，在實例225C (1.30克，3.75毫莫耳）與CaCl2(無水）(0.83克，7.51毫莫耳）内，相繼添加：EtOH (潮濕）(3〇毫升）、THF(20 毫升）及 NaBH4(0.57 克，15.0 毫莫耳）。將所形成之混濁反應混合物於23°C下攪拌1小時 -209- 200301122Example 225D (Earth)-"2-Hydroxy (2-methyl-1qindol-3-ylmethyl) -ethyl 1-aminophosphonic acid tertiary-butyl ester in 500 ml with a stir bar In a round bottom flask, in Example 225C (1.30 g, 3.75 mmol) and CaCl2 (anhydrous) (0.83 g, 7.51 mmol), successively add: EtOH (wet) (30 ml), THF (20 ml ) And NaBH4 (0.57 g, 15.0 mmol). Stir the resulting cloudy reaction mixture at 23 ° C for 1 hour -209- 200301122

(202) ，然後傾倒在1 Μ檸檬酸上，並以EtOAc萃取。將有機萃液以鹽水洗滌，並以MgS04脫水乾燥。添加矽膠與NaHC03 (100 毫克），並於迴轉式蒸發器上移除揮發性物質。急騾式層析（35-50-60% EtOAc/己烷），獲得1.08克（95% )，為白色固體。 Rf =0.51(70% EtOAc / 己烷）；MS m/z 303 (M-H)+ ; 1HNMR (300 MHz， DMSO-D6) (5 ppm 1.35 (s3 9H) 2.31 (s5 3H) 2.71 (m, 2H) 3.29 (t3 J=5.42 Hz, 2H)(202), then poured onto 1 M citric acid and extracted with EtOAc. The organic extract was washed with brine and dried over MgS04. Add silicone and NaHC03 (100 mg) and remove volatiles on a rotary evaporator. Flash chromatography (35-50-60% EtOAc / hexane) gave 1.08 g (95%) as a white solid. Rf = 0.51 (70% EtOAc / hexane); MS m / z 303 (MH) +; 1HNMR (300 MHz, DMSO-D6) (5 ppm 1.35 (s3 9H) 2.31 (s5 3H) 2.71 (m, 2H) 3.29 (t3 J = 5.42 Hz, 2H)

3.57 (m，1H) 4.54 (t，J=5.42 Hz，1H) 6.45 (d，J=8.48 Hz，1H) 6·92 (m，2H) 7.19 (dd， J=6.785 1.02 Hz, 1H) 7.48 (d, J=7.12 Hz, 1H) 10.64 (s? 1H).3.57 (m, 1H) 4.54 (t, J = 5.42 Hz, 1H) 6.45 (d, J = 8.48 Hz, 1H) 6.92 (m, 2H) 7.19 (dd, J = 6.785 1.02 Hz, 1H) 7.48 ( d, J = 7.12 Hz, 1H) 10.64 (s? 1H).

實例225E (土 )-[2-(5-溴-吡啶-3-基氧基）-1-(2-甲基-1H-W哚-3-基曱基乙基1- 胺甲基酸第三-丁酯所要之產物係經由以實例225D取代實例2A中之Boc-色胺酸而製成。Rf=0.41 (50% EtOAc/ 己烷）；MSm/z460,462(M+H)+ ;Example 225E (Earth)-[2- (5-bromo-pyridin-3-yloxy) -1- (2-methyl-1H-W indol-3-ylfluorenylethyl 1-aminomethyl acid The desired product of tri-butyl ester was prepared by replacing Boc-tryptophan in Example 2A with Example 225D. Rf = 0.41 (50% EtOAc / hexane); MSm / z460,462 (M + H) +;

1 H NMR (300 MHz, DMSO-D6) δ ppm 1.35 (s, 9H) 2.30 (s, 3H) 2.86 (m, 2H) 3.97 (s，2H) 6.93 (m，3H) 7.21 (d，J=7.80 Hz，1H) 7.46 (d，JM7.46 Hz，1H) 7.59 (s，1H) 8.13 (dd, J-3.56, 2.20 Hz, 1H) 8.25 (dd, J=5.09, 2.03 Hz, 2H) 10.72 (s? 1H).1 H NMR (300 MHz, DMSO-D6) δ ppm 1.35 (s, 9H) 2.30 (s, 3H) 2.86 (m, 2H) 3.97 (s, 2H) 6.93 (m, 3H) 7.21 (d, J = 7.80 Hz, 1H) 7.46 (d, JM7.46 Hz, 1H) 7.59 (s, 1H) 8.13 (dd, J-3.56, 2.20 Hz, 1H) 8.25 (dd, J = 5.09, 2.03 Hz, 2H) 10.72 (s 1H).

實例225F 基-1H-吲哚-3-基甲基V2-(5-三甲基錫烷基-p比啶-3-某乳基）-乙基1-胺甲基酸第三-丁酉旨將實例 225D (350 毫克，0.76 毫莫耳）、Pd(PPh3 )4(88 毫克，0.08 毫莫耳）及六甲基二錫（300毫克，0.92毫莫耳）合併於具有攪拌棒之25毫升圓底燒瓶中。將燒瓶之氣層抽氣，並以氬置換。添加甲苯（4毫升），並使所形成之反應混合物溫熱至1〇〇 °C ’歷經2小時，然後冷卻至室溫。添加EtOAc與矽膠，並 -210- (203)Example 225F Group-1H-Indol-3-ylmethyl V2- (5-trimethylstannyl-p-pyridin-3-ceryl) -ethyl 1-aminomethyl acid Example 225D (350 mg, 0.76 mmol), Pd (PPh3) 4 (88 mg, 0.08 mmol) and hexamethylditin (300 mg, 0.92 mmol) were combined in 25 ml with a stir bar Round bottom flask. The gas layer of the flask was evacuated and replaced with argon. Toluene (4 ml) was added and the resulting reaction mixture was allowed to warm to 100 ° C 'for 2 hours and then cooled to room temperature. Add EtOAc and Silicone, and -210- (203)

於迴轉式蒸發器上移除揮發性物質。急騾式層析（30-40-50-60 % EtOAc/己烷），獲得294毫克（71% )，為黃色固體。Rf=0.43 (70 % EtOAc / 己烷）；MSm/z546(M+H)+ ; 1H NMR (300 MHz, DMSO-D6) 6 ppm 0.28 (s, 9H) 1.36 (s, 9H) 2.30 (s, 3H) 2.86 (m, 2H) 3.95 (s? 3H) 6.93 (m5 3H) 7.21 (d, J=7.80 Hz, 1H) 7.33 (d5 J=2.03 Hz, 1H) 7.44 (d, J=7.46 Hz, 1H) 8.14 (s, 2H) 10.72 (s，1H)·Remove volatile materials on a rotary evaporator. Flash chromatography (30-40-50-60% EtOAc / hexane) gave 294 mg (71%) as a yellow solid. Rf = 0.43 (70% EtOAc / hexane); MSm / z546 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 6 ppm 0.28 (s, 9H) 1.36 (s, 9H) 2.30 (s, 3H) 2.86 (m, 2H) 3.95 (s? 3H) 6.93 (m5 3H) 7.21 (d, J = 7.80 Hz, 1H) 7.33 (d5 J = 2.03 Hz, 1H) 7.44 (d, J = 7.46 Hz, 1H ) 8.14 (s, 2H) 10.72 (s, 1H) ·

實例225G (土 M2-『5-(3-曱基-1H-吲唑-5-基V吡啶-3-基氧基1-1-(2-甲基-1H-蜊哚-3-基甲基）乙基1-胺甲基酸第三-丁酯將溴-甲基吲唑（71毫克，0.33毫莫耳）、實例225E (200毫克，367毫莫耳）、Pd2dba3(61毫克，0.7毫莫耳）及Ρ(ο4ο1)3(41毫克，0.14毫莫耳）合併於具有攪拌棒之10毫升圓底燒瓶中。添加DMF (2毫升），並將燒瓶之氣層抽氣，且以氬置換兩次。添加Et3N (0.09毫升，0.67毫莫耳），並使反應混合物溫熱至80 °C，歷經5小時，然後冷卻至室溫。添加EtOAc，並使所形成之混合物經過矽藻土過濾。將濾液以Η2 Ο洗滌兩次，及以鹽水一次。添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（70-85-100% EtOAc/己烷），獲得48毫克（28 %)，為黃色固體。Rf=0.30(EtOAc); MSm/z512(M+H)+ ; iHNMR (300 MHz，DMSO-D6) δ ppm 1.36 (s5 9H) 2.31 (s, 3H) 2.54 (s3 3H) 2.90 (m, 2H) 4.05 (m, 3H) 6.93 (m, 3H) 7.20 (m, 2H) 7.58 (m, 3H) 8.06 (s, 1H) 8.20 (d, J=2.71 Hz, 1H) 8.53 (d, J=1.70 Hz, 1H) 10.72 (s, 1H) 12.72 (s3 1H).Example 225G (M2- (5- (3-fluorenyl-1H-indazol-5-yl) V-pyridin-3-yloxy-1--1- (2-methyl-1H-indole-3-ylmethyl Propyl) ethyl 1-aminomethyl acid tert-butyl ester Bromo-methylindazole (71 mg, 0.33 mmol), Example 225E (200 mg, 367 mmol), Pd2dba3 (61 mg, 0.7 Millimoles) and P (ο4ο1) 3 (41 mg, 0.14 millimoles) were combined in a 10 ml round bottom flask with a stir bar. DMF (2 ml) was added, and the gas layer of the flask was evacuated, and the Replace with argon twice. Et3N (0.09 mL, 0.67 mmol) was added and the reaction mixture was allowed to warm to 80 ° C for 5 hours and then cooled to room temperature. EtOAc was added and the resulting mixture was passed through diatoms. The filtrate was washed with Celite. The filtrate was washed twice with Η20 and once with brine. Silicone was added and the volatile materials were removed on a rotary evaporator. Flash chromatography (70-85-100% EtOAc / hexane), 48 mg (28%) was obtained as a yellow solid. Rf = 0.30 (EtOAc); MSm / z512 (M + H) +; iHNMR (300 MHz, DMSO-D6) δ ppm 1.36 (s5 9H) 2.31 (s, 3H ) 2.54 (s3 3H) 2.90 (m, 2H) 4.05 (m, 3H) 6.93 (m, 3H) 7.20 (m, 2 H) 7.58 (m, 3H) 8.06 (s, 1H) 8.20 (d, J = 2.71 Hz, 1H) 8.53 (d, J = 1.70 Hz, 1H) 10.72 (s, 1H) 12.72 (s3 1H).

實例225H (± V2-「5-(3-甲基_1H-㈣唑-5-基V吡啶-3-基氣基1-H2-甲基-1H-W哚- (204) 3-基甲基V乙胺標題化合物係經由以實例225G取代實例27C中之實例27B ，以三氟醋酸鹽製成（31.9毫克，84% )。MSm/z412(M+H)+ ; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.33 (s5 3H) 2.55 (s, 3H) 2.75 (dd, J=14.41, 6.61 Hz，1H) 2.92 (m，1H) 3.18 (s，2H) 3.99 (m，2H) 4.09 (q，J=5.43 Hz，1H) 6.89 (m， 1H) 6.96 (td，J=7.46，l.02 Hz，1H) 7.22 (d，J=7.80 Hz，1H) 7.46 (d，J=7·46 Hz，1H) 7.54 (d，J=8.82 Hz，1H) 7.63 (m，1H) 7.67 (m，1H) 8.08 (s，1H) 8.25 (d，J=2.37 Hz， 1H) 8.54 (d，J=1 ·70 Hz，1H) 10.75 (s，1H) 12.73 (s，1H)· 實例226 7-{5-f(2SV2-胺基吲哚-3-基丙氣基1-吡啶-3-基P奎唑啉-2-基胺Example 225H (± V2-``5- (3-methyl_1H-oxazol-5-yl Vpyridin-3-ylamino 1-H2-methyl-1H-Windole- (204) 3-ylmethyl The title compound was prepared from trifluoroacetate (31.9 mg, 84%) by replacing Example 27B in Example 27C with Example 225G. MSm / z412 (M + H) +; 1 H NMR (300 MHz , DMSO-D6) δ ppm 2.33 (s5 3H) 2.55 (s, 3H) 2.75 (dd, J = 14.41, 6.61 Hz, 1H) 2.92 (m, 1H) 3.18 (s, 2H) 3.99 (m, 2H) 4.09 (q, J = 5.43 Hz, 1H) 6.89 (m, 1H) 6.96 (td, J = 7.46, 1.02 Hz, 1H) 7.22 (d, J = 7.80 Hz, 1H) 7.46 (d, J = 7 · 46 Hz, 1H) 7.54 (d, J = 8.82 Hz, 1H) 7.63 (m, 1H) 7.67 (m, 1H) 8.08 (s, 1H) 8.25 (d, J = 2.37 Hz, 1H) 8.54 (d, J = 1 70 Hz, 1H) 10.75 (s, 1H) 12.73 (s, 1H) Example 226 7- {5-f (2SV2-aminoindol-3-ylpropanyl 1-pyridin-3-yl P quinazolin-2-ylamine

實例226A 7-溴-口奎吐口林-2-基胺將4-溴基-2-氟-苯曱醛（0.61克，3毫莫耳）、胍（1.05克，5.83 毫莫耳）及DMF於140°C下加熱2.5小時。將50毫升水添加至混合物中。將橘色沉澱物過濾，並以水洗滌。使固體溶於2N HC1 中’及過濾。使HC1溶液藉由羥基氨中和。將灰白色固體過濾，及在真空下乾燥，獲得所要之產物（91毫克，14% )。 MS (ESI) m/e 224 (M+l)+ ； 1 H NMR (300 MHz，DMSO-D6) δ ppm 7·00 (寬廣 s，2H) 7.36 (d，J=8.82 Hz，1H) 7.77 (dd，J=9.16, 2·37 Hz，1H) 8·05 (d，J=2.37 Hz，1H) 9.09 (寬廣 s，1H).Example 226A 7-Bromo-kouquetulin-2-ylamine 4-Bromo-2-fluoro-phenylbenzoaldehyde (0.61 g, 3 mmol), guanidine (1.05 g, 5.83 mmol) and DMF Heat at 140 ° C for 2.5 hours. 50 ml of water was added to the mixture. The orange precipitate was filtered and washed with water. The solid was dissolved in 2N HC1 'and filtered. The HC1 solution was neutralized with hydroxyl ammonia. The off-white solid was filtered and dried under vacuum to obtain the desired product (91 mg, 14%). MS (ESI) m / e 224 (M + 1) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 7 · 00 (broad s, 2H) 7.36 (d, J = 8.82 Hz, 1H) 7.77 ( dd, J = 9.16, 2.37 Hz, 1H) 8.05 (d, J = 2.37 Hz, 1H) 9.09 (broad s, 1H).

實例226B 7二{5-[(2S)-2-胺基吲哚-3-某丙氣基1-吡啶-3-基卜奎唑啉-2-某胺所要之產物係經由以實例226A取代實例；32中之6-溴基鄰苯二甲醯亞胺而製成，為三—TFA鹽。MSm/z 11 (M+H)+，（M-H)+ 0301122Example 226B 7Di {5-[(2S) -2-aminoindole-3-propaneyl 1-pyridin-3-ylbuquizoline-2-amine. The desired product was substituted by Example 226A Example: 6-bromophthalimide of 32 is made as a tri-TFA salt. MSm / z 11 (M + H) +, (M-H) + 0301122

(205) ;1H NMR (300 MHz，DMSO-D6) (5 ppm 2:85 (m，1Η) 3·01 (m，1Η) 3·32 (m，1H) 4.06 (m，2H) 6.96 (m，3H) 7.05 (m，1H) 7·22 (d，J=2.03 Hz，1H) 7.34 (d，J=8· 14 Hz， 1H) 7.54 (m, 1H) 7.68 (m5 1H) 8.05 (dd, J=8.99, 2.20 Hz, 1H) 8.19 (d, J=2.03 Hz, 1H) 8.30 (d, J=2.71 Hz, 1H) 8.57 (d, J=2.03 Hz, 1H) 9.16 (s, 1H) 10.88 (s, 1H). 實例227 2-苯基-2-(3-?比咬-4-基-111-口比嗅并|~3,4-131外1:症-6-基）-乙胺(205); 1H NMR (300 MHz, DMSO-D6) (5 ppm 2:85 (m, 1Η) 3.01 (m, 1Η) 3.32 (m, 1H) 4.06 (m, 2H) 6.96 (m , 3H) 7.05 (m, 1H) 7.22 (d, J = 2.03 Hz, 1H) 7.34 (d, J = 8.14 Hz, 1H) 7.54 (m, 1H) 7.68 (m5 1H) 8.05 (dd, J = 8.99, 2.20 Hz, 1H) 8.19 (d, J = 2.03 Hz, 1H) 8.30 (d, J = 2.71 Hz, 1H) 8.57 (d, J = 2.03 Hz, 1H) 9.16 (s, 1H) 10.88 ( s, 1H). Example 227 2-Phenyl-2- (3-? bita-4-yl-111-oral olfactory | ~ 3,4-131ex1: Zheng-6-yl) -ethylamine

實例227A (2,6-^一氣-口比症-3-基）比咬-4-基-甲醇於THF (100毫升）中之二異丙基胺（9·3毫升，66·1毫莫耳）内，在-78°C下’經由注射器逐滴添力口 n_BuLi (在己燒中之23.1毫升2·5 Μ溶液，57.8毫莫耳）。將THF (100毫升）中之2,6-二氟吡啶（5.0毫升，55.1毫莫耳），於-78°C下，經由套管逐滴添加至上文製成之LDA溶液中，獲得透明黃綠色溶液。添加異於鹼醛（6.3毫升，66.1毫莫耳），造成白色沉澱物形成。使反應混合物溫熱至室溫，然後添加冰醋酸（3.3毫升，57·8毫莫耳）。添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（80-100% EtOAc/ 己烷-3-5-7% MeOH/EtOAc)，獲得 8.48 克（69% )，為灰白色固體。Rf=〇j8(5% MeOH/EtOAC); MSm/z223 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 5.91 (d, J=4.41 Hz, .1H) 6.49 (d3 J=4.41 Hz，1H) 7.20 (dd，J=8.31，2·54 Hz，1H) 7·36 (m，2H) 8.19 (m，1H) 8·53 (m， 2H);實測值：223,221;對 ChHAKO之計算值：C，59.46; H，3.63 ;N，12.61·實測值：C: 59.45, H: 3.66, N: 12.62.Example 227A Diisopropylamine (9.3 ml, 66.1 mmol) in THF (100 ml) Ear), at a temperature of -78 ° C, add n-BuLi (23.1 ml of 2.5 M solution in hexane, 57.8 mmol) in a dropwise manner via a syringe. Add 2,6-difluoropyridine (5.0 ml, 55.1 mmol) in THF (100 ml) to the LDA solution prepared above at -78 ° C dropwise through a cannula to obtain a transparent yellow Green solution. The addition of an alkali aldehyde (6.3 ml, 66.1 mmol) resulted in the formation of a white precipitate. The reaction mixture was allowed to warm to room temperature, and then glacial acetic acid (3.3 ml, 57.8 mmol) was added. Add silicone and remove volatiles on the rotary evaporator. Flash chromatography (80-100% EtOAc / hexane-3-5-7% MeOH / EtOAc) gave 8.48 g (69%) as an off-white solid. Rf = 〇j8 (5% MeOH / EtOAC); MSm / z223 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 5.91 (d, J = 4.41 Hz, .1H) 6.49 (d3 J = 4.41 Hz, 1H) 7.20 (dd, J = 8.31, 2.554 Hz, 1H) 7.36 (m, 2H) 8.19 (m, 1H) 8.53 (m, 2H); Found: 223,221; Calculated values for ChHAKO: C, 59.46; H, 3.63; N, 12.61. Found: C: 59.45, H: 3.66, N: 12.62.

實例227B (2’6-^一親j -。比 -3-基）-口比1-4-基-甲酿] -213· (206) 將實例227Α(7·36克，33·1毫莫耳）與Μη02(8·64克，99·4毫莫耳）合併於具有攪拌棒之500毫升圓底燒瓶中。添加1，4-二氧陸圜（120毫升），並使所形成之黑色混合物溫熱至110°C。於接下來之2天内，每兩小時，添加2克量之Μη02 (〜22克）。使反應混合物冷卻至室溫，並經過矽藻土過濾。將濾餅以 EtOAc洗條，然後於迴轉式蒸發器上移除所有揮發性物質。急騾式層析（50-70-80% EtOAc/己烷），獲得4.61克（63% )，為綠色固體。Rf=〇.58(5% MeOH/EtOAc); MSm/z221.(M+H)+ ; iHNMR (300 MHz, DMSO-D6) ά ppm 7.41 (ddd, J=8.145 2.37, 0.68 Hz, 1H) 7.72 (m, 2H) 8.47 (dt，J=9.41，8·01 Hz，1H) 8.85 (m，2H);對 Ci 6H6F2N20 之計算值：C， 60.01; Η，2·75; N，12.72·實測值·· c: 60.05, Η: 2·87，Ν: 12.97.Example 227B (2'6- ^ one parent j-. Than-3-yl)-mouth ratio 1-4-yl-methyl brewer] -213 · (206) Example 227A (7.36 g, 33.1 milligrams) Mol) and Mn02 (8.64 g, 99.4 mmol) were combined in a 500 ml round bottom flask with a stir bar. Add 1,4-dioxolane (120 ml) and warm the resulting black mixture to 110 ° C. Add 2 g of Mη02 (~ 22 g) every two hours for the next 2 days. The reaction mixture was cooled to room temperature and filtered through celite. The filter cake was washed with EtOAc, then all volatiles were removed on a rotary evaporator. Flash chromatography (50-70-80% EtOAc / hexane) gave 4.61 g (63%) of a green solid. Rf = 0.58 (5% MeOH / EtOAc); MSm / z221. (M + H) +; iHNMR (300 MHz, DMSO-D6) ά ppm 7.41 (ddd, J = 8.145 2.37, 0.68 Hz, 1H) 7.72 (m, 2H) 8.47 (dt, J = 9.41, 8.01 Hz, 1H) 8.85 (m, 2H); Calculated value for Ci 6H6F2N20: C, 60.01; Η, 2.75; N, 12.72 · Measured value ·· c: 60.05, Η: 2.87, Ν: 12.97.

實例227C 6-氟基-3-吡啶-4-某-1H-吡唑并「3,4-bl吡啶於1，4-二氧陸圜（100毫升）中之實例227B (4·20克，19.1毫莫耳）内，添加肼水合物（0.93毫升，19.1毫莫耳）。將所形成之黃色反應混合物於23°C下攪拌20分鐘，然後添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急騾式層析（60-80-100% EtOAc/ 己燒-1-5% MeOH/EtOAc)，獲得 2·49 克（61% )，為白色固體。Rf =0,40(5% MeOH/EtO Ac); MS m/z215 (M+H)+; iHNMR (300 MHz， DMSO-D6) δ ppm 7.14 (dd5 J=8.65, 0.85 Hz, 1H) 8.02 (m, 2H) 8.71 (m, 2H) 8.87 (dd，J=8.48, 7·80 Hz，1H) 14·25 (s, 1H);對 q 丨 H7FN4 之計算值：C，61.68 ; H，3·29; N，26.16.實測值：C: 61·35, H: 3.35, N: 25.81·Example 227C Example 6-Fluoro-3-pyridine-4--1H-pyrazolo "3,4-bl pyridine in 1,4-dioxolane (100 ml) 227B (4.20 g, 19.1 mmol), add hydrazine hydrate (0.93 ml, 19.1 mmol). Stir the yellow reaction mixture at 23 ° C for 20 minutes, then add silicone and remove on a rotary evaporator. Volatile materials. Flash chromatography (60-80-100% EtOAc / hexane-l-5% MeOH / EtOAc) gave 2.49 g (61%) as a white solid. Rf = 0.40 ( 5% MeOH / EtO Ac); MS m / z215 (M + H) +; iHNMR (300 MHz, DMSO-D6) δ ppm 7.14 (dd5 J = 8.65, 0.85 Hz, 1H) 8.02 (m, 2H) 8.71 ( m, 2H) 8.87 (dd, J = 8.48, 7.80 Hz, 1H) 14 · 25 (s, 1H); The calculated value for q 丨 H7FN4: C, 61.68; H, 3.29; N, 26.16. Found: C: 61 · 35, H: 3.35, N: 25.81 ·

實例227D 苯基-(3-p比症-4-基-lH-p比吐幷『3,4七1外k症-6-基乙腈 200301122 (207)Example 227D Phenyl- (3-p specific disease-4-yl-lH-p specific acetone 33,4 seventy-one disease -6 disease-based acetonitrile 200301122 (207)

於實例227C (0·96克，4·48毫莫耳」在DMF (20毫升）中之經攪拌混合物内，於-35°C下，添加氰化芊（1.55毫升，13.4毫莫耳），然後是NaH (0·57克，95% NaH，22.4毫莫耳）。將所形成之深紅色混合物攪拌15分鐘，同時慢慢地溫熱至〜-20°C。此時，大部份起泡已停止，然後，使反應混合物迅速地溫熱至室溫，接著至100°C過夜。使反應混合物冷卻至室溫，並添加NH4C1飽和水溶液。以EtOAc萃取混合物，並將有機萃液以Η2 Ο洗滌兩次，及以鹽水一次。添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（60-80-100% EtOAc-3% MeOH/EtOAc)，獲得 1·14 克（82% )，為橘色固體。Rf=0.40(5% MeOH/ EtOAc) ; MS m/z 312 (M+H)+ ; 1 H NMR (300 MHz，DMSO-D6) 5 ppm 6·17 (s， 1H) 7.40 (m，4H) 7.52 (m，2H) 8.00 (m，2H) 8.70 (m，2H) 8.74 (d，J=8.48 Hz，1H) 14.36(s，lH);對 C19HnN5之計算值·· C，73.30; H，4.21; Ν，22·49.實測值：C: 73.09, Η: 4.10, N: 22.58.In Example 227C (0.96 g, 4.48 millimoles "in a stirred mixture in DMF (20 ml), at -35 ° C, thallium cyanide (1.55 ml, 13.4 mmol) was added, Then NaH (0.57 g, 95% NaH, 22.4 mmol). Stir the formed dark red mixture for 15 minutes while slowly warming to ~ -20 ° C. At this point, most of the The bubbling has stopped, and then the reaction mixture is quickly warmed to room temperature, and then to 100 ° C overnight. The reaction mixture is cooled to room temperature, and a saturated aqueous solution of NH4C1 is added. The mixture is extracted with EtOAc, and the organic extract is extracted with ethyl acetate. 0 was washed twice, and once with brine. Silicone was added and the volatiles were removed on a rotary evaporator. Flash chromatography (60-80-100% EtOAc-3% MeOH / EtOAc) gave 1.14 G (82%) as an orange solid. Rf = 0.40 (5% MeOH / EtOAc); MS m / z 312 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 6.17 (s, 1H) 7.40 (m, 4H) 7.52 (m, 2H) 8.00 (m, 2H) 8.70 (m, 2H) 8.74 (d, J = 8.48 Hz, 1H) 14.36 (s, lH); for C19HnN5 Calculated ·· C, 73.30; H, 4.21; Ν, 22.49. Measured : C: 73.09, Η: 4.10, N: 22.58.

實例227E 2-笨基-2-(3-p比啶-4-基-1H-吡唑并「3,4-bl吡啶各基）-乙胺所要之產物係經由以實例227D取代實例41D中之實例41C Φ 而製成（84 毫克，27% )。Rf=0.33 (20% MeOH/CH2Cl2) ; MSm/z316 (M+H)+ ；1 H NMR (300 MHz, DMSO-D6) δ ppm 3.23 (m5 1H) 3.34 (br s? 3H) 3.52 (m，1H) 4.34 (m，1H) 7·27 (m，6H) 7.99 (d，J=6.10 Hz，2H) 8·57 (d，J=8.48 Hz，1H) 8.68 (d, J=6.10Hz, 2H). 實例228 莕冬基-(3-吡啶-4-基-1H-吡唑并吡啶-6-基乙月青所要之產物係經由以2-莕基乙腈取代實例227D中之芊基 -215- (208)Example 227E 2-Benzyl-2- (3-p than pyridin-4-yl-1H-pyrazolo "3,4-bl pyridyl) -ethylamine The desired product was obtained by replacing Example 41D with Example 227D Example 41C Φ (84 mg, 27%). Rf = 0.33 (20% MeOH / CH2Cl2); MSm / z316 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 3.23 (m5 1H) 3.34 (br s? 3H) 3.52 (m, 1H) 4.34 (m, 1H) 7.27 (m, 6H) 7.99 (d, J = 6.10 Hz, 2H) 8.57 (d, J = 8.48 Hz, 1H) 8.68 (d, J = 6.10Hz, 2H). Example 228 Isoferyl- (3-pyridin-4-yl-1H-pyrazolopyridin-6-ylethyridine. The desired product is passed through Substituting 2-fluorenylacetonitrile for fluorenyl-215- in Example 227D (208)

腈而獲得（244 毫克，42% )。Rf= 0.46 (EtOAc) ; MS m/z 362 (M+H)+ ; 1 H NMR (300 MHz, DMSO-D6) δ ppm 6.36 (s, 1H) 7.44 (d, J=8.48 Hz, 1H) 7.57 (m，3H) 7.98 (m，6H) 8.09 (d，J=1 ·36 Hz，1H) 8.69 (m，2H) 8.75 (d，J=8·48 Hz，1H)· 實例229 2-苯-2-基-2-(3-吡啶-4-基-1H-吡唑并f3,4-bl吡啶-6-基V乙胺所要之產物係經由以實例228取代實例41D中之實例41C而製成。MS m/z 366 (M+H)+ ; 1H NMR (300 MHz, DMSO-D6) 5 ppm 3.96 (m， 2H) 4.82 (t，J=7.46 Hz，1H) 7·39 (d，J=8.48 Hz，1H) 7·52 (m，3H) 7.89 (m，4H) 8.20 (d, J=6.10 Hz, 2H) 8.68 (d, J=8.48 Hz? 1H) 8.80 (m5 3H). 實例230 (3-異4啉-6-基-1H-吡唑#『3,4-bl吡啶-6-基V苯基-乙腈實例230A 異喹啉-6-卷曱醛將 6-溴基異喹啉（19.9 克，95.6 毫莫耳）、PdCl2(dppf).CH2Cl2(1.8 克）及三乙胺（30毫升）於曱苯（50毫升）中之溶液，在850 psi H2/CO(l : 1)下，加熱至130°C，歷經4小時。於冷卻至室溫後，將反應混合物過濾。使濾液濃縮，並使殘留物藉急驟式層析純化，以70-80-90-100% EtOAc/己烷溶離，而得6.11克（41 % )醛，為黃色固體。Rf= 0·55 (EtOAc); 1H NMR (300 MHz，DMSO-D6) δ ppm 8.07 (m5 2H) 8.30 (dd5 J=8.48, 0.68 Hz, 1H) 8.64 (s, 1H) 8.67 (d, J=5.76 Hz, 1H) 9.47 (s，1H) 10.23 (s，1H).Obtained from nitrile (244 mg, 42%). Rf = 0.46 (EtOAc); MS m / z 362 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 6.36 (s, 1H) 7.44 (d, J = 8.48 Hz, 1H) 7.57 (m, 3H) 7.98 (m, 6H) 8.09 (d, J = 1 · 36 Hz, 1H) 8.69 (m, 2H) 8.75 (d, J = 8 · 48 Hz, 1H) · Example 229 2-benzene- The desired product of 2-yl-2- (3-pyridin-4-yl-1H-pyrazolof3,4-blpyridin-6-yl V ethylamine was prepared by replacing Example 41C in Example 41D with Example 228 MS m / z 366 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 5 ppm 3.96 (m, 2H) 4.82 (t, J = 7.46 Hz, 1H) 7.39 (d, J = 8.48 Hz, 1H) 7.52 (m, 3H) 7.89 (m, 4H) 8.20 (d, J = 6.10 Hz, 2H) 8.68 (d, J = 8.48 Hz? 1H) 8.80 (m5 3H). Example 230 (3-iso4-line-6-yl-1H-pyrazole # "3,4-bl pyridin-6-yl Vphenyl-acetonitrile Example 230A Isoquinoline-6-rollaldehyde Aldehyde 6-Bromoisoquine Phenylline (19.9 g, 95.6 mmol), PdCl2 (dppf) .CH2Cl2 (1.8 g) and triethylamine (30 ml) in toluene (50 ml) at 850 psi H2 / CO (l: 1 ), Heated to 130 ° C for 4 hours. After cooling to room temperature, the reaction mixture was filtered. The filtrate was concentrated and the residue was subjected to flash chromatography. And dissolved with 70-80-90-100% EtOAc / hexane to give 6.11 g (41%) of aldehyde as a yellow solid. Rf = 0.55 (EtOAc); 1H NMR (300 MHz, DMSO-D6) δ ppm 8.07 (m5 2H) 8.30 (dd5 J = 8.48, 0.68 Hz, 1H) 8.64 (s, 1H) 8.67 (d, J = 5.76 Hz, 1H) 9.47 (s, 1H) 10.23 (s, 1H).

實例230B (3-異喹啉-6-基-1H-吡唑#「3,4-bl吡啶-6-基 >笨基-乙月青所要之產物（2糾毫克，42% )係經由以實例230A取代實例227 200301122 (209) 中之異菸鹼醛而獲得。Rf= 〇·46 (EtOAc); MS m/z 362 (M+H)+ ; 1 H NMR (300 MHz, DMSO-D6) 6 ppm 6.18 (s, 1H) 7.40 (m, 4H) 7.54 (τη, 2H) 7.99 (d5 J= 5.76 Hz, 1H) 8.25 (d, J=8.48 Hz, 1H) 8.36 (m, 1H) 8.56 (d, J=5.42 Hz, 1H) 8.63 (s, 1H) 8.87 (d，J=8.48 Hz，1H) 9·35 (s，1H) 14.27 (s，1H)· 實例231 2-(3-異喹啉-6-基-1H-吡唑并f3,4-bl吡啶各基V2-笨基-乙胺所要之產物係經由以實例230取代實例41D中之實例41C而Example 230B (3-Isoquinoline-6-yl-1H-pyrazole # "3,4-blpyridin-6-yl > benzyl-ethylazulene (2 mg, 42%) via Obtained with Example 230A instead of the isonicotinaldehyde in Example 227 200301122 (209). Rf = 0.46 (EtOAc); MS m / z 362 (M + H) +; 1 H NMR (300 MHz, DMSO-D6 ) 6 ppm 6.18 (s, 1H) 7.40 (m, 4H) 7.54 (τη, 2H) 7.99 (d5 J = 5.76 Hz, 1H) 8.25 (d, J = 8.48 Hz, 1H) 8.36 (m, 1H) 8.56 ( d, J = 5.42 Hz, 1H) 8.63 (s, 1H) 8.87 (d, J = 8.48 Hz, 1H) 9.35 (s, 1H) 14.27 (s, 1H) · Example 231 2- (3-isoquine The desired product of the quinolin-6-yl-1H-pyrazolof3,4-bl pyridine group V2-benzyl-ethylamine was obtained by replacing Example 41C in Example 41D with Example 230.

製成。MS m/z 366 (M+H)+; 1H NMR (300 MHz，DMSO-D6) 5 ppm 3.11 (m，1H) 3.90 (m，1H) 4.66 (dd，J=9.16, 6·10 Hz，1H) 7·31 (m，8H) 8.28 (d，>6.10 Hz，1H) 8.42 (d, J=8.82 Hz, 1H) 8.54 (d5 J=8.48 Hz, 1H) 8.63 (d5 J=6.44 Hz, 1H) 8.78 (s, 1H) 8.82 (d，J=8.48 Hz，1H) 9.59 (s，1H) 14.26 (s，1H)· 實例232 (ISM-芊基-2-(3-吡啶-4-基-1H-吡唑并『3,4-bl吡啶-5-某氪基v乙胺production. MS m / z 366 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 5 ppm 3.11 (m, 1H) 3.90 (m, 1H) 4.66 (dd, J = 9.16, 6.10 Hz, 1H ) 7.31 (m, 8H) 8.28 (d, > 6.10 Hz, 1H) 8.42 (d, J = 8.82 Hz, 1H) 8.54 (d5 J = 8.48 Hz, 1H) 8.63 (d5 J = 6.44 Hz, 1H ) 8.78 (s, 1H) 8.82 (d, J = 8.48 Hz, 1H) 9.59 (s, 1H) 14.26 (s, 1H) · Example 232 (ISM-fluorenyl-2- (3-pyridin-4-yl- 1H-pyrazolo 『3,4-bl pyridin-5-some fluorenyl v ethylamine

實例232B 5-(第三-丁基-二曱基-秒烷基氣基V2-举-毗乞將2-氟基-5-經基p比唉（1.00克’ 8.84愛莫耳）與bdcs試劑 (0.5MTBSC1，於DMF中之ΐ·〇Μ咪唑）(35.4毫升，17.7毫莫耳）之混合物’於室溫下攪掉1小時。將反應物倒入飽和NaHC〇3 水溶液中。以醚萃取水層。將合併之萃液以水、鹽水洗條，以MgSCU脫水乾燥，及濃縮。使殘留物於矽膠上藉急驟式管柱層析純化’以10%醋酸乙酯/己烷溶離，而得標題化合物（1.96克，98% )。Example 232B 5- (Third-Butyl-Difluorenyl-Seconyl Alkyl V2-Cup-Pyridyl) 2-Fluoro-5-Cyridyl p Ratio 唉 (1.00 g '8.84 Amor) with bdcs A mixture of reagents (0.5MTBSC1, ΐ · OM imidazole in DMF) (35.4 ml, 17.7 mmol) was stirred at room temperature for 1 hour. The reaction was poured into a saturated aqueous NaHC03 solution. Ether The aqueous layer was extracted. The combined extracts were washed with water and brine, dehydrated and dried with MgSCU, and concentrated. The residue was purified on silica gel by flash column chromatography 'dissolved in 10% ethyl acetate / hexane, There was obtained the title compound (1.96 g, 98%).

實例232B 5-(第三-丁基二士基氧基V3-吡啶斗某并「3,4_bl -217- 200301122Example 232B 5- (Third-butyldisyloxy V3-pyridine and 3,4_bl -217- 200301122

(210) ηί ' 所要之產物係根據實例227C中使用之程序，經由以實例 232A取代實例227A中之2,6_二氟说矣製成。(210) η ′ 'The desired product was prepared according to the procedure used in Example 227C by replacing Example 2,227A, 2,6_difluoro, with Example 232A.

實例232C 基-二一甲基-矽烷基氧斗墓‘唑并矣小致酸第三-丁兔所要之產物係經由以實例232B取代實例2〇3入中之實例搬匸而製成（75% ) ° 實例232D · gA-基-上被»基-说吐并fUbl毗喧-1-藉酸第三-丁酯將實例232C (91亳克，〇·213亳莫耳）與TBAF (1M，在TiiF中， 213微升，〇·2Π毫莫耳）於THF(1〇毫升）中之混合物，在室溫下攪拌5分鐘。使反應物濃縮。急驟式管柱層析，以5%甲醇/ ci^ci2落離，獲得所要之產物，經純化之殘留物（75% )。Example 232C The dimethyl-dimethyl-silyloxotoxin'zolopyrium tricarboxylic acid tertiary-butyl rabbit product was prepared by substituting Example 232B for Example 203 and substituting Example 203 (75 %) ° Example 232D · gA-based-Hydroyl group, spitting and fUbl, pivalan-1-boronic acid tert-butyl ester Example 232C (91 g, 0.213 mol) and TBAF (1M In TiiF, a mixture of 213 μl, 0.2 μmol) in THF (10 mL) was stirred at room temperature for 5 minutes. The reaction was concentrated. Flash column chromatography, falling off with 5% methanol / ci ^ ci2, to obtain the desired product, purified residue (75%).

實例232E 第三氧基V3‘啶斗某‘砷 l[3,4_bl吡啶-μ教酸第三-丁酯 · 私題化合物係經由以實例232〇取代實例238β中之實例238八，且以Boc-苯基丙胺醇取代實例238B中之B〇C-4，-溴苯基丙胺醇而製成。Example 232E The third oxy-V3 'pyridinium' arsenic [3,4_bl pyridine-μtearic acid third-butyl ester.] The title compound is obtained by replacing Example 238 in Example 238β with Example 232 and replacing it with Boc -Phenylpropylamine was prepared by replacing BOC-4, -bromophenylpropylamine in Example 238B.

實例232F 唑并Jg，4-bl吡啶-5-某氫某y乙脖於CH2C12(4笔升）中之實例23迚（39毫克，71微莫耳）内，添加4-甲氧基苄 < 醇(3〇微升，214微莫耳），然後是丁⑽毫升) -218- 200301122Example 232F Example 23 迚 (39 mg, 71 micromoles) of ZrOJg, 4-bl pyridine-5-a hydrogen and a y ethyl neck in CH2C12 (4 liters). ; Alcohol (30 μl, 214 μmol), then Ding Li ml) -218- 200301122

(211)(211)

。將所形成之黃色反應混合物於23°C下攪拌50分鐘，此時於迴轉式蒸發器上移除所有揮發性物質。添加K2C03(過量）與MeOH (5毫升），並將所形成之混合物於23°C下攪拌1小時，此時添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急騾式層析（EtOAc-5-10-12% MeOH/CH2Cl2)，獲得淡黃色蠟狀產物，使其溶於20% MeOH/CH2Cl2中，並與1NHC1(於Et20中之1 毫升1 N溶液，1毫莫耳）一起攪拌1小時。移除揮發性物質，而得11毫克（17%，歷經兩個步騾）黃色固體，其為雙-HC1 鹽。MS m/z 346 (M+H)+ ; 1H NMR (300 MHz，DMSO-D6) 5 ppm 2.92 (dd，J= 13.73, 8.98 Hz，1H) 3.12 (dd，J=14.24, 5.09 Hz，1H) 4.14 (dd，J=5.59, 1.86 Hz，1H) 4.74 (t，J=5.93 Hz，2H) 7.20 (m，5H) 7.97 (d，J=2.37 Hz，1H) 8.38 (m，5H) 8.90 (d，J= 6.78 Hz，2H) 10.31 (s，1H)· 實例233 2-芊基-345-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1-丙胺所要之產物係經由以（2-芊基各羥基-丙基）-胺甲基酸第三-. The resulting yellow reaction mixture was stirred at 23 ° C for 50 minutes, at which point all volatiles were removed on a rotary evaporator. K2C03 (excess) and MeOH (5 mL) were added, and the resulting mixture was stirred at 23 ° C. for 1 hour, at which time silicone was added and the volatile materials were removed on a rotary evaporator. Flash chromatography (EtOAc-5-10-12% MeOH / CH2Cl2) to obtain a pale yellow waxy product, which was dissolved in 20% MeOH / CH2Cl2 and mixed with 1NHC1 (1 ml of 1 N in Et20 , 1 mmol) and stir for 1 hour. The volatiles were removed and 11 mg (17% over two steps) of a yellow solid was obtained as a bis-HC1 salt. MS m / z 346 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 5 ppm 2.92 (dd, J = 13.73, 8.98 Hz, 1H) 3.12 (dd, J = 14.24, 5.09 Hz, 1H) 4.14 (dd, J = 5.59, 1.86 Hz, 1H) 4.74 (t, J = 5.93 Hz, 2H) 7.20 (m, 5H) 7.97 (d, J = 2.37 Hz, 1H) 8.38 (m, 5H) 8.90 (d , J = 6.78 Hz, 2H) 10.31 (s, 1H) · Example 233 2-fluorenyl-345- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1-propylamine The desired product is passed through (2-fluorenyl-hydroxy-propyl) -aminomethyl acid tertiary-

丁醋（Khumtaveepom，K. ; Ullmann，A. ; Matsumoto, K. ; Davis，B. G. ; Jones， J. B. Tetrahedron: Asymmetry，2001，12, 249)，取代實例 102 中之實例 Boc-色胺酸，以三氟醋酸製成。MSm/z373 (M+H)+，（M-H)VHNMR (300 MHz, DMSO-D6) δ ppm 2.55 (s3 3H) 2.81 (dd, J=7.29, 3.56 Hz, 2H) 2.92 (m, 1H) 3.05 (m，1H) 4.09 (dd，J=10.17, 5.76 Hz，2H) 4.16 (m，2H) 7.28 (m，5H) 7.57 (dd， J二8.48, 0.68 Hz，1H) 7.69 (m，1H) 7.74 (m，1H) 7.82 (s，2H) 8.09 (m，1H) 8.30 (d，J= 2.71 Hz, 1H) 8.62 (d, J=1.70 Hz, 1H). 實例234 nSM-ΠΗ-吲口朵-3-基曱基）-2-(24比啶-4-基-fl，71口奈淀-5-基氣基乙胺 -219- (212)Butyl vinegar (Khumtaveepom, K .; Ullmann, A .; Matsumoto, K .; Davis, BG; Jones, JB Tetrahedron: Asymmetry, 2001, 12, 249), replacing the example Boc-tryptophan in Example 102 with three Made from fluoroacetic acid. MSm / z373 (M + H) +, (MH) VHNMR (300 MHz, DMSO-D6) δ ppm 2.55 (s3 3H) 2.81 (dd, J = 7.29, 3.56 Hz, 2H) 2.92 (m, 1H) 3.05 ( m, 1H) 4.09 (dd, J = 10.17, 5.76 Hz, 2H) 4.16 (m, 2H) 7.28 (m, 5H) 7.57 (dd, J two 8.48, 0.68 Hz, 1H) 7.69 (m, 1H) 7.74 ( m, 1H) 7.82 (s, 2H) 8.09 (m, 1H) 8.30 (d, J = 2.71 Hz, 1H) 8.62 (d, J = 1.70 Hz, 1H). Example 234 nSM-ΠΗ-Indole-3 -Aminomethyl) -2- (24-pyridin-4-yl-fl, 71-methylazine-5-ylaminoethylamine-219- (212)

實例234A h漠基-5-(4-甲氧基-字氣某V毗畦將3-溴基-5-輕基p比違（14.7克，84·3毫莫耳）、琪化四丁基铵（0.3 克’ 0.8毫莫耳）及(14.0克，101毫莫耳）合併於具有授拌棒之乾燥500毫升圓底燒瓶中。添加DMF (170毫升），接著是PMBC1 (12.0亳升，88.5毫莫耳）。將所形成之褐色混合物於 23°C下攪拌3.5天，然後添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（10-20-40% EtOAc /己烷），獲得14.1 克（57% )，為橘色固體。Rf=〇.52 (50% EtOAc / 己烷 yHNMR (300 MHz, DMSO-D6) 5 ppm 3.32 (s, 3H) 5.12 (s5 2H) 6.96 (m, 2H) 7.39 (m, 2H) 7.79 (m, 1H) 8.28 (d5 J=2.03 Hz, 1H) 8.34 (d5 J=2.71 Hz, 1H). 1 3 C NMR (100 MHz, DMS0-D6) δ ppm 55.0, 69.8, 113.8, 119.9, 124.0, 127.8, 129.8, 137.1, 142.1, 155.1, 159.2 ;對 C12H10BrNO 之計算值：C，53.08 ; Η，4·11 ; N，4.76·實測值：C: 53·00，Η: 3·98，Ν: 4·66· 實例234Β 3-胺基-5-(4-甲氧基-爷氣基）-ρ比咬將實例 234Α (16.15 克，54.9 毫莫耳）、Pd2dba3 (0.50 克，0.55 毫莫耳）、外消旋-BINAP (1.03克，1.65毫莫耳）及第三-丁醇鈉（7.39 克，76.9毫莫耳）合併於具有攪拌棒之500毫升圓底燒瓶中。添加二苯曱酮亞胺（1U毫升，65.9毫莫耳），接著是甲苯（180 毫升）。使所形成之反應混合物溫熱至80°C，歷經3小時，然後使其冷卻至室溫，以Et2 〇稀釋，並經過矽藻土過濾。於迴轉式蒸發器上移除揮發性物質。急驟式層析（30-40-50% EtOAc /己燒），產生不純之橘色油，使其溶於THF (180毫升） -220- 200301122 pi3)Example 234A h-molyl-5- (4-methoxy-character gas, a certain V-Pyridine will compare 3-bromo-5-light-based p (14.7 g, 84.3 millimoles), Qihua tetrabutyl Ammonium (0.3 g '0.8 mmol) and (14.0 g, 101 mmol) were combined in a dry 500 ml round bottom flask with a stir bar. DMF (170 ml) was added, followed by PMBC1 (12.0 kL) , 88.5 mmol). The resulting brown mixture was stirred at 23 ° C for 3.5 days, then silicone was added, and the volatile materials were removed on a rotary evaporator. Flash chromatography (10-20-40% EtOAc / hexane) to obtain 14.1 g (57%) as an orange solid. Rf = 0.52 (50% EtOAc / hexane yHNMR (300 MHz, DMSO-D6) 5 ppm 3.32 (s, 3H) 5.12 ( s5 2H) 6.96 (m, 2H) 7.39 (m, 2H) 7.79 (m, 1H) 8.28 (d5 J = 2.03 Hz, 1H) 8.34 (d5 J = 2.71 Hz, 1H). 1 3 C NMR (100 MHz, DMS0-D6) δ ppm 55.0, 69.8, 113.8, 119.9, 124.0, 127.8, 129.8, 137.1, 142.1, 155.1, 159.2; Calculated values for C12H10BrNO: C, 53.08; Η, 4 · 11; N, 4.76 · Measured values : C: 53 · 00, Η: 3.98, N: 4.66 · Example 234B 3-amino-5- (4-methoxy-pyridyl) -ρ ratio bite Example 234A (16.15 g, 54.9 mmol), Pd2dba3 (0.50 g, 0.55 mmol), racemic-BINAP (1.03 g, 1.65 mmol) and tertiary-butoxide (7.39 g, 76.9 Millimoles) were combined in a 500 ml round bottom flask with a stir bar. Dibenzophenone imine (1U ml, 65.9 mmol) was added, followed by toluene (180 ml). The resulting reaction mixture was allowed to warm To 80 ° C for 3 hours, then allowed to cool to room temperature, diluted with Et20, and filtered through diatomaceous earth. Remove the volatiles on a rotary evaporator. Flash chromatography (30-40- 50% EtOAc / hexane) to produce an impure orange oil, which was dissolved in THF (180 ml) -220- 200301122 pi3)

與1 N HCl (60毫升）中。將所形成之橘色混合物攪拌15分鐘，接著於30% EtOAc /己烷與0.5 M HC1之間作分液處理。分離液層，並將有機層以0.5 M HC1洗滌一次。將合併之HCl·層以30 % EtOAc /己烷洗滌一次，然後冷卻至0°C。添加50% NaOH水溶液，直到混合物於石蕊試紙上呈鹼性，然後將混合物以 CH2C12萃取兩次。使合併之有機萃液以Na2S04脫水乾燥，並於迴轉式蒸發器上移除揮發性物質，而得8.92克（71%，歷經兩個步驟），為黃色固體。iHNMRpOOMH^DMSO-De) 5 ppm 3.75 (s，3H) 4.97 (s，2H) 4.97 (s，2H) 5.29 (s，2H) 6.54 (t，J=2.37 Hz，1H) 7.35 (m，2H) 7.50 (d，J=2.37 Hz，1H) 7.54 (d，J=2.37 Hz，1H)，1 3 C NMR (100 MHz，DMSO-D6) δ !)pm 55.0, 68.9, 105.6, 113.8, 125.3, 128.7, 129.3, 129.4, 145.7, 155.1，159.0.With 1 N HCl (60 mL). The resulting orange mixture was stirred for 15 minutes, and then separated between 30% EtOAc / hexane and 0.5 M HC1. The layers were separated and the organic layer was washed once with 0.5 M HC1. The combined HCl·layers were washed once with 30% EtOAc / hexane and then cooled to 0 ° C. Add 50% NaOH solution until the mixture becomes alkaline on litmus paper, then extract the mixture twice with CH2C12. The combined organic extracts were dried over Na2S04 and the volatiles were removed on a rotary evaporator to obtain 8.92 g (71% over two steps) as a yellow solid. iHNMRpOOMH ^ DMSO-De) 5 ppm 3.75 (s, 3H) 4.97 (s, 2H) 4.97 (s, 2H) 5.29 (s, 2H) 6.54 (t, J = 2.37 Hz, 1H) 7.35 (m, 2H) 7.50 (d, J = 2.37 Hz, 1H) 7.54 (d, J = 2.37 Hz, 1H), 1 3 C NMR (100 MHz, DMSO-D6) δ!) pm 55.0, 68.9, 105.6, 113.8, 125.3, 128.7, 129.3, 129.4, 145.7, 155.1, 159.0.

實例234C 「5_(4·甲乳基·卞乳基）_叶匕症-3-基1·胺甲基酸弟二-丁酉旨於實例234B (8.92克，38.7毫莫耳）在THF (240毫升）中之經攪拌溶液内，在23°C下，經由注射器逐滴添加NaHMDS (在甲苯中之129毫升0.6 Μ溶液，77.5毫莫耳）。將所形成之混濁黃褐色混合物攪拌5分鐘，然後立即全部添加Boc20 (8.45克，38.7 · 毫莫耳）。混合物之混濁性消失，留下透明黃褐色溶液。添加0.1 M HC1，並將所形成之水層與有機層分離。水層之pH 值為〜8。將有機層以鹽水洗滌，接著，於迴轉式蒸發器上移除揮發性物質之前，與碎膠合併。急驟式層析（30-40-50-70 % EtOAc/ 己烷-5-10% MeOH/CH2Cl2)，獲得 1.69(10% )雙-Boc 保護之橘色固體，7.04克（55% )所要之單-Boc保護之黃色固體，及1.51克（17% )起始胺，為橘色固體。雙-Boc之數據：Rf = 0.38 (50 -221 - 200301122 (214) % EtOAc / 己烷）1 H NMR (300 MHz，DMSO-D6) 5 ppm 1.35 (s，18H) 3.75 (s， 3H) 5.11 (s，2H) 6.94 (m，2H) 7.39 (m5 2H) 7.43 (dd，J=2.71，2·03 Hz，1H) 8.02 (d，J= 2.03 Hz, 1H) 8.28 (d, J=2.37 Hz, 1H).單-Boc 之數據：Rf= 0.30 (50% EtOAc / 己虎 ^HNMR (300 MHz, DMSO-D6) ά ppm 1.48 (s，9H) 3.76 (s，3H) 5.04Example 234C "5_ (4 · methyllactyl · 卞 lactyl) _ leaf dangle disease-3-yl-1 amine methyl didi-butyrate is aimed at Example 234B (8.92 g, 38.7 mmol) in THF (240 Ml) of the stirred solution, at 23 ° C, NaHMDS (129 ml of 0.6 M solution in toluene, 77.5 mmol) was added dropwise via a syringe. The resulting cloudy yellow-brown mixture was stirred for 5 minutes, Then immediately add all Boc20 (8.45 g, 38.7 · mmol). The turbidity of the mixture disappears, leaving a transparent yellow-brown solution. 0.1 M HC1 is added and the formed aqueous layer is separated from the organic layer. The value is ~ 8. The organic layer was washed with brine and then combined with crushed gum before removing volatiles on a rotary evaporator. Flash chromatography (30-40-50-70% EtOAc / hexane- 5-10% MeOH / CH2Cl2) to obtain 1.69 (10%) bis-Boc protected orange solid, 7.04 g (55%) of the desired mono-Boc protected yellow solid, and 1.51 g (17%) of the starting amine , As an orange solid. Data for bis-Boc: Rf = 0.38 (50 -221-200301122 (214)% EtOAc / hexane) 1 H NMR (300 MHz, DMSO-D6) 5 ppm 1 .35 (s, 18H) 3.75 (s, 3H) 5.11 (s, 2H) 6.94 (m, 2H) 7.39 (m5 2H) 7.43 (dd, J = 2.71, 2.03 Hz, 1H) 8.02 (d, J = 2.03 Hz, 1H) 8.28 (d, J = 2.37 Hz, 1H). Data for single-Boc: Rf = 0.30 (50% EtOAc / Jihu ^ HNMR (300 MHz, DMSO-D6)) ppm 1.48 (s, 9H) 3.76 (s, 3H) 5.04

(s，2H) 6.95 (m，2H) 7·39 (m，2H) 7.60 (t，J=2.20 Hz，1H) 7.96 (d，J=2J1 Hz，1H) 8.22 (d, J=2.03 Hz, 1H) 9.57 (s, 1H). 1 3 CNMR (100 MHz, DMSO-D6) δ ppm 28.0, 55·0, 69.3, 79.6, 110.8, 113.8, 128.3, 129.6, 131.1，132·3, 136.9, 152.7, 154.4, 159.1，對 C18H22N204之計算值：C，65.44; Η，6·71; Ν，8·48·實測值：匸： 65.40, Η: 6.66, Ν: 8.40.(s, 2H) 6.95 (m, 2H) 7.39 (m, 2H) 7.60 (t, J = 2.20 Hz, 1H) 7.96 (d, J = 2J1 Hz, 1H) 8.22 (d, J = 2.03 Hz, 1H) 9.57 (s, 1H). 1 3 CNMR (100 MHz, DMSO-D6) δ ppm 28.0, 55.0, 69.3, 79.6, 110.8, 113.8, 128.3, 129.6, 131.1, 132.3, 136.9, 152.7, 154.4, 159.1, Calculated value for C18H22N204: C, 65.44; Η, 6.71; Ν, 8.48. Measured value: 匸: 65.40, Η: 6.66, Ν: 8.40.

實例234D 『4-甲醯基-5-(4-曱氧基-罕氣基V吡啶-3-基V胺甲基酸第三-丁酯於THF (125毫升）中之實例234C (2.50克，7.54毫莫耳）内，在-78°C下，經由注射器逐滴添加n-BuLi (於己统中之6.64毫升2.5 Μ 溶液，16·6毫莫耳）。使所形成之暗橘色反應混合物慢慢溫熱至-10°C，歷經45分鐘，然後再冷卻至-78°C。經由注射器逐滴添加甲酸曱酯（1.40毫升，22.6毫莫耳），並將反應物於-78 °C下再攪拌1〇分鐘。添加NH4C1飽和水溶液，並使已驟冷之 41 反應混合物溫熱至室溫。添加Η〗Ο與Et〗0，並分離液層。將有機物質以鹽水洗滌，並以MgS04脫水乾燥。急驟式層析（20-40-60-80% EtOAc /己烷），獲得〇·3克（12% )回收起始物質與 1.7 克（63% )，為黃色固體。iHNMRQOOMHADMSCM^) δ ppm 1.47 (s, 9H) 3.75 (s, 3H) 5.28 (s, 2H) 6.95 (d? J=8.59 Hz, 2H) 7.43 (d, J=8.59 Hz, 2H) 8.38 (s，1H) 9.07 (s，1H) 10.17 (s，1H) 10.35 (s，1H)，1 3 C NMR (100 MHz，DMSO-D6) 5 ppm 27.7, 55.0, 70.8, 81.1，113.9, 114.6, 127.7, 129.6, 130.0, 133.3, 134.6， -222- (215)Example 234D Example of "4-Methylmethyl-5- (4-methyloxy-anhydrol-pyridin-3-yl V amine methyl acid tert-butyl ester in THF (125 ml) 234C (2.50 g , 7.54 millimoles), -n-BuLi (6.64 ml of 2.5 M solution, 16.6 millimoles in the system) was added dropwise via syringe at -78 ° C. The resulting dark orange color The reaction mixture was slowly warmed to -10 ° C for 45 minutes and then cooled to -78 ° C. Ethyl formate (1.40 ml, 22.6 mmol) was added dropwise via a syringe, and the reaction was left at -78 Stir for another 10 minutes at ° C. Add a saturated aqueous solution of NH4C1 and warm the quenched 41 reaction mixture to room temperature. Add Η0 and Et0 and separate the liquid layer. Wash the organic material with brine, It was then dried over MgS04. Flash chromatography (20-40-60-80% EtOAc / hexane) yielded 0.3 g (12%) of recovered starting material and 1.7 g (63%) as a yellow solid. iHNMRQOOMHADMSCM ^) δ ppm 1.47 (s, 9H) 3.75 (s, 3H) 5.28 (s, 2H) 6.95 (d? J = 8.59 Hz, 2H) 7.43 (d, J = 8.59 Hz, 2H) 8.38 (s, 1H ) 9.07 (s, 1H) 10.17 (s, 1H) 10.35 (s, 1H), 1 3 C NMR (100 MHz, DMSO-D6) 5 ppm 27.7, 55.0, 70.8, 81.1, 113.9, 114.6, 127.7, 129.6, 130.0, 133.3, 134.6, -222- (215)

151.7，154.7，159.2，192.8，對（：191122&〇5之計算值：€，63.67;11，6.19; Ν，7·82·實測值：C: 63.59, Η: 6.21，N: 7.64.151.7, 154.7, 159.2, 192.8, Calculated values for (: 191122 & 05: €, 63.67; 11, 6.19; N, 7.82. Found: C: 63.59, Η: 6.21, N: 7.64.

實例234E 甲氣基-芊氫基）-Π，71喑啶-2-醇於THF (45毫升）中之雙（2,2,2-三氟乙基）(甲氧羰基甲基）膦酸酯（1.27毫升，5·99毫莫耳）内，在-78°C下，經由注射器逐滴添加KHMDS (於甲苯中之1U毫升〇·5 Μ溶液，5.53毫莫耳）。於-78°C下，將所形成之透明淡黃色溶液經由套管逐滴添加至THF (60毫升）中之實例234D (1.65克，4.60毫莫耳）内。將所形成之混濁黃色反應混合物於-78°C下攪拌20分鐘，此時添加NH4 C1飽和水溶液，並使已驟冷之反應混合物溫熱至室溫。添加H20與Et20，並分離液層。將有機物質以鹽水洗滌，並以MgS04脫水乾燥。急驟式層析（40-50-60-70% EtOAc/己烷），獲得1.98克不純產物，其為Z : E晞烴異構物之5 : 1混合物。於THF (150毫升）中之粗產物内，添加NaHMDS (在甲苯中之11.6毫升0·6 Μ溶液，6.95毫莫耳）。將所形成之反應混合物於23°C下攪拌30分鐘，此時添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（60-100% EtOAc /己烷-5-10% MeOH/CH2Cl2)，獲得〇·23克（12% )E-晞烴，為黃色固體，與所要之產物0.98克（75%，歷經兩個步驟），為白色固體。Example 234E Bis (2,2,2-trifluoroethyl) (methoxycarbonylmethyl) phosphonic acid bis (2,2,2-trifluoroethyl) (II, 71-pyridinyl) -II, 71 pyridin-2-ol in THF (45 ml) KHMDS (1U ml 0.5M solution in toluene, 5.53 mmol) was added dropwise to the ester (1.27 ml, 5.99 mmol) at -78 ° C via a syringe. The formed clear light yellow solution was added dropwise via cannula to -Example 234D (1.65 g, 4.60 mmol) in THF (60 ml) at -78 ° C. The resulting cloudy yellow reaction mixture was stirred at -78 ° C for 20 minutes, at which time a saturated aqueous NH4C1 solution was added and the quenched reaction mixture was allowed to warm to room temperature. H20 and Et20 were added and the layers were separated. The organic material was washed with brine and dried over MgS04. Flash chromatography (40-50-60-70% EtOAc / hexane) gave 1.98 g of an impure product as a 5: 1 mixture of Z: E hydrazone isomers. To the crude product in THF (150 mL) was added NaHMDS (11.6 mL of a 0.6 M solution in toluene, 6.95 mmol). The resulting reaction mixture was stirred at 23 ° C for 30 minutes, at which time silicone was added and volatile materials were removed on a rotary evaporator. Flash chromatography (60-100% EtOAc / hexane-5-10% MeOH / CH2Cl2) gave 0.23 g (12%) of E-fluorene as a yellow solid with 0.98 g (75%) of the desired product , After two steps), as a white solid.

Rf = 0.32 (10 % MeOH/CH2 Cl2), 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.77 (s, 3H) 5,27 (s，2H) 6.68 (d，J=9.51 Hz，1H) 6.98 (m，2H) 7.46 (m，2H) 8.00 (d，J=9.82 Hz，·1Η) 8.18 (s，1H) 8.31 (s，1H) 11.98 (s，1H)，1 3 CNMR (100 MHz，DMSO-D6) 5 ppm 55·0, 70.2, 113.7, 113.9, 125.7, 125.8, 128.1，129.5, 131.0, 132.7, 134.9, 149.3, (216)Rf = 0.32 (10% MeOH / CH2 Cl2), 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.77 (s, 3H) 5,27 (s, 2H) 6.68 (d, J = 9.51 Hz, 1H) 6.98 (m, 2H) 7.46 (m, 2H) 8.00 (d, J = 9.82 Hz, · 1Η) 8.18 (s, 1H) 8.31 (s, 1H) 11.98 (s, 1H), 1 3 CNMR (100 MHz, DMSO-D6) 5 ppm 55.0, 70.2, 113.7, 113.9, 125.7, 125.8, 128.1, 129.5, 131.0, 132.7, 134.9, 149.3, (216)

159.2，161,2，對 C16H14N2〇3 之計算值：C，68.07 ; Η，5·00 ; Ν，9.92·實測值：C : 67.75, Η : 4.89, Ν : 9.88.159.2, 161,2, Calculated value for C16H14N2 03: C, 68.07; Η, 5.00; N, 9.92. Found: C: 67.75, Η: 4.89, Ν: 9.88.

f 例 234F 2-取基-5-(4-甲氧基-卞氧基篇读於實例234D (2.21克，7·83毫莫耳）在DMF (50毫升）中之懸浮液内，於23°C下，添加P〇Cl3(2.2毫升，23.5毫莫耳）。所有固體起始物質均溶解，並使所形成之黃色反應混合物溫熱至 45°C，歷經6小時。反應之顏色由黃色改變成深紅褐色。在 1升Ehrlenmeyer燒瓶中，將反應物傾倒至冰水（250毫升）中之 NaHC03(13.2克，157毫莫耳）上，並激烈攪拌。將產物以EtOAc 與Et2 0萃取，並將有機萃液以H2 0洗滌兩次，及以鹽水一次。添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急騾式層析（20-30-45-50% EtOAc/己烷），獲得1.86克（79% )，為灰f Example 234F 2- Take the base-5- (4-methoxy-fluorenyl) in Example 234D (2.21 g, 7.83 mmol) in a suspension of DMF (50 ml) at 23 At ° C, POCl3 (2.2 ml, 23.5 mmol) was added. All solid starting materials were dissolved and the yellow reaction mixture formed was allowed to warm to 45 ° C over 6 hours. The color of the reaction was yellow Change to dark reddish brown. In a 1 liter Ehrlenmeyer flask, pour the reaction onto NaHC03 (13.2 g, 157 mmol) in ice water (250 ml) and stir vigorously. Extract the product with EtOAc and Et20, The organic extract was washed twice with H20 and once with brine. Silicone was added and the volatiles were removed on a rotary evaporator. Flash chromatography (20-30-45-50% EtOAc / hexane) Alkane) to obtain 1.86 g (79%) as ash

白色固體。RfsO^GO^MeOH/Ci^Ciy/HNMRMOOMHz’DMSO-De) δ ppm 3.79 (s, 3H) 5.35 (s, 2H) 6.99 (d, J=8.59 Hz, 2H) 7.51 (d3 J=8.90 Hz, 2H) 7.77 (d, J=8.90 Hz, 1H) 8.47 (s, 1H) 8.52 (dd, J=8.90, 0.61 Hz, 1H) 8.96 (s? 1H), 1 3 C NMR (100 MHz，DMSO-D6) 5 ppm 55.0, 70.4, 113.9, 121.8, 125.9, 126·5, 127.9, 129.6, 133.7, 142.4, 144.0, 148.5, 151.7, 159.2 ;對 C16H13C1N202 之計算值： C，63.90 ; H，4.36; N，9.31·實測值：C: 63·54, Η: 4.17, Ν: 9·14.White solid. RfsO ^ GO ^ MeOH / Ci ^ Ciy / HNMRMOOMHz'DMSO-De) δ ppm 3.79 (s, 3H) 5.35 (s, 2H) 6.99 (d, J = 8.59 Hz, 2H) 7.51 (d3 J = 8.90 Hz, 2H ) 7.77 (d, J = 8.90 Hz, 1H) 8.47 (s, 1H) 8.52 (dd, J = 8.90, 0.61 Hz, 1H) 8.96 (s? 1H), 1 3 C NMR (100 MHz, DMSO-D6) 5 ppm 55.0, 70.4, 113.9, 121.8, 125.9, 126 · 5, 127.9, 129.6, 133.7, 142.4, 144.0, 148.5, 151.7, 159.2; Calculated values for C16H13C1N202: C, 63.90; H, 4.36; N, 9.31 · Found: C: 63 · 54, Η: 4.17, Ν: 9 · 14.

實例234G 5-(4-甲氧基-字氧基）-2-吡啶-4-基-Π,71苯啶將實例234F (164毫克，0.55毫莫耳）、4-三丁基錫烷基吡啶（401 毫克，1.09毫莫耳）、Pd2dba3(50毫克，〇.〇6毫莫耳）及2-二環己基膦基-2HN，N-二甲胺基）聯苯（43毫克，0.11毫莫耳），合併於 200301122Example 234G 5- (4-methoxy-wordoxy) -2-pyridin-4-yl-Π, 71 phenylpyridine Example 234F (164 mg, 0.55 mmol), 4-tributyltin alkylpyridine ( 401 mg, 1.09 mmoles), Pd2dba3 (50 mg, 0.06 mmoles), and 2-dicyclohexylphosphino-2HN, N-dimethylamino) biphenyl (43 mg, 0.11 mmoles) ), Merged in 200301122

(217)(217)

具有攪拌棒之ίο毫升圓底燒瓶电。將燒瓶之氣層抽氣，並以氬置換兩次。添加DMF (2毫升）與Et3N (0.5毫升，3.27毫莫耳），並使反應混合物溫熱至l〇〇°C，歷經5小時。使反應混合物冷卻至室溫，以EtOAc與Et20稀釋，並經過矽藻土過濾。將濾液以Η2 Ο洗滌兩次，及以鹽水一次。添加矽膠，並藉迴轉式蒸發移除揮發性物質。急驟式層析（70-100% EtOAc / 己烷-2-5% MeOH/CH2Cl2)，獲得92毫克（49% )，為黃色固體。 Rf = 0.39 (10% MeOH/CH2 Cl2), 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.79 (s5 3H) 5.37 (s, 2H) 7.01 (m5 2H) 7.53 (m5 2H) 8.21 (d5 J=5.83 Hz, 2H) 8.43 (m, 2H) 8.64 (d，J=8.59 Hz，1H) 8.80 (d，J=4.30 Hz，2H) 9.13 (s，1H)，1 3 C NMR (100 MHz， DMSO-D6) δ ppm 55.1，70.3, 113.9, 121·3, 122.1，122.6, 126.0, 128.1，129.6, 131.3, 142.7, 144.6, 145.8, 148.4, 150.5, 155.5, 159.2 ;對 C21 % 7 N302 之計算值： C，73.45 ; H，4.99 ; N，12.24.實測值：C : 73·32, Η : 5.10, N : 12.17. 實例2341A milliliter round bottom flask with a stir bar was charged. The gas layer of the flask was evacuated and replaced twice with argon. DMF (2 mL) and Et3N (0.5 mL, 3.27 mmol) were added and the reaction mixture was allowed to warm to 100 ° C for 5 hours. The reaction mixture was allowed to cool to room temperature, diluted with EtOAc and Et20, and filtered through celite. The filtrate was washed twice with Η20 and once with brine. Add silicone and remove volatiles by rotary evaporation. Flash chromatography (70-100% EtOAc / hexane-2-5% MeOH / CH2Cl2) gave 92 mg (49%) as a yellow solid. Rf = 0.39 (10% MeOH / CH2 Cl2), 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.79 (s5 3H) 5.37 (s, 2H) 7.01 (m5 2H) 7.53 (m5 2H) 8.21 (d5 J = 5.83 Hz, 2H) 8.43 (m, 2H) 8.64 (d, J = 8.59 Hz, 1H) 8.80 (d, J = 4.30 Hz, 2H) 9.13 (s, 1H), 1 3 C NMR (100 MHz, DMSO -D6) δ ppm 55.1, 70.3, 113.9, 121 · 3, 122.1, 122.6, 126.0, 128.1, 129.6, 131.3, 142.7, 144.6, 145.8, 148.4, 150.5, 155.5, 159.2; Calculated values for C21% 7 N302: C, 73.45; H, 4.99; N, 12.24. Found: C: 73 · 32, Η: 5.10, N: 12.17. Example 2341

於具有攪拌棒之50毫升圓底燒瓶中，在實例234H (108毫克，0.32毫莫耳）内，添加1 N HC1 (1.6毫升，1.57毫莫耳）在EtOH (8 毫升）中之混合物。使所形成之反應混合物溫熱至90°C，歷經2小時，冷卻至室溫，然後傾倒在100毫升圓底燒瓶中之 K2C〇3(120毫克，0.87毫莫耳）上。添加MeOH(10毫升），並將混合物激烈攪拌1小時，此時添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急驟式層析（3-5-7-12% MeOH/CH2Cl2)，獲得 52 毫克（74% )，為灰白色固體。Rf=0.24(10% MeOH/CH2Cl2) ；MS m/z 224 (M+H)+ ; 1 H NMR (300 MHz, DMS0-D6) 5 ppm 8.20 (s5 1H) -225 - (218)In a 50 ml round bottom flask with a stir bar, to Example 234H (108 mg, 0.32 mmol) was added a mixture of 1 N HC1 (1.6 ml, 1.57 mmol) in EtOH (8 ml). The resulting reaction mixture was allowed to warm to 90 ° C for 2 hours, cooled to room temperature, and then poured onto K2CO3 (120 mg, 0.87 mmol) in a 100 ml round bottom flask. MeOH (10 ml) was added and the mixture was stirred vigorously for 1 hour, at which time silicone was added and the volatiles were removed on a rotary evaporator. Flash chromatography (3-5-7-12% MeOH / CH2Cl2) gave 52 mg (74%) as an off-white solid. Rf = 0.24 (10% MeOH / CH2Cl2); MS m / z 224 (M + H) +; 1 H NMR (300 MHz, DMS0-D6) 5 ppm 8.20 (s5 1H) -225-(218)

8·24 (m，2H) 8·44 (d，J=8.82 Hz，1H) 8.69 (d，J=8.82 Hz，1H) 8·80 (m，2H) 9·01 (s， 1H) 10.91 (Br S, 1H).8 · 24 (m, 2H) 8.44 (d, J = 8.82 Hz, 1H) 8.69 (d, J = 8.82 Hz, 1H) 8 · 80 (m, 2H) 9 · 01 (s, 1H) 10.91 ( Br S, 1H).

實例234J 啕嗓-3-基甲基）-2-(2-吡啶-4-基-[1，71喑啶-5-基氧基乙基1-胺甲基酸第三-丁酯所要之產物係經由以實例2321取代實例27A中之3-溴基-5-羥基吡啶而製成。Rf= 0.41 (10% MeOH/CH2Cl2) : iHNMR(300MHz， DMSO-D6) δ ppm 1.37 (s3 9H) 3.07 (m, 1H) 3.38 (in, 1H) 4.25 (m, 3H) 6.93 (m, 1H) 7.05 (td, J=7.54, 1.19 Hz, 1H) 7.15 (d, J=2.03 Hz, 1H) 7.21 (d, J=7.80 Hz, 1H) 7.33 (d，J=7.80 Hz，1H) 7.56 (d，J=7.80 Hz，1H) 8.27 (m，3H) 8.51 (d，J=8.82 Hz，1H) 8.82 (m，3H) 9.13 (s，1H) 10.82 (s，1H).Example 234J Trimethyl-3-ylmethyl) -2- (2-pyridin-4-yl- [1,71 pyridin-5-yloxyethyl 1-aminomethyl acid tertiary-butyl ester The product was prepared by replacing 3-bromo-5-hydroxypyridine in Example 27A with Example 2321. Rf = 0.41 (10% MeOH / CH2Cl2): iHNMR (300 MHz, DMSO-D6) δ ppm 1.37 (s3 9H) 3.07 (m, 1H) 3.38 (in, 1H) 4.25 (m, 3H) 6.93 (m, 1H) 7.05 (td, J = 7.54, 1.19 Hz, 1H) 7.15 (d, J = 2.03 Hz, 1H) 7.21 ( d, J = 7.80 Hz, 1H) 7.33 (d, J = 7.80 Hz, 1H) 7.56 (d, J = 7.80 Hz, 1H) 8.27 (m, 3H) 8.51 (d, J = 8.82 Hz, 1H) 8.82 ( m, 3H) 9.13 (s, 1H) 10.82 (s, 1H).

實例234K (1SV1_(1H-口弓1 ?朵-3-基甲基）·2-(2-ρ比症-4·基41,7]口奈淀-5-基乳基）-乙胺所要之產物係經由以實例234Κ取代實例232Ε中之實例232D ，以三氟醋酸鹽製成。MS m/z 396 (M+H)+ ; iHNMR (300 MHz， DMSO-D6)(自由態鹼）（5 ppm2.96 (m，1H) 3.11 (m，1H) 3·24 (m，1H) 3·61 (s， 1H) 4.09 (q5 J=5.09 Hz，1H) 4.16 (dd，J=9.49, 6.10 Hz，1H) 4·26 (m，1H) 6.93 (m，1H) 7.06 (td，JN7.46, 1·02 Hz，1H) 7.22 (d，J=2.37 Hz，1H) 7.34 (d，J=8.14 Hz，1H) 7·58 (d, J=8.14 Hz, 1H) 8.27 (m, 3H) 8.51 (d, J=8.82 Hz, 1H) 8.82 (m, 2H) 8.89 (d, J= 8.82 Hz, 1H) 9.14 (s, 1H) 10.88 (s? 1H). 實例235 (IRM-ΠΗ-Ηΐ 口朵-3-基甲基）-2-(2-吡啶-4-基41，7栌奈症-5-基氧基）-乙胺所要之產物係經由以Boc-R-色胺酸取代實例234中之Boc-L-色胺酸而製成。MS m/z : 396 (M+H)+ ; 1 H NMR (300 MHz，DMSO-D6) (219) 5 ppm 3·31 (m，2H) 4.34 (dd，J=10.51，5·42 Hz，1H) 4.50 (dd，J=10.68, 2·54 Hz，1H) 6·95 (m，1H) 7·08 (m，1H) 7.29 (d，J=2.03 Hz，1H) 7.37 (d，J=8.14 Hz，1H) 7.63 (d， J=7.80 Hz，1H) 8.30 (s，1H) 8.65 (m，6H) 8.99 (d，J=5.76 Hz，2H) 9.23 (s，1H) 9.29 (m，1H) 11.04 (d，J=1 ·70 Hz，1H). 實例236 (j_g)小(lH-lndol-3-基甲基）-2-(5-異4琳-6-基-p比咬-3-基硫基）-乙胺Example 234K (1SV1_ (1H-oral arch 1? -3-ylmethyl) · 2- (2-rhobiasid-4 · yl 41,7) Korana lake-5-yl milk group) -Ethylamine The product was prepared from trifluoroacetate by replacing Example 232D in Example 232E with Example 234K. MS m / z 396 (M + H) +; iHNMR (300 MHz, DMSO-D6) (free state base) ( 5 ppm 2.96 (m, 1H) 3.11 (m, 1H) 3.24 (m, 1H) 3.61 (s, 1H) 4.09 (q5 J = 5.09 Hz, 1H) 4.16 (dd, J = 9.49, 6.10 Hz, 1H) 4.26 (m, 1H) 6.93 (m, 1H) 7.06 (td, JN7.46, 1.02 Hz, 1H) 7.22 (d, J = 2.37 Hz, 1H) 7.34 (d, J = 8.14 Hz, 1H) 7.58 (d, J = 8.14 Hz, 1H) 8.27 (m, 3H) 8.51 (d, J = 8.82 Hz, 1H) 8.82 (m, 2H) 8.89 (d, J = 8.82 Hz, 1H) 9.14 (s, 1H) 10.88 (s? 1H). Example 235 (IRM-ΠΗ-Ηΐ 口朵 -3-ylmethyl) -2- (2-pyridin-4-yl 41, 7 The desired product of 5-yloxy) -ethylamine was prepared by replacing Boc-L-tryptophan in Example 234 with Boc-R-tryptophan. MS m / z: 396 (M + H) + ; 1 H NMR (300 MHz, DMSO-D6) (219) 5 ppm 3.31 (m, 2H) 4.34 (dd, J = 10.51, 5.42 Hz, 1H) 4.50 (dd, J = 10.68, 2 · 54 Hz, 1H) 6.95 (m, 1H) 7.08 (m, 1H) 7.29 (d, J = 2.03 Hz, 1H) 7.37 (d, J = 8.14 Hz, 1H) 7.63 (d, J = 7.80 Hz, 1H) 8.30 (s, 1H) 8.65 (m, 6H) 8.99 (d, J = 5.76 Hz, 2H) 9.23 (s, 1H) 9.29 (m, 1H) 11.04 (d, J = 1 · 70 Hz, 1H). Example 236 (j_g) small (lH-lndol-3- Methyl) -2- (5-iso-4-lin-6-yl-p than sulfan-3-ylthio) -ethylamine

實例236A g-溴基-5-(4-甲氧-芊基硫基）-吡啶於氫化鈉（370毫克，60%，在礦油中，9.25毫莫耳）在DMF (30 毫升）中之懸浮液内，添加（4-甲氧基-苯基）-甲硫醇（1,25毫升，9毫莫耳）。將所形成之溶液於室溫下攪拌1小時，並添加至DMF (30毫升）中之3.5-二溴基吡啶（2.13克，8.99毫莫耳）内。將混合物於室溫下攪拌48小時。使反應溶液於謎與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（Na2S04) ，過濾及在真空下濃縮。於矽膠上純化，以5%醋酸乙酯 /己烷溶離，提供標題化合物（1.75克，63% )。MS (DCI/NH3) m/e 310(M+1)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 3.72 (s, 3H) 4.30 (s, 2H) 6.85 (d, J=2.03 Hz, 1H) 6.89 (d, J=2.37 Hz, 1H) 7.26 (d, J=2.37 Hz, 1H) 7.29 (d, J= 2.03 Hz, 1H) 8.04 (dd? J=2.03 Hz5 1H) 8.45 (d, J=2.03 Hz, 1H) 8.48 (d, J=2.03 Hz, 1H). 實例236B 5-溴π比啶-3-硫醇使實例236Α(1·43克，4·6毫莫耳）、間-曱酚（4.9毫升，47毫莫耳）及TFA (4毫升）之混合物回流24小時。於冷卻至室溫後 (220)Example 236A g-bromo-5- (4-methoxy-fluorenylthio) -pyridine in sodium hydride (370 mg, 60% in mineral oil, 9.25 mmol) in DMF (30 ml) To the suspension, (4-methoxy-phenyl) -methyl mercaptan (1,25 ml, 9 mmol) was added. The resulting solution was stirred at room temperature for 1 hour and added to 3.5-dibromopyridine (2.13 g, 8.99 mmol) in DMF (30 ml). The mixture was stirred at room temperature for 48 hours. The reaction solution was separated between the puzzle and water. The organic layer was washed (brine), dried (Na2SO4), filtered and concentrated under vacuum. Purify on silica gel and elute with 5% ethyl acetate / hexane to provide the title compound (1.75 g, 63%). MS (DCI / NH3) m / e 310 (M + 1) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 3.72 (s, 3H) 4.30 (s, 2H) 6.85 (d, J = 2.03 Hz , 1H) 6.89 (d, J = 2.37 Hz, 1H) 7.26 (d, J = 2.37 Hz, 1H) 7.29 (d, J = 2.03 Hz, 1H) 8.04 (dd? J = 2.03 Hz5 1H) 8.45 (d, J = 2.03 Hz, 1H) 8.48 (d, J = 2.03 Hz, 1H). Example 236B 5-Bromopyridine-3-mercaptan makes Example 236A (1.43 g, 4.6 mmol), occasionally -A mixture of acetol (4.9 ml, 47 mmol) and TFA (4 ml) was refluxed for 24 hours. After cooling to room temperature (220)

，藉真空使溶液乾燥。於矽膠上純化，以己烷中之5%醋酸乙酯溶離，提供粗製標題化合物（被二硫化物污染）。The solution was dried by vacuum. Purify on silica gel and elute with 5% ethyl acetate in hexane to provide the crude title compound (contaminated with disulfide).

實1例236C (lSH2-(5-溴-说啶各某硫甚啕哚-3-基甲基V乙羞]-胺甲基醢第三-丁酯於100毫升RBF中，裝填實例236B (0·62〇毫克，3·26毫莫耳）An example of 236C (lSH2- (5-bromo-s-pyridinylthioxantholin-3-ylmethyl V acetamidine) -aminomethylsulfonium tert-butyl ester was charged in 100 ml of RBF, and filled with Example 236B ( 0.62 mg, 3.26 millimoles)

、2-羥基-ΐ-(1Η_Ρ?丨哚各基甲基乙基]-胺甲基酸第三-丁酯（1.077 ，3.71 毫莫耳）、ph3p (ΐ·23 克，4·69 毫莫耳）及 DBAD (1.096 克，4.763 毫莫耳）。於0°C下添加THF (10毫升）。將反應混合物在〇°C下攪拌1小時，及於室溫下22小時。使反應混合物濃縮，並藉急驟式層析（於己烷中之30% EtOAc)分離殘留物，提供0.614 克產物，具有DBAD。, 2-hydroxy- 羟基-(1Η_Ρ? 丨 indolyl methylethyl] -aminomethyl acid third-butyl ester (1.077, 3.71 mmol), ph3p (ΐ · 23 g, 4.69 mmol) Ear) and DBAD (1.096 g, 4.763 mmol). THF (10 ml) was added at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 hour and at room temperature for 22 hours. The reaction mixture was concentrated And the residue was separated by flash chromatography (30% EtOAc in hexanes) to provide 0.614 g of product with DBAD.

實例236DExample 236D

(1SVU1H-啕嗓-3-基甲基）-2-(5-異邊淋-6-基-说啶-3-基硫基乙胺所要之化合物係經由以實例236C取代實例27中之實例2A 而製成。MS (ESI) m/e 411 (M+l)+ ; 1 H NMR (300 MHz，DMS0-D6) 6 ppm 3·13 (m，2H) 3·37 (m，2H) 3.57 (m，1H) 6·90 (t，J=8.14 Hz，1H) 7.02 (t，J=8.14 Hz， 1H) 7.25 (d，J=2.37 Hz，1H) 7.31 (d，J=8.14 Hz，1H) 7.47 (m，1H) 8.06 (寬廣 s，2H) 8.18 (m，2H) 8.28 (t，J=2.03 Hz，1H) 8.46 (m，1H) 8.52 (寬廣 s，1H) 8.67 (d，J=6.10 Hz，1H) 8.69 (d，J=2.03 Hz，1H) 8.97 (d，J=2.03 Hz，1H) 9·66 (寬廣 s，1H) 11.03 (寬廣 s, 1H)· 實例237 嗓-3-基甲基 V2-「5-(3-甲基丨咬-5-基）比咬-3-基硫基1-乙胺 -228- 200301122(1SVU1H-Homo-3-ylmethyl) -2- (5-Isoprine-6-yl-supridin-3-ylthioethylamine The desired compound was obtained by replacing the example in Example 27 with Example 236C 2A. MS (ESI) m / e 411 (M + l) +; 1 H NMR (300 MHz, DMS0-D6) 6 ppm 3 · 13 (m, 2H) 3.37 (m, 2H) 3.57 (m, 1H) 6.90 (t, J = 8.14 Hz, 1H) 7.02 (t, J = 8.14 Hz, 1H) 7.25 (d, J = 2.37 Hz, 1H) 7.31 (d, J = 8.14 Hz, 1H ) 7.47 (m, 1H) 8.06 (broad s, 2H) 8.18 (m, 2H) 8.28 (t, J = 2.03 Hz, 1H) 8.46 (m, 1H) 8.52 (broad s, 1H) 8.67 (d, J = 6.10 Hz, 1H) 8.69 (d, J = 2.03 Hz, 1H) 8.97 (d, J = 2.03 Hz, 1H) 9.66 (broad s, 1H) 11.03 (broad s, 1H) · Example 237 voice-3- Methyl V2- "5- (3-methyl 丨 Bent-5-yl) than Bent-3-ylthio 1-ethylamine-228- 200301122

(221) 標題化合物係經由以實例102C取代實例236中之6-溴基異喹啉而製成。MS (ESI) m/e 414 (M+l)+; 1 H NMR (300 MHz，MeOH) 5 ppm 3·20 (d，J=6.78 Hz，2H) 3.25 (m，1H) 3·50 (m，1H) 3·69 (m，1H) 6·91 (td，J=8.14， 6.10, 1.02 Hz，lH) 7.02 (td，J=8.14, 6.10, 1.02 Hz，lH) 7.15(寬廣 s，lH) 7.26 (d, JN8.14 Hz, 1H) 7·40 (d，J=8.14 Hz，1H) 7.53 (t，J=8.82 Hz，1H) 7.60 (d，J=8.82 Hz， 1H) 7.93 (m，1H) 8.12 (t，J=2.03 Hz，1H) 8.51 (寬廣 s，1H) 8.74 (寬廣 s，1H)· 實例238 (1SVH4-溴-芊基甲基-1H-吲唑-5-基）-吡啶-3-基氧基1-乙胺(221) The title compound was prepared by replacing Example 6C with 6-bromoisoquinoline in Example 236. MS (ESI) m / e 414 (M + l) +; 1 H NMR (300 MHz, MeOH) 5 ppm 3.20 (d, J = 6.78 Hz, 2H) 3.25 (m, 1H) 3.50 (m , 1H) 3.69 (m, 1H) 6.91 (td, J = 8.14, 6.10, 1.02 Hz, lH) 7.02 (td, J = 8.14, 6.10, 1.02 Hz, lH) 7.15 (broad s, lH) 7.26 (d, JN8.14 Hz, 1H) 7.40 (d, J = 8.14 Hz, 1H) 7.53 (t, J = 8.82 Hz, 1H) 7.60 (d, J = 8.82 Hz, 1H) 7.93 (m, 1H) 8.12 (t, J = 2.03 Hz, 1H) 8.51 (broad s, 1H) 8.74 (broad s, 1H) · Example 238 (1SVH4-bromo-fluorenylmethyl-1H-indazol-5-yl)- Pyridin-3-yloxy 1-ethylamine

實例238A 5-(5-羥基-吡啶各基）-3-甲基-吲唑-1-羧酸第三-丁酯所要之產物係經由以3-溴基-5-羥基吡啶取代實例203C中之實例203B而製成。Example 238A 5- (5-Hydroxy-pyridinyl) -3-methyl-indazole-1-carboxylic acid tert-butyl ester The desired product was obtained by substituting 3-bromo-5-hydroxypyridine in Example 203C Example 203B.

實例238B (lS)-{ -卞基贿甲基弓| ^ -5-基)-口比 -3-基 % 基 1-乙基丨-胺甲基酸第三-丁酯所要之產物係根據實例2Α所述之程序，以實例238Α取代實例2Α中之3-溴基-5-羥基吡啶，且以3’-溴-Boc-苯基丙胺醇取代實例2A中之Boc-色胺酸而製成。Example 238B (lS)-{-Methenylmethylmethyl bow | ^ -5-yl) -Methyl-3-yl% 1-ethyl 丨 -aminomethyl acid tertiary-butyl ester The desired product is based on The procedure described in Example 2A was prepared by replacing the 3-bromo-5-hydroxypyridine in Example 2A with Example 238A and replacing the Boc-tryptophan acid in Example 2A with 3'-bromo-Boc-phenylpropylamine. to make.

實例238C (1SVM4-溴-芊基V2-f5-(3-甲基-1H-钊唑-5-基吡啶-3-基氧基1-乙胺所要之產物係經由以實例238B取代實例27中之實例27B，以三氟醋酸鹽製成。MS(ESI)m/e437 (M+l)+ ; iHNMRpOOMHz，三氟醋酸-D) 5 ppm3.16(s，3H)3.46(m，2H)4.48(m，lH)4.86(m，2H)7.34 (m，2H) 7·70 (m，2H) 8·24 (m，2H) 8·57 (m，2H) 8·86 (m，1H) 9·07 (m，1H)· -229- 200301122 (222) 實例239 弓卜朵-3-基甲基-2-「5-(2-甲基奎峻淋-7-基）-i?比淀-3-基氧基1-乙胺實例239Α 7-溴基-2-甲基-口奎峻贫林Example 238C (1SVM4-Bromo-fluorenyl V2-f5- (3-methyl-1H-zazol-5-ylpyridin-3-yloxy 1-ethylamine) The desired product was obtained by substituting Example 238B for Example 27 Example 27B, made of trifluoroacetate. MS (ESI) m / e437 (M + 1) +; iHNMRpOOMHz, trifluoroacetate-D) 5 ppm3.16 (s, 3H) 3.46 (m, 2H) 4.48 (m, lH) 4.86 (m, 2H) 7.34 (m, 2H) 7.70 (m, 2H) 8.24 (m, 2H) 8.57 (m, 2H) 8.86 (m, 1H) 9 · 07 (m, 1H) · -229- 200301122 (222) Example 239 Tobido-3-ylmethyl-2- "5- (2-methylquinone-7-yl) -i-pyridine -3-Alkyloxy 1-ethylamine Example 239A 7-Bromo-2-methyl-quinone

使4-溴基-2-氟-苯甲醛（1克，4.9毫莫耳）、乙脒及DMA混合，並加熱至140°C，歷經5小時。使混合物冷卻至室溫，及在真空下乾燥。使混合物藉急騾式管柱純化，獲得47毫克產物，4% 產率。MS (ESI) m/e 223 (M+l)+ ·4-Bromo-2-fluoro-benzaldehyde (1 g, 4.9 mmol), acetamidine and DMA were mixed and heated to 140 ° C for 5 hours. The mixture was allowed to cool to room temperature and dried under vacuum. The mixture was purified by a flash column to obtain 47 mg of product in 4% yield. MS (ESI) m / e 223 (M + l) +

實例239B (1SV1-QH-W嗓-3-基甲基V2-「5-(2-甲基奎峻琳-7-基）-p比症-3-基氧基1-乙胺Example 239B (1SV1-QH-WV-3-ylmethyl V2- "5- (2-methylquinaline-7-yl) -p ratio syndrome-3-yloxy 1-ethylamine

所要之產物係經由以實例239Α取代實例32中之6-溴基鄰苯二甲醯亞胺而製成。MS(ESI)m/e410(M+l)+ ; iHNMRpOOMHz， DMSO-D6) 5 ppm 2.57 (s, 3H) 3.10 (m, 2H) 3.85 (m5 1H) 4.29 (m, 1H) 4.46 (m, 1H) 739 (m, 5H) 7.62 (dd, J=8.81, 0.68 Hz, 1H) 7.80 (dd5 J=8.81, 1.70 Hz5 1H) 8.28 (d5 J=0.68 Hz, 2H) 8.56 (m, 5H) 8.89 (d, J=1.70 Hz, 1H). 實例240 所要之產物係經由以5-溴基啕哚取代實例32中之6-溴基鄰苯二甲醯亞胺而製成。MS (ESI) m/e 383 (M+l)+; 1H NMR (3〇0 MHz， DMSO-D6) 6 ppm 3·58 (m，1H) 4.09 (m，3H) 4.18 (m，1H) 6.67 (寬廣 s，2H) 6·98 (m，1H) 7_08 (m，1H) 7·27 (m，3H) 7·38 (m, 4H) 7·50 (m，1H) 7·60 (m，2H) 7·88 (寬廣 s，1H) 8·23 (寬廣 s，1H) 8·51 (寬廣 s，1H)· -230- 200301122 (223) 實例241 (1S)-1:QH-吸^^碁甲基）_2」^木(111_四唑_5—基茉某—比啶各基氫基丨-乙胺所要之產物係經由以5-(4-溴苯基）-1Η-四唑取代實例32中之 6-溪基鄰苯二甲醯亞胺而製成。泌（ESI) m/e 412 (M+l)+ ; 1 H NMR (300 MHz，落劑）6 ppm 3 24 (m，2H) 3 99 (m，m) 4 29 ㈣ m) 4 44 ㈣ 1H) 7.04 (m，1H) 7.14 (m，1H) 7.24 (m，1H) 7.39 (m，1H) 7·61 (m，1H) 7.79 (m，1H) 7·86 (m，2H) 8·17 (寬廣 s，ih) 8.20 (寬廣 s，ih) 8.39 (寬廣 s，1H) 8·61 (寬廣 s，義 1H). 實例242 嗓-3-某甲基）-2谷異喹啉·6-基…密啶-4·某氧基V乙胺實例242Α 5-溴-嘧啶-4-酶使嘧哫-4-醇（366毫克，3.8毫莫耳）與AcOH冷卻至〇°C。經由注射器慢添加Βι*2 (0.27毫升）。將混合物於室溫下攪拌3小時。於壓力下移除AcOH。使殘留物溶於ch2 Cl2中，以飽和 NaHC〇3、鹽水洗滌，並以MgS〇4脫水乾燥。移除溶劑，並使鲁產物藉急驟式管柱層析純化，獲得所要之產物毫克，91 % ) 〇 MS (ESI) m/e 175 (M+l)+ ； 1 H NMR (300 MHz, DMSO-D6) 5 ppm 8.23 ( 見廣 s，1H) 8.33 (寬廣 s，1H) 13.08 (寬廣 s，1H)·The desired product was prepared by substituting Example 239A for 6-bromophthalimide in Example 32. MS (ESI) m / e410 (M + l) +; iHNMRpOOMHz, DMSO-D6) 5 ppm 2.57 (s, 3H) 3.10 (m, 2H) 3.85 (m5 1H) 4.29 (m, 1H) 4.46 (m, 1H ) 739 (m, 5H) 7.62 (dd, J = 8.81, 0.68 Hz, 1H) 7.80 (dd5 J = 8.81, 1.70 Hz5 1H) 8.28 (d5 J = 0.68 Hz, 2H) 8.56 (m, 5H) 8.89 (d , J = 1.70 Hz, 1H). Example 240 The desired product was prepared by replacing the 6-bromophthalimide in Example 32 with 5-bromopyridine. MS (ESI) m / e 383 (M + l) +; 1H NMR (300 MHz, DMSO-D6) 6 ppm 3.58 (m, 1H) 4.09 (m, 3H) 4.18 (m, 1H) 6.67 (Broad s, 2H) 6.98 (m, 1H) 7_08 (m, 1H) 7.27 (m, 3H) 7.38 (m, 4H) 7.50 (m, 1H) 7.60 (m, 2H) 7.88 (broad s, 1H) 8.23 (broad s, 1H) 8.51 (broad s, 1H)--230- 200301122 (223) Example 241 (1S) -1: QH-absorbing ^^碁 methyl) _2 ″ ^ wood (111_tetrazol_5—ylmozine—pyridine hydrogen radicals 丨 -ethylamine The desired product is via 5- (4-bromophenyl) -1Η-tetrazole It was prepared by substituting 6-brookylphthalimide in Example 32. (ESI) m / e 412 (M + l) +; 1 H NMR (300 MHz, dropping agent) 6 ppm 3 24 ( m, 2H) 3 99 (m, m) 4 29 ㈣ m) 4 44 ㈣ 1H) 7.04 (m, 1H) 7.14 (m, 1H) 7.24 (m, 1H) 7.39 (m, 1H) 7.61 (m , 1H) 7.79 (m, 1H) 7.86 (m, 2H) 8.17 (broad s, ih) 8.20 (broad s, ih) 8.39 (broad s, 1H) 8.61 (broad s, meaning 1H) Example 242 Gluta-3-methyl) -2 glutisoquinoline · 6-yl ... pyrimidine-4 · Certain oxy V ethylamine Example 242A 5-bromo-pyrimidine-4-enzyme makes pyrimidine-4- Alcohol (366 mg, 3.8 mmol) cooled with AcOH Square ° C. Bil * 2 (0.27 ml) was slowly added via a syringe. The mixture was stirred at room temperature for 3 hours. The AcOH was removed under pressure. The residue was dissolved in ch2Cl2, washed with saturated NaHC03, brine, and dried over MgS04. The solvent was removed and the Lu product was purified by flash column chromatography to obtain the desired product mg, 91%). MS (ESI) m / e 175 (M + 1) +; 1 H NMR (300 MHz, DMSO -D6) 5 ppm 8.23 (see broad s, 1H) 8.33 (wide s, 1H) 13.08 (wide s, 1H) ·

實例242B (Lsl·卜(m-Kj·兔-3-基甲基）-2-(5-異口奎淋-6-某-嘧咬-4·某氧基乙胺標題化合物係經由以實例242A取代實例27中之3-漠基-5_#呈基口比淀而製成。MS (ESI) m/e 396 (M+l)+ ; 1 H NMR (300 MHz，DMSO-D6) -231 - 200301122Example 242B (Lsl · Bu (m-Kj · Rabbit-3-ylmethyl) -2- (5-Isoquinone-6-a-pyrimidine-4 · a certain ethoxyethylamine) The title compound is given by way of example 242A was prepared by substituting 3-molyl-5_ # in Example 27 with a base ratio. MS (ESI) m / e 396 (M + 1) +; 1 H NMR (300 MHz, DMSO-D6) -231 -200301122

(224) 5 ppm 3.10 (m，2H) 4·35 (m，1H) 4.48 (m，1H) 4.72 (m，1H) 6.96 (m，2H) 7.31 (m， 3H) 8.26 (m，3H) 8·50 (m，3H) 8.68 (m5 1H) 8.88 (s，2H) 9.74 (寬廣 s，1H) 10.99 (寬廣s，1H) 實例243 (1SV1-+基-2-『3-(3-甲基-lH-p引也-5-基）-笨氧基1-乙胺(224) 5 ppm 3.10 (m, 2H) 4.35 (m, 1H) 4.48 (m, 1H) 4.72 (m, 1H) 6.96 (m, 2H) 7.31 (m, 3H) 8.26 (m, 3H) 8 50 (m, 3H) 8.68 (m5 1H) 8.88 (s, 2H) 9.74 (broad s, 1H) 10.99 (broad s, 1H) Example 243 (1SV1- + yl-2- "3- (3-methyl -lH-pin-5-yl) -benzyloxy 1-ethylamine

實例243AExample 243A

[1-爷基-2-(3-溴-苯氧基）-乙基1-胺甲基酸第三-丁酉旨所要之產物係經由以3-溴酚取代實例2A中之3-溴基-5-羥基口比淀’且以L-Boc-苯基丙胺醇取代實例2A中之L-Boc-色胺酸而製成。[1-Cryl-2- (3-bromo-phenoxy) -ethyl 1-aminomethyl acid tertiary-butyridine The desired product was obtained by replacing the 3-bromo group in Example 2A with 3-bromophenol -5-Hydroxylipidol 'was prepared by replacing L-Boc-tryptophan acid in Example 2A with L-Boc-phenylpropanolamine.

實例243B 5-『3-((2S)-2-第三-丁氧羰基胺基-3-茉基-丙氧基）-笨基1-3-甲某-㈣唑-1-羧酸第三-丁酯所要之產物係經由以實例243A取代實例102E中之實例2A 而製成。Example 243B 5- [3-((2S) -2-Third-butoxycarbonylamino-3-mosyl-propoxy) -benzyl1-3-methyl-oxazole-1-carboxylic acid The desired product of tri-butyl ester was prepared by replacing Example 2A in Example 102E with Example 243A.

實例243CExample 243C

(1SV1-卞基-2_「3_(3-甲基-1H-口弓j吐-5-基）_苯氧基1-乙胺所要之產物係經由以實例243B取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (ESI) m/e 358 (M+H)+ ; iHNMR (500 MHz， DMSO-D6) δ ppm 2.54 (s, 3H) 3.06 (m, 2H) 3.82 (m, 1H) 4.02 (dd, J=10.61, 5.62 Hz，1H) 4·18 (dd，J=10.61，3.12 Hz，1H) 6.93 (dd，J=7.80, 1.56 Hz, 1H) 7.28 (d，J= 2.18 Hz，1H) 7·36 (m，7H) 7.53 (d，J=8.42 Hz，1H) 7.62 (m，1H) 7.94 (s，1H) 8·27 (s， 2H) 12.68(bs，1H);對 C23H23N30· 1.45TFA 之分析計算值·· C，59.50 ; Η，4·71; Ν，8·04;實測值·· C，59·46; Η，4·69，Ν，8·25· -232- 0301122 (225) 實例244 qSM-芊基-246-(3-甲基-1H-吲唑-5-基）-吡啶-2-基氣基1-乙胺所要之產物係經由以實例3-溴基-6-羥基吡啶取代實例243 中之3-溴酚，以三氟醋酸鹽製成。MS (ESI) m/e 359 (M+H)+ ; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.54 (s, 3H) 3.05 (m, 2H) 3.90 (m, 1H) 4.33 (dd，>11·70, 6·27 Hz，1H) 4.60 (dd，J=11.87, 3.39 Hz，1H) 6.80 (d，J=8.14 Hz， 1H) 7.33 (m，5H) 7.49 (d，J=7.80 Hz，1H) 7.68 (d，J=7.12 Hz，1H) 7.83 (m5 1H) 7.96 (dd，J=8.81，1.70 Hz，1H) 8·20 (s，2H) 8·35 (s, 1H) 12.69 (bs5 1H);對 C22H22N40 • 1.4 TFA · 1 H2 O 之分析計算值：C，55.56 ; H，4·78 ; N，10.45 ;實測值：C，55.45 ; Η，4·51，Ν，10·50· 實例245 (lSV2-『5-(3-甲基-1H-钊唑-5-基）-吡啶-3-基氣基1-H4-噻吩-3-基-芊(1SV1-fluorenyl-2_ "3_ (3-methyl-1H-methylpyridin-5-yl) _phenoxy1-ethylamine The desired product is obtained by replacing Example 27B in Example 27C with Example 243B, Made of trifluoroacetate. MS (ESI) m / e 358 (M + H) +; iHNMR (500 MHz, DMSO-D6) δ ppm 2.54 (s, 3H) 3.06 (m, 2H) 3.82 (m, 1H) 4.02 (dd, J = 10.61, 5.62 Hz, 1H) 4.18 (dd, J = 10.61, 3.12 Hz, 1H) 6.93 (dd, J = 7.80, 1.56 Hz, 1H) 7.28 (d, J = 2.18 Hz, 1H) 7.36 (m, 7H) 7.53 (d, J = 8.42 Hz, 1H) 7.62 (m, 1H) 7.94 (s, 1H) 8.27 (s, 2H) 12.68 (bs, 1H); C23H23N30 · 1.45TFA Analytical calculation value · C, 59.50; Η, 4.71; Ν, 8.04; Measured value · C, 59 · 46; Η, 4.69, Ν, 8.25 ·- 232-0301122 (225) Example 244 qSM-fluorenyl-246- (3-methyl-1H-indazol-5-yl) -pyridin-2-ylamino1-ethylamine The desired product was obtained by using Example 3 -Bromo-6-hydroxypyridine was substituted for the 3-bromophenol in Example 243 and was made from trifluoroacetate. MS (ESI) m / e 359 (M + H) +; 1 H NMR (300 MHz, DMSO- D6) δ ppm 2.54 (s, 3H) 3.05 (m, 2H) 3.90 (m, 1H) 4.33 (dd, > 11.70, 6.27 Hz, 1H) 4.60 (dd, J = 11. 87, 3.39 Hz, 1H) 6.80 (d, J = 8.14 Hz, 1H) 7.33 (m, 5H) 7.49 (d, J = 7.80 Hz, 1H) 7.68 (d, J = 7.12 Hz, 1H) 7.83 (m5 1H ) 7.96 (dd, J = 8.81, 1.70 Hz, 1H) 8.20 (s, 2H) 8.35 (s, 1H) 12.69 (bs5 1H); Analytical calculations for C22H22N40 • 1.4 TFA · 1 H2 O: C, 55.56; H, 4.78; N, 10.45; Found: C, 55.45; H, 4.51, N, 10.50. Example 245 (lSV2- "5- (3-methyl-1H-zhao Azol-5-yl) -pyridin-3-ylamino 1-H4-thien-3-yl-fluorene

基）-乙胺實例245A (1SVC2-羥基-1-(4-碘-芊基）-乙某-胺甲基酸第三-丁酯此物質係根據 M. Rodriguez，M.LHnares，S.Doulut，A.Heitz，J· Martinez) -Ethylamine Example 245A (1SVC2-Hydroxy-1- (4-iodo-fluorenyl) -Ethyl-aminomethyl acid tertiary-butyl ester. This substance is based on , A. Heitz, J. Martinez

Tetrahedron Letters 1991，32 (7)，923-926 所述之程序，製自 L-B〇〇(4-碘苯基）丙胺酸。Tetrahedron Letters 1991, 32 (7), 923-926, from L-B00 (4-iodophenyl) alanine.

實例245B (lSH2-(5-溴-吡啶-3-基氧基）小(4-破-芊基乙基1-胺甲基酸第三，丁酯所要之產物係經由以實例245A取代實例2A中之L-Boc-色胺酸而製成。Example 245B (lSH2- (5-bromo-pyridin-3-yloxy) small (4-oxo-fluorenylethyl 1-aminomethyl acid) Third, butyl ester The desired product was obtained by replacing Example 2A with Example 245A Made of L-Boc-tryptophan.

實例245C (226) (lSH2-(5-溴-吡生全羞.吩-3_基-芊某）乙墓胺甲某 1 丁酯將實例245B (200亳克；〇·37亳莫耳）、3_噻吩二羥基硼烷（5〇耄克，〇·39耄莫耳）、Pd(PPh3)4(25毫克；〇〇2毫莫耳）及CsF⑴5 耄克；0.76耄莫耳）於1 ·· 2 MeOH : DME (5毫升）中之溶液，加熱至回流，歷經4小時，冷卻，以水稀釋，並以Et〇Ac萃取。將萃液以鹽水沖洗，脫水乾燥（MgS04)，蒸發並藉急驟式層析（30% Eh〇/己烷）純化，提供所要之產物（145毫克，79% )。Example 245C (226) (lSH2- (5-bromo-pyranoxan. Phen-3_yl-methyl) ethoxymethyl 1-butyl ester Example 245B (200 g; 0.37 mole) , 3-thiophene dihydroxyborane (50 g, 0.39 mole), Pd (PPh3) 4 (25 mg; 0.02 mmol) and CsF (5 g; 0.76 mole) • A solution in 2 MeOH: DME (5 ml) was heated to reflux for 4 hours, cooled, diluted with water, and extracted with EtoAc. The extract was washed with brine, dried (MgSO4), evaporated, and purified by flash chromatography (30% EhO / hexane) to provide the desired product (145 mg, 79%).

±_iL245D (lS)-「2-[5-(_3-i基-111-吸_隹-5-基V吡啶-3-基氣基哈各基-字基）-乙基1-胺甲某醢第三-丁酯所要之產物係經由以實例245C取代實例102E中之實例2八而製成。± _iL245D (lS)-"2- [5-(_ 3-iyl-111-sucking 隹 -5-yl Vpyridin-3-ylcarbyl- each radical) -ethyl 1-carbamic acid醢 The desired product of the third-butyl ester was prepared by replacing Example 28 in Example 102E with Example 245C.

實例245E (lS)-2-[5-(3-甲基-1H-W嗤-5-基）-ρ比咬-3-基氧基VH4-違吩-3-基-爷基V乙胺所要之產物係經由以實例245D取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS(ESI)m/e441 (M+H)+ ; 1HNMR(300MHz， DMSO-D6) δ ppm 2.54 (s, 3H) 3.06 (d, J=7.12 Hz, 2H) 3.89 (m3 1H) 4.16 (dd5 J= 10.68, 5.59 Hz, 1H) 4.33 (dd, J=10.68, 2.88 Hz, 1H) 7.37 (d, J=8.48 Hz, 2H) 7.55 (m, 2H) 7.63 (m，1H) 7.70 (m，3H) 7.76 (m，1H) 7.85 (dd，J=3.05, 1.36 Hz，1H) 8·08 (s， 1H) 8.22 (m, 2H) 8.35 (d, J=2.71 Hz, 1H) 8.64 (d? J=1.70 Hz, 1H) 12.47 (bs, 1H). 實例246 (1SVH4-碘-芊基V245-(3-甲基-1H-W唑-5-基吡啶-3-基氧基1-乙胺 (227)Example 245E (1S) -2- [5- (3-Methyl-1H-W | -5-yl) -ρ ratio bite-3-yloxy VH4-phenphen-3-yl-methylylethylamine The desired product was prepared by replacing Example 27B in Example 27C with Example 245D and using trifluoroacetate. MS (ESI) m / e441 (M + H) +; 1HNMR (300MHz, DMSO-D6) δ ppm 2.54 (s, 3H) 3.06 (d, J = 7.12 Hz, 2H) 3.89 (m3 1H) 4.16 (dd5 J = 10.68, 5.59 Hz, 1H) 4.33 (dd, J = 10.68, 2.88 Hz, 1H) 7.37 (d, J = 8.48 Hz, 2H) 7.55 (m, 2H) 7.63 (m, 1H) 7.70 (m, 3H) 7.76 (m, 1H) 7.85 (dd, J = 3.05, 1.36 Hz, 1H) 8.08 (s, 1H) 8.22 (m, 2H) 8.35 (d, J = 2.71 Hz, 1H) 8.64 (d? J = 1.70 Hz, 1H) 12.47 (bs, 1H). Example 246 (1SVH4-iodo-fluorenyl V245- (3-methyl-1H-Wazole-5-ylpyridin-3-yloxy1-ethylamine (227 )

所要之產物係經由以Boc-3，-溴苯基丙胺醇取代實例238中之實例245A，以三氟醋酸鹽製成。MS(ESI)m/e485 (M+H)+ ; 1 H NMR (300 MHz, DMS0-D6) 5 ppm 2.55 (s, 3H) 3.00 (d, J=7.12 Hz, 2H) 3.85 (m，1H) 4.13 (m，1H) 4·30 (m，1H) 7.16 (d，J=8.14 Hz，2H) 7.58 (d，J=8.82 Hz，1H) 7.70 (m，3H) 8.08 (s，1H) 8.19 (d，>3·05 Hz，2H) 8.32 (d，J=2.71 Hz，1H) 8.63 (d，J= 1.70 Hz，1H) 8.97 (s，1H) 12.72 (bs，1H). 實例247 f4-((2S)-2-胺基-3-苯基-丙乳基）-2-(3-甲基-1Η-4丨峻-5-基）-苯基1-甲醇實例247Α (1SM1·芊基-2-(3-氯基-4-甲醯基苯氧基V乙某1-胺甲基酸第三-丁酯所要之產物係經由以2-氯基-4-羥基苯甲醛取代實例2Α中之3-溴基-5-羥基吡啶，且以L-Boc-苯基丙胺醇取代實例2Α中之L-Boc-色胺酸而製成。The desired product was prepared as trifluoroacetate by replacing Example 245A in Example 238 with Boc-3, -bromophenylpropylamine. MS (ESI) m / e485 (M + H) +; 1 H NMR (300 MHz, DMS0-D6) 5 ppm 2.55 (s, 3H) 3.00 (d, J = 7.12 Hz, 2H) 3.85 (m, 1H) 4.13 (m, 1H) 4.30 (m, 1H) 7.16 (d, J = 8.14 Hz, 2H) 7.58 (d, J = 8.82 Hz, 1H) 7.70 (m, 3H) 8.08 (s, 1H) 8.19 ( d, > 3.05 Hz, 2H) 8.32 (d, J = 2.71 Hz, 1H) 8.63 (d, J = 1.70 Hz, 1H) 8.97 (s, 1H) 12.72 (bs, 1H). Example 247 f4- ((2S) -2-Amino-3-phenyl-propanoyl) -2- (3-methyl-1Η-4Η-5-yl) -phenyl 1-methanol Example 247A (1SM1 · 芊2- (3-Chloro-4-methylphenoxyphenoxy V ethyl 1-aminomethyl acid tert-butyl ester The desired product is substituted by 2-chloro-4-hydroxybenzaldehyde 3-bromo-5-hydroxypyridine in 2A, and substituted with L-Boc-phenylalaninol in L-Boc-tryptophan acid in Example 2A.

實例247B (lS)-n-芊基-244-甲醯某-3-(3-甲基-1H-吲唑-5-基苯氣某1-乙基μ 胺甲基酸第三-丁酯將實例102D (230毫克；〇·78毫莫耳）與實例247A(300亳克；0.77 毫莫耳）於DMF (4毫升）中之溶液，以Pd2(dba)3(73毫克；0.0.08 爱莫耳）、2-二環己基鱗基-2-(Ν，Ν·一甲胺基）聯苯（61亳克；0.15 毫莫耳）及三乙胺（97毫克；0·96毫莫耳）處理，於ll〇°c下加熱4小時，於鹽水與EtOAc之間作分液處理，經過Celite®過遽，並以EtOAc萃取。將萃液以鹽水沖洗，脫水乾燥（MgS04) ，濃縮並藉急驟式層析（4〇% Et〇Ac /己烷）純化，提供所要之產物（235毫克；63% )。 200301122Example 247B (1S) -n-fluorenyl-244-formamidine-3- (3-methyl-1H-indazol-5-ylbenzene) certain 1-ethyl μ aminomethyl acid tert-butyl ester A solution of Example 102D (230 mg; 0.78 mmol) and Example 247A (300 μg; 0.77 mmol) in DMF (4 mL) was mixed with Pd2 (dba) 3 (73 mg; 0.0.08). Emole), 2-dicyclohexyl squamyl-2- (N, N · monomethylamino) biphenyl (61 μg; 0.15 mmol) and triethylamine (97 mg; 0.96 mmol) (Ear), heated at 110 ° C for 4 hours, separated between brine and EtOAc, passed through Celite®, and extracted with EtOAc. The extract was washed with brine, dried (MgS04), and concentrated Purification by flash chromatography (40% EtoAc / hexane) provided the desired product (235 mg; 63%). 200301122

(228) t ίΠ 247Γ (Iglil·芊基-2-[4-經甲基..-3:(3-甲^吲唑士基）_苯氣某其卜胺甲基酸第三-丁醋將實例247Β (225毫克；0.46毫莫耳）於Et0H (4毫升）中之溶液，以NaBH4(26毫克；0.70毫莫耳）分次處理，並攪拌3〇分鐘，以水稀釋，及萃取於EtOAc中。將萃液以鹽水沖洗，脫水乾燥（MgS〇4)，濃縮並藉急騾式層析（60% Et0Ac /己烷）純化，提供所要之產物（150亳克；66% )。(228) t 247Γ (Iglil · fluorenyl-2- [4- via methyl ..- 3: (3-methyl ^ indazolyl) -benzene A solution of Example 247B (225 mg; 0.46 mmol) in EtOH (4 ml) was treated with NaBH4 (26 mg; 0.70 mmol) in portions, stirred for 30 minutes, diluted with water, and extracted with The extract was washed with brine, dried (MgSO.sub.4), concentrated, and purified by flash chromatography (60% EtAc / hexane) to provide the desired product (150 g; 66%).

實例247DExample 247D

[4-((2_S)-2-胺基-3-笨基-丙氧基）-2-(3-甲某-1H-吲唑-5-基）-笨基1-甲醇將實例247C (115毫克；0.23毫莫耳）在不含溶劑下，於19〇。〇下加熱45分鐘，然後於矽膠上藉急驟式層析純化，以1〇% MeOH/C^Cl2溶離，提供所要之產物（π毫克；19% )。MS (ESI) m/e 388 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.50 (s5 3H) 2.60 (dd3 J=[4-((2_S) -2-amino-3-benzyl-propoxy) -2- (3-methyl-1H-indazol-5-yl) -benzyl 1-methanol Example 247C ( 115 mg; 0.23 mmol) at 190 without solvent. After heating for 45 minutes at 0 ° C, it was purified by flash chromatography on silica gel and dissolved in 10% MeOH / C ^ Cl2 to provide the desired product (π mg; 19%). MS (ESI) m / e 388 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.50 (s5 3H) 2.60 (dd3 J =

13.22,7.80 Hz, 1H) 2.83 (dd, J=13.22, 5.76 Hz, 1H) 3.25 (m5 1H) 3.82 (t5 J=5.59 Hz, 2H) 4·33 (d，J=5.09 Hz，2H) 4·99 (t，J=5.26 Hz，1H) 6.81 (d，J=2.37 Hz，1H) 6.93 (dd， J=8.48, 2.37 Hz，1H) 7.23 (m，5H) 7.36 (d，J=8.48 Hz, 1H) 7.46 (m，3H) 7.69 (s，2H) 12.66 (s，1H)· 實例248 丨5-(lH-苯i三唑-5_基）·吡啶各基氧基i小哚各基甲基 V乙胺實例248A 4->臭-苯-1,2-胺將4-溴基-2-硝基苯胺（1克；4 6毫莫耳）與SnCi2 · 2 H20 (6.2克 -236- 20030112213.22, 7.80 Hz, 1H) 2.83 (dd, J = 13.22, 5.76 Hz, 1H) 3.25 (m5 1H) 3.82 (t5 J = 5.59 Hz, 2H) 4.33 (d, J = 5.09 Hz, 2H) 4 · 99 (t, J = 5.26 Hz, 1H) 6.81 (d, J = 2.37 Hz, 1H) 6.93 (dd, J = 8.48, 2.37 Hz, 1H) 7.23 (m, 5H) 7.36 (d, J = 8.48 Hz, 1H) 7.46 (m, 3H) 7.69 (s, 2H) 12.66 (s, 1H) · Example 248 5- (lH-Benzitriazol-5-yl) · Pyridyloxyl small idols Example of Ethyl V Ethylamine 248A 4- > O-Benzene-1,2-Amine 4-Bromo-2-nitroaniline (1 g; 4 6 mmol) with SnCi2 · 2 H20 (6.2 g -236 -200301122

(229) ;27·6毫莫耳）在MeOH (30毫升）與5-6滴濃HC1中之混合物，加熱至回流，歷經5小時，濃縮，懸浮於飽和NaHC03(水溶液）中’並以EtOAc萃取。將萃液以鹽水沖洗，脫水乾燥（MgS〇4) ，及濃縮，提供產物，具有足夠純度以繼續進行。(229); 27.6 mmol) in MeOH (30 mL) and 5-6 drops of concentrated HC1, heated to reflux for 5 hours, concentrated, suspended in saturated NaHC03 (aq.) 'And EtOAc extraction. The extract was washed with brine, dried (MgS04), and concentrated to provide the product with sufficient purity to proceed.

實例248B 5-溴基-1H-笨并三唑將實例248A (262毫克；1.4毫莫耳）於1〇% h2 S04(4毫升）中之混合物，以水（1毫升）中之NaN〇2(12〇亳克；L7毫莫耳）處理鲁，攪拌30分鐘，以水稀釋，並以Et〇Ac萃取。將萃液以鹽水沖洗’脫水乾燥（NadO4)，濃縮，並藉急驟式層析（5% MeOH/ CH2 CL)純化，提供所要之產物。Example 248B 5-bromo-1H-benzotriazoleA mixture of Example 248A (262 mg; 1.4 mmol) in 10% h 2 S04 (4 ml) was treated with NaNO 2 in water (1 ml). (12.0 g; L7 mmol) was treated, stirred for 30 minutes, diluted with water, and extracted with EtoAc. The extract was washed with brine 'and dried (NadO4), concentrated, and purified by flash chromatography (5% MeOH / CH2CL) to provide the desired product.

實例248C jr溴-苯并三嗅-1-数酸第三-丁嘴在-20 C下，將實例248B (770毫克；5毫莫耳）於丁册（5毫升）中之溶液添加至20%光氣在曱苯（10毫升）中之溶液内，於—％ °C下攪拌1小時，然後在室溫下2小時，蒸發，並溶於thf(4 毫升）中。於-2(TC下，將此溶液添加至t，Bu〇H(1毫升）與吡啶籲 (426毫克；5·4毫莫耳）在THF (3毫升）中之溶液内，然後於室溫下攪拌過夜。藉過濾移除固體，並以Et〇Ac沖洗。將濾液以水及鹽水沖洗，脫水乾燥（MgS〇4)，濃縮，並藉急驟式層析（1 ·· 1 Et2〇 :己燒）分離，提供所要之產物（97〇毫克；％ % ) 〇Example 248C A solution of Example 248B (770 mg; 5 mmol) in T-brochure (5 mL) was added to 20 at a temperature of -20 C. A solution of% phosgene in toluene (10 ml) was stirred at-% ° C for 1 hour, then at room temperature for 2 hours, evaporated, and dissolved in thf (4 ml). This solution was added to a solution of t, BuOH (1 ml) and pyridine (426 mg; 5.4 mmol) in THF (3 ml) at -2 ° C, then at room temperature It was stirred overnight under filtration. The solid was removed by filtration and rinsed with Et0Ac. The filtrate was rinsed with water and brine, dried (MgS04), concentrated, and subjected to flash chromatography (1 ·· 1 Et20: hexane). (Boiled) to provide the desired product (97 mg; %%).

實例248D 【~先二唑I基吡啶-3-基氧吲哚各某甲其 -237 - 200301122 (230) )-乙胺’ 所要之產物係經由以實例248C取代實例32中之6-溴基鄰苯二曱醯亞胺，以三氟醋酸鹽製成。MS (ESI) m/e 385 (M+H)+ ;Example 248D [~ xidadiazole I-pyridin-3-yloxindole each methyl-237-200301122 (230))-ethylamine 'The desired product was obtained by replacing the 6-bromo group in Example 32 with Example 248C. O-Phenylenediimide, made from trifluoroacetate. MS (ESI) m / e 385 (M + H) +;

1H NMR (300 MHz, DMSO-D6) δ ppm 3.17 (d5 J=7.12 Hz, 2H) 3.86 (m, 1H) 4.21 (dd，J=10.68, 6.27 Hz，1H) 4·38 (dd，J=10.68, 2.88 Hz，1H) 7.01 (t，J=6.95 Hz，1H) 7.10 (t，J=7.12 Hz，1H) 7.30 (d，J=2.37 Hz，1H) 7.38 (d，J=8.14 Hz，1H) 7.63 (d，J= 7.80 Hz，1H) 7.78 (m，1H) 8.01 (m，1H) 8.18 (m，3H) 8.27 (m，1H) 8.38 (d，J=2.71 Hz，1H) 8.66 (d，J=1 ·36 Hz，1H) 11.03 (s，1H). 實例249 (1SV245-(1H-笨并三唑-5-基V吡啶-3-基氧基1-1·芊某-乙胺1H NMR (300 MHz, DMSO-D6) δ ppm 3.17 (d5 J = 7.12 Hz, 2H) 3.86 (m, 1H) 4.21 (dd, J = 10.68, 6.27 Hz, 1H) 4.38 (dd, J = 10.68 , 2.88 Hz, 1H) 7.01 (t, J = 6.95 Hz, 1H) 7.10 (t, J = 7.12 Hz, 1H) 7.30 (d, J = 2.37 Hz, 1H) 7.38 (d, J = 8.14 Hz, 1H) 7.63 (d, J = 7.80 Hz, 1H) 7.78 (m, 1H) 8.01 (m, 1H) 8.18 (m, 3H) 8.27 (m, 1H) 8.38 (d, J = 2.71 Hz, 1H) 8.66 (d, J = 1 · 36 Hz, 1H) 11.03 (s, 1H). Example 249 (1SV245- (1H-benzyltriazol-5-ylVpyridin-3-yloxy1-1 · 芊 -ethylamine)

實例249A (lSHl-y基-2-(5-溴-p比啶-3-基氣某V乙基1-胺甲基酸第三-丁酉旨所要之產物係經由以L-Boc-苯基丙胺醇取代實例2A中之L-Boc-色胺酸而製成。Example 249A (lSHl-yyl-2- (5-bromo-p-pyridin-3-yl) V-ethyl 1-aminomethyl acid tertiary-butyrate The desired product is via L-Boc-phenyl Alanine was prepared in place of L-Boc-tryptophan acid in Example 2A.

實例249B (遇-〇-芊基-2-(5-三甲基錫燒基比咬_3_基氧基乙某-胺Jf基醆第三-丁酯所要之產物係經由以實例249A取代實例32A中之實例2A而製成。Example 249B (Medium-O-fluorenyl-2- (5-trimethyltinyl) is more than 3-methyloxyethyl-amine Jf-based tertiary-butyl ester. The desired product is substituted by Example 249A. It was prepared as Example 2A in Example 32A.

實例249C 弟二-丁氧幾基脖基各草基-丙氧基比淀基」-本并 lAddi-M第三-丁酯將實例249B (400毫克；〇·8ΐ毫莫耳）與實例73C (255毫克；0.85 毫莫耳）於DMF (6毫升）中之溶液，以叫⑽吨⑴丨毫克；o.u -238 - (231)Example 249C Di-dioxobutoxy, oxalyl-propoxypyridyl "-benzyl Addi-M tertiary-butyl ester Example 249B (400 mg; 0.8 micromolar) and Example 73C (255 mg; 0.85 mmol) in DMF (6 ml), called xanthene⑴mg; ou -238-(231)

毫莫耳）、三-鄰-甲苯基膦（74毫克.；0·24毫莫耳）及三乙胺（1〇2 毫克，1.0¾莫耳）處理，在ll〇°C下加熱4小時，於鹽水與段qac 之間作分液處理，經過Celite®過濾，並以EtOAc萃取。將萃液以鹽水沖洗，脫水乾燥（MgS〇4)，濃縮，並藉急驟式層析 (80% EtOAc/CH2Cl2)純化，提供所要之產物（11〇亳克；25% )。Millimoles), tri-o-tolylphosphine (74 mg .; 0.24 millimoles) and triethylamine (102 mg, 1.0¾ mole), heated at 110 ° C for 4 hours Separate the solution between brine and segment qac, filter through Celite®, and extract with EtOAc. The extract was washed with brine, dried (MgSO4), concentrated, and purified by flash chromatography (80% EtOAc / CH2Cl2) to provide the desired product (110 g; 25%).

實例249D (lS)-2-「5-(lH-苯并三嗤-5-基）-ρ比淀-3-基氧基1-1-字基-乙胺所要之產物係經由以實例249C取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS(ESI)m/e346 (M+H)+ ; iHNMRpOOMHz， DMSO-D6) 5 ppm 3.04 (m，2H) 3.86 (m，1H) 4.14 (m，1H) 4.30 (m，1H) 7.32 (m， 5H) 7.78 (m5 2H) 8.02 (m, 1H) 8.22 (m, 3H) 8.38 (d3 J=2.37 Hz, 1H) 8.66 (d, J=2.03 Hz，lH);對C20H19N5O.2.6TFA之分析計算值·· C，47.16; H，3.39; N，10.91;實測值：C，46.90 ; H，3·26; Ν，11·01· 實例250 OSM-芊基-245-(3-嗎福淋-4-基-1H-叫1唑-5-基吡啶-3-基氧基V乙胺所要之產物係經由以實例111A取代實例249中之實例249A ，以三氟醋酸鹽製成。MS (ESI) m/e 430 (M+H)+ ; 1 H NMR (400 MHz， DMSO-D6) δ ppm 3.04 (m3 2H) 3.36 (m, 4H) 3.81 (m3 4H) 3.87 (m? 1H) 4.13 (dd5 J=10.74, 5·83 Hz，1H) 4·29 (dd，J=10.74, 2.76 Hz，1H) 7.30 (m，5H) 7.49 (d，J=8.90 Hz，1H) 7.64 (d，J=8.59 Hz，1H) 7.71 (s，1H) 8.09 (s，1H) 8.26 (bs，2H) 8·32 (d，JN 2·15 Hz，1H) 8.64 (s，1H) 12.20 (bs，1H)· 實例251 (1S)-1-卞基-2-{5-「3-(4-甲基-六氮卩比口井-1-基峻-5-基l-p比咬-3-基乳基}_乙胺 200301122 (232) 所要之產物係經由以實例114A取代實例249中之實例249A ，以三氟醋酸鹽製成。MS (ESI) m/e 443 (M+H)+ ; 1 H NMR (300 MHz， DMSO-D6) 5 ppm 2.53 (s，3H) 2.90 (m，4H) 3.04 (m，2H) 3.17 (m，2H) 3·53 (m，2H) 3.84 (m, 1H) 4.10 (m5 1H) 4.27 (dd5 J=11.023 3.22 Hz, 1H) 7.32 (m, 5H) 7.52 (d5 J= 8.82 Hz，1H) 7.66 (m，2H) 8.15 (s，1H) 8.24 (m，2H) 8.32 (d，JN2.71 Hz，1H) 8.66 (d， J=1.70Hz，1H) 12.36 (s，1H);對 C26H3〇N60 · 3TFA 之分析計算值： C，48.98 ; Η，4·21 ; N，10.71 ;實測值：C，48.60 ; Η，4·39 ; N, 11.05.Example 249D (lS) -2- "5- (lH-benzotrifluoren-5-yl) -p-pyridine-3-yloxy1-1-yl-ethylamine The desired product was obtained by using Example 249C Replaced Example 27B in Example 27C with trifluoroacetate. MS (ESI) m / e346 (M + H) +; iHNMRpOOMHz, DMSO-D6) 5 ppm 3.04 (m, 2H) 3.86 (m, 1H) 4.14 (m, 1H) 4.30 (m, 1H) 7.32 (m, 5H) 7.78 (m5 2H) 8.02 (m, 1H) 8.22 (m, 3H) 8.38 (d3 J = 2.37 Hz, 1H) 8.66 (d, J = 2.03 Hz, lH); Analytical calculated values for C20H19N5O.2.6TFA ·· C, 47.16; H, 3.39; N, 10.91; Found: C, 46.90; H, 3.26; Ν, 11.01 · Example 250 OSM-fluorenyl-245- (3-morpholin-4-yl-1H-named 1azol-5-ylpyridin-3-yloxy V ethylamine The desired product was replaced by Example 111A in Example 249 Example 249A, made of trifluoroacetate. MS (ESI) m / e 430 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.04 (m3 2H) 3.36 (m, 4H ) 3.81 (m3 4H) 3.87 (m? 1H) 4.13 (dd5 J = 10.74, 5.83 Hz, 1H) 4.29 (dd, J = 10.74, 2.76 Hz, 1H) 7.30 (m, 5H) 7.49 (d , J = 8.90 Hz, 1H) 7.64 (d, J = 8.59 Hz, 1H) 7.71 (s, 1H) 8.09 (s, 1H) 8.26 (bs, 2H) 8 · 3 2 (d, JN 2.15 Hz, 1H) 8.64 (s, 1H) 12.20 (bs, 1H) · Example 251 (1S) -1-fluorenyl-2- {5- "3- (4-methyl- Hexaazepine is more than 1-yl-Jun-5-yllp ratio bite-3-yllactyl} _ethylamine 20031122 (232) The desired product is obtained by replacing Example 249A in Example 249 with Example 114A, Made from fluoroacetate. MS (ESI) m / e 443 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.53 (s, 3H) 2.90 (m, 4H) 3.04 (m, 2H) 3.17 (m, 2H) 3.53 (m, 2H) 3.84 (m, 1H) 4.10 (m5 1H) 4.27 (dd5 J = 11.023 3.22 Hz, 1H) 7.32 (m, 5H) 7.52 (d5 J = 8.82 Hz, 1H) 7.66 (m, 2H) 8.15 (s, 1H) 8.24 (m, 2H) 8.32 (d, JN2.71 Hz, 1H) 8.66 (d, J = 1.70Hz, 1H) 12.36 (s, 1H) ; Analytical calculated values for C26H30N60 · 3TFA: C, 48.98; Η, 4.21; N, 10.71; Found: C, 48.60; Η, 4.39; N, 11.05.

實例252 (1S)_{5_「5_(2-胺基-3-本基-丙乳基）-口比淀-3-基xsjL -3-基}-二甲基_胺Example 252 (1S) _ {5_ "5_ (2-Amino-3-benzyl-propionyl) -Hupido-3-yl xsjL-3-yl} -dimethyl_amine

所要之產物係經由以實例115A取代實例249中之實例249A ，以三氟醋酸鹽製成。MS(ESI)m/e 388 (M+H)+ ; iHNMRpOOMHz， DMSO-D6) δ ppm 3·03 (m，8Η) 3.83 (m，1Η) 4.13 (m，1Η) 4·29 (m，1Η) 7.34 (m， 5H) 7.46 (d，J=8.81 Hz，1H) 7.63 (dd，J=8.65, 1·53 Hz，1H) 7.75 (m，1H) 8.08 (s，1H) 8.21 (m，2H) 8.33 (d，J=2.71 Hz，1H) 8.64 (d，J=1.70 Hz，1H) 12·01 (bs，1H)；對 C23H25N50.3TFA之分析計算值：C，47.74; H,3.87; Ν，9·60;實測值：C，47.76 ; H，3.76; N，9.52. 實例253The desired product was made from trifluoroacetate by replacing Example 249A in Example 249 with Example 115A. MS (ESI) m / e 388 (M + H) +; iHNMRpOOMHz, DMSO-D6) δ ppm 3.03 (m, 8Η) 3.83 (m, 1Η) 4.13 (m, 1Η) 4 · 29 (m, 1Η ) 7.34 (m, 5H) 7.46 (d, J = 8.81 Hz, 1H) 7.63 (dd, J = 8.65, 1.53 Hz, 1H) 7.75 (m, 1H) 8.08 (s, 1H) 8.21 (m, 2H ) 8.33 (d, J = 2.71 Hz, 1H) 8.64 (d, J = 1.70 Hz, 1H) 12.01 (bs, 1H); Analytical calculated value for C23H25N50.3TFA: C, 47.74; H, 3.87; Ν , 9.60; Found: C, 47.76; H, 3.76; N, 9.52. Example 253

胺基-3-苯基-丙氧基）-口比症-3-基嗤-3-基}-(2-甲乳基-乙基）-胺實例253A (5-溴基-1H-W唑-3-基H2-甲氧基-乙基V胺於實例35A與鄰-曱基乙醇胺間之反應，係根據11.^\^^(^〇11〇，1^ Majewska，J. Dudzinska-Usarewicz，M. Bemas，Phurmzie，1986, 41，472-474 所述 -240- (233)Amino-3-phenyl-propoxy) -orobiosis-3-ylfluoren-3-yl}-(2-methyllactyl-ethyl) -amine Example 253A (5-Bromo-1H-W The reaction of azole-3-yl H2-methoxy-ethyl Vamine between Example 35A and o-fluorenylethanolamine was based on 11. ^ \ ^^ (^ 〇11〇, 1 ^ Majewska, J. Dudzinska- Usarewicz, M. Bemas, Phrmzie, 1986, 41, 472-474, -240- (233)

之程序進行。Procedure.

實例253A (lS)-{5-「5-(2-胺基一3-$ 基 _丙基)_外匕 < -3-基 I-IH-^?] ^ _3_基}-(2_ 甲乳基-乙基）-胺所要之產物係經由以實例253A取代實例249中之實例249A ，以三氟醋酸鹽製成。MS (ESI) m/e 418 (M+H)+ ; iHNMR (300 MHz， DMSO-D6) δ ppm 3.04 (m，2H) 3.30 (s，3H) 3.46 (m5 2H) 3·57 (m，2H) 3.83 (m， 1H) 4.11 (dd，J=10.68, 5.60 Hz，1H) 4.28 (m，1H) 7.34 (m，5H) 7.64 (dd，J=10.68， 1.87 Hz，3H) 8.21 (s，3H) 8.30 (d，J=2.37 Hz，1H) 8.58 (d，J=1.70 Hz，1H) 11.67 bs， 1H);對 C24H27N502 .3TFA之分析計算值：C，46.34; Η，4·15; N，9.01 ；實測值：C，46.54 ; H，4·34 ; N，8.79. 實例254 {545-((2S)-2-胺基-3-苯基-丙氧基V吡啶-3-基HH-钊唑-3-基丨-(2-嗎福口林-4-基-乙基）-胺Example 253A (1S)-{5- "5- (2-Amino-3- $ yl_propyl) _exo < -3-yl I-IH- ^?] ^ _3_yl}-(2_ The desired product of methyllactyl-ethyl) -amine was prepared from trifluoroacetate by replacing Example 249A in Example 249 with Example 253A. MS (ESI) m / e 418 (M + H) +; iHNMR ( 300 MHz, DMSO-D6) δ ppm 3.04 (m, 2H) 3.30 (s, 3H) 3.46 (m5 2H) 3.57 (m, 2H) 3.83 (m, 1H) 4.11 (dd, J = 10.68, 5.60 Hz , 1H) 4.28 (m, 1H) 7.34 (m, 5H) 7.64 (dd, J = 10.68, 1.87 Hz, 3H) 8.21 (s, 3H) 8.30 (d, J = 2.37 Hz, 1H) 8.58 (d, J = 1.70 Hz, 1H) 11.67 bs, 1H); Analytical calculated value for C24H27N502 .3TFA: C, 46.34; Η, 4.15; N, 9.01; Found: C, 46.54; H, 4.34; N, 8.79. Example 254 {545-((2S) -2-amino-3-phenyl-propoxy Vpyridin-3-yl HH-zazol-3-yl)-(2-morpholine-4 -Yl-ethyl) -amine

實例254A (5-溴基-lH-β丨唑-3-基M2-嗎福啉-4-基-乙基）-胺於實例35Α與4-(2-胺基乙基）嗎福啉間之反應，係根據 U. Wrzeciono, K. Majewska, J. Dudzinska-Usarewicz, M. Bemas, Pharmzie, 1986, 41, 472-474所述之程序進行。Example 254A (5-Bromo-lH-βazozol-3-yl M2-morpholin-4-yl-ethyl) -amine between Example 35A and 4- (2-aminoethyl) morpholin The reaction was performed according to the procedure described by U. Wrzeciono, K. Majewska, J. Dudzinska-Usarewicz, M. Bemas, Pharmzie, 1986, 41, 472-474.

實例254B {5-f5-((2S)-2-胺基-3-苯基-丙氧基吡啶-3-基1-1H-啕唑-3-基丨-(2-嗎福口林-4-基-乙基V胺所要之產物係經由以實例254A取代實例249中之實例249A ，以三氟醋酸鹽製成。MS (ESI) m/e 473 (M+H)+ ; 1 H NMR (300 ΜΗ 之， 200301122 (234) DMSO-D6) δ ppm 2.50 (m, 8H) 3.04 (m, 2H) 3.43 (m, 2H) 3.68 (m5 2H) 3.87 (m5 1H) 4.10 (m，1H) 4·28 (m，1H) 7·36 (m，7H) 7.65 (m，2H) 8.07 (s，1H) 8.21 (m，2H) 8.31 (d，J=2.71 Hz，1H) 8.55 (d，>1·70 Hz，1H) 11.83 (bs，1H) 實例255Example 254B (5-f5-((2S) -2-Amino-3-phenyl-propoxypyridin-3-yl 1-1H-oxazol-3-yl)-(2-morpholine- The desired product of 4-yl-ethyl Vamine was prepared from trifluoroacetate by replacing Example 249A in Example 249 with Example 254A. MS (ESI) m / e 473 (M + H) +; 1 H NMR (300 MW, 200301122 (234) DMSO-D6) δ ppm 2.50 (m, 8H) 3.04 (m, 2H) 3.43 (m, 2H) 3.68 (m5 2H) 3.87 (m5 1H) 4.10 (m, 1H) 4 · 28 (m, 1H) 7.36 (m, 7H) 7.65 (m, 2H) 8.07 (s, 1H) 8.21 (m, 2H) 8.31 (d, J = 2.71 Hz, 1H) 8.55 (d, > 1 · 70 Hz, 1H) 11.83 (bs, 1H) Example 255

5-『5-((2SV2-胺基-3-苯基-丙氣基）-吡啶-3-基1-1H-㈣唑-3-某胺所要之產物係經由以實例249A取代實例97中之實例2A，以三氟醋酸鹽製成。MS (ESI) m/e 360 (M+H)+ ; 1HNMR (300 MHz， DMSO-D6) δ ppm 3.04 (m, 2H) 3.85 (m5 1H) 4.11 (dd3 J=10.68? 5.59 Hz, 1H) 4.28 (dd5 J=10.68, 2.88 Hz, 1H) 7.35 (m, 6H) 7.65 (m, 2H) 8.14 (s, 1H) 8.21 (m, 4H) 831 (d，J=2.71 Hz，1H) 8.56 (d，J=2.03 Hz，1H) 11.87 (bs，1H);對 C2 ! H2 i N5 0 · 3.1 TFA之分析計算值：C，45.83 ; Η，3·41 ; Ν，9·82 ;實測值：C，45.58 ;H，3.34 ; N，9·57· 實例256 N-{5-[5-((2S)-2-胺.羞：3_-苯基-丙氧某）·吡啶各基i-1H-吲唑_3_基}·2,2,2· S氟乙赫脖實例256Α 基-1H-叫丨岫 '莘眩所要之產物係經由以5-溴基-2-氟苯甲腈取代實例35A中之 5->臭基-2-乱苯甲路：而製成。5- "5-((2SV2-Amino-3-phenyl-propanyl) -pyridin-3-yl1-1H-oxazole-3-Amine The desired product was obtained by replacing Example 97 with Example 249A Example 2A, made of trifluoroacetate. MS (ESI) m / e 360 (M + H) +; 1HNMR (300 MHz, DMSO-D6) δ ppm 3.04 (m, 2H) 3.85 (m5 1H) 4.11 (dd3 J = 10.68? 5.59 Hz, 1H) 4.28 (dd5 J = 10.68, 2.88 Hz, 1H) 7.35 (m, 6H) 7.65 (m, 2H) 8.14 (s, 1H) 8.21 (m, 4H) 831 (d , J = 2.71 Hz, 1H) 8.56 (d, J = 2.03 Hz, 1H) 11.87 (bs, 1H); Analytical calculation for C2! H2 i N5 0 · 3.1 TFA: C, 45.83; Η, 3.41 ; Ν, 9.82; found: C, 45.58; H, 3.34; N, 9.57. Example 256 N- {5- [5-((2S) -2-amine. ：: 3_-phenyl- Propoxy group) · Pyridyl groups i-1H-indazole_3_yl} · 2,2,2 · S fluoroethyl Neck Example 256A group-1H-called 丨岫 'dizziness The desired product is -Bromo-2-fluorobenzonitrile was substituted for 5- > Styrol-2-ranylbenzene in Example 35A: and prepared.

免例256B V2,2,2·三氟 _乙醯胺將256A (2.5克，12毫莫耳）與三氟醋酸酐（3·4毫升；24毫莫耳）於说咬（50愛升）中之溶液，在室溫下攪拌2天，以1〇% Ηα ( 水溶液）酸彳匕’並以EtOAc萃取。將萃液以水及鹽水沖洗， -242- (235) 脫水乾燥（MgS04)，濃縮並藉急驟式層析（1 : 1 EtOAc :己烷）純化，提供所要之產物（3.〇克；84% )。Example 256B V2,2,2 · trifluoroacetamide: 256A (2.5 g, 12 mmol) with trifluoroacetic anhydride (3.4 ml; 24 mmol) and say bite (50 liters) The solution was stirred at room temperature for 2 days, extracted with 10% Ηα (aqueous solution) acid and extracted with EtOAc. The extract was washed with water and brine, -242- (235) was dried (MgS04), concentrated and purified by flash chromatography (1: 1 EtOAc: hexane) to provide the desired product (3.0 g; 84 %).

實例256C 胺甚-3-1某-丙氫基V吡啶-3-基1-1H-吲唑各某卜212-三氟-乙醯胺所要之產物係經由以實例256B取代實例249中之實例249A ，以三氟醋酸鹽製成。MS (ESI) m/e 454 (M-H)+ ; 1 H NMR (300 MHz， DMS0-D6) (5 ppm 3.04 (m，2H) 3.84 (m，1H) 4·11 (dd，J=10.85, 5.76 Hz，1H) 4.28 (dd，J=l〇.68, 2·88 Hz，1H) 7.35 (m，6H) 7.68 (m，2H) 8.16 (s，1H) 8.22 (m，3H) 8.32 (d，J=2.71 Hz，1H) 8·57 (d，J=1.70 Hz，1H) 11.87 (bs，1H)· 實例257 (2S)-2-胺基-N-「5-(3-曱基-1H-吲唑-5-基吡啶-3-基1-3-苯基-丙醯胺Example 256C Amine-3-1-propanyl-V-pyridin-3-yl1-1H-indazol 212-trifluoro-acetamidamine The desired product was obtained by replacing Example 249 with Example 256B 249A, made of trifluoroacetate. MS (ESI) m / e 454 (MH) +; 1 H NMR (300 MHz, DMS0-D6) (5 ppm 3.04 (m, 2H) 3.84 (m, 1H) 4.11 (dd, J = 10.85, 5.76 Hz, 1H) 4.28 (dd, J = 10.68, 2.88 Hz, 1H) 7.35 (m, 6H) 7.68 (m, 2H) 8.16 (s, 1H) 8.22 (m, 3H) 8.32 (d, J = 2.71 Hz, 1H) 8.57 (d, J = 1.70 Hz, 1H) 11.87 (bs, 1H) · Example 257 (2S) -2-amino-N- "5- (3-fluorenyl-1H -Indazol-5-ylpyridin-3-yl1-3-phenyl-propanamide

實例257A 5-(5-胺基-吡啶-3-基V3-甲基-吲唑-1-羧酸第三-丁酯所要之產物係經由以實例203B取代實例27B中之實例27A ，且以實例23B取代實例27B中之實例2A而製成。Example 257A The desired product of 5- (5-amino-pyridin-3-yl V3-methyl-indazole-1-carboxylic acid tertiary-butyl ester is obtained by replacing Example 27A in Example 27B with Example 203B, and Example 23B was prepared in place of Example 2A in Example 27B.

實例257B l[5-((2S)-2-第三-丁氣羰基胺基各笨某-丙醯基胺基吡啶-3-基1- 3-甲基-4丨唑-1-幾酸第三-丁酯所要之產物係經由以實例257A取代實例25E，且以L-Boc-苯丙胺酸取代實例25G中之Boc-色胺酸而製成。Example 257B l [5-((2S) -2-Third-butanecarbonylamino group The desired product of the third-butyl ester was prepared by replacing Example 25E with Example 257A and substituting B-tryptophan in Example 25G with L-Boc-phenylalanine.

實例257C (2S)-2-胺基-N-〖5-(3-甲基-1H-H1吐-5-某W比咬-3-基1-3-苯基-丙酿胺Example 257C (2S) -2-Amino-N- [5- (3-methyl-1H-H1) -5-

所要之產物係經由以實例257B取代實例27C中之實例27B 200301122 (236) ，以三氟醋酸鹽製成。MS (ESI) m/e 372 (M+H)+ ; 1 H NMR (300 MHz， DMSO-D6) 5 ppm 2.55 (s，3H) 3.19 (m，2H) 4.23 (m，1H) 7·32 (m，6H) 7·62 (s，1H) 8.01 (s，1H) 8.19 m，1H) 8.36 (s，2H) 8.68 (d，J=2.03 Hz，1H) 8.74 (d，J=2.03 Hz，1H) 1〇.7〇0，111)12.85〇^，111);對<：221121]^5〇.2.6丁?人之分析計算值：（：， 48.91 ; H，3·56 ; N，10.49 ;實測值：C，48.96 ; Η，3·71 ; N，10.64. 實例258 (lSV2-『5-(3-芊基-1H-W唑-5-基）-吡啶-3-基氣基哚-3-基甲The desired product was made from trifluoroacetate by replacing Example 27B 200301122 (236) in Example 27C with Example 257B. MS (ESI) m / e 372 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) 5 ppm 2.55 (s, 3H) 3.19 (m, 2H) 4.23 (m, 1H) 7.32 ( m, 6H) 7.62 (s, 1H) 8.01 (s, 1H) 8.19 m, 1H) 8.36 (s, 2H) 8.68 (d, J = 2.03 Hz, 1H) 8.74 (d, J = 2.03 Hz, 1H ) 10.7.00, 111) 12.85 〇 ^, 111); Analysis of <: 221121] ^ 5〇.2.6 Ding Ren calculated value: (:, 48.91; H, 3.56; N, 10.49 ; Found: C, 48.96; Hf, 3.71; N, 10.64. Example 258 (lSV2- "5- (3-fluorenyl-1H-Wazol-5-yl) -pyridin-3-ylcarbamoyl -3-yl

基V乙胺所要之產物係經由以氯化芊基鎂取代實例102中之溴化曱基鎂，以三氟醋酸鹽製成。MS(ESI)m/e474(M+H)+ ; 1HNMR (300 MHz, DMSO-D6) δ ppm 3.17 (m, 2H) 3.86 (τη, 1H) 4.17 (dd, J=10.68, 5.93 Hz, 1H) 4.35 (s, 2H) 4.42 (dd, J=10.68, 5.93 Hz, 1H) 7.02 (t, J=7.12 Hz, 1H) 7.08 (m, 1H) 7.29 (m, 7H) 7.61 (m5 4H) 7.98 (s3 1H) 8.15 (m, 3H) 8.32 (d, J=2.71 Hz, 1H) 8.55 (d5 J=1.70Hz，1H) 11.03(s，1H);對 C30H27N5CN3.9TFA之分析計算值：C， 49.44 ; Η，3·39; N，7.63;實測值：C，49.07 ; H，3·75; N，7.42. 實例259The desired product was prepared by replacing the fluorenylmagnesium bromide in Example 102 with fluorenylmagnesium chloride in Example 102 and trifluoroacetate. MS (ESI) m / e474 (M + H) +; 1HNMR (300 MHz, DMSO-D6) δ ppm 3.17 (m, 2H) 3.86 (τη, 1H) 4.17 (dd, J = 10.68, 5.93 Hz, 1H) 4.35 (s, 2H) 4.42 (dd, J = 10.68, 5.93 Hz, 1H) 7.02 (t, J = 7.12 Hz, 1H) 7.08 (m, 1H) 7.29 (m, 7H) 7.61 (m5 4H) 7.98 (s3 1H) 8.15 (m, 3H) 8.32 (d, J = 2.71 Hz, 1H) 8.55 (d5 J = 1.70Hz, 1H) 11.03 (s, 1H); Analysis and calculation value for C30H27N5CN3.9TFA: C, 49.44; Η , 3.39; N, 7.63; Found: C, 49.07; H, 3.75; N, 7.42. Example 259

(1SV1-芊基-2-「5-(3-芊基-1HW丨唑-5-基V吡啶-3·基氧基1-乙胺所要之產物係經由以249B取代實例258中之實例2A，以三氟醋酸鹽製成。MS(ESI)m/e435 (M+H)+ ; iHNMRpOOMHADMSO-DS) δ ppm 3.03 (m, 2H) 3.86 (m3 1H) 4.11 (dd, J=10.85, 5.76 Hz, 1H) 4.28 (dd, J= 10.68, 2·88 Hz，1H) 5.72 (s，2H) 7.30 (m，8H) 7.72 (m，3H) 7.84 (m，1H) 8.13 (s，1H) 8.21 (m, 3H) 8.33 (d, J=2.71 Hz, 1H) 8.60 (d5 J=1.70 Hz, 1H) 實例260 (lS)-245-(3-芊基-1H-W唑-5-基）-吡啶-3-基氧基1-1-甲基-乙胺 -244- 200301122(1SV1-fluorenyl-2- "5- (3-fluorenyl-1HW) azole-5-yl Vpyridin-3.yloxy 1-ethylamine The desired product was obtained by replacing Example 2A in Example 258 with 249B , Made of trifluoroacetate. MS (ESI) m / e435 (M + H) +; iHNMRpOOMHADMSO-DS) δ ppm 3.03 (m, 2H) 3.86 (m3 1H) 4.11 (dd, J = 10.85, 5.76 Hz , 1H) 4.28 (dd, J = 10.68, 2.88 Hz, 1H) 5.72 (s, 2H) 7.30 (m, 8H) 7.72 (m, 3H) 7.84 (m, 1H) 8.13 (s, 1H) 8.21 ( m, 3H) 8.33 (d, J = 2.71 Hz, 1H) 8.60 (d5 J = 1.70 Hz, 1H) Example 260 (lS) -245- (3-fluorenyl-1H-Wazole-5-yl) -pyridine -3-yloxy 1-methyl-ethylamine-244- 200301122

(237)(237)

260A ilgH2-(5-溴-外1：啶-3-基氧基）士甲基嫌甲基酸第三U 所要之產物係經由以Boo丙胺醇取代實例2A中之Boc-色胺醇而製成。260A ilgH2- (5-bromo-exo 1: pyridin-3-yloxy) methyl methyl methanoate Third U The desired product is prepared by replacing Boc-tryptamine in Example 2A with Boo propylamine. to make.

t例 260B ilgHl-曱基-2-(5-三甲基錫烷募4比啶各基氧基）_乙基1-胺甲基酸 i三-丁酯Example t 260B ilgHl-fluorenyl-2- (5-trimethylstannyl 4 to pyridyloxy) _ethyl 1-aminomethyl acid i-tri-butyl ester

所要之產物係經由以實例260A取代實例249B中之實例249A 而製成。The desired product was prepared by replacing Example 249A in Example 249B with Example 260A.

實例260C (lS)-2-「5-(3-卞基-1H-口弓1咬-5-基）-口比咬-3-基乳基>1-甲基-乙胺所要之產物係經由以260B取代實例258中之實例32A，以三氟醋酸鹽製成。MS (ESI) m/e 359 (M+H)+ ; iHNMR(300 MHz， DMSO-D6) δ ppm 1.31 (m, 3H) 4.10 (m, 1H) 4.30 (m, 1H) 4.35 (s, 2H) 4.41 (m, 1H) 7.17 (m, 1H) 7.29 (m, 2H) 7.36 (m, 2H) 7.61 (s, 2H) 7.69 (s, 2H) 8.02 (bs, 2H) 8.33 (d，J=2.37 Hz，1H) 8.56 (s，1H) 12.71 (bs，1H);對 C22H22N40 · 3.2TFA 之分析計算值：C，47.16 ; Η，3·51 ; Ν，7·75 ;實測值：c，47.27 ; H，3.60 _ ;Ν，7,60· 實例261Example 260C (lS) -2- "5- (3-fluorenyl-1H-oral arch 1 bite-5-yl) -oral ratio bite-3-yl milk group > 1-methyl-ethylamine desired product Made by replacing 260B with Example 32A in Example 258 and using trifluoroacetate. MS (ESI) m / e 359 (M + H) +; iHNMR (300 MHz, DMSO-D6) δ ppm 1.31 (m, 3H) 4.10 (m, 1H) 4.30 (m, 1H) 4.35 (s, 2H) 4.41 (m, 1H) 7.17 (m, 1H) 7.29 (m, 2H) 7.36 (m, 2H) 7.61 (s, 2H) 7.69 (s, 2H) 8.02 (bs, 2H) 8.33 (d, J = 2.37 Hz, 1H) 8.56 (s, 1H) 12.71 (bs, 1H); Analytical calculated value for C22H22N40 · 3.2TFA: C, 47.16; Η, 3.51; Ν, 7.75; found: c, 47.27; H, 3.60 _; Ν, 7, 60 · Example 261

_基-3-(lH$U—-3-基上^氧基v毗咗·ν甚卜嗱嗾冰某、· 基基-胳_ t 26U (6-溴二4啉:基-胺將實例34D(500毫克；2.5毫莫耳）與苯胺（1·5毫升）於Me〇H⑴ -245-_Yl-3- (lH $ U--3-yl, ^ oxyv, ν, 甚, 嗱嗾, 甚, 嗱嗾, 基, 基, 基 -t_26U (6-bromodi-4line: yl-amine will Example 34D (500 mg; 2.5 mmol) with aniline (1.5 ml) in MeOH-245-

(238) 毫升）中之溶液，在室溫下攪拌·2·5小時，收集所形成之沉澱物’以水沖洗，及在真空下乾燥，提供所要之產物（4〇〇毫克；62% )。實例261Β (6-{5-「(2S)-2-胺基沔| 嗓-3-基丙氧基 1-?比淀 _3-基成-4-基本基-胺所要之產物係經由以實例261Α取代實例27中之實例27Α，以三氟醋酸鹽製成。MS (ESI) m/e 487 (Μ+Η)+ ; 1 H NMR (500 ΜΗζ， DMSO-D6) 5 ppm 3.18 (m, 2Η) 3.86 (m3 1Η) 4.25 (dd, J=10.61, 5.93 Hz, 1H) 4.39 (m5 1H) 6.99 (t, J=7.49 Hz, 1H) 7.09 (t, J=7.02 Hz, 1H) 7.31 (d5 J=2.50 Hz, 1H) 7.38 (d，J=8.11 Hz，1H) 7.45 (t，J=7.33 Hz，1H) 7.60 (m，6H) 7·90 (m，1H) 8.19 (d，J=9.05 Hz，1H) 8·35 (bs，2H) 8.44 (m，2H) 8·64 (s，1H) 8.81 (d，J=1.56 Hz，1H) 9.08 (s，1H) 11.04 (d, J=1.87 Hz, 1H). 實例262 (lSV2-『5-(lH-吲唑-6-基V吡啶-3-基氧基1-1-(1H-吲哚-3-基甲基）-乙胺所要之產物係經由以4-溴基-2-氟基苯甲醛取代實例35中之 5-溴基-2-氟基苯甲醛，以三氟醋酸鹽製成。MS(ESI)m/e384 (M+H)+ ； 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.97 (m, 2H) 3.60 (m, 1H) 4.13 (m，2H) 6.99 (m，2H) 7.24 (m，1H) 7.38 (m，2H) 7·61 (m，3H) 7.84 (m，3H) 8.11 (m， 1H) 8.31 (m，1H) 8.55 (m，1H) 11.03 (m，1H) 12.98 (m，1H) 實例263 5-{5-f(2SV2-胺基-3-ΠΗ-ΘΙ 哚-3-基 V丙氣基 1-吡啶-3-基}-2,3-二氫-異— 口弓1 口朵-1-酉同(238) ml) of the solution, stirred at room temperature for 2.5 hours, the formed precipitate was collected 'washed with water, and dried under vacuum to provide the desired product (400 mg; 62%) . Example 261B (6- {5-"(2S) -2-Aminopyrene | Hydroxy-3-ylpropoxy 1-? Pyridine_3-yl--4-basic-amine- 261A replaces Example 27A in Example 27 and is made of trifluoroacetate. MS (ESI) m / e 487 (Μ + Η) +; 1 H NMR (500 ΜΗζ, DMSO-D6) 5 ppm 3.18 (m, 2Η ) 3.86 (m3 1Η) 4.25 (dd, J = 10.61, 5.93 Hz, 1H) 4.39 (m5 1H) 6.99 (t, J = 7.49 Hz, 1H) 7.09 (t, J = 7.02 Hz, 1H) 7.31 (d5 J = 2.50 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.45 (t, J = 7.33 Hz, 1H) 7.60 (m, 6H) 7.90 (m, 1H) 8.19 (d, J = 9.05 Hz , 1H) 8.35 (bs, 2H) 8.44 (m, 2H) 8.64 (s, 1H) 8.81 (d, J = 1.56 Hz, 1H) 9.08 (s, 1H) 11.04 (d, J = 1.87 Hz , 1H). Example 262 (1SV2- "5- (lH-indazol-6-yl Vpyridin-3-yloxy 1- (1H-indole-3-ylmethyl) -ethylamine The product was prepared from tribromoacetate by replacing 4-bromo-2-fluorobenzaldehyde in Example 35 with 4-bromo-2-fluorobenzaldehyde. MS (ESI) m / e384 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.97 (m, 2H) 3.60 (m, 1H) 4.13 (m, 2H) 6.99 (m, 2H) 7.24 (m, 1H) 7.38 (m , 2H) 7.61 (m, 3H ) 7.84 (m, 3H) 8.11 (m, 1H) 8.31 (m, 1H) 8.55 (m, 1H) 11.03 (m, 1H) 12.98 (m, 1H) Example 263 5- {5-f (2SV2-amino -3-ΠΗ-ΘΙ indol-3-yl V-propanyl 1-pyridin-3-yl} -2,3-dihydro-iso-

實例263A -246- (239) (239)200301122 基-2-甲基-笨甲_甲酯將4-溴基-2-甲基苯甲酸（1·〇克；4·7毫莫耳）於·〇Η(24毫升）與20滴濃HC1中之溶液，在回流下加熱6小時，濃縮，提供所要之產物（1.1克；100% )。Example 263A -246- (239) (239) 200301122 4-Bromo-2-methylbenzoic acid (1.0 g; 4.7 mmol) 〇Η (24 ml) and 20 drops of concentrated HC1 solution, heated under reflux for 6 hours, and concentrated to provide the desired product (1.1 g; 100%).

實例263B 4"澳基-2-遙基曱某-笨曱酸甲酉旨將實例263Α(1·02克；4·5毫莫耳）於CC14(22毫升）中之溶液，以AIBN (65毫克；0.4毫莫耳）處理，在回流下加熱4小時，以水洗務，脫水乾燥（Na〗SO4)及濃縮，提供所要之產物（u 克；79% )。Example 263B 4 " Aoyl-2-tetramethyl-methane-benzylformate was prepared from a solution of Example 263A (1.02 g; 4.5 mmol) in CC14 (22 ml) with AIBN (65 (Mg; 0.4 mmol), heated under reflux for 4 hours, washed with water, dried (NaSO4) and concentrated to provide the desired product (u g; 79%).

實例263CExample 263C

_5-溴基-2,3-二氫-異㈣嘴-1-酮實例263D 5-{5-[(2S)-2-胺基卜朵-3-基）-丙氧基比咬各基}-2,3-二敷-異啕哚-1-酮所要之產物係經由以實例263C取代實例36中之5-溴基氧化吲哚，以三氟醋酸鹽製成。MS (ESI) m/e 399 (M+H)+ ; 1 H NMR (d6-DMSO, 300 MHz) (5 : 11.03 (bs，1H)，8·63 (s，1H)，8.57 (s，1H)，8.35 (bs，3H)， 7.90 (s，1H)，7.78 (s，2H)，7.67 (s，1H)，7.61 (d，J=8 Hz，1H)，7.37 (d，J=8 Hz，1H)， 7.79 (d, J=2 Hz, 1H), 7.03-7.10 (m, 1H), 6.96-7.01 (m, 1H), 4.32-4.36 (m5 1H), 4.17-4.22 (m，1H)，3.80-3.83 (m，1H)，3.18 (d，J=8 Hz，2H)，2.50 (s，2H). 實例264 6J5-f(2S)-2-胺基-3-ΠΗ-Θ1 哚-3-基 V丙氧基 1-吡啶-3-基啉-4-酮所要之產物係經由以實例34A取代實例32中之6-溴基鄰苯 -247- (240)_5-Bromo-2,3-dihydro-isoamyl-1-one Example 263D 5- {5-[(2S) -2-Aminobutor-3-yl) -propoxy specific groups } The desired product of -2,3-bis-isoisodol-1-one was prepared by replacing the 5-bromooxyindole in Example 36 with Example 263C and using trifluoroacetate. MS (ESI) m / e 399 (M + H) +; 1 H NMR (d6-DMSO, 300 MHz) (5: 11.03 (bs, 1H), 8.63 (s, 1H), 8.57 (s, 1H ), 8.35 (bs, 3H), 7.90 (s, 1H), 7.78 (s, 2H), 7.67 (s, 1H), 7.61 (d, J = 8 Hz, 1H), 7.37 (d, J = 8 Hz , 1H), 7.79 (d, J = 2 Hz, 1H), 7.03-7.10 (m, 1H), 6.96-7.01 (m, 1H), 4.32-4.36 (m5 1H), 4.17-4.22 (m, 1H) , 3.80-3.83 (m, 1H), 3.18 (d, J = 8 Hz, 2H), 2.50 (s, 2H). Example 264 6J5-f (2S) -2-amino-3-ΠΗ-Θ1 indole- The desired product of 3-yl Vpropoxy 1-pyridin-3-ylline-4-one was obtained by substituting 6-bromo-o-phenyl-247- in Example 32 with Example 34A (240)

二曱醯亞胺，以三氟醋酸鹽製成。MS(ESI)m/e412(M+H)+ ; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 3.19 (d, J-7.18 Hz, 2H) 3.84 (m3 1H) 4.24 (dd，J=10.61，5·93 Hz，1H) 4.39 (dd，J=10.61，3.12 Hz，1H) 7.01 (t，J=7.02 Hz，1H) 7.10 (t，J=7.18 Hz，1H) 7.31 (d，J=2.50 Hz，1H) 7·38 (d，J=8· 11 Hz，1H) 7.64 (d，J= 7.80 Hz，1H) 7.76 (d，J=8.73 Hz，1H) 7.80 (m，2H) 7.96 (s，1H) 8.17 (dd，J=8.73， 2·18 Hz，1H) 8.32 (d，J=2.18 Hz, 2H) 8.40 (d，JN2.81 Hz，1H) 8.65 (d，J=1.87 Hz，1H) 11.05 (d，J=1.56 Hz，1H) 13.72 (bs，1H);對 C24H2 丨 N5 02 · 3TFA 之分析計算值：C，47.82; H，3.21; Ν，9·29;實測值·· C，47.88 ; Η，3·41; N，9.35. 實例265 (lS)-l-(lH^l嗓-3-基甲基）-2-[~5-(4-苯基p林-6_基V比淀-3-基氧基1_ 乙胺Diamidine, made from trifluoroacetate. MS (ESI) m / e412 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) 5 ppm 3.19 (d, J-7.18 Hz, 2H) 3.84 (m3 1H) 4.24 (dd, J = 10.61 , 5.93 Hz, 1H) 4.39 (dd, J = 10.61, 3.12 Hz, 1H) 7.01 (t, J = 7.02 Hz, 1H) 7.10 (t, J = 7.18 Hz, 1H) 7.31 (d, J = 2.50 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.64 (d, J = 7.80 Hz, 1H) 7.76 (d, J = 8.73 Hz, 1H) 7.80 (m, 2H) 7.96 (s , 1H) 8.17 (dd, J = 8.73, 2.18 Hz, 1H) 8.32 (d, J = 2.18 Hz, 2H) 8.40 (d, JN2.81 Hz, 1H) 8.65 (d, J = 1.87 Hz, 1H ) 11.05 (d, J = 1.56 Hz, 1H) 13.72 (bs, 1H); Analytical calculated value for C24H2 丨 N5 02 · 3TFA: C, 47.82; H, 3.21; Ν, 9.29; measured value · C , 47.88; hydrazone, 3.41; N, 9.35. Example 265 (lS) -l- (lH ^ l-3-ylmethyl) -2- [~ 5- (4-phenylplin-6_ Phenyl V than lake-3-yloxy 1-ethylamine

實例265A 引—嗓-3-基甲基）-2-f5-(4-笨基-冷琳-6·基X淀-3-基氣基1-乙胺將實例34C (200毫克；0.8毫莫耳）於THF (10毫升）中之溶液，以Et2〇中之3.0M溴化苯基鎂（1·6毫升；4.8毫莫耳）處理，在室溫下攪拌4小時，添加飽和NH4 C1 (水溶液），並以EtOAc 萃取。將萃液以鹽水沖洗，脫水乾燥（MgS04)，濃縮，並藉急驟式層析（30% EtOAc /己烷）純化，提供所要之產物（67毫克；29% )。Example 265A Introducing 3-methyl-3-ylmethyl) -2-f5- (4-benzyl-Lenyl-6-ylxyl-3-ylamino1-ethylamine Example 34C (200 mg; 0.8 mmol) A solution of mol) in THF (10 ml), treated with 3.0 M phenyl magnesium bromide (1.6 ml; 4.8 mmol) in Et20, stirred at room temperature for 4 hours, and added saturated NH4 C1 (Aqueous) and extracted with EtOAc. The extract was washed with brine, dried (MgSO4), concentrated, and purified by flash chromatography (30% EtOAc / hexane) to provide the desired product (67 mg; 29% ).

實例265B 吲嗓-3-基甲基）-2-「5-(4-苯基-峰淋-6-基X咬·3-某氧某1- 乙胺所要之產物係經由以實例265Α取代實例32中之6-溴基鄰琴一甲醯亞胺，以三氟醋酸鹽製成。MS (ESI) m/e 472 (Μ+Η); 200301122Example 265B Indo-3-ylmethyl) -2- "5- (4-Phenyl-Phenyl-6-yl X bite 3-3-Oxygen 1-Ethylamine The desired product was substituted by Example 265A 6-bromo-ortho-methylformimine of Example 32, made from trifluoroacetate. MS (ESI) m / e 472 (Μ + Η); 200301122

(241) 1 H NMR (500 m/z5 DMSO-D6) δ ppm 3.15 (d5 J=7.18 Hz, 2H) 3.84 (m, 1H) 4.17 (dd，J=1(X61，5.93 Hz，1H) 4.33 (dd，J=10.61，3·12 Hz，1H) 6.98 (t，J=7.49 Hz，1H) 7.08 (t，J=7.49 Hz，1H) 7.28 (d，J=2.18 Hz，·1Η) 7.37 (d，J=8.11 Hz，1H) 7.64 (m，5H) 7.70 (d，J=1.87 Hz，1H) 7.78 (d，J=6.55 Hz, 2H) 8.16 (bs，2H) 8.30 (dd，J=8.89, 1.72 Hz, 1H) 8.42 (d5 J=2.50 Hz, 1H) 8.61 (d3 J=1.56 Hz, 1H) 8.69 (d5 J=9.05 Hz, 1H) 9·41 (s，1H) 1L01 (s，1H);對 C3〇H25N50.1.9TFA之分析計算值：C，58.99 ;H，3.94 ; N，10·18 ;實測值：C，58.87 ; H，3.85 ; N，10.08.(241) 1 H NMR (500 m / z5 DMSO-D6) δ ppm 3.15 (d5 J = 7.18 Hz, 2H) 3.84 (m, 1H) 4.17 (dd, J = 1 (X61, 5.93 Hz, 1H) 4.33 ( dd, J = 10.61, 3.12 Hz, 1H) 6.98 (t, J = 7.49 Hz, 1H) 7.08 (t, J = 7.49 Hz, 1H) 7.28 (d, J = 2.18 Hz, · 1Η) 7.37 (d , J = 8.11 Hz, 1H) 7.64 (m, 5H) 7.70 (d, J = 1.87 Hz, 1H) 7.78 (d, J = 6.55 Hz, 2H) 8.16 (bs, 2H) 8.30 (dd, J = 8.89, 1.72 Hz, 1H) 8.42 (d5 J = 2.50 Hz, 1H) 8.61 (d3 J = 1.56 Hz, 1H) 8.69 (d5 J = 9.05 Hz, 1H) 9.41 (s, 1H) 1L01 (s, 1H); Analytical calculated value for C30H25N50.1.9TFA: C, 58.99; H, 3.94; N, 10.18; Found: C, 58.87; H, 3.85; N, 10.08.

(6-{5-f(2SV2-胺基吲哚-3-基V丙氧基1-吡啶-3-基μ蟑啉-4-基V 芊基-胺實例266Α 芊基-(6-溴-峰琳·4-基）-胺將34D (100毫克；0.41毫莫耳）與苄胺（0.5毫升）於MeOH (3毫升）中之溶液，在室溫下攪拌24小時，濃縮，懸浮於Et20中，並收集沉澱物，提供所要之產物（100毫克；78% )。(6- {5-f (2SV2-amino indol-3-yl V propoxy 1-pyridin-3-yl μcockolin-4-yl V fluorenyl-amine example 266A fluorenyl- (6-bromo -Fenglin · 4-yl) -amine A solution of 34D (100 mg; 0.41 mmol) and benzylamine (0.5 ml) in MeOH (3 ml) was stirred at room temperature for 24 hours, concentrated, and suspended in Et20, and the precipitate was collected to provide the desired product (100 mg; 78%).

實例266B (6-{5-f(2SV2-胺基哚-3-基丙氧基V吡啶-3-基丨-蟑啉-4-某V · 芊基-胺所要之產物係經由以實例266A取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (ESI) m/e 541 (M+H)+ ; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.18 (d, J=7.18 Hz, 2H) 3.87 (m, 1H) 4.23 (dd，J=10.61，5.62 Hz，1H) 4.38 (dd，J=10.45, 2·96 Hz，1H) 5.00 (d，JN5.62 Hz，2H) 7.00 (t, J=7.49 Hz, 1H) 7.09 (t, J=7.18 Hz, 1H) 7.30 (d5 J=2.50 Hz, 1H) 7.37 (m, 4H) 7.50 (d，J=7.49 Hz，2H) 7.62 (d，J=8.11 Hz，1H) 7.83 (d，J=2.18 Hz，1H) 8.10 (d，J= -249- (242)Example 266B (6- {5-f (2SV2-Aminoindol-3-ylpropoxy Vpyridin-3-yl 丨 -cockroline-4-a V. fluorenyl-amine The desired product is obtained by using Example 266A Substituted 6-bromophthalimide in Example 32, made of trifluoroacetate. MS (ESI) m / e 541 (M + H) +; 1 H NMR (500 MHz, DMSO-D6 ) δ ppm 3.18 (d, J = 7.18 Hz, 2H) 3.87 (m, 1H) 4.23 (dd, J = 10.61, 5.62 Hz, 1H) 4.38 (dd, J = 10.45, 2.96 Hz, 1H) 5.00 ( d, JN5.62 Hz, 2H) 7.00 (t, J = 7.49 Hz, 1H) 7.09 (t, J = 7.18 Hz, 1H) 7.30 (d5 J = 2.50 Hz, 1H) 7.37 (m, 4H) 7.50 (d , J = 7.49 Hz, 2H) 7.62 (d, J = 8.11 Hz, 1H) 7.83 (d, J = 2.18 Hz, 1H) 8.10 (d, J = -249- (242)

9·05 Hz，1H) 8.29 (bs，2H) 8·40 (dd，J=8.89, 1.40 Hz，1H) 8.45 (d，J=2.50 Hz，1H) 8.78 (d，J=l.56 Hz，1H) 8.80 (s，1H) 8.98 (s，1H) 10.35 (bs，1H) 11.03 (s，1H); 對 C31H28N60.3.1TFA之分析計算值：C，52.31; Η，3·67; N，9.84; 實測值·· C，52.36 ; H，3.47 ; N，9.67. 實例267 (6-{5-f(2S)-2-胺基嗓-3-基V丙氧基Ι-t?比淀-3-基丨-峰g林-4-基）· 甲基-胺所要之產物係經由以甲胺取代實例266中之芊胺，以三氟醋酸鹽製成。MS (ESI) m/e 425 (M+H)+ ; 1 H NMR (500 MHz，DMSO-D6) δ ppm 2.50 (d, J=1.87 Hz, 3H) 3.19 (m, 2H) 3.85 (m5 1H) 4.26 (dd, J=10.92, 5.93 Hz, 1H) 4.40 (dd，J=10.61，3·12 Hz，1H) 6.99 (t，J=7.49 Hz，1H) 7.09 (t，J=7.33 Hz，1H) 7.32 (d, J=1.87 Hz, 1H) 7.37 (d, J=8.11 Hz, 1H) 7.63 (d? J=8.11 Hz, 1H) 7.87 (s, 1H) 8.10 (d, J=9.05 Hz, 1H) 8.37 (m, 3H) 8.43 (d? J=2.81 Hz, 1H) 8.72 (s5 1H) 8.76 (d, J= 1.56 Hz, 1H) 8.93 (s5 1H) 10.00 (bs, 1H) 11.04 (d, J=1.25 Hz, 1H) 實例268 6-{5彳(25)-2-胺基-3-(1沁蜊哚-3-基）-丙氧基1-吡啶各基丨-4啉-4-基胺所要之產物係經由以氨取代實例266中之芊胺，以三氟醋酸鹽製成。MS(ESI)m/e411(M+H)+ ; iHNMRpOOMHADMSO-DG) 5 ppm 3.18M2H) 3.86 (m5 1H) 4.27 (m5 1H) 4.41 (m5 1H) 6.99 (m? 1H) 7.08 (m5 1H) 7.36 (m，2H) 7.64 (d，J=6.55 Hz，1H) 7.89 (s，1H) 8.10 (d，J=8.42 Hz，1H) 8·46 (m， 4H) 8.59 (s? 1H) 8.76 (s, 1H) 9.00 (s, 1H) 10.06 (s, 2H) 11.08 (s, 1H) 實例269 「(3SV3-(5-異喹啉-6-基-吡啶-3-基氧基曱基VU，3,4-四氫-b-咔啉-9- 基1-甲醇 -250- (243) 將實例27 (100毫克；〇·19毫莫耳-)與37%曱醛（水溶液）(18微升）於水（1毫升）與2滴濃H2 S04中之溶液，於回流下加熱3小時，蒸發，並於C18管柱上藉逆相HPLC純化，使用0-100% CH3 CN/H2 0/0.1% TFA，提供所要之產物，為三氟醋酸鹽。Ms (ESI) m/e 412 (M+H)+ ； 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.04 (m5 1H) 3.20 (m, 3H) 4.19 (bs, 1H) 4.53 (m, 6.75 Hz, 1H) 4.64 (m, 1H) 4.70 (m, 1H) 5.52 (m5 2H) 7.12 (t，J=7.67 Hz，1H) 7·22 (t，J=7.67 Hz，1H) 7.52 (d，J=7.98 Hz，1H) 7.58 (d，J= 8.29 Hz, 1H) 8.05 (s, 1H) 8.26 (d, J=6.44 Hz, 1H) 8.33 (d5 J=8.59 Hz, 1H) 8.53 (m, 2H) 8.63 (s, 1H) 8.68 (d, J=5.83 Hz, 1H) 8.83 (s, 1H) 9.71 (s5 1H) 9.94 (bs, 1H) 實例270 3-(5-異喹啉-6-基-吡啶-3-基氣基甲基）-2,3,4,9-四氫咔啉將實例27 (100毫克；0.19毫莫耳）與37%甲醛（水溶液）(171微升）於水（1毫升）與H2 S04 (6微升）中之溶液，於室溫下攪捽過夜，以NH3/MeOH中和，濃縮並藉急驟式層析（10% MeOH/CH2Cl2) 純化，提供所要之產物。MS (ESI) m/e 407 (M+H)+; 1 H NMR (500 MHz， DMSO-D6) δ ppm 2.58 (dd, J=14.66, 9.98 Hz, 1H) 2.85 (dd5 J=14.975 3.74 Hz, 1H) 3.38 (m, 2H) 4.02 (d3 J=4.99 Hz, 1H) 4.33 (m, 2H) 6.95 (t, J=7.02 Hz, 1H) 7.02 (t5 J= 7.49 Hz, 1H) 7.29 (d5 J=8.1 Hz, 1H) 7.39 (d, J=8.11 Hz, 1H) 7.91 (m5 2H) 8.12 (dd, J=8.42,1.56 Hz, 1H) 8.25 (d, J=8.42 Hz, 1H) 8.41 (s, 1H) 8.45 (t, J=2.65 Hz, 1H) 8.56 (d，JN5.62 Hz，1H) 8·69 (d，J=l.56 Hz，1H) 9·37 (s，1H) 10.72 (s，1H)· 實例271 5-{5-「(2S)-2-胺基-3-ΠΗ-吲哚-3-基V丙氧基1-吡啶-3-基KIH-吲唑-3- 羧酸實例271Α 2003011229.05 Hz, 1H) 8.29 (bs, 2H) 8.40 (dd, J = 8.89, 1.40 Hz, 1H) 8.45 (d, J = 2.50 Hz, 1H) 8.78 (d, J = l.56 Hz, 1H) 8.80 (s, 1H) 8.98 (s, 1H) 10.35 (bs, 1H) 11.03 (s, 1H); Analytical calculated value for C31H28N60.3.1TFA: C, 52.31; Η, 3.67; N, 9.84 ; Found, C, 52.36; H, 3.47; N, 9.67. Example 267 (6- {5-f (2S) -2-amino group-3-yl Vpropoxyl-t? Biyodo- The desired product was obtained by substituting methylamine in Example 266 for methylamine, and using trifluoroacetate. MS (ESI) m / e 425 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.50 (d, J = 1.87 Hz, 3H) 3.19 (m, 2H) 3.85 (m5 1H) 4.26 (dd, J = 10.92, 5.93 Hz, 1H) 4.40 (dd, J = 10.61, 3.12 Hz, 1H) 6.99 (t, J = 7.49 Hz, 1H) 7.09 (t, J = 7.33 Hz, 1H) 7.32 (d, J = 1.87 Hz, 1H) 7.37 (d, J = 8.11 Hz, 1H) 7.63 (d? J = 8.11 Hz, 1H) 7.87 (s, 1H) 8.10 (d, J = 9.05 Hz, 1H) 8.37 (m, 3H) 8.43 (d? J = 2.81 Hz, 1H) 8.72 (s5 1H) 8.76 (d, J = 1.56 Hz, 1H) 8.93 (s5 1H) 10.00 (bs, 1H) 11.04 (d, J = 1.25 Hz, 1H) Example 268 6- {5 彳 (25) -2-Amino-3- (1aqindol-3-yl) -propoxyl-pyridinyl group-4-olin-4-yl The desired product of amine was made from trifluoroacetate by replacing ammonia in Example 266 with ammonia. MS (ESI) m / e411 (M + H) +; iHNMRpOOMHADMSO-DG) 5 ppm 3.18M2H) 3.86 (m5 1H) 4.27 (m5 1H) 4.41 (m5 1H) 6.99 (m? 1H) 7.08 (m5 1H) 7.36 (m, 2H) 7.64 (d, J = 6.55 Hz, 1H) 7.89 (s, 1H) 8.10 (d, J = 8.42 Hz, 1H) 8.46 (m, 4H) 8.59 (s? 1H) 8.76 (s , 1H) 9.00 (s, 1H) 10.06 (s, 2H) 11.08 (s, 1H) Example 269 "(3SV3- (5-isoquinolin-6-yl-pyridin-3-yloxyfluorenyl VU, 3 , 4-tetrahydro-b-carboline-9-yl 1-methanol-250- (243) Example 27 (100 mg; 0.19 mmoles) and 37% formaldehyde (aqueous solution) (18 μl ) Solution in water (1 ml) and 2 drops of concentrated H2 S04, heated at reflux for 3 hours, evaporated, and purified by reverse phase HPLC on a C18 column using 0-100% CH3 CN / H2 0 / 0.1 % TFA, provides the desired product as trifluoroacetate. Ms (ESI) m / e 412 (M + H) +; 1 H NMR (400 MHz, DMSO-D6) δ ppm 3.04 (m5 1H) 3.20 (m , 3H) 4.19 (bs, 1H) 4.53 (m, 6.75 Hz, 1H) 4.64 (m, 1H) 4.70 (m, 1H) 5.52 (m5 2H) 7.12 (t, J = 7.67 Hz, 1H) 7.22 ( t, J = 7.67 Hz, 1H) 7.52 (d, J = 7.98 Hz, 1H) 7.58 (d, J = 8.29 Hz, 1H) 8.05 (s, 1H) 8.26 (d, J = 6.44 Hz, 1H) 8.33 (d5 J = 8.59 Hz, 1H) 8.53 (m, 2H) 8.63 (s, 1H) 8.68 (d, J = 5.83 Hz, 1H) 8.83 (s, 1H) 9.71 (s5 1H) 9.94 (bs, 1H) 270 3- (5-Isoquinoline-6-yl-pyridin-3-ylaminomethyl) -2,3,4,9-tetrahydrocarboline Example 27 (100 mg; 0.19 mmol) and A solution of 37% formaldehyde (aqueous solution) (171 microliters) in water (1 mL) and H2S04 (6 microliters), stir at room temperature overnight, neutralize with NH3 / MeOH, concentrate and apply the flash layer Purification (10% MeOH / CH2Cl2) provided the desired product. MS (ESI) m / e 407 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 2.58 (dd, J = 14.66, 9.98 Hz, 1H) 2.85 (dd5 J = 14.975 3.74 Hz, 1H) 3.38 (m, 2H) 4.02 (d3 J = 4.99 Hz, 1H) 4.33 (m, 2H) 6.95 (t, J = 7.02 Hz, 1H) 7.02 (t5 J = 7.49 Hz, 1H) 7.29 (d5 J = 8.1 Hz, 1H) 7.39 (d, J = 8.11 Hz, 1H) 7.91 (m5 2H) 8.12 (dd, J = 8.42, 1.56 Hz, 1H) 8.25 (d, J = 8.42 Hz, 1H) 8.41 (s, 1H ) 8.45 (t, J = 2.65 Hz, 1H) 8.56 (d, JN5.62 Hz, 1H) 8.69 (d, J = l.56 Hz, 1H) 9.37 (s, 1H) 10.72 (s, 1H) Example 271 5- {5-`` (2S) -2-Amino-3-ΠΗ-indol-3-yl Vpropoxy 1-pyridin-3-yl KIH-indazole-3-carboxylic acid Example 271A 200301122

(244) IH-Hl 峻-3-# 跋 Ui- 將3·羧基吲唑（2.0克；12.3毫莫耳）與濃HC1 (2毫升）於MeOH (5〇亳升）中之溶液，在回流下加熱過夜，濃縮，以2NNa0H ( 水溶液）稀釋，並以EtOAc萃取。將萃液以鹽水沖洗，脫水乾燥（MgS04)，及濃縮，提供所要之產物。(244) IH-Hl Jun-3- # ba Ui- A solution of 3. · carboxyindazole (2.0 g; 12.3 mmol) and concentrated HC1 (2 ml) in MeOH (50 亳 L) under reflux Heated overnight, concentrated, diluted with 2NNaOH (aq.), And extracted with EtOAc. The extract was washed with brine, dried (MgSO4), and concentrated to provide the desired product.

實例271B 5-碘基-1H-吲唑-3-羧多甲酯將實例271A (300毫克；1.7毫莫耳）、雙（三氟乙醯氧基）琪苯 (8〇〇亳克；1.9毫莫耳）及碘（253毫克；1·〇毫莫耳）於CH2C12(10 亳升）中之溶液，在室溫下攪拌過夜，並以亞硫酸氫鈉（水溶液）處理。收集沉殿物，以水及己燒沖洗，並在真空下乾燥，提供所要之產物（180毫克；36% )。Example 271B 5-iodo-1H-indazole-3-carboxypolymethyl ester Example 271A (300 mg; 1.7 mmol), bis (trifluoroacetoxy) qibenzene (800 g); 1.9 A solution of mM) and iodine (253 mg; 1.0 mM) in CH2C12 (10 μl) was stirred at room temperature overnight and treated with sodium bisulfite (aqueous solution). The sunken objects were collected, rinsed with water and hexane, and dried under vacuum to provide the desired product (180 mg; 36%).

實例271C HK(2S)-2-第三-丁氣羰基胺基-3-ΠΗ-钊哚-3-卷上丙氣某p比被-3_ 基卜1H-41吐-3-叛酸甲酉旨所要之產物係經由以實例271B取代實例32B中之6-溴基鄰笨二甲醯亞胺而製成。Example 271C HK (2S) -2-Third-butanecarbonylamino-3-Πfluorene-zhaodol-3-propane gas on a certain ratio of acetic acid is -3-gib 1H-41 The intended product was prepared by substituting Example 271B for 6-bromoo-benzyldimethylimine in Example 32B.

實例271D HH(2S)-2-胺基-3_:迎4哚-3-基）-丙氧^j^^^-基Mh^唑净羧酸甲酯所要之產物係經由以實例271C取代音彻π。丄、—，，Example 271D HH (2S) -2-amino-3_: 4- 4inol-3-yl) -propoxy ^ j ^^^-yl Mh ^ azole net carboxylic acid methyl ester The desired product is obtained by replacing the tone with Example 271C Thorough π.丄、 — ，，

八：T例27C中又實例27B 而製成。Eight: T case 27C and 27B were made.

實例271E 違二3-基}-1Η-㈣唑-3- 5-{5彳(25)-2-胺基-3-(1沁吲哚-3-基）-丙氣^^ -252-Example 271E-Di-3-yl} -1H-oxazole-3- 5- {5H (25) -2-amino-3- (1 indol-3-yl) -propane ^^ -252-

200301122 (245) 羧酸‘ 將實例271D(150毫克；0.34毫莫耳）與lNNaOH(5毫升）於 MeOH (1毫升）中之溶液，加熱至回流，歷經6小時，濃縮，並於C18管柱上藉逆相HPLC純化，使用0-100% CH3CN/H2 0/0.1 % TFA，提供所要之產物，為三氟醋酸鹽。MS (ESI) m/e 428 (M+H)+ ；1 H NMR (500 MHz, DMSO-D6) δ ppm 3.18 (d, J=7.49 Hz, 2H) 3.86 (m, 1H) 4.21 (dd, J=10.29, 5.93 Hz, 1H) 4.37 (dd, J=10.29, 2.50 Hz, 1H) 7.01 (t, J=7.33 Hz,200301122 (245) Carboxylic acid 'A solution of Example 271D (150 mg; 0.34 mmol) and 1NNaOH (5 mL) in MeOH (1 mL) was heated to reflux for 6 hours, concentrated, and applied to a C18 column Purified by reverse phase HPLC using 0-100% CH3CN / H2 0 / 0.1% TFA to provide the desired product as trifluoroacetate. MS (ESI) m / e 428 (M + H) +; 1 H NMR (500 MHz, DMSO-D6) δ ppm 3.18 (d, J = 7.49 Hz, 2H) 3.86 (m, 1H) 4.21 (dd, J = 10.29, 5.93 Hz, 1H) 4.37 (dd, J = 10.29, 2.50 Hz, 1H) 7.01 (t, J = 7.33 Hz,

1H) 7.10 (t，J=7.33 Hz，1H) 7.30 (d，J=1.87 Hz，1H) 7·38 (d，J=8.11 Hz，1H) 7.63 (d， J=7.80 Hz，1H) 7.71 (s，1H) 7.77 (m，2H) 8·26 (s，3H) 8·32 (s，1H) 8·37 (s，1H) 8.59 (s，1H) 11.03 (s，1H) 13.64 (m，1H). 實例272 5-[5__-((2S)-g·-第三-丁氧羰基胺基—3-與基-丙氣基）·吡啶·3_基ι_3·甲基_-吲也-1-羧酸第三-丁酯在具有攪摔棒之100毫升圓底燒瓶中，使實例203 (719毫克，1·22耄莫耳）溶於30毫升EtOAc中。連接組合真空/ Ar / Η2 歧管’並將燒瓶抽氣，且充填Αγ兩次。添加pd/c (8〇〇毫克， 10重量％(以乾重為基準）），並將燒瓶抽氣，且充填^兩次· 將所形成之黑色混合物激烈攪拌，並溫熱至50它，歷經20 小時，此時TLC顯示〜70%起始物質消耗。添加另外48〇毫克並連接新的H2氣瓶。將反應物於5〇它下再授拌％小時 ’此時使其冷卻至室溫’並將燒瓶抽氣，1充填々。使已、_飞、反應此口物匕過矽藻土過;慮’並將濾餅以扭心洗務。使遽液接受迴轉式蒸發，然後以室内真空乾燥，產生所要〈產物(540毫克，89%)，為無色泡沫物/固體。〜=〇26 -253 - (246) (EtOAc) ； MS m/z 499 (M+H)+ ； 1H NMR (300 MHz, DMSO-D6) 5 ppm L39 (s, 9H) 1·66 (s，9H) 2·60 (s，3H) 3·50 (m，2H) 3.82 (m，1H) 4.17 (m，2H) 4.83 (t，J=5.59 Hz, 1H) 6.82 (d, J=8.14 Hz, 1H) 7.79 (s5 1H) 8.02 (dd5 J=8.65, 1.53 Hz, 1H) 8.12 (m5 1H) 8.27 (d, J=1.02 Hz, 1H) 8.29 (d, J=2.71 Hz, 1H) 8.61 (d, J=2.03 Hz, 1H). 實例273 5-f5-((2SV氮丙啶-2-基甲氧基V吡啶-3-基1-3-甲基-1H-W唑1H) 7.10 (t, J = 7.33 Hz, 1H) 7.30 (d, J = 1.87 Hz, 1H) 7.38 (d, J = 8.11 Hz, 1H) 7.63 (d, J = 7.80 Hz, 1H) 7.71 ( s, 1H) 7.77 (m, 2H) 8.26 (s, 3H) 8.32 (s, 1H) 8.37 (s, 1H) 8.59 (s, 1H) 11.03 (s, 1H) 13.64 (m, 1H). Example 272 5- [5 __- ((2S) -g · -Third-butoxycarbonylamino-3- and radical-propanyl) Tertiary-butyl-1-carboxylic acid was dissolved in 30 ml of EtOAc in a 100 ml round bottom flask with a stir bar. Connect the combined vacuum / Ar / Η2 manifold 'and evacuate the flask and fill with Aγ twice. Add pd / c (800 mg, 10% by weight (based on dry weight), and evacuate the flask and fill it twice. Stir the formed black mixture vigorously and warm to 50 ° C. After 20 hours, TLC showed ~ 70% consumption of the starting material. Add another 48 mg and connect a new H2 cylinder. The reaction was stirred at 50 ° C for an additional% hours. 'At this time, it was cooled to room temperature' and the flask was evacuated and filled with 々. The reaction has been passed through the diatomaceous earth, and the filter cake was washed with a twist of heart. The mash was subjected to rotary evaporation and then vacuum-dried in a room to give the desired product (540 mg, 89%) as a colorless foam / solid. ~ = 〇26 -253-(246) (EtOAc); MS m / z 499 (M + H) +; 1H NMR (300 MHz, DMSO-D6) 5 ppm L39 (s, 9H) 1.66 (s, 9H) 2.60 (s, 3H) 3.50 (m, 2H) 3.82 (m, 1H) 4.17 (m, 2H) 4.83 (t, J = 5.59 Hz, 1H) 6.82 (d, J = 8.14 Hz, 1H) 7.79 (s5 1H) 8.02 (dd5 J = 8.65, 1.53 Hz, 1H) 8.12 (m5 1H) 8.27 (d, J = 1.02 Hz, 1H) 8.29 (d, J = 2.71 Hz, 1H) 8.61 (d, J = 2.03 Hz, 1H). Example 273 5-f5-((2SV aziridin-2-ylmethoxyVpyridin-3-yl1-3-methyl-1H-Wazole

實例273A (11^)-「2-(5->臭-ρ比咬-3-基乳基）-1-(第二-丁基-二甲基-碎燒> 基氧基甲基V乙基1-胺甲基酸第三-丁酯於100毫升RBF中，裝填3-溴基-5-羥基吡啶（1.20克，6.87毫莫耳）、（R)-[l-(第二-丁基-二甲基-碎：基氣基甲基）-2-幾基··乙基]-胺甲基酸第三-丁酯（2.1克，6.87毫莫耳）及Ph3P (2.34克，8.93 毫莫耳），並以氮滌氣。於0°C下添加THF (30毫升）。在〇°C下攪拌10分鐘後，經由注射器添加DEAD (1·41毫升，8.93毫莫耳）^將反應混合物在〇°C下攪拌〇·5小時，及在室溫下2小時。使反應混合物濃縮，並藉急騾式層析（於己烷中之5-25 % EtOAc)分離殘留物，提供所要之產物（3.14克，99% )。 MS (DCI) m/z 461，463 (M+l)+ ·Example 273A (11 ^)-"2- (5- > Odor-ratio-3-yllactyl) -1- (Second-butyl-dimethyl-crusted > oxyoxymethyl V ethyl 1-aminomethyl acid tertiary-butyl ester in 100 ml of RBF, filled with 3-bromo-5-hydroxypyridine (1.20 g, 6.87 mmol), (R)-[l- (Second -Butyl-dimethyl-branched: carbamoylmethyl) -2-quinyl · · ethyl] -aminomethyl acid tert-butyl ester (2.1 g, 6.87 mmol) and Ph3P (2.34 g , 8.93 millimoles), and purged with nitrogen. THF (30 ml) was added at 0 ° C. After stirring for 10 minutes at 0 ° C, DEAD (1.41 ml, 8.93 millimoles) was added via a syringe. ^ The reaction mixture was stirred at 0 ° C for 0.5 hours and at room temperature for 2 hours. The reaction mixture was concentrated and the residue was separated by flash chromatography (5-25% EtOAc in hexane). Provide the desired product (3.14 g, 99%). MS (DCI) m / z 461, 463 (M + l) + ·

實例273B (lSH2-(5-溴-吡啶-3-基氧基VI-羥甲基-乙基V胺甲基酸第三-丁酯在室溫下，於實例273A (3.14克，6.8毫莫耳）在THF (40毫升）中之溶液内，添加TBAF (7.14毫升，7.14毫莫耳）。將此溶液在室溫下攪拌1小時，及濃縮。使殘留油藉急驟式層析（於己烷中之40-80% EtOAc)純化，而得所要之產物（2.19克，93% ) (247) 。MS (DCI) m/z 347, 349 (M+l)+.Example 273B (lSH2- (5-Bromo-pyridin-3-yloxy VI-hydroxymethyl-ethyl V amine methyl acid tert-butyl ester) at room temperature in Example 273A (3.14 g, 6.8 mmol To the solution in THF (40 ml), TBAF (7.14 ml, 7.14 mmol) was added. The solution was stirred at room temperature for 1 hour and concentrated. The residual oil was subjected to flash chromatography (on hexane). 40-80% EtOAc in hexane) was purified to give the desired product (2.19 g, 93%) (247). MS (DCI) m / z 347, 349 (M + 1) +.

i^M273C (2S)-2-(5-溴-喊症-3-基氧基甲某V·氮丙咬小数酸第三-丁酉旨使 Ph3P (1.13 克，4.32 毫莫耳）溶於 9 : 1 THF/CH3 CN (30 毫升）中，並以冰/水浴冷卻至4°C。慢慢添加DIAD (850微升，4·32毫莫耳）。攪摔15分鐘後，慢慢添加實例273Β (1.0克，2·88毫莫耳）於THF (4毫升）中之溶液。使溶液溫熱至室溫，並攪拌過夜。使溶液濃縮，並使殘留油藉急騾式層析（於己烷中之20-40% EtOAc)純化，而得所要之產物（1.〇克，75% )。 MS (DCI) m/z 329, 331 (M+l)+.i ^ M273C (2S) -2- (5-bromo-symptomatic-3-yloxymethyl) V. aziridine fractional acid tertiary-butyridine aims to dissolve Ph3P (1.13 g, 4.32 mmol) : 1 THF / CH3 CN (30 ml) and cooled to 4 ° C in an ice / water bath. Add DIAD (850 μl, 4.32 mmol) slowly. After stirring for 15 minutes, slowly add the example 273B (1.0 g, 2.88 mmol) in THF (4 ml). The solution was allowed to warm to room temperature and stirred overnight. The solution was concentrated and the residual oil was purified by flash chromatography (on 20-40% EtOAc in hexanes) to give the desired product (1.0 g, 75%). MS (DCI) m / z 329, 331 (M + 1) +.

實例273D 第三-丁氧羰基-氮丙咬-2-基甲氧基V外1:咬-3-基1-3-甲基-吲唑小羧酸第三-丁酯友诛1·於100毫升RBF中，裝填實例273C (950毫克，2.88毫莫耳）、實例 203Β(1·14 克，Z88 毫莫耳）、pd2(dba)3(263 毫克，0.288 毫莫耳）及三-鄰-甲苯基膦（263毫克），並以N2滌氣。經由注射器添加無水DMF (35毫升）與Et3N (1·2毫升）。將此溶液以N2 再滌氣一次，並於72°C下加熱4小時。冷卻後，添加醋酸乙酯（150毫升）。將混合物以鹽水（200毫升）及水（200亳升）洗滌。使醋酸乙酯溶液濃縮，並藉急驟式層析（於己烷中之5〇-8〇 % EtOAc)分離殘留油，而得所要之產物（634毫克，65% )。 MS(APCI) m/z 481 (M+l)+. 皮法2··在〇°C下，於PPh3(2.16克，8.24毫莫耳）在THF(130毫升）與CH3 CN (20毫升）中之經授拌溶液内，經由注射器慢慢添 200301122Example 273D The third-butoxycarbonyl-azetidin-2-ylmethoxy group VEx1: bite-3-yl1-3-methyl-indazole small carboxylic acid third-butyl ester 1 In 100 ml of RBF, Example 273C (950 mg, 2.88 mmol) was loaded, Example 203B (1.14 g, Z88 mmol), pd2 (dba) 3 (263 mg, 0.288 mmol) and tri-neighbor -Tolylphosphine (263 mg) and scrubbed with N2. Anhydrous DMF (35 mL) and Et3N (1.2 mL) were added via an injector. This solution was purged again with N2 and heated at 72 ° C for 4 hours. After cooling, ethyl acetate (150 ml) was added. The mixture was washed with brine (200 ml) and water (200 ml). The ethyl acetate solution was concentrated and the residual oil was separated by flash chromatography (50-80% EtOAc in hexane) to give the desired product (634 mg, 65%). MS (APCI) m / z 481 (M + l) +. Phi 2 ··· at 0 ° C in PPh3 (2.16 g, 8.24 mmol) in THF (130 ml) and CH3 CN (20 ml) Slowly add 200301122 to the mixed solution in the syringe

(248) 加DIAD (1.62毫升，8·24毫莫耳）。·20分鐘後，將所形成之淡黃色溶液以套管加入THF (150毫升）中之實例272 (2.74克，5·50 毫莫耳）。將反應混合物於23°C下攪拌6小時，然後添加矽膠，並於迴轉式蒸發器上移除揮發性物質。急騾式層析 (50-60-70-80% EtOAc/己烷），獲得3.72克白色固體，為氧化三苯麟·亂丙矣之1·33 : 1混合物。Rf=〇.5〇(EtOAc)。使用之無需進一步純化。(248) Add DIAD (1.62 ml, 8.24 mmol). • After 20 minutes, the resulting pale yellow solution was cannula added to Example 272 (2.74 g, 5.50 mmol) in THF (150 ml). The reaction mixture was stirred at 23 ° C for 6 hours, then silicone was added and the volatiles were removed on a rotary evaporator. Flash chromatography (50-60-70-80% EtOAc / hexanes) gave 3.72 g of a white solid as a 1.33: 1 mixture of triphenylene oxide and propanidine. Rf = 0.50 (EtOAc). It was used without further purification.

實例273E 5-|~5-((2S)-$t丙淀-2-基甲氧基比症-3-基1-3-甲基-1Η·Ήΐ峻所要之產物係經由以實例273D取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 281 (M+l)+ ; 1 H NMR (300 MHz， CD3 OD) δ 2.63 (s, 3H), 3.31 (dd3 J=3.30, 1.83 Hz, 2H), 3.62 (dd5 J=6.23,1.83 Hz, 2H)，3.89 (m，1H)，4.60 (m，2H)，7.64 (d，J=8.79 Hz，1H)，7.77 (d，J=8.79 Hz，1H)， 8.15 (s, 1H), 8.22 (s, 1H). 實例274 (lS)-2-「5-(3-甲基嗅-5-基比咬-3-基氣某1-1-(3-三氟曱氧基一芊基V·乙胺_Example 273E 5- | ~ 5-((2S)-$ tpropyl lake-2-ylmethoxybiosis-3-yl1-3-methyl-1Η · Η Jun The desired product was replaced by Example 273D Example 27B in Example 27C, made from trifluoroacetate. MS (APCI) m / z 281 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 2.63 (s, 3H), 3.31 ( dd3 J = 3.30, 1.83 Hz, 2H), 3.62 (dd5 J = 6.23, 1.83 Hz, 2H), 3.89 (m, 1H), 4.60 (m, 2H), 7.64 (d, J = 8.79 Hz, 1H), 7.77 (d, J = 8.79 Hz, 1H), 8.15 (s, 1H), 8.22 (s, 1H). Example 274 (lS) -2- "5- (3-methylol-5-yl ratio bite- 3-Base Gas 1-1- (3-trifluorofluorenyloxy-fluorenyl V · ethylamine_

實例274A g-」5-「(2S)-2-第二.-工„乳羰基胺基-3-(3-三氟i甲氣基-笨某）·丙氣基％口比症j-基甲某-g弓1峻-1-卷酸第三-丁酿在大約-35 C下’於CuBr-SMe2(25宅克’ 0.12毫莫耳）與實例273D (100毫克，0·21毫莫耳）在THF(6毫升）中之懸浮液内，添加3_ 三氟曱氧基苯基溴化鎂（在THF中之〇·5Μ溶液，ι.6毫升，〇·8 毫莫耳）。於40分鐘内，使所形成之透明溶液溫熱至.。c， -256- (249)Example 274A g- "5-" (2S) -2-Second.-Work "lactocarbonylamino-3- (3-trifluoroimethylamino-benzyl) · propanyl% Oral syndrome Gemma-g bow 1 Jun-1-rollic acid third-butyrate brewed at about -35 C in CuBr-SMe2 (25 gram g '0.12 mmol) with Example 273D (100 mg, 0.21 mmol In a suspension in THF (6 ml), 3-trifluoroalkoxyphenylmagnesium bromide (0.5 M solution in THF, 1.6 ml, 0.8 mmol) was added. Within 40 minutes, warm the formed transparent solution to. c, -256- (249)

並於醚與水之間作分液處理。使有機層濃縮，並藉急驟式層析（於己烷中之4〇-65% Et0Ac)分離殘留物，而得所要之產物（88 毫克，66% )。MS(APCI)m/z643 (M+l)+.And the liquid was separated between ether and water. The organic layer was concentrated and the residue was separated by flash chromatography (40-65% Et0Ac in hexane) to give the desired product (88 mg, 66%). MS (APCI) m / z643 (M + l) +.

實例274B (lSV2-f5-(3-甲基-1H-W唑-5-基）-吡啶-3-基氣基1小(3-三氟甲氧基- 卞基）-乙胺所要之產物係經由以實例274A取代實例實例27C中之27B ，以三氟醋酸鹽製成 °MS (APCI) m/z 444 (M+l)+ ; 1H NMR (300 MHz， CD3 OD) δ 2.62 (s, 3H), 3.22 (dd, J=7.29, 5.26 Hz, 2H), 4.00 (m, 1H), 4.26 (dd, J= 10.51，5.09 Hz，1H)，4·43 (dd，J=10.85, 3.05 Hz，1H)，7·25 (d，J=8.48 Hz，1H)，7.30 (s， 1H), 7.36 (d5 J=7.46 Hz, 1H), 7.49 (t5 J=7,97 Hz, 1H), 7.62 (d3 J=8.48 Hz, 1H), 7.72 (dd, J=8.82, 1.70 Hz, 1H), 8.00 (s3 1H)5 8.08 (s, 1H), 8.40 (d5 J=2.03 Hz, 1H), 8.68 (s, 1H)·對 C23H21F3N402 .2.6TFA之分析計算值：C，45.84; Η，3·22; Ν，7·58· 實測值：C，45.87; Η，3·17; Ν，7·28· 下列化合物係經由以適當Grignard試劑取代實例274中之3-三氟甲氧基苯基溴化鎂而製成。實例275 (1SVH3,5-二氯-芊基甲基-1H-吲唑-5-某V吡啶-3-基氫基1- 乙胺 MS (APCI) m/z 427 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ 2.63 (s, 3H), 3.18 (dd5 J=7.325 3.30 Hz, 2H), 4.02 (m, 1H), 4.32 (dd, J=10.44, 5.31 Hz, 1H), 4.47 (dd, J= 10.62, 2.93 Hz, 1H), 7.37 (s, 1H)5 7.39 (d, J=8.06 Hz, 1H), 7.63 (d, J=8.79 Hz, 1H), 7.74 (d, J=8.06 Hz, 1H), 8.10 (s, 3H), 8.44 (s, 1H), 8.73 (s, 1H)；對C22H2〇C12N40.3.2TFA之分析計算值：C，43.38; Η，2·98; Ν，7·18· (250) 實測值：C，43.49 ; H，3.18; N，6.92. 實例276 (lSM-(2,3-二氯-芊基）-245-(3-甲基-1HW丨唑-5-基V吡啶-3-基氧基1- 乙胺 MS (APCI) m/z 427 (M+l)+ ； 1H NMR (300 ΜΗζ? CD3 OD) δ 2.63 (s, 3H)5 3.40 (dd, J=7.32, 5.13 Hz, 2H), 4.10 (m, 1H), 4.33 (dd3 J=10.62, 4.76 Hz, 1H), 4.47 (dd, J= 10.99, 2.93 Hz, 1H), 7.30 (t, J=7.69 Hz, 1H), 7.39 (d, J=7.32 Hz, 1H), 7.52 (d, J=7.69 Hz, 1H), 7.63 (d, J=8.79 Hz, 1H), 7.74 (d, J=8.79 Hz, 1H), 8.11 (s, 2H), 8.45 (s5 1H), 8.75 (s, 1H)； M C22H2〇C12N4〇*3.5TFA^ ^ ^ i\ % it ^ C, 42.15； H52.87 ;N，6.78·實測值：C，41.86 ; H，3·05; N，6.60. 實例277 聯 I -3-基甲基一2-f5-(3鑛甲基-5-基)·口比 < -3-基 i 基 1- 乙胺 MS (APCI) m/z 435 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ 2.61 (s, 3H), 3.25 (d, J=7.69 Hz, 2H), 4.05 (m, 1H), 4.33 (dd, J=10.62, 5.13 Hz, 1H), 4.46 (d? J=10.25 Hz, 1H), 7.36 (m5 4H), 7.46 (t, J=7.14 Hz, 1H), 7.57 (m, 6H)5 8.06 (s, 2H), 8.42 (s, 1H), 8.69 (s，1H);對 C28H26N40 · 3.2 TFA之分析計算值·· C，51.68 ; H，3.68 ;Ν，7·01·實測值：C，51.94 ; H，3·66; N，6.85. 實例278 (lS)-l-(3-氯基斗氟-芊基）-245-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1-乙胺 MS (APCI) m/z 411 (M+lf ； 1 H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H) 3.15 (t，J=7.12 Hz，2H) 3·98 (m，1H) 4.28 (dd，J=10.51，5.42 Hz，1H) 4.44 (dd，J=10.51， 3.05 Hz，1H) 7,23 (d，J=8.48 Hz，1H) 7.30 (m，1H) 7.51 (dd，J=7.12, 2.03 Hz，1H) 200301122 (251) 7.62 (d, J=8.81 Hz? 1H) 7.72 (dd, J=8.48, 1.36 Hz, 1H) 7.99 (s, 1H) 8.08 (s5 1H) 8.39 (s，1H) 8.68 (s，1H);對 C2 2 H2 〇 C1FN4 Ο · 2·7 TFA 之分析計算值：C，45.79 ;H，3·18; Ν，7·80·實測值：C，45.86 ; H，3.44; N，7.66. 實例279 (1SVH4-氯基-3-氟-芊基甲基-1H-W唑-5-基V吡啶-3-基氣基1-乙胺 MS (APCI) m/z 411 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) 6 2.63 (s, 3H), 3.17 (t, J=6.95 Hz，2H)，4.00 (m，1H)，4.28 (dd，J=10.51，5.43 Hz，1H)，4.44 (dd，J=10.51， 3.05 Hz，1H)，7.17 (dd，J=8.14, 1.70 Hz，1H)，7.29 (dd，J=10.00, 1.87 Hz，1H)，7.49 (t， J=7.97 Hz，1H)，7.62 (d，J=8.82 Hz，1H)，7.73 (d，J=7.12 Hz，1H)，8·01 (m，1H)，8.09 (s，1H)，8·40 (d，J=2.37 Hz，1H)，8.68 (d，J=1.70 Hz，1H);對 C2 2 H2 〇 C1FN4 0 · 2.7 TFA之分析計算值·· C，45.79 ; H，3.18; N，7.80·實測值：C，45.86 ；H5 3.44 ； N, 7.66. 實例280 (lS)-2-[5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氧基H-(4-三氟甲氧基- 卞基）-乙胺 MS (APCI) m/z 443 (M+l)+ ； 1 H NMR (300 MHz5 CD3 OD) δ 2.62 (s, 3H) 3.20 (t, J=6.95 Hz, 2H) 3.98 (m, 1H) 4.28 (dd, J=10.51, 5.42 Hz, 1H) 4.43 (dd, J=10.51, 2.71 Hz, 1H) 7.30 (d, J=7.80 Hz, 2H) 7.45 (d, J=8.48 Hz, 2H) 7.62 (d, J=8.48 Hz, 1H) 7.73 (d，J=8.81 Hz，1H) 8.00 (s，1H) 8.08 (s，1H) 8.40 (s，1H) 8·68 (s，1H). 對 C23H21F3N402 .2.4TFA之分析計算值：C，46.63; Η，3·29; Ν，7·82· 實測值·· C，46.57 ; Η，3·30; N，7.80. 實例281 (lS)-l-(2-乱基-4-二氣曱基-卞基）_2-『5-(3_甲基吐-5-基）_口比淀- -259- (252)Example 274B (lSV2-f5- (3-methyl-1H-Wazole-5-yl) -pyridin-3-ylamino 1 small (3-trifluoromethoxy-fluorenyl) -ethylamine It was prepared by replacing 27B in Example 27C with Example 274A and using trifluoroacetate ° MS (APCI) m / z 444 (M + l) +; 1H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H), 3.22 (dd, J = 7.29, 5.26 Hz, 2H), 4.00 (m, 1H), 4.26 (dd, J = 10.51, 5.09 Hz, 1H), 4.43 (dd, J = 10.85, 3.05 Hz , 1H), 7.25 (d, J = 8.48 Hz, 1H), 7.30 (s, 1H), 7.36 (d5 J = 7.46 Hz, 1H), 7.49 (t5 J = 7,97 Hz, 1H), 7.62 (d3 J = 8.48 Hz, 1H), 7.72 (dd, J = 8.82, 1.70 Hz, 1H), 8.00 (s3 1H) 5 8.08 (s, 1H), 8.40 (d5 J = 2.03 Hz, 1H), 8.68 ( s, 1H). Analysis and calculation of C23H21F3N402.2.6TFA: C, 45.84; Η, 3.22; Ν, 7.58. Found: C, 45.87; Η, 3.17; Ν, 7 · 28 · The following compound was prepared by replacing 3-trifluoromethoxyphenylmagnesium bromide in Example 274 with an appropriate Grignard reagent. Example 275 (1SVH3,5-dichloro-fluorenylmethyl-1H-indazole-5 -A certain V-pyridin-3-ylhydrol 1-ethylamine MS (APCI) m / z 427 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 2.6 3 (s, 3H), 3.18 (dd5 J = 7.325 3.30 Hz, 2H), 4.02 (m, 1H), 4.32 (dd, J = 10.44, 5.31 Hz, 1H), 4.47 (dd, J = 10.62, 2.93 Hz , 1H), 7.37 (s, 1H) 5 7.39 (d, J = 8.06 Hz, 1H), 7.63 (d, J = 8.79 Hz, 1H), 7.74 (d, J = 8.06 Hz, 1H), 8.10 (s , 3H), 8.44 (s, 1H), 8.73 (s, 1H); Analytical calculated value for C22H20C12N40.3.2TFA: C, 43.38; Η, 2.98; Ν, 7.18 · (250) Measured Values: C, 43.49; H, 3.18; N, 6.92. Example 276 (lSM- (2,3-dichloro-fluorenyl) -245- (3-methyl-1HW 丨 azole-5-yl Vpyridine-3 -Yloxy 1-ethylamine MS (APCI) m / z 427 (M + l) +; 1H NMR (300 ΜΗζ? CD3 OD) δ 2.63 (s, 3H) 5 3.40 (dd, J = 7.32, 5.13 Hz , 2H), 4.10 (m, 1H), 4.33 (dd3 J = 10.62, 4.76 Hz, 1H), 4.47 (dd, J = 10.99, 2.93 Hz, 1H), 7.30 (t, J = 7.69 Hz, 1H), 7.39 (d, J = 7.32 Hz, 1H), 7.52 (d, J = 7.69 Hz, 1H), 7.63 (d, J = 8.79 Hz, 1H), 7.74 (d, J = 8.79 Hz, 1H), 8.11 ( s, 2H), 8.45 (s5 1H), 8.75 (s, 1H); MC22H2〇C12N4〇 * 3.5TFA ^^^ i \% it ^ C, 42.15; H52.87; N, 6.78 · Measured value: C , 41.86; H, 3.05; N, 6.60. Example 277 I-3-ylmethyl-2-f5- (3mine -5-yl) · mouth ratio < -3-yl i-yl 1-ethylamine MS (APCI) m / z 435 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ 2.61 (s, 3H ), 3.25 (d, J = 7.69 Hz, 2H), 4.05 (m, 1H), 4.33 (dd, J = 10.62, 5.13 Hz, 1H), 4.46 (d? J = 10.25 Hz, 1H), 7.36 (m5 4H), 7.46 (t, J = 7.14 Hz, 1H), 7.57 (m, 6H) 5 8.06 (s, 2H), 8.42 (s, 1H), 8.69 (s, 1H); Analysis of C28H26N40 · 3.2 TFA Calculated · C, 51.68; H, 3.68; N, 7.01 · Measured: C, 51.94; H, 3.66; N, 6.85. Example 278 (lS) -l- (3-Chlorobutanol -Fluorenyl) -245- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1-ethylamine MS (APCI) m / z 411 (M + lf; 1 H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H) 3.15 (t, J = 7.12 Hz, 2H) 3.98 (m, 1H) 4.28 (dd, J = 10.51, 5.42 Hz, 1H) 4.44 (dd, J = 10.51, 3.05 Hz, 1H) 7,23 (d, J = 8.48 Hz, 1H) 7.30 (m, 1H) 7.51 (dd, J = 7.12, 2.03 Hz, 1H) 200301122 (251) 7.62 (d, J = 8.81 Hz? 1H) 7.72 (dd, J = 8.48, 1.36 Hz, 1H) 7.99 (s, 1H) 8.08 (s5 1H) 8.39 (s, 1H) 8.68 (s, 1H); For C2 2 H2 〇C1FN4 〇 · Calculated value of 2 · 7 TFA: C, 45.79; H, 3.18; N, 7.80. Found: C, 45.86; H, 3.44; N, 7.66. Example 279 (1SVH4-chloro-3-fluoro-fluorenylmethyl-1H-Wazole-5-yl Vpyridine-3 -Base Gas 1-Ethylamine MS (APCI) m / z 411 (M + 1) +; 1H NMR (300 MHz, CD3 OD) 6 2.63 (s, 3H), 3.17 (t, J = 6.95 Hz, 2H ), 4.00 (m, 1H), 4.28 (dd, J = 10.51, 5.43 Hz, 1H), 4.44 (dd, J = 10.51, 3.05 Hz, 1H), 7.17 (dd, J = 8.14, 1.70 Hz, 1H) , 7.29 (dd, J = 10.00, 1.87 Hz, 1H), 7.49 (t, J = 7.97 Hz, 1H), 7.62 (d, J = 8.82 Hz, 1H), 7.73 (d, J = 7.12 Hz, 1H) , 8.01 (m, 1H), 8.09 (s, 1H), 8.40 (d, J = 2.37 Hz, 1H), 8.68 (d, J = 1.70 Hz, 1H); for C2 2 H2 〇C1FN4 0 · 2.7 Analytical calculation of TFA · C, 45.79; H, 3.18; N, 7.80 · Measured value: C, 45.86; H5 3.44; N, 7.66. Example 280 (lS) -2- [5- (3- 甲-1H-indazol-5-yl Vpyridin-3-yloxy H- (4-trifluoromethoxy-fluorenyl) -ethylamine MS (APCI) m / z 443 (M + 1) +; 1 H NMR (300 MHz5 CD3 OD) δ 2.62 (s, 3H) 3.20 (t, J = 6.95 Hz, 2H) 3.98 (m, 1H) 4.28 (dd, J = 10.51, 5.42 Hz, 1H) 4.43 (dd, J = 10.51, 2.71 Hz, 1H) 7.30 (d, J = 7.80 H z, 2H) 7.45 (d, J = 8.48 Hz, 2H) 7.62 (d, J = 8.48 Hz, 1H) 7.73 (d, J = 8.81 Hz, 1H) 8.00 (s, 1H) 8.08 (s, 1H) 8.40 (s, 1H) 8.68 (s, 1H). Analysis and calculation of C23H21F3N402.2.4TFA: C, 46.63; Η, 3.29; Ν, 7.82 · Measured value ·· C, 46.57; Η, 3.30; N, 7.80. Example 281 (lS) -l- (2-Lanyl-4-difluorofluorenyl-fluorenyl) _2- "5- (3_methylthio-5-yl) _port Hiyodo- -259- (252)

3-基氣基V乙胺 MS (APCI) m/z 445 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H), 3.31 (m, 2H), 4.04 (m, 1H)5 4.29 (dd, J=10.85, 5.09 Hz, 1H), 4.45 (dd5 J=10.85, 3.39 Hz, 1H)5 7.54 (d，J=8.81 Hz, ·1Η)，7.55 (s，1H)，7.60 (dd，J=4.07, 3.39 Hz，1H)，7.63 (s，1H)， 7.72 (dd，J=8.81，1·70 Hz，1H)，7.96 (s，1H)，8·07 (s，1H)，8.39 (s，1H)，8.67 (s，1H). 實例282 (1SVH3-氟基-5-三氟甲基-芊基V2-「5-(3-甲基-1H-W唑-5-基）-吡啶- 3-基氣基1-乙胺 MS (APCI) m/z 445 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H), 3.30 (m, 2H)，4.06 (m，1H)，4.29 (dd，J=10.51，5·09 Hz，1H)，4.45 (dd，J=10.85, 3·05 Hz，1H)， 7.45 (dd5 J=7.80, 5.76 Hz, 2H), 7.55 (s? 1H), 7.62 (d, J=8.81 Hz, 1H), 7.73 (d, J=8.48 Hz, 1H), 7.98 (s, 1H), 8.07 (s, 1H), 8.42 (br s, 1H), 8.73 (br s, 1H). 實例283 (lS)-l-(2-甲氧基-芊基）-245-(3-曱基-1H-吲唑-5-基）-吡啶-3-基氧基1- 乙胺 MS (APCI) m/z 389 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ 2.62 (s5 3H)5 3.16 (d, J=7.46 Hz，2H)，3.85 (s，3H)，3.99 (m，1H)，4.23 (dd，J=10.51，5·76 Hz，1H)，4.39 (dd， J=10.85, 3.39 Hz, 1H), 6.94 (t, J=7.46 Hz, 1H), 7.03 (d, J=8.14 Hz, 1H), 7.23 (d5 J= 7·46 Hz，1H)，7.32 (dd，J=8.14, 7.46 Hz，1H)，7.62 (d，J=8.48 Hz，1H)，7.71 (d，J= 8·82 Hz，1H)，7.91 (d，J=2.03 Hz，1H)，8·06 (s，1H)，8.34 (d，J=2.71 Hz，1H)，8·65 (s， 1H). 實例284 (3-{(2S)-2-胺基-3-『5-(3-甲基峻-5-基）-口比咬-3-基乳基V丙基 200301122 (253) MS (DCI/NH3) m/e 402 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 = 8.73 (s； 1H)3 8.43 (s； lH)?8.10(m； 2H)57.74 (d； 1H； J=7.5 Hz), 7.63 (d； 1H； J-7.5 Hz), 7.38 (t; 1H; J=7.5Hz)，7.09 (s; 1H)，7.08 (d; 1H; J=7.5Hz)，7.04 (d; 1H; J=7.5Hz)， 4.45 (dd； 1H； J=10.8Hz； J=3.0 Hz), 4.31 (dd； 1H； J=10.8Hz； J=6.0 Hz)5 4.00 (m ； 1H)，3.17 (m ; 2H)，3.05 (s ; 6H)，2.64 (s ; 3H). 實例285 (lS)-l-(4-氣基-2-甲基-卞基）-2-f5-(3-甲基嗅-5-基）_口比淀-3-基3-Base Gas V-Ethylamine MS (APCI) m / z 445 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H), 3.31 (m, 2H), 4.04 ( m, 1H) 5 4.29 (dd, J = 10.85, 5.09 Hz, 1H), 4.45 (dd5 J = 10.85, 3.39 Hz, 1H) 5 7.54 (d, J = 8.81 Hz, · 1Η), 7.55 (s, 1H ), 7.60 (dd, J = 4.07, 3.39 Hz, 1H), 7.63 (s, 1H), 7.72 (dd, J = 8.81, 1.70 Hz, 1H), 7.96 (s, 1H), 8.07 ( s, 1H), 8.39 (s, 1H), 8.67 (s, 1H). Example 282 (1SVH3-fluoro-5-trifluoromethyl-fluorenyl V2- "5- (3-methyl-1H-W Azole-5-yl) -pyridine-3-ylamino1-ethylamine MS (APCI) m / z 445 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ 2.62 (s, 3H), 3.30 (m, 2H), 4.06 (m, 1H), 4.29 (dd, J = 10.51, 5.09 Hz, 1H), 4.45 (dd, J = 10.85, 3.05 Hz, 1H), 7.45 (dd5 J = 7.80, 5.76 Hz, 2H), 7.55 (s? 1H), 7.62 (d, J = 8.81 Hz, 1H), 7.73 (d, J = 8.48 Hz, 1H), 7.98 (s, 1H), 8.07 (s , 1H), 8.42 (br s, 1H), 8.73 (br s, 1H). Example 283 (lS) -l- (2-methoxy-fluorenyl) -245- (3-fluorenyl-1H-ind Azol-5-yl) -pyridin-3-yloxy 1-ethylamine MS (APCI) m / z 389 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 2.62 (s5 3H) 5 3.16 (d, J = 7.46 Hz, 2H), 3.85 (s, 3H), 3.99 (m, 1H), 4.23 (dd, J = 10.51, 5.76 Hz, 1H), 4.39 (dd, J = 10.85, 3.39 Hz, 1H), 6.94 (t, J = 7.46 Hz, 1H), 7.03 (d, J = 8.14 Hz, 1H), 7.23 (d5 J = 7.46 Hz, 1H), 7.32 (dd, J = 8.14 , 7.46 Hz, 1H), 7.62 (d, J = 8.48 Hz, 1H), 7.71 (d, J = 8.82 Hz, 1H), 7.91 (d, J = 2.03 Hz, 1H), 8.06 (s , 1H), 8.34 (d, J = 2.71 Hz, 1H), 8.65 (s, 1H). Example 284 (3-{(2S) -2-amino-3- "5- (3-methyl Jun-5-yl) -Hydroxy-3-yllactyl V-propyl 200301122 (253) MS (DCI / NH3) m / e 402 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.73 (s; 1H) 3 8.43 (s; lH)? 8.10 (m; 2H) 57.74 (d; 1H; J = 7.5 Hz), 7.63 (d; 1H; J-7.5 Hz), 7.38 (t; 1H; J = 7.5Hz), 7.09 (s; 1H), 7.08 (d; 1H; J = 7.5Hz), 7.04 (d; 1H; J = 7.5Hz), 4.45 (dd; 1H; J = 10.8Hz; J = 3.0 Hz), 4.31 (dd; 1H; J = 10.8Hz; J = 6.0 Hz) 5 4.00 (m; 1H), 3.17 (m; 2H), 3.05 (s; 6H), 2.64 (s; 3H) Example 285 (lS) -l- (4-Gas-2-methyl-fluorenyl) -2-f5- (3-methylol-5-yl) _koubito-3-yl

乳基1_乙胺 MS (DCI/NH3) m/e 407 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s； 1H), 8.41 (s； 1H)58.10(s； 1H)，8.04 (s ; 1H)，7.73 (d ; 1H ； J=8.1 Hz), 7.62 (d ； 1H ；J=8.1Hz)57.28 (s； lH),7.22(m； 2H),4.40(dd； 1H ； J=10.8Hz； J=3.0Hz), 4.26 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.94 (m ； 1H)，3.17 (m ; 2H)，2.62 (s ; 3H), 239 (s ； 3H). 實例286 碘-芊基V2-f5-(3-甲基-1H-啕唑-5-基V吡啶-3-基氧基1-乙胺Milky 1-ethylamine MS (DCI / NH3) m / e 407 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s; 1H), 8.41 (s; 1H) 58.10 ( s; 1H), 8.04 (s; 1H), 7.73 (d; 1H; J = 8.1 Hz), 7.62 (d; 1H; J = 8.1Hz) 57.28 (s; lH), 7.22 (m; 2H), 4.40 (dd; 1H; J = 10.8Hz; J = 3.0Hz), 4.26 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.94 (m; 1H), 3.17 (m; 2H), 2.62 (s 3H), 239 (s; 3H). Example 286 Iodo-fluorenyl V2-f5- (3-methyl-1H-oxazol-5-yl Vpyridin-3-yloxy 1-ethylamine

MS (DCI/NH3) m/e 485 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 = 8.65 (s； 1H), 8.36 (s； 1H)5 8.07 (s； 1H), 7.92 (s； 1H)57.75 (s； 1H), 7.72 (d； 1H； J=8.1 Hz), 7.68 (d ； 1H ； J=7.8 Hz), 7.62 (d ； 1H ； J=8.1 Hz), 7.35 (d ； 1H ； J=7.8 Hz), 7.16 (d； 1H； J=7.8Hz),4.40(dd； 1H； J=10.8Hz； J=3.0 Hz), 4.24 (dd； 1H； J=10.8Hz ；J=4.5 Hz), 3.96 (m ； 1H)5 3.12 (m ； 2H), 2.62 (s ； 3H). 實例287 (1SM1SVH3-氟基-4-甲某-芊基V2-「5-(3-曱基-1H-W唑-5-基）-吡啶-3- 某氫基1-乙胺 MS (DCI/NH3) m/e 391 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.73 (s； 1H), -261 - 200301122 (254) 8.42(s; lH)，8.12(s; 1H)，8.10 (s; 1H)，7.74 (d; 1H; J=8.1Hz)，7.63 (d; 1H ；J=8.1 Hz),7.24(t ； 1H ； J=8.4 Hz), 7.05 (m ； 2H), 4.44 (dd ； 1H ； J=10.8 Hz ;J=3.0Hz)，4.28 (dd; 1H; JN10.8 Hz; J=4.5Hz)，3.97 (m; 1H)，3.13 (m; 2H)， 2.62 (s ； 3H), 2.23 (s ； 3H). 實例288 (1SVM3-氟基-4-甲氣基-芊基甲基-1H-W唑-5-基V吡啶-3- 基氧基1-乙胺 MS (DCI/NH3) m/e 407 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.73 (s； 1H), 8.42 (s ； 1H), 8.12 (s ； 1H)58.10(s； lH),7.74(d； 1H ； J=8.1 Hz), 7.63 (d ； 1H ;J=8.1 Hz)，7.24(t ; 1H ； J=8.4 Hz), 7.05 (m ； 2H), 4.44 (dd ； 1H ； J=10.8 Hz ；J=3.0 Hz), 4.28 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.97 (m ； 1H), 3.13 (m ； 2H), 2.62 (s ； 3H), 2.23 (s ； 3H). 實例289 (lSV2-「6-氯基-5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氣基1-1-(3,4-二氯- 芊基V乙胺 MS (DCI/NH3) m/e 462 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.16 (s； 1H), 7.78 (s; 1H)，7.54 (Μ; 4H)，7.48 (d; 1H; J=8.1 Hz)，7.25 (d; 1H; J=8.1 Hz)，4.32 (dd ；1H ； J=10.8 Hz ； J-3.0 Hz), 4.15 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.93 (m ；1H), 3.12 (m ； 2H), 2.58 (s ； 3H). 實例290 (lS)-l-(2-^ 基-6-二氣甲基-卞基）-2-[5-(3-曱基-1Η*Ή| 口坐-5-基）·ρ比淀· 3-基氧基]-乙胺 MS (DCI/NH3) m/e 445 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 = 8.69 (s； 1H), 8.36 (s ； 1H), 8.08 (s ； 1H), 7.96 (s ； 1H), 7.73 (d ； 1H ； J=8.1 Hz), 7.63 (M ； -262- 200301122 鼸 (255) 3H), 7.50 (t ； 1H ； J=9.0 Hz), 4.44 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.32 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.08 (m ； 1H), 3.48 (m ； 1H), 335 (m ； 1H), 2.62 (s ； 3H). 實例291 (lS)-l-(4-氟基-3-三氟甲基-芊基V2-『5-(3-甲基-1H-啕唑-5-基V吡啶- 3-基氣基1-乙胺 MS (DCI/NH3) m/e 445 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.70 (s； 1H), 8.41 (s ; 1H)，8.09 (s ; 1H)，8·04 (s ; 1H)，7.74 (d ; 1H ; J=8.1 Hz)，7.68 (m ; 1H), 7.62 (d ； 1H ； J=8.1 Hz), 7.36 (t ； 1H ； J=9.0 Hz), 4.44 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.28 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.02 (m ； 1H), 3.23 (m ；2H), 2.62 (s ； 3H). 實例292 (IS)小呋喃-2-基甲基-2-f5-(3-甲基-1H-W唑-5-基）-吡啶-3-基氧基1- 乙胺 MS (DCI/NH3) m/e 349 (M+lf ； 1H NMR (300 MHz, CD3 OD) 5 = 8.68 (s； 1H), 8.39 (s ; 1H)，8.09 (m ; 1H)，8.00 (s : 1H)，7.73 (d ; 1H ; J=9.0 Hz)，7·62 (d ; 1H; J=9.0Hz)，7.50(s; 1H)，6.42 (m; 1H)，6.33 (m; 1H)，4.49 (dd; 1H; J=10.8 Hz ；J=3.0 Hz), 4.31 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.02 (m ； 1H), 3.24 (m ； 2H)5 2.62 (s ； 3H). 實例293 (1S)-1-笨并咬喃-2-基甲基甲基峻-5-基）-p比淀-3-基乳基1-乙胺 MS (DCI/NH3) m/e 398 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) 5 = 8.72 (s； 1H), 8.42 (s; 1H)，8.09 (m; 2H)，7.72(d; 1H; J=9.0Hz)，7.62 (d; 1H; J=9.0Hz)，7.55 -263 - 200301122 (256) (d； 1H； J=8.4 Hz), 7.45 (d ； 1H ； J=8.4 Hz), 7.44 (m ； 2H), 6.78 (s ； 1H)? 4.58 (dd ； 1H ; J=10.8 Hz ; J=3.0 Hz)，4.44 (dd ; 1H ； J=10.8 Hz ； J=4.5 Hz)? 4.18 (m ； 1H)，3.41 (m ; 2H)，2.62 (s ; 3H)· 實例294 (1SVH3-氟基-4-三氟甲基-芊基）-245-(3-甲基-1H-㈣唑-5-基V吡啶- 3-基氧基1-乙胺 MS (DCI/NH3) m/e 445 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ =8.74 (s ； 1H), 8.44 (s; 1H)，8.13 (m; 2H)，7.75(d; 1H; J=8.1Hz)，7.70 (t; 1H; J=8.4Hz)，7.43 (d ； 1H ； J=8.4 Hz), 7.40 (d ； 1H ； J=12.0 Hz), 7.38 (d ； 1H ； J=8.1 Hz), 4.48 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.32 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.08 (m ； 1H)，3.28 (m ; 2H)，2·62 (s ; 3H). 實例295 (1SVH4-氣基-3-甲基-芊基）-2-[5-(3-甲基-1H-吲唑-5-基）-吡啶各基氧基1-乙胺 MS (DCI/NH3) m/e 407 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s； 1H), 8.41 (s ; 1H)，8.10 (s ; 1H)，8.05 (s ; 1H), 7.73 (d ； 1H ； J=8.4 Hz), 7.63 (d ； 1H ； J=8.4 Hz), 7.36 (d ； 1H ； J=8.4 Hz), 7.27 (s ； lH),7.15(d； 1H ； J=8.4 Hz), 4.44 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.28 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.96 (m ; 1H)，3.11 (m ; 2H)，2.62 (s ; 3H)，2.34 (s ; 3H)· , 實例296 口夫喃-3-基曱基-2-f5-(3-甲基-1H-P引峻-5-基）·外匕淀-3-基氧基乙胺 MS (DCI/NH3) ni/e 349 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 = 8.73 (s； 1H), 8.43 (s； lH)38.12(m； 2H), 7.74 (d； 1H； J=8.4 Hz), 7.63 (d； 1H； J=8.4 Hz), 7.53 (m -264- 200301122MS (DCI / NH3) m / e 485 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.65 (s; 1H), 8.36 (s; 1H) 5 8.07 (s; 1H), 7.92 (s; 1H) 57.75 (s; 1H), 7.72 (d; 1H; J = 8.1 Hz), 7.68 (d; 1H; J = 7.8 Hz), 7.62 (d; 1H; J = 8.1 Hz), 7.35 (d; 1H; J = 7.8 Hz), 7.16 (d; 1H; J = 7.8Hz), 4.40 (dd; 1H; J = 10.8Hz; J = 3.0 Hz), 4.24 (dd; 1H; J = 10.8Hz J = 4.5 Hz), 3.96 (m; 1H) 5 3.12 (m; 2H), 2.62 (s; 3H). Example 287 (1SM1SVH3-fluoro-4-methyl-methyl-fluorenyl V2- "5- (3 -Fluorenyl-1H-Wazole-5-yl) -pyridine-3-one hydrogen 1-ethylamine MS (DCI / NH3) m / e 391 (M + 1) +; 1H NMR (300 MHz, CD3 OD ) δ = 8.73 (s; 1H), -261-200301122 (254) 8.42 (s; lH), 8.12 (s; 1H), 8.10 (s; 1H), 7.74 (d; 1H; J = 8.1Hz), 7.63 (d; 1H; J = 8.1 Hz), 7.24 (t; 1H; J = 8.4 Hz), 7.05 (m; 2H), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0Hz), 4.28 ( dd; 1H; JN10.8 Hz; J = 4.5Hz), 3.97 (m; 1H), 3.13 (m; 2H), 2.62 (s; 3H), 2.23 (s; 3H). Example 288 (1SVM3-fluoro 4-methylamino-fluorenylmethyl-1H-Wazole-5-yl Vpyridin-3-yloxy 1-ethylamine MS (D CI / NH3) m / e 407 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.73 (s; 1H), 8.42 (s; 1H), 8.12 (s; 1H) 58.10 (s LH), 7.74 (d; 1H; J = 8.1 Hz), 7.63 (d; 1H; J = 8.1 Hz), 7.24 (t; 1H; J = 8.4 Hz), 7.05 (m; 2H), 4.44 (dd ; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.28 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.97 (m; 1H), 3.13 (m; 2H), 2.62 (s; 3H ), 2.23 (s; 3H). Example 289 (1SV2- "6-chloro-5- (3-methyl-1H-indazol-5-yl) -pyridin-3-ylamino 1-1- ( 3,4-Dichloro-fluorenyl Vethylamine MS (DCI / NH3) m / e 462 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.16 (s; 1H), 7.78 ( s; 1H), 7.54 (M; 4H), 7.48 (d; 1H; J = 8.1 Hz), 7.25 (d; 1H; J = 8.1 Hz), 4.32 (dd; 1H; J = 10.8 Hz; J-3.0 Hz), 4.15 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.93 (m; 1H), 3.12 (m; 2H), 2.58 (s; 3H). Example 290 (lS) -l- ( 2- ^ yl-6-dioxomethyl-fluorenyl) -2- [5- (3-fluorenyl-1Η * Ή | moxa-5-yl) · ρ 比淀 · 3-yloxy]- Ethylamine MS (DCI / NH3) m / e 445 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.69 (s; 1H), 8.36 (s; 1H) , 8.08 (s; 1H), 7.96 (s; 1H), 7.73 (d; 1H; J = 8.1 Hz), 7.63 (M; -262- 200301122 鼸 (255) 3H), 7.50 (t; 1H; J = 9.0 Hz), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.32 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.08 (m; 1H), 3.48 (m; 1H ), 335 (m; 1H), 2.62 (s; 3H). Example 291 (1S) -l- (4-Fluoro-3-trifluoromethyl-fluorenyl V2- "5- (3-methyl- 1H-oxazol-5-yl V-pyridine-3-ylamino1-ethylamine MS (DCI / NH3) m / e 445 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.70 (s; 1H), 8.41 (s; 1H), 8.09 (s; 1H), 8.04 (s; 1H), 7.74 (d; 1H; J = 8.1 Hz), 7.68 (m; 1H), 7.62 ( d; 1H; J = 8.1 Hz), 7.36 (t; 1H; J = 9.0 Hz), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.28 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.02 (m; 1H), 3.23 (m; 2H), 2.62 (s; 3H). Example 292 (IS) Small furan-2-ylmethyl-2-f5- (3-methyl -1H-Wazole-5-yl) -pyridin-3-yloxy 1-ethylamine MS (DCI / NH3) m / e 349 (M + lf; 1H NMR (300 MHz, CD3 OD) 5 = 8.68 ( s; 1H), 8.39 (s; 1H), 8.09 (m; 1H), 8.00 (s: 1H), 7.73 (d; 1H; J = 9.0 Hz), 7.62 (d; 1H; J = 9.0Hz), 7.50 (s; 1H), 6.42 (m; 1H), 6.33 (m; 1H), 4.49 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.31 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.02 (m; 1H), 3.24 (m; 2H) 5 2.62 (s; 3H) Example 293 (1S) -1-benzyl-2-ylmethylmethyl-5-yl) -p ratio Lake 3-yllactyl 1-ethylamine MS (DCI / NH3) m / e 398 (M + l) +; 1H NMR (300 MHz, CD3 OD) 5 = 8.72 (s; 1H), 8.42 (s; 1H), 8.09 (m; 2H), 7.72 (d; 1H; J = 9.0Hz ), 7.62 (d; 1H; J = 9.0Hz), 7.55 -263-200301122 (256) (d; 1H; J = 8.4 Hz), 7.45 (d; 1H; J = 8.4 Hz), 7.44 (m; 2H ), 6.78 (s; 1H)? 4.58 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.44 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz)? 4.18 (m; 1H), 3.41 (m; 2H), 2.62 (s; 3H) · Example 294 (1SVH3-Fluoro-4-trifluoromethyl-fluorenyl) -245- (3-methyl-1H-oxazol-5-yl V Pyridine- 3-yloxy1-ethylamine MS (DCI / NH3) m / e 445 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.74 (s; 1H), 8.44 (s 1H), 8.13 (m; 2H), 7.75 (d; 1H; J = 8.1Hz), 7.70 (t; 1H; J = 8.4Hz), 7.43 (d; 1H J = 8.4 Hz), 7.40 (d; 1H; J = 12.0 Hz), 7.38 (d; 1H; J = 8.1 Hz), 4.48 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.32 (dd ; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.08 (m; 1H), 3.28 (m; 2H), 2.62 (s; 3H). Example 295 (1SVH4-amino-3-methyl- Fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridyloxy 1-ethylamine MS (DCI / NH3) m / e 407 (M + l) + ; 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s; 1H), 8.41 (s; 1H), 8.10 (s; 1H), 8.05 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.36 (d; 1H; J = 8.4 Hz), 7.27 (s; lH), 7.15 (d; 1H; J = 8.4 Hz), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.28 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.96 (m; 1H), 3.11 (m; 2H), 2.62 (s; 3H) , 2.34 (s; 3H) ·, Example 296 Xanthan-3-ylfluorenyl-2-f5- (3-methyl-1H-Pin-5-yl) · Exo-3-yloxy Ethylamine MS (DCI / NH3) ni / e 349 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.73 (s; 1H), 8.43 (s; lH) 38.12 (m; 2H ), 7.74 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.5 3 (m -264- 200301122

(257) ；2H), 6.47 (m ； 1H), 4.49 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.33 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.91 (m ； 1H), 3.00 (m ； 2H), 2.62 (s ； 3H). 實例297 (1SVH2-氣基-5-甲基-芊基）-245-(3-甲基-1H-㈣唑-5-基）-吡啶-3-某氣基1-乙胺(257); 2H), 6.47 (m; 1H), 4.49 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.33 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.91 ( m; 1H), 3.00 (m; 2H), 2.62 (s; 3H). Example 297 (1SVH2-Gas-5-methyl-fluorenyl) -245- (3-methyl-1H-oxazole-5 -Yl) -pyridine-3-an alkyl 1-ethylamine

MS (DCI/NH3 ) m/e 391 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.65 (s； 1H), 8.36 (s ； 1H), 8.05 (s ； 1H), 7.90 (s ； 1H)5 7.70 (d ； 1H ； J=8.4 Hz), 7.62 (d ； 1H ； J=8.4 Hz), 7.09 (s ； 1H), 7.27 (d ； 1H ； J=8.1 Hz)7.18 (t ； 1H ； J=8.1 Hz), 439 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.25 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.04 (m ； 1H), 3.28 (m ； 2H), 2.62 (s ； 3H), 2.30 (s ； 3H). 實例298 (lS)-l-(3-氯基-5-說基-卞基）-2-[5-(3-甲基-lH-Hj嗅-5-基）-卩比淀-3-基乳基1-乙胺 MS (DCI/NH3) m/e 411 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s； 1H),MS (DCI / NH3) m / e 391 (M + l) +; 1H NMR (300 MHz, CD3 OD) δ = 8.65 (s; 1H), 8.36 (s; 1H), 8.05 (s; 1H), 7.90 (s; 1H) 5 7.70 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.09 (s; 1H), 7.27 (d; 1H; J = 8.1 Hz) 7.18 ( t; 1H; J = 8.1 Hz), 439 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.25 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.04 (m; 1H) , 3.28 (m; 2H), 2.62 (s; 3H), 2.30 (s; 3H). (3-Methyl-lH-Hjol-5-yl) -pyridine-3-yllactyl1-ethylamine MS (DCI / NH3) m / e 411 (M + 1) + 300 MHz, CD3 OD) δ = 8.71 (s; 1H),

8.41 (s ； 1H), 8.10 (s ； 1H), 8.06 (s ； 1H), 7.73 (d ； 1H ； J=8.4 Hz), 7.63 (d ； 1H ； J=8.4 Hz), 7.26 (s ； 1H), 7.18 (d ； 1H ； J=8.4 Hz), 7.12 (d ； 1H ； J=8.4 Hz), 4.46 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.30 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.02 (m ； 1H), 3.18 (m ； 2H), 2.62 (s ； 3H). 實例299 (lSV2-f5-(3-甲基-1H-W唑-5-基）-吡啶-3-基氣基VH3A5-三氟-芊基>· 乙胺 MS (DCI/NH3) m/e 413 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.73 (s； 1H), 8.44 (s； 1H), 8.10(m； 2H),7.74(d； 1H； J=8.4 Hz), 7.63 (d； 1H； J=8.4 Hz), 7.17 (t； 2H； J=9.0 Hz), 4.47 (dd ； 1H ； J=10.8Hz； J=3.0 Hz), 4.32 (dd ； 1H ； J=10.8 •265- 200301122 (258)8.41 (s; 1H), 8.10 (s; 1H), 8.06 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.26 (s; 1H ), 7.18 (d; 1H; J = 8.4 Hz), 7.12 (d; 1H; J = 8.4 Hz), 4.46 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.30 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.02 (m; 1H), 3.18 (m; 2H), 2.62 (s; 3H). Example 299 (lSV2-f5- (3-methyl-1H-Wazole-5 -Yl) -pyridin-3-ylamino VH3A5-trifluoro-fluorenyl > · Ethylamine MS (DCI / NH3) m / e 413 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ = 8.73 (s; 1H), 8.44 (s; 1H), 8.10 (m; 2H), 7.74 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.17 (t; 2H; J = 9.0 Hz), 4.47 (dd; 1H; J = 10.8Hz; J = 3.0 Hz), 4.32 (dd; 1H; J = 10.8 • 265- 200301122 (258)

Hz ； J=4.5 Hz), 4.00 (m ； 1H), 3.15 (m ； 2H)? 2.62 (s ； 3H). 實例300 (1SVH4-氟基-3-甲基-芊某V24H3-曱基-1H-吲唑-5-基）-吡啶-3-基氫基1-乙胺 MS (DCI/NH3) m/e 391 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) 5 = 8.73 (s; 1H)，Hz; J = 4.5 Hz), 4.00 (m; 1H), 3.15 (m; 2H)? 2.62 (s; 3H). Example 300 (1SVH4-fluoro-3-methyl-fluorene V24H3-fluorenyl-1H -Indazol-5-yl) -pyridin-3-ylhydrol 1-ethylamine MS (DCI / NH3) m / e 391 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.73 (s; 1H),

8.42 (s ； 1H), 8.12 (s ； 1H), 8.08 (s ； 1H), 7.73 (d ； 1H ； J=8.4 Hz), 7.62 (d ； 1H ； J=8.4 Hz), 7.18 (m ； 2H), 7.03 (t ； 1H ； J=9.0 Hz), 4.44 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.28 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.94 (m ； 1H)3 3.10 (m ; 2H)，2.62 (s ; 3H)，2.24 (s ; 3H). 實例301 (1SVH2,4-二氣-芊基V2-「5-(3-甲基唑-5-基V吡啶·3-基氧基1- 乙胺 MS (DCI/NH3) m/e 428 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.69 (s； 1H),8.42 (s; 1H), 8.12 (s; 1H), 8.08 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.18 (m; 2H ), 7.03 (t; 1H; J = 9.0 Hz), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.28 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.94 ( m; 1H) 3 3.10 (m; 2H), 2.62 (s; 3H), 2.24 (s; 3H). Example 301 (1SVH2,4-digas-fluorenyl V2- "5- (3-methylazole- 5-yl V-pyridine · 3-yloxy 1-ethylamine MS (DCI / NH3) m / e 428 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.69 (s; 1H) ,

8.40 (s ； 1H), 8.10 (s ； 1H), 8.00 (s ； 1H), 7.73 (d ； 1H ； J=8.4 Hz), 7.62 (d ； 1H; J=8.4Hz)，7,56 (s; 1H)，7.41 (d; 1H; J=8.1Hz)，7.36 (d; 1H; J=8.1)，4.43 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.28 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.05 (m ; 1H)，3.31 (m ; 2H)，2·62 (s ; 3H)· 實例302 (1SV1-⑷氣基-3-三氟甲基-芊基）-245-(3-甲基-1H-吲唑-5-基V吡啶- 3-基氣基1-乙胺 MS (DCI/NH3) m/e 461 (M+l)+ ; 1 H NMR (300 MHz, CD3 OD) δ = 8.69 (s； 1H), 8.39(s; 1H)，8.08 (s; 1H)，8.00 (s; 1H)，7.79 (s; 1H)，7.72 (d; 1H; J=8.4Hz)， 7.62 (m； 3H)?4.44(dd； 1H ; J=l〇.8 Hz ; J=3.0 Hz)，4.28 (dd ; 1H ； J=10.8 Hz ； J=4.5 Hz), 4.02 (m ； 1H)，3.26 (m ; 2H)，2.62 (s ; 3H). -266- 2003011228.40 (s; 1H), 8.10 (s; 1H), 8.00 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4Hz), 7,56 (s 1H), 7.41 (d; 1H; J = 8.1Hz), 7.36 (d; 1H; J = 8.1), 4.43 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.28 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.05 (m; 1H), 3.31 (m; 2H), 2.62 (s; 3H) · Example 302 (1SV1-fluorenyl-3-trifluoromethyl- Fluorenyl) -245- (3-methyl-1H-indazol-5-yl-V-pyridine- 3-ylamino1-ethylamine MS (DCI / NH3) m / e 461 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.69 (s; 1H), 8.39 (s; 1H), 8.08 (s; 1H), 8.00 (s; 1H), 7.79 (s; 1H), 7.72 (d; 1H; J = 8.4Hz), 7.62 (m; 3H)? 4.44 (dd; 1H; J = 1108 Hz; J = 3.0 Hz), 4.28 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz ), 4.02 (m; 1H), 3.26 (m; 2H), 2.62 (s; 3H). -266- 200301122

(259)(259)

A-766820.6 實例303 (lS)-2-[5-(3-甲基-1H-4丨咬-5-基）-p比咬-3-基氧基1-1-(2-三氣甲氧基· 芊基V乙胺 MS (DCI/NH3) m/e 443 (M+l)+ ; 1H NMR (300 MHz，CD3 OD) 5 = 8.70 (s; 1H)， 8.39 (s ； 1H), 8.09 (s ； 1H), 8.01 (s ； 1H).7.73 (d ； 1H ； J=8.4 Hz), 7.63 (d ； 1H ； J=8.4 Hz), 7.42 (Μ ； 4H), 4.40 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.24 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.00 (m ； 1H), 3.28 (m ； 2H), 2.62 (s ； 3H). 實例304 (lSM-(2,5-二甲氧基-芊基V2-「5-(3-甲基-1H-W唑-5-基）-吡啶-3-基氧基V乙胺 MS (DCI/NH3) m/e 419 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s； 1H), 8.40 (s ； 1H), 8.10 (s ； 1H)3 8.04 (s ； 1H), 7.73 (d ； 1H ； J=8.4 Hz), 7.63 (d ； 1H ； J=8.4 Hz)，6.95 (d ; 1H ; J=9.0 Hz)，6.85 (m ; 2H)，4.43 (dd ; 1H ; J=10.8 Hz ; J=3.0Hz),4.27(dd； 1H； J=10.8Hz； J=4.5 Hz), 4.00 (m ； lH),3.80(s； 3H), 3.69 (s ; 3H)，3.13 (m ; 2H)，2.62 (s ; 3H)· 實例305A-766820.6 Example 303 (1S) -2- [5- (3-Methyl-1H-4 丨 B-5-yl) -p Oxy · fluorenyl V ethylamine MS (DCI / NH3) m / e 443 (M + 1) +; 1H NMR (300 MHz, CD3 OD) 5 = 8.70 (s; 1H), 8.39 (s; 1H), 8.09 (s; 1H), 8.01 (s; 1H). 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.42 (Μ; 4H), 4.40 (dd; 1H J = 10.8 Hz; J = 3.0 Hz), 4.24 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.00 (m; 1H), 3.28 (m; 2H), 2.62 (s; 3H). Example 304 (1SM- (2,5-dimethoxy-fluorenyl V2- "5- (3-methyl-1H-Wazole-5-yl) -pyridin-3-yloxy V ethylamine MS ( DCI / NH3) m / e 419 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.71 (s; 1H), 8.40 (s; 1H), 8.10 (s; 1H) 3 8.04 ( s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 6.95 (d; 1H; J = 9.0 Hz), 6.85 (m; 2H), 4.43 ( dd; 1H; J = 10.8 Hz; J = 3.0Hz), 4.27 (dd; 1H; J = 10.8Hz; J = 4.5 Hz), 4.00 (m; lH), 3.80 (s; 3H), 3.69 (s; 3H), 3.13 (m; 2H), 2.62 (s; 3H) · Example 305

(lSV2-「5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1小(4-甲硫基-芊基V 乙胺 MS (DCI/NH3) m/e 405 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 6 = 8.73 (s； 1H), 8.62 (s ; 1H)，8,12 (s ; 1H)，8·08 (s ; 1H)，7.73 (d ; 1H ; J=8.4 Hz)，7.63 (d ; 1H ; -267- 200301122(1SV2- "5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1 small (4-methylthio-fluorenyl V ethylamine MS (DCI / NH3) m / e 405 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 6 = 8.73 (s; 1H), 8.62 (s; 1H), 8, 12 (s; 1H), 8.08 (s ; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; -267- 200301122

(260) J=8.4 Ηζ)，7·28 (s ; 4H)，4.44 (dd ; 1H ; J=10.8 Hz ; J=3.0 Hz)，4.29 (dd ; 1H ； J=10.8 Hz ； J=4.5 Hz), 3.95 (m ； 1H)，3.12 (m ; 2H)，2.62 (s ; 3H)，2.44 (s ; 3H). 實例306 (18)-1-(2-¾己基-卞基）-2-『5-(3-甲基-1H-口峻-5-基）-口比淀-3-基氧基1· 乙胺(260) J = 8.4 Ηζ), 7.28 (s; 4H), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.29 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz ), 3.95 (m; 1H), 3.12 (m; 2H), 2.62 (s; 3H), 2.44 (s; 3H). Example 306 (18) -1- (2-¾hexyl-fluorenyl) -2- "5- (3-Methyl-1H-Houjun-5-yl) -Houbidian-3-yloxy1 · Ethylamine

MS (DCI/NH3) m/e 441 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.70 (s； 1H), 8.40 (s ； 1H)5 8.07 (s ； 1H), 8.01 (s ； 1H), 7.71 (d ； 1H ； J=8.4 Hz), 7.62 (d ； 1H ； J=8.4 Hz), 7.34 (d ； 1H ； J=7.8 Hz), 7.25 (m ； 2H), 7.16 (t ； 1H ； J=7.8 Hz), 4.37 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.23 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.38 (m ; 1H)，3.27 (m ; 2H)，2.77 (m ; 1H)，2.62 (s ; 3H)，1·85 (m ; 1H)，1.74 (m ; 4H)，L48 (m ; 3H)，1·29 (m，2H). 實例307 (lS)-l-(2,5-二氯-芊基）-2-[5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基]-乙胺 MS (DCI/NH3) m/e 428 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.71 (s； 1H),MS (DCI / NH3) m / e 441 (M + l) +; 1H NMR (300 MHz, CD3 OD) δ = 8.70 (s; 1H), 8.40 (s; 1H) 5 8.07 (s; 1H), 8.01 (s; 1H), 7.71 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.34 (d; 1H; J = 7.8 Hz), 7.25 (m; 2H), 7.16 (t; 1H; J = 7.8 Hz), 4.37 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.23 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.38 (m; 1H ), 3.27 (m; 2H), 2.77 (m; 1H), 2.62 (s; 3H), 1.85 (m; 1H), 1.74 (m; 4H), L48 (m; 3H), 1.29 ( m, 2H). Example 307 (lS) -l- (2,5-dichloro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridine-3- Alkyloxy] -ethylamine MS (DCI / NH3) m / e 428 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ = 8.71 (s; 1H),

8.41 (s ; 1H)，8.10 (s ; 1H)，8.04 (s ; 1H)，7.73 (d ; 1H ; J=8.4 Hz)，7.63 (d ; 1H ； J=8.4 Hz), 7.48 (m ； 2H), 7.36 (d ； 1H ； J=8.4 Hz), 4.44 (dd ； 1H ； J=10.8Hz； J=3.0Hz),4.28(dd； 1H； J=10.8Hz； J=4.5 Hz), 4.07 (m； lH),3.36(m； 2H), 2.62 (s ； 3H). 實例308 (1S)-M2,5-二甲基-宇基V2-「5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基 V乙胺 MS (DCI/NH3) m/e 387 (M+l)4* ； 1H NMR (300 MHz, CD3 OD) δ = 8.74 (s； 1H), 8.2 (s ； 1H), 8.11 (s ； 1H), 8.08 (s ； 1H), 7.73 (d ； 1H ； J=8.4 Hz), 7.63 (d ； 1H ； -268- 200301122 (261) J=8.4 Ηζ)，7·11 (d ; 1H ; J=8.1 Hz)，7.03 (m ; 2H)，4.41 (dd ; 1H ； J=10.8 Hz ； J=3.0Hz),4.28(dd； 1H； J=10.8Hz； J=4.5 Hz), 3.94 (m； lH),3.14(m； 2H), 2.62 (s ； 3H), 2.34 (s ； 3H), 2.23 (s ； 3H). 實例309 (1SVH2,3-二甲基-芊基）-245-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氣墓 V乙胺 MS (DCI/NH3) m/e 387 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) 5 = 8.65 (s; 1H)，8.41 (s; 1H), 8.10 (s; 1H), 8.04 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.48 (m; 2H ), 7.36 (d; 1H; J = 8.4 Hz), 4.44 (dd; 1H; J = 10.8Hz; J = 3.0Hz), 4.28 (dd; 1H; J = 10.8Hz; J = 4.5 Hz), 4.07 ( m; lH), 3.36 (m; 2H), 2.62 (s; 3H). Example 308 (1S) -M2,5-dimethyl-uryl V2- "5- (3-methyl-1H-indazole -5-yl) -pyridin-3-yloxy V ethylamine MS (DCI / NH3) m / e 387 (M + 1) 4 *; 1H NMR (300 MHz, CD3 OD) δ = 8.74 (s; 1H ), 8.2 (s; 1H), 8.11 (s; 1H), 8.08 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; -268- 200301122 (261) J = 8.4 Ηζ), 7 · 11 (d; 1H; J = 8.1 Hz), 7.03 (m; 2H), 4.41 (dd; 1H; J = 10.8 Hz; J = 3.0Hz), 4.28 (dd; 1H; J = 10.8Hz; J = 4.5 Hz), 3.94 (m; lH), 3.14 (m; 2H), 2.62 (s; 3H), 2.34 (s; 3H), 2.23 (s; 3H). Example 309 (1SVH2,3 -Dimethyl-fluorenyl) -245- (3-methyl-1H-indazol-5-yl) -pyridin-3-yl gas tome V ethylamine MS (DCI / NH3) m / e 387 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.65 (s; 1H),

8.35 (s ; 1H)，8·05 (s ; 1H)，7.90 (s ; 1H)，7·70 (d ; 1H ; J=8.4 Hz)，7.60 (d ; 1H ； J=8.4 Hz), 7.07 (τη ； 3H), 4.35 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.22 (dd ； 1H ； J=10.8 Hz； J=4.5 Hz), 3.88 (m； 1H), 3.21 (m； 2H), 2.62 (s； 3H), 2.31 (s； 3H), 2.28 (s ； 3H). 實例310 (15)-1-(3,4-二氯-芊基）-2-「5-(3-甲基-111-糾唑-5-基）-吡啶-3-基氧基1- 乙胺 MS (DCI/NH3) m/e 428 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.68 (s； 1H),8.35 (s; 1H), 8.05 (s; 1H), 7.90 (s; 1H), 7.70 (d; 1H; J = 8.4 Hz), 7.60 (d; 1H; J = 8.4 Hz), 7.07 (τη; 3H), 4.35 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.22 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.88 (m; 1H), 3.21 (m 2H), 2.62 (s; 3H), 2.31 (s; 3H), 2.28 (s; 3H). Example 310 (15) -1- (3,4-dichloro-fluorenyl) -2- "5- (3-methyl-111-pyrazol-5-yl) -pyridin-3-yloxy 1-ethylamine MS (DCI / NH3) m / e 428 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ = 8.68 (s; 1H),

8.39 (s ； 1H), 8.08 (s ； 1H), 7.98 (s ； 1H), 7.72 (d ； 1H ； J=8.4 Hz), 7.62 (d ； 1H ； J=8.4 Hz), 7.56 (s ； 1H), 7.54 (d ； 1H ； J=8.4 Hz), 7.28 (d ； 1H ； J=8.4 Hz), 4.43 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.27 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.99 (m ; 1H)，3.16 (m ; 2H)，2.62 (s ; 3H)· 實例311 (lSVl-(2,4-二甲基-芊基甲基-1H-蜊唑-5-基）-吡啶-3-基氧基 1·乙胺 MS (DCI/NH3) m/eJ387 (M+lf ； 1H NMR (300 MHz, CD3 OD) δ = 8.68 (s； 1H), 8.37 (s ； 1H), 8.08 (s ； 1H)? 7.96 (s ； 1H), 7.71 (d ； 1H ； J=8.4 Hz), 7.61 (d ； 1H ； -269- 200301122 (262)8.39 (s; 1H), 8.08 (s; 1H), 7.98 (s; 1H), 7.72 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.56 (s; 1H ), 7.54 (d; 1H; J = 8.4 Hz), 7.28 (d; 1H; J = 8.4 Hz), 4.43 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.27 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.99 (m; 1H), 3.16 (m; 2H), 2.62 (s; 3H) · Example 311 (lSVl- (2,4-dimethyl-fluorenylmethyl- 1H-clamazol-5-yl) -pyridin-3-yloxy 1 · ethylamine MS (DCI / NH3) m / eJ387 (M + lf; 1H NMR (300 MHz, CD3 OD) δ = 8.68 (s; 1H), 8.37 (s; 1H), 8.08 (s; 1H)? 7.96 (s; 1H), 7.71 (d; 1H; J = 8.4 Hz), 7.61 (d; 1H; -269- 200301122 (262)

J=8.4 Hz)，7.10 (d ; 1H ; J=7.5 Ηζ)，7·06 (s ; 1H)，6·98 (d ; 1H ; J=7.5 Hz)，4.37 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.24 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.90 (m ； 1H)，3.14 (m ; 2H)，2.62 (s ; 3H)，2.35 (s ; 3H)，2·26 (s ; 3H)· 實例312 (1SVM3-氟基-4-三氣甲基-芊基V2-『5-(3-甲基-1H-钊唑-5-基）-吡啶- 3-基氣基1-乙胺 MS (DCI/NH3) m/e 445 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 = 8.68 (s； 1H), 8.39 (s ; 1H)，8.08 (s ; 1H), 7.98 (s ； 1H), 7.72 (d ； 1H ； J=8.4 Hz), 7.70 (d ； 1H ； J=8.4 Hz)，7.62 (d ; 1H ； J=8.4 Hz), 7.39 (d ； 1H ； J=12.0 Hz), 7.35 (d ； 1H ； J=8.4 Hz)，4.44 (dd ; 1H ； J=10.8 Hz ； J=3.0 Hz), 4.28 (dd ； 1H ； J=10.8Hz； J=4.5 Hz), 4.05 (m ； 1H)5 3.28 (m ； 2H), 2.62 (s ； 3H). 實例313 (lSVl-(3,5-二甲基-芊基）-245-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基 1-乙胺 MS (DCI/NH3) ni/e 387 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.68 (s； 1H), 8.38 (s ； 1H), 8.08 (s ； 1H)，7.97 (s ; 1H)，7.71 (d ; 1H ; J=8.4 Hz)，6·94 (m ; 3H), 4.41 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.25 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.92 (m ； 1H)，3.07 (m ; 2H)，2.62 (s ; 3H)，2.26 (s ; 6H). 實例314J = 8.4 Hz), 7.10 (d; 1H; J = 7.5 Ηζ), 7.06 (s; 1H), 6.98 (d; 1H; J = 7.5 Hz), 4.37 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.24 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.90 (m; 1H), 3.14 (m; 2H), 2.62 (s; 3H), 2.35 (s; 3H), 2.26 (s; 3H). Example 312 (1SVM3-fluoro-4-trifluoromethyl-fluorenyl V2- "5- (3-methyl-1H-zazol-5-yl)- Pyridine-3-ylamino1-ethylamine MS (DCI / NH3) m / e 445 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.68 (s; 1H), 8.39 (s 1H), 8.08 (s; 1H), 7.98 (s; 1H), 7.72 (d; 1H; J = 8.4 Hz), 7.70 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.39 (d; 1H; J = 12.0 Hz), 7.35 (d; 1H; J = 8.4 Hz), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.28 (dd; 1H ; J = 10.8Hz; J = 4.5 Hz), 4.05 (m; 1H) 5 3.28 (m; 2H), 2.62 (s; 3H). Example 313 (lSVl- (3,5-dimethyl-fluorenyl) -245- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1-ethylamine MS (DCI / NH3) ni / e 387 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.68 (s; 1H), 8.38 (s; 1H), 8.08 (s; 1H), 7.97 (s; 1H), 7.71 (d; 1H; J = 8.4 Hz), 6.94 (m; 3H), 4.41 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.25 (dd; 1H ; J = 10.8 Hz; J = 4.5 Hz), 3.92 (m; 1H), 3.07 (m; 2H), 2.62 (s; 3H), 2.26 (s; 6H). Example 314

(1SH-聯笨冬基甲基-2-『5-(3-曱基-1H-吲唑-5-基V吡啶各基氣基V 乙胺 MS (DCI/NH3) m/e 435 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) 5 = 8.64 (s; 1H)， 8.11 (s ; 1H)，8.05 (s ; 1H)，7·70 (d ; 1H ; J=8.4 Hz)，7.68 (s ; 1H)，7.63 (d ; 1H ; J=8.4 Hz), 7.34 (Μ ； 9H), 4.12 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 3.89 (dd ； 1H ； -270- 200301122(1SH-bibenzylmethyl-2- "5- (3-fluorenyl-1H-indazol-5-yl Vpyridine each radical Vethylamine MS (DCI / NH3) m / e 435 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.64 (s; 1H), 8.11 (s; 1H), 8.05 (s; 1H), 7.70 (d; 1H; J = 8.4 Hz ), 7.68 (s; 1H), 7.63 (d; 1H; J = 8.4 Hz), 7.34 (M; 9H), 4.12 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 3.89 (dd; 1H ; -270- 200301122

(263) J=10.8Hz; J=4.5Hz)，3.64 (m; 1H)，3.39 (dd; 1H; J=14.4 Hz; J=9.3Hz)，3.16 (dd ； 1H ； J=14.4 Hz, J=4.5 Hz), 2.62 (s ； 3H). 實例315 (lSVl-(3,4-二甲基-芊基）-245-(3-甲基-1H-⑷唑-5-基V吡啶各基氣基 1-乙胺 MS (DCI/NH3) m/e 387 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.69 (s； 1H), 8.38 (s ； 1H), 8.08 (s ； 1H), 7.99 (s ； 1H), 7.72 (d ； 1H ； J=8.4 Hz), 7.62 (d ； 1H ； J=8.4 Hz), 7.08 (m ； 3H), 4.41 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.26 (dd ； 1H ； J=10.8 Hz; J=4.5Hz)，3.91(m; 1H)，3.08 (m; 2H)，2.62(s; 3H)，2.29 (s; 3H)，2,23 (s ； 3H). 實例316 (lSVl-(2,3-二氣-笨并l)-2-『5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氣基1- 乙胺 MS (DCI/NH3) m/e 395 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) 5 = 8.74 (s; 1H)， 8.44 (s； 1H), 8.12(s； 2H),7.74(d； 1H； J=8.4 Hz), 7.62 (d ； 1H； J=8.4 Hz), 7.19 (m ； 3H), 4.48 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz)? 4.32 (dd ； 1H ; J=10.8 Hz ; J=4.5 Hz), 4.03 (m ； 1H), 3.30 (m ； 2H), 2.62 (s ； 3H). 實例317 nS)-l-(2,5-二氟-芊基V2-「5-(3-甲基-1H-啕唑-5-基V吡啶-3-基氧基l·· 乙胺 MS (DCI/NH3) m/e 395 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.77 (s； 1H), 8.46 (s ； 1H), 8.18 (s ； 1H), 8.13 (s ； 1H), 7.75 (d ； 1H ； J=8.4 Hz), 7.63 (d ； 1H ； J=8.4 Hz)，7.17 (m ; 3H)，4·49 (dd ; 1H ; J=10.8 Hz ; J=3.0 Hz)，4.33 (dd ; 1H ; J=10.8 Hz ； J=4.5 Hz), 4.02 (m ； 1H)，3.12 (m ; 2H)，2·62 (s ; 3H). -271 - 200301122 (264) 實例3ί8 (15)小(2,6-二氯-芊基）-2-「5-(3-甲基-11^?1唑-5-基）-吡啶-3-基氣基1- 乙胺(263) J = 10.8Hz; J = 4.5Hz), 3.64 (m; 1H), 3.39 (dd; 1H; J = 14.4 Hz; J = 9.3Hz), 3.16 (dd; 1H; J = 14.4 Hz, J = 4.5 Hz), 2.62 (s; 3H). Example 315 (lSVl- (3,4-dimethyl-fluorenyl) -245- (3-methyl-1H-oxazol-5-yl Vpyridine each group Gas 1-ethylamine MS (DCI / NH3) m / e 387 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.69 (s; 1H), 8.38 (s; 1H), 8.08 (s; 1H), 7.99 (s; 1H), 7.72 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.08 (m; 3H), 4.41 (dd; 1H ;; J = 10.8 Hz; J = 3.0 Hz), 4.26 (dd; 1H; J = 10.8 Hz; J = 4.5Hz), 3.91 (m; 1H), 3.08 (m; 2H), 2.62 (s; 3H), 2.29 (s; 3H), 2,23 (s; 3H). Example 316 (lSVl- (2,3-digas-benzyl) -2- "5- (3-methyl-1H-indazole-5 -Yl V-pyridin-3-ylamino 1-ethylamine MS (DCI / NH3) m / e 395 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.74 (s; 1H), 8.44 (s; 1H), 8.12 (s; 2H), 7.74 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4 Hz), 7.19 (m; 3H), 4.48 (dd; 1H ; J = 10.8 Hz; J = 3.0 Hz)? 4.32 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.03 (m; 1H), 3.30 (m; 2H ), 2.62 (s; 3H). Example 317 nS) -l- (2,5-difluoro-fluorenyl V2- "5- (3-methyl-1H-oxazol-5-yl Vpyridine-3- Alkoxyl · · ethylamine MS (DCI / NH3) m / e 395 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.77 (s; 1H), 8.46 (s; 1H) , 8.18 (s; 1H), 8.13 (s; 1H), 7.75 (d; 1H; J = 8.4 Hz), 7.63 (d; 1H; J = 8.4 Hz), 7.17 (m; 3H), 4.49 ( dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.33 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.02 (m; 1H), 3.12 (m; 2H), 2.62 ( s; 3H). -271-200301122 (264) Example 3 ί 8 (15) small (2,6-dichloro-fluorenyl) -2- "5- (3-methyl-11 ^? 1azole-5-yl ) -Pyridin-3-ylamino 1-ethylamine

MS (DCI/NH3) m/e 428 (M+lf ； 1 H NMR (300 MHz, CD3 OD) δ = 8.64 (s； 1H), 8.33 (s ; 1H)，8.05 (s ; 1H)，7.88 (s ; 1H)，7.70 (d ; 1H ; J=8.4 Hz)，7.61 (d ; 1H ; J=8.4Hz)57.48 (d； 2H； J=7.2 Hz)5 7.33 (t ； 1H； J=7.2 Hz), 4.40 (dd ； 1H； J=10.8 Hz ； J=3.0 Hz), 4.29 (dd ； 1H ; J=10.8 Hz ; J=4.5 Hz)，4·10 (m ; 1H), 3.67 (dd ； 1H ； J=15.0 Hz ； J=9.6 Hz), 3.43 (dd ； 1H ； J=15.0 Hz ； J=5.4 Hz), 2.62 (s ； 3H). 實例319 (lSVl-(2,4-二氟-芊基V2-「5-(3-甲基-1H-峋唑-5-基）-吡啶-3-基氣基1- 乙胺 MS (DCI/NH3) m/e 395 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ = 8.67 (s； 1H), 8.37 (s ; 1H)，8.08 (s ; 1H)，7.94 (s ; 1H)，7.71 (d ; 1H ; J=8.4 Hz)，7.61 (d ; 1H ; J=8.4 Hz)，7.40 (m ; 1H)，7.01 (m; 2H)，4.43 (dd; 1H; J=10.8 Hz; J=3.0 Hz), 4.27 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.96 (m ； 1H)5 3.10 (m ； 2H), 2.62 (s ；MS (DCI / NH3) m / e 428 (M + lf; 1 H NMR (300 MHz, CD3 OD) δ = 8.64 (s; 1H), 8.33 (s; 1H), 8.05 (s; 1H), 7.88 ( s; 1H), 7.70 (d; 1H; J = 8.4 Hz), 7.61 (d; 1H; J = 8.4Hz) 57.48 (d; 2H; J = 7.2 Hz) 5 7.33 (t; 1H; J = 7.2 Hz ), 4.40 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.29 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4 · 10 (m; 1H), 3.67 (dd; 1H J = 15.0 Hz; J = 9.6 Hz), 3.43 (dd; 1H; J = 15.0 Hz; J = 5.4 Hz), 2.62 (s; 3H). Example 319 (lSVl- (2,4-difluoro-fluorene) V2- "5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-ylamino 1-ethylamine MS (DCI / NH3) m / e 395 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ = 8.67 (s; 1H), 8.37 (s; 1H), 8.08 (s; 1H), 7.94 (s; 1H), 7.71 (d; 1H; J = 8.4 Hz ), 7.61 (d; 1H; J = 8.4 Hz), 7.40 (m; 1H), 7.01 (m; 2H), 4.43 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.27 (dd; 1H J = 10.8 Hz; J = 4.5 Hz), 3.96 (m; 1H) 5 3.10 (m; 2H), 2.62 (s;

3H). 實例320 (lSVl-(2,6-二甲基-芊基甲基-1H-吲唑-5-基吡啶-3-基氧基 1-乙胺 MS (DCI/NH3) m/e 387 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.62 (s； 1H), 8.32 (s ； 1H), 8.03 (s ； 1H), 7.83 (s ； 1H), 7.69 (d ； 1H ； J=8.4 Hz), 7.60 (d ； 1H ； J=8.4 Hz)，7.70 (m ; 3H), 4.29 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.16 (dd ； 1H ； J=10.8Hz； J=4.5Hz),3.92(m； lH),337(dd； 1H； J=15.0Hz； J=10.5 Hz), 3.15 -272 - 200301122 (265) (dd ； 1H ； J=15.0 Hz ； J=5.4 Hz), 2.62 (s ； 3H), 2.38 (s ； 6H). 實例321 (1S)-H2,3-二氫-苯并ΠΛΙ二氧陸圜烯-6-基甲基）-2-「5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1-乙胺 MS (DCI/NH3) m/e 417 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 6 = 8.64 (s； 1H), 8.36 (s ; 1H)，8.07 (s ; 1H)，7.91 (s ; 1H)，7·71 (d ; 1H ; J=8.4 Hz)，7.61 (d ; 1H ; J=8.4 Hz), 6.80 (m ； 3H), 4.40 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.23 (dd ； 1H ； J=10.8Hz; J=4.5Hz)，4.20 (s; 4H)，3.88 (m; lH)，3.03(m; 2H)，2.62 (s; 3H). 實例322 (lS)-l-(3,5-二耽-卞基）-2-f5-(3-甲基-1H-口弓I 峻-5-基）-p比淀-3-基乳基 1· 乙胺 MS (DCI/NH3) m/e 395 (M+l)+ ； 1H NMR (300 MHz, CD3 OD) δ = 8.67 (s； 1H), 8.39 (s ; 1H)，8.08 (s ; 1H)，7.98 (s ; 1H)，7.73 (d ; 1H ; J=8.4 Hz)，7.61 (d ; 1H ; J=8.4 Hz), 6.97 (m ； 3H), 4.44 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.29 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 4.01 (m ； 1H)，3.19 (m ; 2H)，2.62 (s ; 3H). 實例323 (lS)-l-(2,6-二氟-芊基）-245-(3-甲基-1H-W 唑-5-基）-吡啶-3-基氧基 1- 乙胺 MS (DCI/NH3) m/e 395 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 = 8.41 (s； 1H), 8.31 (s ； 1H), 8.04 (s ； 1H), 7.84 (s ； 1H), 7.70 (d ； 1H ； J=8.4 Hz), 7.60 (d ； 1H ； J=8.4 Hz), 7.40 (m ； 1H), 7.06 (m ； 2H), 4.42 (dd ； 1H ； J=10.8 Hz ； J=3.0Hz)3 4.24 (dd ； 1H ； J=10.8 Hz ； J=4.5 Hz), 3.97 (m ； 1H)3 3.31 (m ； 2H), 2.62 (s ； 3H). -273- 200301122 臓 (266)3H). Example 320 (1SVl- (2,6-dimethyl-fluorenylmethyl-1H-indazol-5-ylpyridin-3-yloxy1-ethylamine MS (DCI / NH3) m / e 387 (M + l) +; 1H NMR (300 MHz, CD3 OD) δ = 8.62 (s; 1H), 8.32 (s; 1H), 8.03 (s; 1H), 7.83 (s; 1H), 7.69 (d ; 1H; J = 8.4 Hz), 7.60 (d; 1H; J = 8.4 Hz), 7.70 (m; 3H), 4.29 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.16 (dd; 1H ; J = 10.8Hz; J = 4.5Hz), 3.92 (m; lH), 337 (dd; 1H; J = 15.0Hz; J = 10.5 Hz), 3.15 -272-200301122 (265) (dd; 1H; J = 15.0 Hz; J = 5.4 Hz), 2.62 (s; 3H), 2.38 (s; 6H). Example 321 (1S) -H2,3-dihydro-benzo ΠΛΙ dioxaloxene-6-ylmethyl Group) -2- "5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1-ethylamine MS (DCI / NH3) m / e 417 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 6 = 8.64 (s; 1H), 8.36 (s; 1H), 8.07 (s; 1H), 7.91 (s; 1H), 7.71 (d; 1H; J = 8.4 Hz), 7.61 (d; 1H; J = 8.4 Hz), 6.80 (m; 3H), 4.40 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.23 (dd; 1H; J = 10.8Hz; J = 4.5Hz), 4.20 (s; 4H), 3.88 (m; lH), 3.03 (m; 2H), 2.62 (s; 3H). Example 322 (lS) -l- (3,5-Dithio-fluorenyl) -2-f5- (3-methyl-1H-orbyl I-5-yl) -p Biyodo-3-yl milk base 1. Ethylamine MS (DCI / NH3) m / e 395 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ = 8.67 (s; 1H), 8.39 (s 1H), 8.08 (s; 1H), 7.98 (s; 1H), 7.73 (d; 1H; J = 8.4 Hz), 7.61 (d; 1H; J = 8.4 Hz), 6.97 (m; 3H), 4.44 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.29 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.01 (m; 1H), 3.19 (m; 2H), 2.62 (s 3H). Example 323 (1S) -l- (2,6-difluoro-fluorenyl) -245- (3-methyl-1H-Wazol-5-yl) -pyridin-3-yloxy 1 -Ethylamine MS (DCI / NH3) m / e 395 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 = 8.41 (s; 1H), 8.31 (s; 1H), 8.04 (s; 1H), 7.84 (s; 1H), 7.70 (d; 1H; J = 8.4 Hz), 7.60 (d; 1H; J = 8.4 Hz), 7.40 (m; 1H), 7.06 (m; 2H), 4.42 ( dd; 1H; J = 10.8 Hz; J = 3.0Hz) 3 4.24 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 3.97 (m; 1H) 3 3.31 (m; 2H), 2.62 (s; 3H). -273- 200301122 臓 (266)

實例324 (1S)-1-苯并π，31二氧伍圜烯基-5-基甲基-2-f5-(3-甲基-1H-吲唑-5-基Example 324 (1S) -1-benzoπ, 31 dioxolenyl-5-ylmethyl-2-f5- (3-methyl-1H-indazol-5-yl

)-口比淀-3-基氧基1-乙胺 MS (APCI) m/z 404 (M+l)+ ； 1H NMR (500 MHz, CD3 OD) 5 ppm 2.63 (s, 3H), 3.08 (dd，J=7.64,2.65 Hz，2H)，3·92 (m，1H)，4·32 (dd，J=10.45,5.77 Hz, 1H)，4.46 (dd， J=10.61,2.81 Hz, 1H), 5.92 (d5 J=1.87 Hz, 2H), 6.80 (d, J=1.87 Hz, 2H), 6.85 (s, 1H), 7.64 (d, J=8.73 Hz, 1H), 7.74 (dd, J=8.73,1.56 Hz, 1H), 8.12 (s, 1H), 8.14 (d, J=1.87 Hz，lH)，8.45(d，J=1.87Hz，lH)，8.74(s，1H);對 C23H22N403 之分析計算值：C，48.46 : Η，3·55; Ν，8·02·實測值：C，48.59 ; H，3.65; N，8.13. 實例325 (lS)-l-(4-乱基-3-甲基-卞基)-2-f5-(3-曱基-1H-口弓I峻一5_基)一p比淀.3_基) -Hipido-l-3-yloxy1-ethylamine MS (APCI) m / z 404 (M + 1) +; 1H NMR (500 MHz, CD3 OD) 5 ppm 2.63 (s, 3H), 3.08 ( dd, J = 7.64, 2.65 Hz, 2H), 3.92 (m, 1H), 4.32 (dd, J = 10.45, 5.77 Hz, 1H), 4.46 (dd, J = 10.61,2.81 Hz, 1H) , 5.92 (d5 J = 1.87 Hz, 2H), 6.80 (d, J = 1.87 Hz, 2H), 6.85 (s, 1H), 7.64 (d, J = 8.73 Hz, 1H), 7.74 (dd, J = 8.73 , 1.56 Hz, 1H), 8.12 (s, 1H), 8.14 (d, J = 1.87 Hz, lH), 8.45 (d, J = 1.87Hz, lH), 8.74 (s, 1H); Analysis and calculation of C23H22N403 Value: C, 48.46: Thallium, 3.55; Ν, 8.02. Found: C, 48.59; H, 3.65; N, 8.13. Example 325 (lS) -l- (4- disorderyl-3-formaldehyde) Base-fluorenyl) -2-f5- (3-fluorenyl-1H-portal bow I-5-5 radical) -p ratio. 3_ radical

氣基1-乙胺 MS (APCI) m/z 392 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.24 (s, 3H), 2.63 (s，3H)，3·11 (dd，J=7.64, 3·90 Hz，2H)，3.94 (m，1H)，4.29 (dd，J=10.61，5.62 Hz, 1H)，4.44 (dd，J=10.61，2·81 Hz，1H)，7.03 (m，1H)，7.16 (m，1H)，7.21 (d，J=7.18 Hz， 1H)，7.63 (d，J=8.73 Hz，1H)，7.74 (d，J=1.87 Hz，1H)，8.06 (s，1H)，8.10 (s，1H)， 8.42 (s，1H)，8.71 (s，1H);對 C2 3 H2 3 FN4 0 之分析計算值：C，50.79 ; Η，3·91; N，8.58·實測值·· C，51.10 ; H，4.02; N，8.43. 實例326 -274- 200301122 (267) 基）-乙胺 MS (APCI) m/z 402 (M+lf ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.21 (s, 3H)5 2.34 (s，6H)，2.62 (s，3H)，3.14 (dd, J=14.19, 5.46 Hz, 2H)，3.92 (m，JN8.73, 4.99 Hz， 1H)，4.26 (dd，J=10.45, 4.84 Hz，1H)，4.36 (m，1H)，6.89 (s，2H)，7.63 (d，J=8.74 Hz， 1H)，7.72 (dd，J=8.73, 1·56 Hz，1H)，8·11 (s，2H)，8.42 (s，1H)，8·75 (s，1H);對 C25H28N40 之分析計算值·· C，52·56; Η，4·48; N，8·17·實測值：C，52.49Gas-based 1-ethylamine MS (APCI) m / z 392 (M + l) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.24 (s, 3H), 2.63 (s, 3H), 3.11 (dd, J = 7.64, 3.90 Hz, 2H), 3.94 (m, 1H), 4.29 (dd, J = 10.61, 5.62 Hz, 1H), 4.44 (dd, J = 10.61, 2.81 Hz, 1H ), 7.03 (m, 1H), 7.16 (m, 1H), 7.21 (d, J = 7.18 Hz, 1H), 7.63 (d, J = 8.73 Hz, 1H), 7.74 (d, J = 1.87 Hz, 1H ), 8.06 (s, 1H), 8.10 (s, 1H), 8.42 (s, 1H), 8.71 (s, 1H); Analytical calculations for C2 3 H2 3 FN4 0: C, 50.79; Η, 3 · 91; N, 8.58 · Measured value · C, 51.10; H, 4.02; N, 8.43. Example 326 -274- 200301122 (267) group)-Ethylamine MS (APCI) m / z 402 (M + lf; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.21 (s, 3H) 5 2.34 (s, 6H), 2.62 (s, 3H), 3.14 (dd, J = 14.19, 5.46 Hz, 2H), 3.92 (m, JN8.73, 4.99 Hz, 1H), 4.26 (dd, J = 10.45, 4.84 Hz, 1H), 4.36 (m, 1H), 6.89 (s, 2H), 7.63 (d, J = 8.74 Hz, 1H), 7.72 (dd, J = 8.73, 1.556 Hz, 1H), 8.11 (s, 2H), 8.42 (s, 1H), 8.75 (s, 1H); Analysis and calculation of C25H28N40 ... C , 52 · 56; Η, 4.48; N , 8.17 · Measured value: C, 52.49

;H，4.41 ; N，8·06· 實例327 (lSM-(2,4-二甲氧基-芊基）-245-(3-甲基-1H-沔丨唑-5-基）-吡啶-3-基氣基1-乙胺 MS (APCI) m/z 419 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s, 3H), 3.08 (dd, J=7.33, 2.96 Hz, 2H), 3.77 (s, 3H), 3.83 (s, 3H), 3.94 (m, 1H), 4.26 (dd, J= 10.45, 5.77 Hz, 1H), 4.41 (dd, J=10.61, 3.12 Hz, 1H), 6.50 (dd3 J=8.27, 2.34 Hz, 1H), 6.59 (d, J=2.50 Hz, 1H), 7.12 (d5 J=8.42 Hz, 1H), 7.63 (d, J=8.73 Hz, 1H), 7.72 (m, 1H)，8.00 (s，1H), 8.09 (s，1H)，8.40 (s，1H)，8.71 (s，1H).H, 4.41; N, 8.06. Example 327 (lSM- (2,4-dimethoxy-fluorenyl) -245- (3-methyl-1H-fluorenazol-5-yl) -pyridine 3-Methylamino 1-ethylamine MS (APCI) m / z 419 (M + 1) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s, 3H), 3.08 (dd, J = 7.33, 2.96 Hz, 2H), 3.77 (s, 3H), 3.83 (s, 3H), 3.94 (m, 1H), 4.26 (dd, J = 10.45, 5.77 Hz, 1H), 4.41 (dd, J = 10.61 , 3.12 Hz, 1H), 6.50 (dd3 J = 8.27, 2.34 Hz, 1H), 6.59 (d, J = 2.50 Hz, 1H), 7.12 (d5 J = 8.42 Hz, 1H), 7.63 (d, J = 8.73 Hz, 1H), 7.72 (m, 1H), 8.00 (s, 1H), 8.09 (s, 1H), 8.40 (s, 1H), 8.71 (s, 1H).

實例328 (lSV2-「5-(3-甲基-1H-4唑-5-基V吡啶各基氧基1-H4-三氟甲基-芊基V乙胺 MS (APCI) m/z 428 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) 5 ppm 2.63 (s5 3H), 3.28 (m，2H)，4.05 (m，1H)，4.32 (dd，J=10.61，5.30 Hz，1H)，4.47 (dd，J=10.61，2.81 Hz, 1H), 7.56 (d5 J=7.80 Hz, 2H), 7.63 (d, J=8.74 Hz, 1H), 7.69 (d5 J=8.11 Hz, 2H), 7·74 (dd，J=8.74, 1·56 Hz，1H)，8·12 (d，J=6.55 Hz，2H)，8.45 (br s，1H)，8·74 (br s， 1H);對C23H21F3N40之分析計算值：C，46.45; Η，3·25; Ν，7·63· -275 - 200301122 (268) 實測值：C，46,55 ; Η，3·30 ; Ν，7·64· - 實例329 (lS)-l-(5-氣基-2-甲基-卞基）-2-f5-(3-甲基峻-5-基）-口比咬-3·基氣基1-乙胺 MS (APCI) m/z 391 (M+l)+ ； 1H NMR (500 MHz, CD3 OD) δ ppm 2.36 (s, 3H),Example 328 (1SV2-``5- (3-methyl-1H-4azol-5-yl Vpyridyl each oxy 1-H4-trifluoromethyl-fluorenyl V ethylamine MS (APCI) m / z 428 (M + l) +; 1 H NMR (500 MHz, CD3 OD) 5 ppm 2.63 (s5 3H), 3.28 (m, 2H), 4.05 (m, 1H), 4.32 (dd, J = 10.61, 5.30 Hz, 1H), 4.47 (dd, J = 10.61, 2.81 Hz, 1H), 7.56 (d5 J = 7.80 Hz, 2H), 7.63 (d, J = 8.74 Hz, 1H), 7.69 (d5 J = 8.11 Hz, 2H) , 7.74 (dd, J = 8.74, 1.556 Hz, 1H), 8.12 (d, J = 6.55 Hz, 2H), 8.45 (br s, 1H), 8.74 (br s, 1H) ; Analysis and calculation value for C23H21F3N40: C, 46.45; Η, 3.25; Ν, 7.63 · -275-200301122 (268) Found: C, 46, 55;;, 3.30; Ν, 7 · 64 ·-Example 329 (lS) -l- (5-Gasyl-2-methyl-fluorenyl) -2-f5- (3-methyljun-5-yl) -orbital bite-3 · radical 1-ethylamine MS (APCI) m / z 391 (M + l) +; 1H NMR (500 MHz, CD3 OD) δ ppm 2.36 (s, 3H),

2.62 (s，3H)，3·16 (dd，J=14.19, 6.71 Hz，1H)，3.23 (m，1H), 3.97 (m，1H)，4.29 (dd， J=10.45, 4.84 Hz, 1H), 4.42 (dd3 J=10.61, 3.12 Hz, 1H), 6.95 (td, J=8.42, 2.81 Hz, 1H)? 7.04 (dd, J=9.67, 2.81 Hz, 1H), 7.25 (dd, J=8.42, 5.93 Hz, 1H), 7.63 (d, J=8.74 Hz, 1H), 7.73 (dd, J=8.73, 1.56 Hz, 1H)5 8.05 (s, 1H), 8.09 (s3 1H), 8.42 (s, 1H), 8.71 (s，lH);對 C23H23FN40 之分析計算值：C，49.31; Η，3·76; Ν，8·16· 實測值·· C，49·28 ; Η，3·61 ; N，8.10. 實例330 (lSVl-(3,5-雙-三氟甲基-芊基）-245-(3-甲基-1H-吲唑-5-基V吡啶-3- 基氧基1-乙胺2.62 (s, 3H), 3.16 (dd, J = 14.19, 6.71 Hz, 1H), 3.23 (m, 1H), 3.97 (m, 1H), 4.29 (dd, J = 10.45, 4.84 Hz, 1H) , 4.42 (dd3 J = 10.61, 3.12 Hz, 1H), 6.95 (td, J = 8.42, 2.81 Hz, 1H)? 7.04 (dd, J = 9.67, 2.81 Hz, 1H), 7.25 (dd, J = 8.42, 5.93 Hz, 1H), 7.63 (d, J = 8.74 Hz, 1H), 7.73 (dd, J = 8.73, 1.56 Hz, 1H) 5 8.05 (s, 1H), 8.09 (s3 1H), 8.42 (s, 1H ), 8.71 (s, lH); Analytical calculated value for C23H23FN40: C, 49.31; Η, 3.76; Ν, 8.16. Measured value · C, 49 · 28; Η, 3.61; N, 8.10. Example 330 (1SVl- (3,5-bis-trifluoromethyl-fluorenyl) -245- (3-methyl-1H-indazol-5-yl Vpyridin-3-yloxy 1-ethyl amine

MS (APCI) m/z 495 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.62 (s, 3H), 3.35 (m5 1H), 3.42 (m5 1H), 4.12 (m, 1H), 4.31 (dd5 J=10.61, 5.30 Hz, 1H)5 4.49 (dd, J=10.61, 3.12 Hz, 1H), 7.63 (d, J=8.73 Hz, 1H), 7.73 (dd5 J=8.74, 1.87 Hz, 1H), 7.94 (s，1H)，8.01 (s，2H)，8·05 (s，1H), 8.08 (s，1H)，8.43 (s, 1H)，8·72 (s，1H);對 C24H2〇F6N40 之分析計算值·· C，43.69; H，2·82; N，6.89.實測值：C, 43.70 ； H, 2.65 ； N, 6.82. 實例331 (1SVM4-氟基-2-甲基-芊基甲基-1H-吲唑-5-基）-吡啶各基氧基1-乙胺 MS (APCI) m/z 392 (M+l)+ ； 1H NMR (500 MHz, CD3 OD) δ ppm 2.40 (s, 3H), -276- 200301122 (269) 2·62 (s，3H)，3·15 (dd，J=14.19, 6.40 Hz，1H)，3.22 (m，1H)，3.94 (m，1H)，4·29 (dd， J=10.61, 4.99 Hz, 1H)? 4.42 (dd, J=10.61, 2.81 Hz? 1H), 6.91 (td, J=8.42, 2.50 Hz? 1H)，7·00 (dd，J=9.83, 2·34 Hz，1H)，7·26 (dd，J=8.42, 5.93 Hz，1H)，7.63 (d，J=8.74 Hz，1H)，7.73 (dd，J=8.74, 1.25 Hz，1H)，8.08 (s，1H)，8.10 (s，1H)，8.43 (s，1H)，8.72 (s，lH);對 C23H23FN40之分析計算值：C，48.40; Η，3·66; Ν，7·89· 實測值：C，48.59 ; H，3.85 ; N，7.90. 實例332MS (APCI) m / z 495 (M + l) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.62 (s, 3H), 3.35 (m5 1H), 3.42 (m5 1H), 4.12 (m, 1H), 4.31 (dd5 J = 10.61, 5.30 Hz, 1H) 5 4.49 (dd, J = 10.61, 3.12 Hz, 1H), 7.63 (d, J = 8.73 Hz, 1H), 7.73 (dd5 J = 8.74, 1.87 Hz, 1H), 7.94 (s, 1H), 8.01 (s, 2H), 8.05 (s, 1H), 8.08 (s, 1H), 8.43 (s, 1H), 8.72 (s, 1H) ; Analytical calculated values for C24H20F6N40 ·· C, 43.69; H, 2.82; N, 6.89. Found: C, 43.70; H, 2.65; N, 6.82. Example 331 (1SVM4-Fluoro-2- Methyl-fluorenylmethyl-1H-indazol-5-yl) -pyridyloxy 1-ethylamine MS (APCI) m / z 392 (M + l) +; 1H NMR (500 MHz, CD3 OD ) δ ppm 2.40 (s, 3H), -276- 200301122 (269) 2.62 (s, 3H), 3.15 (dd, J = 14.19, 6.40 Hz, 1H), 3.22 (m, 1H), 3.94 (m, 1H), 4 · 29 (dd, J = 10.61, 4.99 Hz, 1H)? 4.42 (dd, J = 10.61, 2.81 Hz? 1H), 6.91 (td, J = 8.42, 2.50 Hz? 1H), 7.00 (dd, J = 9.83, 2.34 Hz, 1H), 7.26 (dd, J = 8.42, 5.93 Hz, 1H), 7.63 (d, J = 8.74 Hz, 1H), 7.73 (dd, J = 8.74, 1.25 Hz, 1H), 8.08 (s, 1H), 8.10 (s, 1H), 8.43 (s, 1H), 8.72 (s, 1H); Analytical calculated value for C23H23FN40: C, 48.40; Η, 3.66; Ν, 7.89. Found: C, 48.59; H, 3.85; N, 7.90. Example 332

(lS)-l-(5·^ -2-甲 i 基-卞基甲基-1H-1 ^ -5-基)一ρ比 < ~3- 基氣基1-乙胺 MS (APCI) m/z 408 (M+l)+ ； 1H NMR (500 MHz, CD3 OD) 6 ppm 2.63 (s, 3H)? 3.16 (d, J=7.18 Hz, 2H), 3.84 (s, 3H), 4.02 (m3 1H)? 430 (dd3 J=10.613 5.93 Hz, 1H), 4.45 (dd3 J=10.45, 2.96 Hz, 1H), 7.04 (m, 3H), 7.64 (d, J=8.73 Hz, 1H), 7.74 (d, J= 8.74 Hz，1H)，8.12 (s，2H)，8.43 (s，1H)，8.74 (s，1H);對 C2 3 H2 3 FN4 02 之分析計算值：C，44·73 ; Η，3·32 ; Ν，6·96·實測值：C，44.77 ; H，3.46 ; N, 6.83. 實例333(lS) -l- (5.1 z 408 (M + l) +; 1H NMR (500 MHz, CD3 OD) 6 ppm 2.63 (s, 3H)? 3.16 (d, J = 7.18 Hz, 2H), 3.84 (s, 3H), 4.02 (m3 1H )? 430 (dd3 J = 10.613 5.93 Hz, 1H), 4.45 (dd3 J = 10.45, 2.96 Hz, 1H), 7.04 (m, 3H), 7.64 (d, J = 8.73 Hz, 1H), 7.74 (d, J = 8.74 Hz, 1H), 8.12 (s, 2H), 8.43 (s, 1H), 8.74 (s, 1H); Analysis and calculation of C2 3 H2 3 FN4 02: C, 44 · 73; Η, 3 · 32; Ν, 6.96 · Measured values: C, 44.77; H, 3.46; N, 6.83. Example 333

(lS)-2-『5-(3-甲基-1H-啕唑-5-基吡啶-3-基氧基1-H2-甲基-茬小基甲基）-乙胺 MS (APCI) m/z 424 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.58 (s, 3H), 2.61 (s，3H)，3.61 (dd，J=14.19, 4·84 Hz，1H)，3.84 (dd，J=14.19, 10·76 Hz，1H)，4.06 (m，J=9.20, 4·21 Hz，1H)，4.14 (dd，J=10.29, 3.74 Hz，1H)，4.28 (dd，J=10.45, 2.65 Hz， 1H)，7.41 (m，3H)，7·60 (d，J=8.42 Hz，1H)，7·65 (m，1H)，7.75 (d，J=8.42 Hz，1H)， 7.84 (m，2H)，8Ό1 (s，1H)，8.12 (d，J=8· 11 Hz，1H)，8.33 (s，1H)，8.66 (s，1H);對 C27H26N40 之分析計算值：C，52.30; H，3.87; N，7.44·實測值·· C，52.56 -277- 200301122(1S) -2- "5- (3-methyl-1H-oxazol-5-ylpyridin-3-yloxy 1-H2-methyl-stubylmethyl) -ethylamine MS (APCI) m / z 424 (M + 1) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.58 (s, 3H), 2.61 (s, 3H), 3.61 (dd, J = 14.19, 4.84 Hz, 1H), 3.84 (dd, J = 14.19, 10.76 Hz, 1H), 4.06 (m, J = 9.20, 4.21 Hz, 1H), 4.14 (dd, J = 10.29, 3.74 Hz, 1H), 4.28 (dd, J = 10.45, 2.65 Hz, 1H), 7.41 (m, 3H), 7.60 (d, J = 8.42 Hz, 1H), 7.65 (m, 1H), 7.75 (d, J = 8.42 Hz, 1H), 7.84 (m, 2H), 8Ό1 (s, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.33 (s, 1H), 8.66 (s, 1H); for C27H26N40 Analytical calculation value: C, 52.30; H, 3.87; N, 7.44. Measured value. C, 52.56 -277- 200301122

(270) ;Η，4·00; Ν，7·38· 實例334 二氟-苯并|~1，31二氧伍圜烯基-4-基甲基）-245-(3-曱某-1Η-⑻咬-5-基）-π比咬-3-基氣基1-乙胺 MS (APCI) mJz 437 (M-l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s? 3H),(270); pyrene, 4.00; N, 7.38. Example 334 Difluoro-benzo | ~ 1,31 dioxolenyl-4-ylmethyl) -245- (3-fluorene- 1Η-⑻-5-yl) -π ratio -3--3-ylamino 1-ethylamine MS (APCI) mJz 437 (Ml) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s? 3H),

3.28 (m，2H)，4.07 (m，1H)，4.34 (dd，J=10.61，4·99 Hz，1H)，4.51 (dd，J=10.61，2.81 Hz，1H)，7.17 (m，3H)，7.64 (d，J=8.73 Hz，1H)，7.75 (d，J=8.73 Hz，1H)，8.12 (s，1H)， 8.16(s，1H)，8.46(s，1H)，8.76(s，1H);對 C23H2〇F2N403之分析計算值： C，44.63; Η，2·97; Ν，7·18·實測值：C，44.74; H，3.08; Ν，7.23· 實例335 (1SVH4-氣-茬-1-基甲基）-2-「5-(3-甲基-1Η-吲唑-5-基）-吡啶各基氣基1-乙胺 MS (APCI) m/z 428 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) 5 ppm 2.62 (s, 3H),3.28 (m, 2H), 4.07 (m, 1H), 4.34 (dd, J = 10.61, 4.99 Hz, 1H), 4.51 (dd, J = 10.61, 2.81 Hz, 1H), 7.17 (m, 3H) , 7.64 (d, J = 8.73 Hz, 1H), 7.75 (d, J = 8.73 Hz, 1H), 8.12 (s, 1H), 8.16 (s, 1H), 8.46 (s, 1H), 8.76 (s, 1H); Analytical calculated value for C23H2OF2N403: C, 44.63; H2, 2.97; N, 7.18. Found: C, 44.74; H, 3.08; N, 7.23 1-1-ylmethyl) -2- "5- (3-methyl-1fluorene-indazol-5-yl) -pyridyl radical 1-ethylamine MS (APCI) m / z 428 (M + l) +; 1 H NMR (500 MHz, CD3 OD) 5 ppm 2.62 (s, 3H),

3·60 (dd，J=14.04, 6·55 Hz，1H)，3·66 (m，1H)，4.09 (m，1H)，4.29 (dd，J=10.61，4.99 Hz，1H)，4·42 (dd，J=10.61，3.12 Hz，1H)，7.19 (dd，JN10.29, 7.80 Hz，1H)，7·47 (dd， J=7.80, 5·30 Hz，1H)，7.61 (d，J=8.73 Hz，2H)，7.64 (d，J=7.18 Hz，1H)，7·68 (t，J= 8·11 Hz，1H)，7.96 (s，1H)，8.05 (s，1H)，8.15 (d，J=8.11 Hz，1H)，8.18 (d，J=8.42 Hz5 1H)，8.38 (s，1H)，8.68 (s，1H). 實例336 (18)-2-『5-(3-甲基-1沁<唑-5-基）-吡啶-3-基氧基1小(2,2,3,3-四氟基-2,3-二氫-苯并fl，4~|二氧陸圜婦-6-基甲基V乙胺 MS (APCI) m/z 487 (M-l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s3 3H), 3.18 (dd，J=14.19, 7.02 Hz，1H)，3·24 (m，1H)，4.02 (m，J=5.15, 2.65 Hz，1H)，4·33 (dd，J=10.45, 5·46 Hz，1H)，4.47 (dd，J=10.61，3·12 Hz，1H)，7.29 (m，2H)，7·34 (s， -278 - 0301122 (271) 1H)，7.63 (d，J=8.73 Hz，1H)，7.74 (dd，J=8.74，1.25 Hz，1H)，8.11 (s，2H)，8·44 (s， 1H)，8.72 (s，lH);對 C23H2〇F2N403之分析計算值：C，43.08 ;H，2.77; N，6.65.實測值：C，42.94 ; H，2·79 ; N，6.64. 實例337 (lSV2-『5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1-H4-甲基-苯-1-基甲基乙胺 MS (APCI) m/z 421 (M-l)+ ； 1H NMR (500 MHz, CD3 OD) δ ppm 2.61 (d, J=8.11 Hz，3H)，2.67 (s，3H)，3.62 (m，2H)，4.09 (m，1H)，4·28 (dd，J=10.61，4·99 Hz，1H)， 4.40 (dd，J=10.61，3.12 Hz，1H)，7·32 (d，J=7.49 Hz，1H)，7.38 (m，1H)，7·58 (m，2H)， 7·62 (d，J=8.73 Hz，1H)，7.68 (m，1H)，7.97 (s，1H)，8.06 (s，1H)，8.10 (m，1H)，8.15 (m，1H)，8·37 (d，J=2.50 Hz, 1H)，8.68 (s，1H);對 C2 7 H2 6 N4 O 之分析計算值：C，52.79 ; Η，3·91; Ν，7·55·實測值：C，52.64; Η，3·85; Ν，7·53· 實例338 (〇-2-『5-(3-甲基-1沁吲唑-5-基）-吡啶-3-基氧基1小(2,4,6-三氟-芊基>· 乙胺 MS (APCI) m/z 411 (M-l)+ ; 1H NMR (500 MHz，CD3 OD) (5 ppm 2.63 (s，3Η)， 3.19 (m，2H)，3.97 (m，1H)，4.32 (dd，J=10.61，4·99 Hz，1H)，4·49 (dd，J=10.61，3·12 Hz，1H)，6.95 (t，J=8.27 Hz，2H)，7.63 (d，J=8.73 Hz，1H)，7·74 (dd，J=8.74, 1·56 Hz, 1H)，8.08 (d，J=2.18 Hz，1H)，8·10 (s，1H)，8.41 (s，1H)，8.72 (s，1H); 對C22H19F3N40之分析計算值·· C，44.57; Η，2·94; Ν，7·43.實測值·· C，44.47 ; Η，2·78 ; Ν，7.46. f Μ 339 (lS)-2-f5-(3-甲基-1Η-吲唑-5-某V毗啶-3-基氧基]小(2,3,4-4氟-芊基乙胺 -279- 2003011223 · 60 (dd, J = 14.04, 6.55 Hz, 1H), 3.66 (m, 1H), 4.09 (m, 1H), 4.29 (dd, J = 10.61, 4.99 Hz, 1H), 4 · 42 (dd, J = 10.61, 3.12 Hz, 1H), 7.19 (dd, JN10.29, 7.80 Hz, 1H), 7.47 (dd, J = 7.80, 5.30 Hz, 1H), 7.61 (d, J = 8.73 Hz, 2H), 7.64 (d, J = 7.18 Hz, 1H), 7.68 (t, J = 8.11 Hz, 1H), 7.96 (s, 1H), 8.05 (s, 1H), 8.15 (d, J = 8.11 Hz, 1H), 8.18 (d, J = 8.42 Hz5 1H), 8.38 (s, 1H), 8.68 (s, 1H). Example 336 (18) -2- 『5- (3 -Methyl-1pyrin < azole-5-yl) -pyridin-3-yloxy 1 small (2,2,3,3-tetrafluoro-2,3-dihydro-benzo fl, 4 ~ Dioxolan-6-ylmethyl V ethylamine MS (APCI) m / z 487 (Ml) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s3 3H), 3.18 (dd, J = 14.19, 7.02 Hz, 1H), 3.24 (m, 1H), 4.02 (m, J = 5.15, 2.65 Hz, 1H), 4.33 (dd, J = 10.45, 5.46 Hz, 1H) , 4.47 (dd, J = 10.61, 3.12 Hz, 1H), 7.29 (m, 2H), 7.34 (s, -278-0301122 (271) 1H), 7.63 (d, J = 8.73 Hz, 1H ), 7.74 (dd, J = 8.74, 1.25 Hz, 1H), 8.11 (s, 2H), 8.44 (s, 1H), 8.72 (s, 1H); for C23H2OF2N Analytical calculated value of 403: C, 43.08; H, 2.77; N, 6.65. Found: C, 42.94; H, 2.79; N, 6.64. Example 337 (lSV2- "5- (3-methyl-1H -Indazol-5-yl) -pyridin-3-yloxy 1-H4-methyl-phenyl-1-ylmethylethylamine MS (APCI) m / z 421 (Ml) +; 1H NMR (500 MHz , CD3 OD) δ ppm 2.61 (d, J = 8.11 Hz, 3H), 2.67 (s, 3H), 3.62 (m, 2H), 4.09 (m, 1H), 4.28 (dd, J = 10.61, 4 99 Hz, 1H), 4.40 (dd, J = 10.61, 3.12 Hz, 1H), 7.32 (d, J = 7.49 Hz, 1H), 7.38 (m, 1H), 7.58 (m, 2H) , 7.62 (d, J = 8.73 Hz, 1H), 7.68 (m, 1H), 7.97 (s, 1H), 8.06 (s, 1H), 8.10 (m, 1H), 8.15 (m, 1H), 8 · 37 (d, J = 2.50 Hz, 1H), 8.68 (s, 1H); Analytical calculation for C2 7 H2 6 N4 O: C, 52.79; Η, 3.91; Ν, 7.55 · Measured Value: C, 52.64; Hf, 3.85; N, 7.53. Example 338 (〇-2- 『5- (3-methyl-1pentinazol-5-yl) -pyridin-3-yloxy Base 1 small (2,4,6-trifluoro-fluorenyl) > Ethylamine MS (APCI) m / z 411 (Ml) +; 1H NMR (500 MHz, CD3 OD) (5 ppm 2.63 (s, 3Η ), 3.19 (m, 2H), 3.97 (m, 1H), 4.32 (dd, J = 10.61, 4.99 Hz, 1H), 4.49 (dd, J = 10.61, 3.12 Hz, 1H), 6.95 (t, J = 8.27 Hz, 2H), 7.63 (d, J = 8.73 Hz, 1H), 7.74 (dd, J = 8.74, 1.556 Hz, 1H), 8.08 (d, J = 2.18 Hz, 1H), 8.10 (s, 1H), 8.41 (s, 1H), 8.72 (s, 1H); Analytical calculated values for C22H19F3N40 ·· C, 44.57; Η, 2.94; Ν, 7.43. Measured values · C, 44.47; Η, 2.78; Ν, 7.46. F M 339 (1S) -2 -f5- (3-methyl-1fluorene-indazole-5-a certain V-pyridin-3-yloxy] small (2,3,4-4fluoro-fluorenylethylamine-279- 200301122

(272) 1 H NMR (500 MHz, CD3 OD) 5 ppm 2·62 (s，3H)，3.23 (m，2H)，4.00 (m，1H)，4.31 (dd，J=10.61，5.30 Hz，1H)，4.46 (dd，J=10.61，3.12 Hz，1H)，7.17 (m，2H)，7.62 (d，J= 8.73 Hz，1H)，7.73 (dd，J=8.74, 1.56 Hz，1H)，8,02 (s，1H)，8.08 (s，1H)，8.40 (s5 1H)， 8.69(s，1H);對 C22H19F3N40之分析計算值：C，45.31; Η，3·00; Ν，7·66· 實測值·· C, 45.59 ; H，2·73 ; N，7·84. 實例340 (IS)-Η4-溴基-2-氟-芊基）-245-(3-甲基_1Η-㈣唑-5-基V吡啶-3-基氧基1-乙胺 1 H NMR (500 MHz，CD3 OD) 5 ppm 2.63 (s，3Η)，3·22 (m，2Η)，4.00 (m，1Η)，4.34 (dd，J二 10.61，5.30 Hz，1H)，4.49 (dd，J=10.61，3·12 Hz，1H)，7.33 (t，J=8.11 Hz，1H)， 7.37 (d，J=1.56 Hz，1H)，7.41 (m，1H)，7.64 (d，J=8.73 Hz，1H)，7.75 (dd，J=8.74， 1·56 Hz，1H)，8·13 (s，1H)，8.19 (s，1H)，8.46 (s，1H)，8.77 (s，1H); 對 C22H20BrFN4O 之分析計算值：C，42.80 ; Η，2·97 ; Ν，7·23·實測值：C，42.73 ; Η，3·17; Ν，7·02· 實例341 (IS)-1-(4->臭基-卞基)-2-「5_(3-甲基口坐基)_口比 < _3—基乳基1-乙胺 MS (ESI) m/z 456 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s? 3H), 3.18 (m, 2H), 4.01 (m, 1H), 4.32 (dd, J=10.61, 5.62 Hz, 1H)? 4.46 (dd5 J=10.61, 2.81 Hz，1H)，7.11 (dd，J=8.11，1·56 Hz，1H)，7.26 (dd，J=9.36, 1.87 Hz，1H)，7.62 (d，J二 7·18 Hz，1H)，7.63 (d，J=8.42 Hz，1H)，7.74 (dd，J=8.73, 1.56 Hz，1H)，8.10 (d，J= 4.06 Hz，2H)，8.43 (s，1H)，8.72 (s，1H);對 C2 2 H2 〇 BrFN4 O 之分析計算值 :C，43.46; Η，3·03; Ν，7·45·實測值·· C，43.52: H，3.07; N，7,43. 實例342 -280- 20030Π22 (273) (1SV1_(2-’/臭基-4,6-二乱-卞基）-2-『5-(3-甲基也-5-基）-卩比淀-3-基氧基1-乙胺 1 H NMR (500 MHz，CD3 0D) 5 ppm 2.63 (s，3H)，3·32 (m，1H)，3.48 (m，1H)，4.03 (m，1H)，4.34 (dd，J=10.45, 4.84 Hz，1H)，4.48 (dd，J=10.61，3_43 Hz，1H)，7.13 (t，J= 8·11 Hz，1H)，7.40 (d，J=8.11 Hz，1H)，7.63 (d，J=8.73 Hz，1H)，7·74 (dd，J=8.73， 1.56 Hz，1H)，8.09 (s，1H)，8.11 (s，1H)，8.42 (s，1H)，8.73 (s，1H); 對(：2211198逆2^0之分析計算值：C，41.24; H，2.72; Ν，6·87·實測(272) 1 H NMR (500 MHz, CD3 OD) 5 ppm 2.62 (s, 3H), 3.23 (m, 2H), 4.00 (m, 1H), 4.31 (dd, J = 10.61, 5.30 Hz, 1H ), 4.46 (dd, J = 10.61, 3.12 Hz, 1H), 7.17 (m, 2H), 7.62 (d, J = 8.73 Hz, 1H), 7.73 (dd, J = 8.74, 1.56 Hz, 1H), 8 , 02 (s, 1H), 8.08 (s, 1H), 8.40 (s5 1H), 8.69 (s, 1H); Analysis and calculation of C22H19F3N40: C, 45.31; Η, 3.00; Ν, 7.66 Measured value C, 45.59; H, 2.73; N, 7.84. Example 340 (IS) -fluorene 4-bromo-2-fluoro-fluorenyl) -245- (3-methyl_1fluorene- Oxazol-5-yl Vpyridin-3-yloxy 1-ethylamine 1 H NMR (500 MHz, CD3 OD) 5 ppm 2.63 (s, 3Η), 3.22 (m, 2Η), 4.00 (m, 1Η), 4.34 (dd, J = 10.61, 5.30 Hz, 1H), 4.49 (dd, J = 10.61, 3.12 Hz, 1H), 7.33 (t, J = 8.11 Hz, 1H), 7.37 (d, J = 1.56 Hz, 1H), 7.41 (m, 1H), 7.64 (d, J = 8.73 Hz, 1H), 7.75 (dd, J = 8.74, 1.56 Hz, 1H), 8.13 (s, 1H) , 8.19 (s, 1H), 8.46 (s, 1H), 8.77 (s, 1H); Analytical calculated value for C22H20BrFN4O: C, 42.80; 97, 2.97; Ν, 7.23 · Measured value: C, 42.73; Η, 3.17; Ν, 7 · 02 · Example 341 (IS) -1- (4- > Styrenyl-fluorenyl) -2- "5_ (3-methyl-swapyl) _port ratio < _3-based milk base 1 -Ethylamine MS (ESI) m / z 456 (M + 1) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.63 (s? 3H), 3.18 (m, 2H), 4.01 (m, 1H) , 4.32 (dd, J = 10.61, 5.62 Hz, 1H)? 4.46 (dd5 J = 10.61, 2.81 Hz, 1H), 7.11 (dd, J = 8.11, 1.56 Hz, 1H), 7.26 (dd, J = 9.36, 1.87 Hz, 1H), 7.62 (d, J = 7.18 Hz, 1H), 7.63 (d, J = 8.42 Hz, 1H), 7.74 (dd, J = 8.73, 1.56 Hz, 1H), 8.10 ( d, J = 4.06 Hz, 2H), 8.43 (s, 1H), 8.72 (s, 1H); Analytical calculated value for C2 2 H2 〇BrFN4 O: C, 43.46; Η, 3.03; Ν, 7 · 45 · Measured value · C, 43.52: H, 3.07; N, 7, 43. Example 342 -280- 20030Π22 (273) (1SV1_ (2-'/ Sulky-4,6-Diran-fluorenyl)- 2- [5- (3-Methyl also-5-yl) -pyridine-3-yloxy 1-ethylamine 1 H NMR (500 MHz, CD3 0D) 5 ppm 2.63 (s, 3H), 3 32 (m, 1H), 3.48 (m, 1H), 4.03 (m, 1H), 4.34 (dd, J = 10.45, 4.84 Hz, 1H), 4.48 (dd, J = 10.61, 3_43 Hz, 1H), 7.13 (t, J = 8.11 Hz, 1H), 7.40 (d, J = 8.11 Hz, 1H), 7.63 (d, J = 8.73 Hz, 1H), 7.74 (dd, J = 8.73, 1.56 Hz, 1H), 8.09 (s, 1H), 8.11 (s, 1H), 8.42 (s, 1H), 8.73 (s, 1H); Analytical calculation for (: 2211198 inverse 2 ^ 0): C, 41.24; H, 2.72; Ν, 6.87 · Measured

值：C，41.35 ; Η，2·68; Ν，6·76. 實例343 (1SVH4-溴基-3-甲基-芊基）-245-(3-甲基-1H-W唑-5-基V吡啶-3-基氣基1-乙胺 MS (ESI) m/z 452 (M+lf ； 1 H NMR (500 MHz, CD3 OD) δ ppm 2.37 (s, 3H),Value: C, 41.35; Hf, 2.68; N, 6.76. Example 343 (1SVH4-bromo-3-methyl-fluorenyl) -245- (3-methyl-1H-Wazole-5- Vpyridin-3-ylamino 1-ethylamine MS (ESI) m / z 452 (M + lf; 1 H NMR (500 MHz, CD3 OD) δ ppm 2.37 (s, 3H),

2.63 (s，3H)，3.11 (m，2H)，3.97 (m，1H)，4.29 (dd，J=10.61，5.62 Hz，1H)，4.44 (dd， J=10.61，3.12 Hz，1H)，7.07 (dd，J=8.11，1·87 Hz，1H)，7.27 (s，1H)，7.54 (d，J=8.11 Hz，1H)，7.63 (d，J=8.73 Hz，1H)，7.73 (d，J=8.73 Hz，1H)，8.06 (s，1H)，8.10 (s，1H)， 8.41 (s，1H)，8.71 (s，1H);對 C2 3 H2 3 BrN4 0 之分析計算值：C，44.93 ; Η，3·41; Ν，7·38·實測值：C，45.11; Η，3·36; Ν，7·28· 實例344 (1SV溴-芊基V2-『5-(3-甲某-1H-W唑-5-基V吡啶-3-基氧基1-乙胺 1 H NMR (500 MHz, CD3 OD) δ ppm 2.62 (s, 3H), 3.37 (m, 2H), 4.10 (m5 1H), 4.30 (dd，>10.61，4.99 Hz，1H)，4.43 (dd，J=10.61，3.12 Hz, 1H)，7.25 (t，】=6·71 Hz，1H)， 7.37 (t，J=6.86 Hz，1H)，7.42 (m，1H)，7.63 (d，J=8.74 Hz，1H)，7,66 (d，J=8.11 Hz， 1H)，7.73 (dd，J=8.73, L56 Hz, 1H)，8.03 (d，J=1 ·87 Hz，1H)，8·09 (s，1H)，8.40 (s， 1H)，8.70 (s，lH);對C22H21BrN40之分析計算值：C，43.48 ; Η，3·14; -281 - (274)2.63 (s, 3H), 3.11 (m, 2H), 3.97 (m, 1H), 4.29 (dd, J = 10.61, 5.62 Hz, 1H), 4.44 (dd, J = 10.61, 3.12 Hz, 1H), 7.07 (dd, J = 8.11, 1.87 Hz, 1H), 7.27 (s, 1H), 7.54 (d, J = 8.11 Hz, 1H), 7.63 (d, J = 8.73 Hz, 1H), 7.73 (d, J = 8.73 Hz, 1H), 8.06 (s, 1H), 8.10 (s, 1H), 8.41 (s, 1H), 8.71 (s, 1H); Analytical calculation for C2 3 H2 3 BrN4 0: C, 44.93; Thallium, 3.41; N, 7.38. Found: C, 45.11; Thallium, 3.36; N, 7.28. Example 344 (1SV bromo-fluorenyl V2- "5- (3-formaldehyde) -1H-Wazole-5-yl Vpyridin-3-yloxy 1-ethylamine 1 H NMR (500 MHz, CD3 OD) δ ppm 2.62 (s, 3H), 3.37 (m, 2H), 4.10 ( m5 1H), 4.30 (dd, > 10.61, 4.99 Hz, 1H), 4.43 (dd, J = 10.61, 3.12 Hz, 1H), 7.25 (t,) = 6.71 Hz, 1H), 7.37 (t, J = 6.86 Hz, 1H), 7.42 (m, 1H), 7.63 (d, J = 8.74 Hz, 1H), 7,66 (d, J = 8.11 Hz, 1H), 7.73 (dd, J = 8.73, L56 Hz, 1H), 8.03 (d, J = 1.87 Hz, 1H), 8.09 (s, 1H), 8.40 (s, 1H), 8.70 (s, 1H); Analytical calculation for C22H21BrN40: C , 43.48; Η, 3.14; -281-(274)

N，7.30.實測值：C, 43.67 ; H，3.06; N，7.10. 實例345 (1S)-H3-甲氧-芊基）-2-「5-(3-甲基-1H4丨唑-5-基V吡啶-3-基氧基1-乙胺 MS m/z 389 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.57 (s, 3H) 3.00 (dd，J=13.56, 9·16 Hz，1H) 3·12 (m，1H) 3.73 (s，3H) 4.28 (dd，J=10.85, 5.43 Hz，1H) 4.44 (m，2H) 6.85 (dd，J=8.48, 2·37 Hz，1H) 6.91 (m，2H) 7.27 (t，J=7.80 Hz，1H) 7.61 (d，J=8.82 Hz，1H) 7.79 (dd，J=8.82, 1·70 Hz，1H) 8.23 (s，1H) 8.26 (s，1H) 8.53 (d，J=2.37 Hz，4H) 8.86 (s，1H). 實例346 (1SVH3-溴-芊基V2-「5-(3-甲基_1H-W唑-5-基V吡啶-3-基氧基1-乙胺 MS m/z 437, 439 (M+H)+ ； 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.57 (s, 3H) 3.08 (m，2H) 4·27 (dd，J=10.85, 5·43 Hz，1H) 4.43 (m，1H) 7·34 (m，2H) 7.49 (dt，J= 7.54, 1.65 Hz，1H) 7.61 (m，2H) 7.77 (dd，J=8.65, 1·53 Hz，1H) 8·14 (s，1H) 8.22 (s， 1H) 8.49 (s，2H) 8·82 (s，1H)· 實例347 甲氧基-茬小基甲基V2-『5-(3-甲基-1H-吲唑-5-基）-吡啶-3- 基氧基1-乙胺 MS (ESI) m/e 439 (M+l)+ ; 1 H NMR (300 MHz，溶劑）（5 ppm 2·62 (s, 3H) 3·55 (m，1H) 3.74 (m5 1H) 3·97 (s，3H) 4·03 (m，1H) 4·23 (m，1H) 4.39 (m，1H) 7·33 (m， 1H) 7.46 (m，2H) 7.64 (m，2H) 7.84 (m，1H) 7.92 (m，2H) 8.03 (m，2H) 8.34 (寬廣 s·，1H) 8.67 (寬廣 s，1H). 實例348 編卞基甲基-ΙΗ-^l ^ -5·基)-叶匕 < -3-基基 1-乙胺N, 7.30. Found: C, 43.67; H, 3.06; N, 7.10. Example 345 (1S) -H3-methoxy-fluorenyl) -2- "5- (3-methyl-1H4 丨 azole-5 -Methylpyridin-3-yloxy 1-ethylamine MS m / z 389 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.57 (s, 3H) 3.00 (dd, J = 13.56, 9 · 16 Hz, 1H) 3.12 (m, 1H) 3.73 (s, 3H) 4.28 (dd, J = 10.85, 5.43 Hz, 1H) 4.44 (m, 2H) 6.85 (dd, J = 8.48 , 2.37 Hz, 1H) 6.91 (m, 2H) 7.27 (t, J = 7.80 Hz, 1H) 7.61 (d, J = 8.82 Hz, 1H) 7.79 (dd, J = 8.82, 1.70 Hz, 1H ) 8.23 (s, 1H) 8.26 (s, 1H) 8.53 (d, J = 2.37 Hz, 4H) 8.86 (s, 1H). Example 346 (1SVH3-bromo-fluorenyl V2- "5- (3-methyl _1H-Wazole-5-ylVpyridin-3-yloxy1-ethylamine MS m / z 437, 439 (M + H) +; 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.57 ( s, 3H) 3.08 (m, 2H) 4.27 (dd, J = 10.85, 5.43 Hz, 1H) 4.43 (m, 1H) 7.34 (m, 2H) 7.49 (dt, J = 7.54, 1.65 Hz, 1H) 7.61 (m, 2H) 7.77 (dd, J = 8.65, 1.53 Hz, 1H) 8.14 (s, 1H) 8.22 (s, 1H) 8.49 (s, 2H) 8.82 (s ， 1H) · Example 347 methoxy-stubbyl methyl V2- "5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yl 1-ethylamine MS (ESI) m / e 439 (M + l) +; 1 H NMR (300 MHz, solvent) (5 ppm 2.62 (s, 3H) 3.55 (m, 1H) 3.74 ( m5 1H) 3.97 (s, 3H) 4.03 (m, 1H) 4.23 (m, 1H) 4.39 (m, 1H) 7.33 (m, 1H) 7.46 (m, 2H) 7.64 (m , 2H) 7.84 (m, 1H) 7.92 (m, 2H) 8.03 (m, 2H) 8.34 (broad s ·, 1H) 8.67 (broad s, 1H). Example 348 Editing a methyl group-IΗ- ^ l ^ -5 (Yl) -leaf < -3-yl 1-ethylamine

實例348A 200301122Example 348A 200301122

(275) 5-f5-((2RVl-第三-丁氣羰基-氮丙啶-2-基甲氧基）-吡啶-3-基1各甲基唑小羧酸第三-丁酯所要之產物係經由以（S)-[l-(第三-丁基-二甲基-碎烷基氧基甲基）-2-經基-乙基]-胺甲基酸第三-丁酯，取代實例273D中之 (RM1-(第三-丁基·二甲基-碎燒基氧基甲基）-2-經基-乙基]•胺甲基酸第三-丁酯而製成。MS(APCI)m/z48l (Μ+1)+· 實例348Β 氯-卞基)_2_「5-(3-甲基 ^ -5-基)一口比 < -3-基基 1-乙胺(275) 5-f5-((2RVl-Third-butanecarbonyl-azetidin-2-ylmethoxy) -pyridin-3-yl 1 Required for each methylazole small carboxylic acid tert-butyl ester The product is obtained via (S)-[l- (third-butyl-dimethyl-crucyloxymethyl) -2-acryl-ethyl] -aminomethyl acid tert-butyl ester, (RM1- (Third-butyl-dimethyl-crudeyloxymethyl) -2-trisyl-ethyl] • amine methyl acid tertiary-butyl ester in Example 273D was substituted. MS (APCI) m / z 48l (M + 1) + Example 348B chloro-fluorenyl) _2_ "5- (3-methyl ^ -5-yl) bite ratio < -3-yl 1-ethylamine

所要之產物係經由以實例348A取代實例274中之實例273D ，且以4-氯苯基溴化鎂取代實例274中之3-三氟甲氧基苯基溴化鎂，以三氟醋酸鹽製成。MS(APCI)ra/z 393 (M+l)+ ; iHNMR (300 MHz, CD3 OD) δ 2.63 (s，3H)，3.16 (dd，J=7.63, 2·54 Hz，2H)，3·98 (m，1H)， 4.30 (dd，J=10.51，5.42 Hz，1H)，4.45 (dd，J=10.51，3.05 Hz, 1H)，7.34 (d，J=8.81 Hz, 2H)，7·39 (d，J=8.81 Hz，2H)，7.63 (d，J=8.81 Hz，1H)，7.74 (dd，J=8.81，1·70 Hz，1H)， 8.11 (m，2H)，8.43 (d，J=2.03 Hz，1H)，8.73 (s，1H);對 C2 2 H2 i C1N4 O · 3 TFA 之分析計算值：C，45·76 ; H，3.29 ; N，7.62·實測值：C，45.86 ; H，3.28 ；N,7.72. 下列化合物係經由以適當Girgnard試劑取代實例348中之3-三氟基曱氧苯基溴化鎂而製成。實例349 (1RV1-笨并Π，31二氧伍圜烯-5-基甲基-245-(3-甲基-1HW1唑-5-基）- 口比淀·3-基氧基]_乙胺 MS (APCI) m/z 403 (Μ+1)+ ； 1 H NMR (300 MHz, CD3 OD) δ 2.63 (s, 3H), 3.08 (dd，J=8.14, 2·03 Hz，2H)，3.92 (m，1H)，4·31 (dd，JN10.51，5.76 Hz，1H)，4·46 (dd，J= -283 - 200301122 (276) 10.51，3·05 Hz，1Η)，5·92 (s，2H)，6·79 (d，J=8.14 Hz，1H)，6.81 (d，J=8.14 Hz，m)， 6.85 (s，1H)，7.64 (d，J=8.81 Hz，1H)，7.75 (d，J=8.81 Hz，1H)，8.14 (m，2H)，8.44 (d， J=2.37Hz，lH)，8.75(d，J=1.70Hz，1H);對 C23C22N403 .3.3 TFA 之分析計算值·· C，45.65 ; Η，3·27; N，7.19.實測值：C，45.71 ; Η，3·15; Ν，7·21· 實例350 (1RVH3-氟基-4-甲基-芊基甲基-1Η-啕唑-5-基）-吡啶-3-基氣基V乙胺 MS (APCI) mJz 391 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 2.24 (d5 J=1.70 Hz, 3H)，2.63 (s，3H)，3·11 (d，J=8.14 Hz，2H)，3.96 (m，1H)，4.31 (dd，J=10.51，5.76 Hz， 1H)，4.46 (dd，J=10.85, 3.05 Hz，1H)，7.03 (t，J=8.48 Hz，1H)，7.15 (m，1H)，7.21 (d， J=7.46 Hz, 1H), 7.64 (d, J=8.48 Hz, 1H), 7.74 (dd, J=8.81, 1.70 Hz, 1H), 8.14 (m,The desired product was prepared by replacing Example 273D in Example 274 with Example 348A, and replacing 3-trifluoromethoxyphenyl magnesium bromide in Example 274 with 4-chlorophenyl magnesium bromide. to make. MS (APCI) ra / z 393 (M + l) +; iHNMR (300 MHz, CD3 OD) δ 2.63 (s, 3H), 3.16 (dd, J = 7.63, 2.554 Hz, 2H), 3.98 (m, 1H), 4.30 (dd, J = 10.51, 5.42 Hz, 1H), 4.45 (dd, J = 10.51, 3.05 Hz, 1H), 7.34 (d, J = 8.81 Hz, 2H), 7.39 ( d, J = 8.81 Hz, 2H), 7.63 (d, J = 8.81 Hz, 1H), 7.74 (dd, J = 8.81, 1.70 Hz, 1H), 8.11 (m, 2H), 8.43 (d, J = 2.03 Hz, 1H), 8.73 (s, 1H); Analytical calculated value for C2 2 H2 i C1N4 O · 3 TFA: C, 45 · 76; H, 3.29; N, 7.62 · Measured value: C, 45.86; H, 3.28; N, 7.72. The following compounds were prepared by replacing 3-trifluorophosphoniumoxyphenylmagnesium bromide in Example 348 with an appropriate Girgnard reagent. Example 349 (1RV1-benzylidene, 31 dioxolene-5-ylmethyl-245- (3-methyl-1HW1azole-5-yl) -Kipido · 3-yloxy] _ethyl Amine MS (APCI) m / z 403 (Μ + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 2.63 (s, 3H), 3.08 (dd, J = 8.14, 2.03 Hz, 2H), 3.92 (m, 1H), 4.31 (dd, JN10.51, 5.76 Hz, 1H), 4.46 (dd, J = -283-200301122 (276) 10.51, 3.05 Hz, 1Η), 5. · 92 (s, 2H), 6.79 (d, J = 8.14 Hz, 1H), 6.81 (d, J = 8.14 Hz, m), 6.85 (s, 1H), 7.64 (d, J = 8.81 Hz, 1H ), 7.75 (d, J = 8.81 Hz, 1H), 8.14 (m, 2H), 8.44 (d, J = 2.37Hz, 1H), 8.75 (d, J = 1.70Hz, 1H); for C23C22N403 .3.3 TFA Analytical calculated values: · C, 45.65; Η, 3.27; N, 7.19. Found: C, 45.71; Η, 3.15; Ν, 7.21. · Example 350 (1RVH3-fluoro-4-A Methyl-fluorenylmethyl-1fluoren-oxazol-5-yl) -pyridin-3-ylamino Vethylamine MS (APCI) mJz 391 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 2.24 (d5 J = 1.70 Hz, 3H), 2.63 (s, 3H), 3.11 (d, J = 8.14 Hz, 2H), 3.96 (m, 1H), 4.31 (dd, J = 10.51, 5.76 Hz , 1H), 4.46 (dd, J = 10.85, 3.05 Hz, 1H) 7.03 (t, J = 8.48 Hz, 1H), 7.15 (m, 1H), 7.21 (d, J = 7.46 Hz, 1H), 7.64 (d, J = 8.48 Hz, 1H), 7.74 (dd, J = 8.81 , 1.70 Hz, 1H), 8.14 (m,

2H)，8.45 (d，J=2.37 Hz，1H)，8.75 (d，J=1.36 Hz，1H);對 C2 3 H2 3 FN4 O · 2.9TFA 之分析計算值：C，47.97 ; H，3·62; N，7.77·實測值·· C，48.09 ; Η，3·75 ;N，7.87. 實例351 (1SV1-芊基-246-氣基-5-(3-甲某-1H-W唑-5-基V吡啶-3-基l·乙胺2H), 8.45 (d, J = 2.37 Hz, 1H), 8.75 (d, J = 1.36 Hz, 1H); Analytical calculation for C2 3 H2 3 FN4 O · 2.9TFA: C, 47.97; H, 3 · 62; N, 7.77. Found ... C, 48.09; H3, 3.75; N, 7.87. Example 351 (1SV1-fluorenyl-246-amino-5- (3-methyl-1H-Wazole- 5-yl V-pyridin-3-yl l · ethylamine

實例351A 5-(2-氯基-5-羥基-吡啶各某V3-甲某唑_士羧酸於250毫升RBF中，裝填實例12B (1·58克，7.59毫莫耳）、實例 203Β(3·0 克，7.59 毫莫耳）、Pd2(dba)3(696 毫克，〇·76 毫莫耳）及三·鄰-甲苯基膦（696毫克），並以N2滌氣。經由注射器添加無水DMF (60毫升）與Et3N (3.17毫升）。將此溶液以N2再滌氣一次，並於70°C下加熱15小時。冷卻後，添加錯酸乙酯（300 毫升）。將混合物以鹽水（5〇〇毫升）及水（500毫升）洗滌。使 -284- 200301122Example 351A 5- (2-Chloro-5-hydroxy-pyridine, each V3-methoxazole_shicarboxylic acid in 250 ml of RBF, was charged with Example 12B (1.58 g, 7.59 mmol), Example 203B ( 3.0 grams, 7.59 millimoles), Pd2 (dba) 3 (696 mg, 0.776 millimoles), and tri-o-tolylphosphine (696 mg) and purged with N2. Anhydrous was added via syringe DMF (60 ml) and Et3N (3.17 ml). This solution was purged with N2 again and heated at 70 ° C for 15 hours. After cooling, ethyl acetate (300 ml) was added. The mixture was washed with brine (300 ml). 500 ml) and water (500 ml). -284- 200301122

(277) 酷酸乙醋溶液濃縮，並藉急驟式層析（於己烷中之40-65% EtOAc)分離殘留油，而得所要之產物⑽6克，6咖）。娜⑶ m/z 360 (Μ+1)+·(277) The ethyl acetate solution was concentrated, and the residual oil was separated by flash chromatography (40-65% EtOAc in hexane) to obtain the desired product (6 g, 6 coffee). Na ⑶ m / z 360 (Μ + 1) + ·

實例35IB 基-3-笨某-丙氣某V2-氢4啶-3-基1-唑-1-衮酸第三-丁酯Example 35IB 3-Methyl-3-benzyl-propanyl V2-hydro-4pyridin-3-yl1-azole-1-acetic acid tert-butyl ester

於25晕升rbf中，裝填實例351A(15〇毫克，〇 417毫莫耳）、 Boc-苯基丙胺醇（157毫克，〇 625毫莫耳）、DBA〇 (144毫克，〇 625 當莫耳）及PhP (163亳克，〇·625毫莫耳），並以氮滌氣。於〇 C下’添加THF (8毫升）。在〇它下攪拌3〇分鐘後，移除冰-η2〇浴’並將反應混合物於室溫下攪拌過夜。使反應混合物濃縮’並藉急驟式層析（於己烷中之20-40% EtOAc)分離殘留物，提供所要之產物（215.0 毫克，87% )。MS(APCI)m/z 593 (Μ+1)+·In 25 liters of rbf, Example 351A (150 mg, 0417 mmol), Boc-phenylpropanol (157 mg, 0625 mmol), and DBA (144 mg, 0625 mmol) ) And PhP (163 g, 0.625 mmol), and purged with nitrogen. THF (8 mL) was added at 0 ° C. After stirring for 30 minutes at it, the ice-η20 bath 'was removed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated 'and the residue was separated by flash chromatography (20-40% EtOAc in hexanes) to provide the desired product (215.0 mg, 87%). MS (APCI) m / z 593 (Μ + 1) + ·

實例351CExample 351C

(1SH-芊基冬『6-氣基-5-(3_甲基-1H-W唑-5-基V吡啶-3-基氧基1-乙胺所要之產物係經由以實例351Β取代實例27C中之實例27Β ，以三氟醋酸鹽製成。MS (APCI) m/z 393 (M+l)+; 1 H NMR (300 ΜΗζ， CD3 0D) δ 2.58 (s, 3Η), 3.12 (d5 J=7.46 Hz, 2H), 3.91 (m5 1H)? 4.14 (dd, J=10.51, 5·43 Hz，1H)，4·30 (dd，JN10.51，3.05 Hz，1H)，7.34 (m，5H)，7.47 (dd，JM8.65, 1.53 Hz，1H)，7.52 (d，J=3.05 Hz，1H)，7.56 (d，J=8.82 Hz，1H)，7·78 (s，1H)，8.14 (d，J= 2.71 Hz，1H);對 C22H21C1N40· 1.6TFA之分析計算值·· C，52.61; Η，3·96 ;Ν，9·74·實測值：C，52.87; Η，3·90; Ν，9·81· 下列化合物係經由以適當Boc-胺基醇取代實例351中之 Boc-苯基丙胺醇而製成。 - 285 - 200301122(1SH-fluorenyl) 6-amino-5- (3-methyl-1H-Wazole-5-yl Vpyridin-3-yloxy 1-ethylamine The desired product is obtained by substituting the example with Example 351B Example 27B in 27C, made of trifluoroacetate. MS (APCI) m / z 393 (M + 1) +; 1 H NMR (300 ΜΗζ, CD3 0D) δ 2.58 (s, 3Η), 3.12 (d5 J = 7.46 Hz, 2H), 3.91 (m5 1H)? 4.14 (dd, J = 10.51, 5.43 Hz, 1H), 4.30 (dd, JN10.51, 3.05 Hz, 1H), 7.34 (m, 5H), 7.47 (dd, JM8.65, 1.53 Hz, 1H), 7.52 (d, J = 3.05 Hz, 1H), 7.56 (d, J = 8.82 Hz, 1H), 7.78 (s, 1H), 8.14 (d, J = 2.71 Hz, 1H); Analytical calculated value for C22H21C1N40 · 1.6TFA ·· C, 52.61; Η, 3.96; N, 9.74 · Measured value: C, 52.87; Η, 3 · 90; Ν, 9 · 81 · The following compounds were prepared by substituting the Boc-phenylalaninol in Example 351 with an appropriate Boc-aminol.-285-200301122

(278) 實例352 (lS)-l-(4-溴-芊基V246-氯基-5-(3-甲基-1H-啕唑-5-基）-吡啶-3-基氧基1-乙胺 MS (APCI) m/z 471, 473 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 2.59 (s? 3H)? 3.10 (dd, J=7.63, 2.88 Hz? 2H)? 3.90 (m, 1H)5 4.15 (dd, J=10.8 5 55.43 Hz, 1H)? 4.30Example 352 (1S) -l- (4-bromo-fluorenyl V246-chloro-5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy 1- Ethylamine MS (APCI) m / z 471, 473 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 2.59 (s? 3H)? 3.10 (dd, J = 7.63, 2.88 Hz? 2H) 3.90 (m, 1H) 5 4.15 (dd, J = 10.8 5 55.43 Hz, 1H)? 4.30

(dd，J=10.51，3·05 Hz，1H)，7.24 (d，J=8.48 Hz，2H)，7.47 (dd，J=8.65, 1.53 Hz，1H)， 7.51 (s，1H)，7.54 (s，1H)，7.56 (d，J=8.48 Hz，2H)，7.79 (s，1H)，8·15 (d，J=3.05 Hz， 111);對（：22112(^1€11^40.1.5丁?入之分析計算值：（：，46.71;11，3.37 ;N，8J2·實測值：C，46·62 ; H，3.29 ; N，8.64. 實例353 (1SVH4-氣-芊基V2-「6-氟基-5-(3-曱基-1H-吲唑-5-基V吡啶-3-基氧基1-乙胺 MS (APCI) m/z 427 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) 5 2.59 (s，3H)，3.12(dd, J = 10.51, 3.05 Hz, 1H), 7.24 (d, J = 8.48 Hz, 2H), 7.47 (dd, J = 8.65, 1.53 Hz, 1H), 7.51 (s, 1H), 7.54 ( s, 1H), 7.56 (d, J = 8.48 Hz, 2H), 7.79 (s, 1H), 8.15 (d, J = 3.05 Hz, 111); pair (22112 (^ 1 € 11 ^ 40.1. 5 Calculated calculated values: (:, 46.71; 11, 3.37; N, 8J2; Found: C, 46 · 62; H, 3.29; N, 8.64. Example 353 (1SVH4-Gas-fluorenyl V2- `` 6-Fluoro-5- (3-fluorenyl-1H-indazol-5-yl Vpyridin-3-yloxy1-ethylamine MS (APCI) m / z 427 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 2.59 (s, 3H), 3.12

(dd，J=7.63, 2·54 Hz，2H)，3.91 (m，1H)，4.15 (dd，J=10.51，5·43 Hz，1H)，4·30 (dd，J= 10.51, 3.05 Hz, 1H)5 7.30 (d, J=8.48 Hz, 2H), 7.37 (d, J=8.82 Hz, 2H), 7.47 (dd, J= 8.65, 1.53 Hz，·1Η)，7.53 (d，J=3.05 Hz，1H)，7.56 (d，J=8.48 Hz，1H)，7.79 (s，1H)， 8.15(d，J=3.05Hz，lH);對 C22H20C12N4CNL6TFA之分析計算值：C， 49.64; Η，3·57; N，9.19·實測值：C，49.99 ; Η，3·56; Ν，9·22· 實例354 (lS)-2-『6-氣基-5-(3-甲基-1Η-4丨唑-5-基）-吡啶-3-基氣基1小環己基甲基-乙胺 MS (APCI) m/z 399 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ 1.01 (m, 2H), 1.31 (m，4H)，1.49 (m，1H)，1.65 (q，J=6_89 Hz，2H)，1·78 (m，4H)，2,59 (s，3H)，3.74 (m， 1H)，4.18 (dd，J=10.51，6·44 Hz，1H)，4.37 (dd，J=10.51，3·39 Hz，1H)，7.49 (dd，J= -286- 200301122(dd, J = 7.63, 2.554 Hz, 2H), 3.91 (m, 1H), 4.15 (dd, J = 10.51, 5.43 Hz, 1H), 4.30 (dd, J = 10.51, 3.05 Hz , 1H) 5 7.30 (d, J = 8.48 Hz, 2H), 7.37 (d, J = 8.82 Hz, 2H), 7.47 (dd, J = 8.65, 1.53 Hz, · 1Η), 7.53 (d, J = 3.05 Hz, 1H), 7.56 (d, J = 8.48 Hz, 1H), 7.79 (s, 1H), 8.15 (d, J = 3.05Hz, lH); Analytical calculation for C22H20C12N4CNL6TFA: C, 49.64; Η, 3 · 57; N, 9.19 · Found: C, 49.99; Η, 3.56; Ν, 9.22. Example 354 (1S) -2- 『6-Gas-5- (3-methyl-1Η- 4 丨 azole-5-yl) -pyridin-3-ylamino 1 small cyclohexylmethyl-ethylamine MS (APCI) m / z 399 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 1.01 (m, 2H), 1.31 (m, 4H), 1.49 (m, 1H), 1.65 (q, J = 6_89 Hz, 2H), 1.78 (m, 4H), 2,59 (s, 3H ), 3.74 (m, 1H), 4.18 (dd, J = 10.51, 6.44 Hz, 1H), 4.37 (dd, J = 10.51, 3.39 Hz, 1H), 7.49 (dd, J = -286- 200301122

(279) 8·82, 1·70 Hz，1H)，7.56 (dd，J=8.48, 0·68 Hz，1H)，7·59 (d，J=3.05 Hz，1H)，7·80 (s， 1H)，8.17 (d，J=3_05 Hz，1H);對 C2 2 H2 7 C1N4 0 · 1.75 TFA 之分析計算值： C，51.18; Η，4·84; Ν，9·36·實測值·· C，51.13; Η，4·75; Ν，9.20· 實例355 (lSV2-『6-氯基-5-(3-甲基-1Η-吲唑-5-基吡啶-3-基氧基1-1-(2,6-二甲基-卞基V乙胺 MS (DCI/NH3) m/e 421 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 6 = 8.10 (d ； 1H ;J=8.4 Hz)，7·75 (d ; 1H ; J=8.4 Hz)，7·55 (s ; 1H)，7·53 (s ; 1H)，7.44 (m，3H)， 7.04 (s ； 1H), 4.30 (dd ； 1H ； J=10.8 Hz ； J=3.0 Hz), 4.09 (dd ； 1H ； J=10.8 Hz ；J=4.5 Hz), 4.87 (m ； 1H), 3.30 (m ； 2H), 2.62 (s ； 3H)5 236 (s ； 6H). 實例356 qSVl-K氯基-5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氣某甲某1-2-1 基-丙胺所要之產物係經由以實例UB取代實例1〇2中之3-溴基-5-羥基吡啶，且以Boc-3-甲基-苯基丙胺醇取代實例1〇2中之Boc-色胺酸而製成。MS (DCI/NH3) m/e 407 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) (5 = 8.20 (d ； 1H ； J=3.0 Hz), 7.81 (s ； 1H), 7.61 (d ； 1H ; J=3.0 Hz)，7.57 (d ; 1H ； J=8.4 Hz), 7.40 (m ； 6H), 4.44 (d ； 2H ； J=4.5 Hz), 3.88 (m ； 1H), 3.28 (m ； 1H), 2.59 (s ； 3H), 1.42 (d ； 3H ； J=7.5 Hz). 實例357 (1SVH6-氯基-5-(3-甲基-1H-W唑-5-基V吡啶-3-基氣基甲某V2.2-二笨基乙胺所要之產物係經由以實例12B取代實例1〇2中之3-溴基-5-羥基吡啶，且以Boc-3,3-二苯基丙胺醇取代實例1〇2中之Boo色 -287- 200301122 (280) 99ΒΗΒ83Β29ΗΒΒΒΒΕ93ΚΕ5^Ξ 胺酸而製成。MS (DCI/NH3) m/e 469 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) (5 = 8.08 (d ； 1H ; J=3.0 Hz)，7.74 (s ; 1H)，7.55 (m ; 3H)，7.43 (m ; 5H)，7.31 (m; 3H)，7.21(m; 2H)，4.65 (d; 1H; J=ll.lHz)，4.44 (d; 1H; J=ll.lHz)，4.31 (d ； 1H； J=ll.l Hz),4.09(d ； 1H ； J=ll.l Hz), 2.59 (s ； 3H). 實例358(279) 8.82, 1.70 Hz, 1H), 7.56 (dd, J = 8.48, 0.68 Hz, 1H), 7.59 (d, J = 3.05 Hz, 1H), 7.80 (s , 1H), 8.17 (d, J = 3_05 Hz, 1H); Analytical calculated value for C2 2 H2 7 C1N4 0 · 1.75 TFA: C, 51.18; Η, 4.84; Ν, 9.36 · Measured value · C, 51.13; H, 4.75; N, 9.20. Example 355 (1SV2-'6-chloro-5- (3-methyl-1H-indazol-5-ylpyridin-3-yloxy 1 -1- (2,6-dimethyl-fluorenyl Vethylamine MS (DCI / NH3) m / e 421 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 6 = 8.10 (d; 1H; J = 8.4 Hz), 7.75 (d; 1H; J = 8.4 Hz), 7.55 (s; 1H), 7.53 (s; 1H), 7.44 (m, 3H), 7.04 (s ; 1H), 4.30 (dd; 1H; J = 10.8 Hz; J = 3.0 Hz), 4.09 (dd; 1H; J = 10.8 Hz; J = 4.5 Hz), 4.87 (m; 1H), 3.30 (m; 2H ), 2.62 (s; 3H) 5 236 (s; 6H). Example 356 qSVl-Kchloro-5- (3-methyl-1H-indazol-5-yl Vpyridin-3-yl gas The desired product of 1-2-1 propyl-propylamine was obtained by replacing 3-bromo-5-hydroxypyridine in Example 102 with Example UB, and replacing Example 1 with Boc-3-methyl-phenylpropylamine. Made from Boc-tryptophan acid in 2. MS (DCI / NH3) m / e 407 (M + l) +; 1 H NMR (300 MHz, CD3 OD) (5 = 8.20 (d; 1H; J = 3.0 Hz), 7.81 (s; 1H), 7.61 (d; 1H; J = 3.0 Hz), 7.57 (d; 1H; J = 8.4 Hz), 7.40 (m; 6H), 4.44 (d; 2H; J = 4.5 Hz), 3.88 (m; 1H), 3.28 (m; 1H), 2.59 (s; 3H), 1.42 (d; 3H; J = 7.5 Hz). Example 357 (1SVH6-chloro-5- (3-methyl-1H-Wazole-5-yl Vpyridin-3-yl gas) The desired product of a methyl 2.2-dibenzylethylamine was obtained by replacing the 3-bromo-5-hydroxypyridine in Example 102 with Example 12B, and replacing it with Boc-3,3-diphenylpropanolamine. It was prepared by replacing Boo-287-200301122 (280) 99BΗΒ83B29ΗΒΒΒΒΕ93ΚΕ5 ^ Ε amino acid in Example 102. MS (DCI / NH3) m / e 469 (M + l) +; 1 H NMR (300 MHz, CD3 OD) (5 = 8.08 (d; 1H; J = 3.0 Hz), 7.74 (s; 1H), 7.55 (m; 3H), 7.43 (m; 5H), 7.31 (m; 3H), 7.21 (m; 2H), 4.65 (d; 1H; J = ll.lHz), 4.44 (d; 1H; J = ll. lHz), 4.31 (d; 1H; J = ll.l Hz), 4.09 (d; 1H; J = ll.l Hz), 2.59 (s; 3H). Example 358

(lSVH5-(3-甲基-1H-钊唑-5-基）·吡啶-3-基氣基曱基1-2-笨基-丙胺所要之產物係經由以Boc-3-曱基-苯基丙胺醇取代實例102 中之 Boc-色胺酸而製成。MS(DCI/NH3)m/e 373 (M+l)+ ; !HNMR (300 MHz, CD3 OD) (5 = 8.11 (s ； 2H), 8.05 (s ； 2H), 7.74 (d ； 1H ； J=8.4 Hz), 7.62 (d; 1H; J=8.4Hz)，7.40(m; 1Η)，7·39(ιη; 5H)，4.56 (m; 2H)，3.92 (m; 2Η)，2·62 (s ； 3H)?1.6(d； 3H； J=7.5 Hz). 實例359 (15)-1-『5-(3-甲基-1沁吲唑-5-基）-吡啶-3-基氣基甲基1-2,2-二笨基-乙胺所要之產物係經由以Boc-3,3-二苯基丙胺醇取代實例102中(1SVH5- (3-methyl-1H-zazol-5-yl) · pyridin-3-ylaminomethylfluorenyl1-2-benzyl-propylamine The desired product is via Boc-3-fluorenyl-benzene Was prepared by replacing the Boc-tryptophan acid in Example 102. MS (DCI / NH3) m / e 373 (M + 1) +;! HNMR (300 MHz, CD3 OD) (5 = 8.11 (s; 2H), 8.05 (s; 2H), 7.74 (d; 1H; J = 8.4 Hz), 7.62 (d; 1H; J = 8.4Hz), 7.40 (m; 1Η), 7.39 (ιη; 5H), 4.56 (m; 2H), 3.92 (m; 2Η), 2.62 (s; 3H)? 1.6 (d; 3H; J = 7.5 Hz). Example 359 (15) -1- 『5- (3- 甲-Yl-1, indazol-5-yl) -pyridin-3-ylaminomethyl 1-2,2-dibenzyl-ethylamine The desired product is via Boc-3,3-diphenylpropanolamine Replace example 102

之 Boc-色胺酸而製成。MS(DCI/NH3)m/e435 (M+l)+ ; ^NMR (300 MHz, CD3 OD) δ = 8.62 (s ； 1H), 831 (s ； 1H), 8.02 (s ； 1H), 7.82 (s ； 1H), 7.67 (d ； 1H ； J=8.4 Hz), 7.60 (d ； 1H ； J=8.4 Hz), 7.58 (d ； 1H ； J=6.9 Hz), 7.43 (m ; 4H)，7·30 (m ; 5H)，4.61 (d ; 1H ; J=12.0 Hz)，4.48 (d ; 1H ; J=12 Hz)，4·40 (dd ； 1H ； J=11.4 Hz ； J=3.0 Hz), 4.00 (dd ； 1H ； J=11.4 Hz), 2.62 (s ； 3H). 實例360 (1SV3-甲基甲基-1HW1唑-5-基吡啶-3-基氧基甲基1-丁胺所要之產物係經由以實例12B取代實例102中之3-溴基-5-羥基吡啶，且以Boc-白胺醇取代實例102中之Boc-色胺酸而製成。MS (APCI) m/z 357 (M-l)+ ; 1 H NMR (500 MHz，CD3 OD) 5 ppm 1·02 (m， -288 - 200301122Made of Boc-tryptophan. MS (DCI / NH3) m / e435 (M + l) +; ^ NMR (300 MHz, CD3 OD) δ = 8.62 (s; 1H), 831 (s; 1H), 8.02 (s; 1H), 7.82 ( s; 1H), 7.67 (d; 1H; J = 8.4 Hz), 7.60 (d; 1H; J = 8.4 Hz), 7.58 (d; 1H; J = 6.9 Hz), 7.43 (m; 4H), 7 · 30 (m; 5H), 4.61 (d; 1H; J = 12.0 Hz), 4.48 (d; 1H; J = 12 Hz), 4.40 (dd; 1H; J = 11.4 Hz; J = 3.0 Hz), 4.00 (dd; 1H; J = 11.4 Hz), 2.62 (s; 3H). Example 360 (1SV3-methylmethyl-1HW1 azole-5-ylpyridin-3-yloxymethyl 1-butylamine The product was prepared by replacing the 3-bromo-5-hydroxypyridine in Example 102 with Example 12B and replacing the Boc-tryptophan acid in Example 102 with Boc-leumol. MS (APCI) m / z 357 (Ml) +; 1 H NMR (500 MHz, CD3 OD) 5 ppm 1.02 (m, -288-200301122

(281) J=6.40, 3.90 Hz，6H)，1.67 (m，2H)，1.80 (dd，J=13.57, 6·71 Hz，1Η)，2·59 (s，3H)， 3.71 (m，J=6.86, 3·12 Hz，1H)，4.20 (dd，J=10.61，6·55 Hz, 1H)，4.38 (dd，J=10.45， 3·28 Hz，1H)，7.49 (dd，J=8.58, 1.72 Hz，1H)，7.56 (d，J=8.11 Hz，1H)，7·59 (d，J= 3.12Hz，lH)，7.80(s，lH)，8.17(d，J=3.12Hz，lH);對 C19H23C1N40之分析計算值：C，49.56; H，5.21; N，10.88.實測值·· C，49.86; H，4.83; N，10.49. 實例361 (lS)-2-f6-氣基-5-(3-甲基-1H-吲唑-5-基V吡啶-3-基氧基1小(1H-W哚-(281) J = 6.40, 3.90 Hz, 6H), 1.67 (m, 2H), 1.80 (dd, J = 13.57, 6.71 Hz, 1Η), 2.59 (s, 3H), 3.71 (m, J = 6.86, 3.12 Hz, 1H), 4.20 (dd, J = 10.61, 6.55 Hz, 1H), 4.38 (dd, J = 10.45, 3.28 Hz, 1H), 7.49 (dd, J = 8.58 , 1.72 Hz, 1H), 7.56 (d, J = 8.11 Hz, 1H), 7.59 (d, J = 3.12 Hz, lH), 7.80 (s, lH), 8.17 (d, J = 3.12 Hz, lH ); Analytical calculation for C19H23C1N40: C, 49.56; H, 5.21; N, 10.88. Measured value · C, 49.86; H, 4.83; N, 10.49. 5- (3-methyl-1H-indazol-5-yl Vpyridin-3-yloxy 1 small (1H-W indol-

3-基甲基乙胺所要之產物係經由以實例12B取代實例102中之3-溴基-5-羥基吡啶而製成。MS (APCI) m/z 533 (M+l)+ ; 1 H NMR (500 MHz，CD3 OD) 5ppm 2.58 (s，3H)，3.28 (m，2H)，3.96 (m，1H)，4·20 (dd，J=10.45, 5.77 Hz，1H)， 4.34 (dd，J=10.61，3.12 Hz，1H)，7.02 (t，J=7.49 Hz，1H)，7·12 (t，J=7.64 Hz，1H)， 7.22 (s，1H)，7·37 (d，J=8.42 Hz，1H)，7·44 (dd，】=8·42, 1·56 Hz，1H)，7.47 (d，J=3.12 Hz, 1H), 7.54 (d, J=8.42 Hz, 1H), 7.57 (d, J=8.11 Hz, 1H), 7.74 (s, 1H), 8.12.(d, J= 2.81 Hz，1H);對 C24H22C1N50之分析計算值：C，52.08; Η，4·12; N，11.61· 實測值：C，52.45 ; Η，4·08 ; N，11.24·3-ylmethylethylamine The desired product was prepared by substituting 3-bromo-5-hydroxypyridine in Example 102 with Example 12B. MS (APCI) m / z 533 (M + l) +; 1 H NMR (500 MHz, CD3 OD) 5ppm 2.58 (s, 3H), 3.28 (m, 2H), 3.96 (m, 1H), 4.20 (dd, J = 10.45, 5.77 Hz, 1H), 4.34 (dd, J = 10.61, 3.12 Hz, 1H), 7.02 (t, J = 7.49 Hz, 1H), 7.12 (t, J = 7.64 Hz, 1H), 7.22 (s, 1H), 7.37 (d, J = 8.42 Hz, 1H), 7.44 (dd,] = 8.42, 1.56 Hz, 1H), 7.47 (d, J = 3.12 Hz, 1H), 7.54 (d, J = 8.42 Hz, 1H), 7.57 (d, J = 8.11 Hz, 1H), 7.74 (s, 1H), 8.12. (D, J = 2.81 Hz, 1H); Analysis and calculation of C24H22C1N50: C, 52.08; Η, 4 · 12; N, 11.61 · Measured value: C, 52.45; Η, 4.08; N, 11.24 ·

實例362 (lS)-2-(6-氯基-5-遠吩并f2,3-ch比淀-2-基-I?比咬-3-基氧基）-1-(111-41嗓 -3·基甲基V乙胺實例362Α 氣基-5-ρ塞吩并「2,3-印比咬-2-基-p比咬-3-基氧基唤-3-基甲某V乙基1-胺曱某酸第三-丁酯標題化合物係經由以實例13八取代實例27B中之實例2A，且以實例38A取代實例27B中之實例27A而製成。 -289· 200301122 (282)Example 362 (lS) -2- (6-Chloro-5-tepheno f2,3-ch than Yodo-2-yl-I? Pyridin-3-yloxy) -1- (111-41 Example of 3-Methylmethyl V Ethylamine 362A Gasoyl-5-ρ thiophene "2,3-Inpyridine-2-yl-p The title compound of ethyl 1-aminosulfonic acid third-butyl ester was prepared by replacing Example 2A in Example 27B with Example 13A and substituting Example 27A in Example 27B with Example 38A. -289 · 200301122 (282 )

實例362B (lSV2-(6-氣基-5-口塞吩并f2.3-cl吡啶-2-基-吡啶-3-基氧基）-1-(1Η-θ1哚 -3-某甲基乙胺標題化合物係經由以實例362Α取代實例27C中之實例27Β 而製成。MS (APCI) m/z 436 (M+l)+; 1 H NMR (300 MHz，CD3 OD) 5 3·29 (m， 2Η)，4.00 (m，1Η)，4.26 (dd，J=10.51，5.76 Ηζ，1Η)，4.40 (dd，J=10.51，3·05 Ηζ，1Η)， 7·02 (t，J=7.63 Hz，1H)，7.10 (t，J=6.95 Hz，1H)，7.23 (s，1H)，7·36 (d，J=8.14 Hz，1H)， 7.58 (d，J=7.80 Hz，1H)，7.74 (d，J=3.05 Hz，1H)，8.05 (s，1H)，8.29 (d5 J=3.05 Hz， 1H)，8·35 (d，J=6.10 Hz，1H)，8.64 (d，J=6.10 Hz，1H)，9·57 (s，1H); 對（：23^119(：1>1403.2.6丁?八之分析計算值：<：，46.31;11，2.98;凡7.66. 實測值：C，46·22 ; H，2·94 ; N，7·52. 實例363 5-「(2SV2-胺基-3-ΠΗ-吲哚-3-基丙氫基1-3-異喹啉-6-基-吡啶-2-甲腈實例363Α (lSM2-(6-氯基-5-異喹啉-6-某-毗啶-3-基氧基VH1H-吲哚-3-基-甲基）-乙基1-胺甲基酸第三-丁酯標題化合物係經由以實例13A取代實例27B中之實例2A而製成。MS (APCI) m/z 529 (M+l)+.Example 362B (1SV2- (6-Gasyl-5-oxo-phenenof2.3-cl pyridin-2-yl-pyridin-3-yloxy) -1- (1Η-θ1 indol-3-methyl) The ethylamine title compound was prepared by replacing Example 27B in Example 27C with Example 362A. MS (APCI) m / z 436 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 3 · 29 ( m, 2Η), 4.00 (m, 1Η), 4.26 (dd, J = 10.51, 5.76 Ηζ, 1Η), 4.40 (dd, J = 10.51, 3.05 Ηζ, 1Η), 7 · 02 (t, J = 7.63 Hz, 1H), 7.10 (t, J = 6.95 Hz, 1H), 7.23 (s, 1H), 7.36 (d, J = 8.14 Hz, 1H), 7.58 (d, J = 7.80 Hz, 1H) , 7.74 (d, J = 3.05 Hz, 1H), 8.05 (s, 1H), 8.29 (d5 J = 3.05 Hz, 1H), 8.35 (d, J = 6.10 Hz, 1H), 8.64 (d, J = 6.10 Hz, 1H), 9.57 (s, 1H); Analytical calculations for (: 23 ^ 119 (: 1 > 1403.2.6, Ding 八 8): <:,46.31; 11, 2.98; where 7.66. Found: C, 46 · 22; H, 2.94; N, 7.52. Example 363 5-"(2SV2-Amino-3-Π 基 -indol-3-ylpropanyl1-3-iso Example of quinolin-6-yl-pyridine-2-carbonitrile 363A (1SM2- (6-chloro-5-isoquinolin-6-some-pyridin-3-yloxy VH1H-indol-3-yl -Methyl) -ethyl 1-aminomethyl acid - butyl ester The title compound of example 13A through 27B, examples of the substituted Example 2A made .MS (APCI) m / z 529 (M + l) +.

實例363B (lS)-[2-(6二象基異喹啉基-吡啶各基氣基Vl-OH-K丨哚-3-基甲基乙基上胺甲某酸第三-丁酯於10毫升RBF中，裝填實例363A (100毫克，〇 189毫莫耳）、氰化鋅（56毫克，0.47毫莫耳）及Pd(PPh3 )4 (糾毫克，〇.〇378毫莫耳），並以氮滌氣。添加無水DMF (3毫升），並將此溶液以 -290- 200301122 (283) 氮再滌氣一次。將反應混合物於90°C下攪拌70小時。在冷卻後，使混合物於醋酸乙酯與鹽水之間作分液處理，並將有機相以水洗滌。使有機層濃縮’並藉急騾式層析（於己燒中之40-100% EtOAc)分離殘留物’而得所要之產物（87.4愛克，89%)。MS(APCI)m/z 520 (M+l)+·Example 363B (lS)-[2- (6-Dioxoisoquinolinyl-pyridine radicals Vl-OH-Kindol-3-ylmethylethyl on a tertiary butyl acid 10 ml of RBF was filled with Example 363A (100 mg, 0189 mmol), zinc cyanide (56 mg, 0.47 mmol) and Pd (PPh3) 4 (corrected mg, 0.0378 mmol), It was purged with nitrogen. Anhydrous DMF (3 ml) was added and the solution was purged again with -290- 200301122 (283) nitrogen. The reaction mixture was stirred at 90 ° C for 70 hours. After cooling, the mixture was allowed to cool. Separate the solution between ethyl acetate and brine and wash the organic phase with water. The organic layer is concentrated 'and the residue is separated by flash chromatography (40-100% EtOAc in hexane)' and The desired product was obtained (87.4 Aike, 89%). MS (APCI) m / z 520 (M + l) + ·

實例363CExample 363C

5-「(2SV2-胺基-3-ΠΗ-吲哚-3-基）-丙氫某1各異喹啉-6-基-吡啶-2-甲腈所要之產物係經由以實例363B取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 421 (M+l)+ ; 1 H NMR (300 MHz， CD3 〇D) δ 3.31 (m, 2H), 4.03 (m, 1H), 4.34 (dd, J=10.85, 5.76 Hz, 1H), 4.48 (dd, JN10.85, 3.39 Hz，1H)，7.00 (t，J=7.46 Hz，1H)，7.10 (t，J=6.95 Hz，1H)，7·23 (s，1H)， 7.35 (d，J=8· 14 Hz，1H)，7.57 (d，J=7.80 Hz，1H)，7.64 (d，J=2.71 Hz，1H)，8·08 (dd， JM8.48, 1.69 Hz，1H)，8·39 (d，J=7.46 Hz，1H)，8·37 (d，J=6.44 Hz，1H)，8.55 (d，J= 7·12 Hz，1H)，8.56 (m，1H)，8.65 (d，J=6.10 Hz，1H)，9.72 (s，1H);對 C2 6 H2 i N5 O • 2.9TFA 之分析計算值：C，50.92 ; H，3·21 ; N，9.34.實測值：C，50.98 ;H，3.23 ; N，9.48.5-"(2SV2-Amino-3-ΠΗ-indol-3-yl) -propanone 1 Isoquinolin-6-yl-pyridine-2-carbonitrile The desired product is obtained by substituting Example 363B Example 27B in 27C, made from trifluoroacetate. MS (APCI) m / z 421 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 3.31 (m, 2H), 4.03 ( m, 1H), 4.34 (dd, J = 10.85, 5.76 Hz, 1H), 4.48 (dd, JN10.85, 3.39 Hz, 1H), 7.00 (t, J = 7.46 Hz, 1H), 7.10 (t, J = 6.95 Hz, 1H), 7.23 (s, 1H), 7.35 (d, J = 8.14 Hz, 1H), 7.57 (d, J = 7.80 Hz, 1H), 7.64 (d, J = 2.71 Hz , 1H), 8.08 (dd, JM8.48, 1.69 Hz, 1H), 8.39 (d, J = 7.46 Hz, 1H), 8.37 (d, J = 6.44 Hz, 1H), 8.55 ( d, J = 7.12 Hz, 1H), 8.56 (m, 1H), 8.65 (d, J = 6.10 Hz, 1H), 9.72 (s, 1H); Analysis of C2 6 H2 i N5 O • 2.9TFA Calculated: C, 50.92; H, 3.21; N, 9.34. Found: C, 50.98; H, 3.23; N, 9.48.

實例364 gSM-ΠΗ-啕嗓-3-基甲基V2-f5-(3-苯基-異口奎啉-6-基V吡啶-3-基氧Example 364 g SM-II-H-S-3-ylmethyl V2-f5- (3-phenyl-isoquinolin-6-yl Vpyridin-3-yloxy

基V乙胺實例364A (1SV丨M1H-吲哚-3-基甲基）-245-(3-笨基-異喹啉-6·基V吡啶-3-某^ 基1-乙基丨-胺甲基酸第三-丁酯於實例80E(150毫克，0.28毫莫耳）、（1，1，1·三丁基錫烷基）苯 (137毫克，0.57毫莫耳）、參（二苯亞甲基丙酮）-二鈀（27毫克 -291- 200301122 (284) ，0·028毫莫耳）及2-二環己基膦基-2’-二甲胺基-1，Γ-聯苯（22毫克，0.057毫莫耳）在無水DMF (10毫升）中之溶液内，在Ν2下添加三乙胺。將所形成之溶液於100°C下攪掉3小時。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（Na2S04)，過濾及在真空下濃縮。於矽膠上純化，使用60%醋酸乙酯/己烷，提供標題化合物（70毫克，47%)。MS(DCI/NH3)m/e571(M+l)+.Example of Benzyl V Ethylamine 364A (1SV 丨 M1H-Indol-3-ylmethyl) -245- (3-benzyl-isoquinoline-6 · yl Tertiary-butyl amino methanoate in Example 80E (150 mg, 0.28 mmol), (1,1,1.1 tributyltinalkyl) benzene (137 mg, 0.57 mmol), ginseng (diphenylene) Methylacetone) -Dipalladium (27 mg-291- 200301122 (284), 0.028 mmol) and 2-dicyclohexylphosphino-2'-dimethylamino-1, Γ-biphenyl (22 Mg, 0.057 mmol) in a solution in anhydrous DMF (10 ml), triethylamine was added under N2. The resulting solution was stirred at 100 ° C for 3 hours. The reaction solution was mixed with ethyl acetate and The solution was separated between water. The organic layer was washed (brine), dried (Na2S04), filtered and concentrated under vacuum. Purified on silica gel using 60% ethyl acetate / hexane to provide the title compound (70 mg , 47%). MS (DCI / NH3) m / e571 (M + l) +.

實例364B nSVl-ΠΗ-口弓1嗓-3-某甲基）-2-「5-(3-苯某-異口奎淋-6-基口比啶-3-基氣基1-乙胺Examples

標題化合物係經由以實例354A取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS(DCI/NH3)m/e471(M+l)+ ; iHNMR (300MHz,D6-DMSO) δ 11.04 (s ； 1Η), 9.49 (s ； 1H)，8.74 (s ; 1H), 8.45 (s ； 1H), 8.44(s ； 1H), 8.39(s ； 1H)? 8.28 (d ； 1H ； J=8.4 Hz), 8.23 (d ； 1H ； J=7.5 Hz), 8.08 (s ； 2H), 8.02 (d ； 1H ； J=8.4 Hz), 7.83 (s ； 1H), 7.63 (d ； 1H ； J=8.4 Hz)? 7.55 (t ； 3H ； J=7.5 Hz), 7.47 (d ； 1H ; J二7.5 Hz)，7.37 (d ; 1H ； J=8.4 Hz)，7.31 (s ; 1H), 7.10 (t ； 1H ; J=7.2 Hz)，7.00 (t ; 1H ； J=7.2 Hz), 4.40 (m; 1H)，4.23 (m; 1H)，3.88 (m; 1H)，3.18 (m; 2H) 下列化合物係經由以適當三丁基錫烷基試劑取代實例364 中之（1,1,1-三丁基錫烷基）苯而製成。實例365 (lS)-2-「5-(3-乙基-異4啉-6-基V毗啶-3-基氧基VW1H-W哚-3-基甲一基）_乙胺 MS (DCI/NH3) m/e 423 (M+l)+ ； 1H NMR (300 MHz, D6 -DMSO) 5 = 11.04 •292- 200301122 (285) (s ; 1H)，9·61 (s ; 1Η)，8·77 (s ; 1H)，8·47 (s ; 1Η)，8·45 (s ; 1Η)，8·42 (d ; 1H ; J=9.0 Hz), 8.20 (s ； 2H), 8.14(d； 2H； J=9.0 Hz), 8.03 (s ； 2H)? 7.85 (s ； 1H)5 7.63 (d； 1H； J=7.5Hz)57.38(d； 1H； J=7.5 Hz), 7.30 (s； lH),7.10(t； 1H： J=7.5 Hz), 7.00 (t ； 1H ； J=7.5 Hz), 4.40 (m ； 1H), 4.22 (m ； 1H), 3.88 (m ； 1H), 3.18 (m ； 2H)? 3.04 (q ； 2H ； J=7.5 Hz), 1.37 (t ； 3H ； J=7.5 Hz). 實例366 钊嗓一3-基甲基V2-『5-(3-口比淀-4-基-異口奎淋-6·基Vp比淀-3-The title compound was made from trifluoroacetate by replacing Example 27B in Example 27C with Example 354A. MS (DCI / NH3) m / e471 (M + 1) +; iHNMR (300MHz, D6-DMSO) δ 11.04 (s; 1Η), 9.49 (s; 1H), 8.74 (s; 1H), 8.45 (s; 1H), 8.44 (s; 1H), 8.39 (s; 1H)? 8.28 (d; 1H; J = 8.4 Hz), 8.23 (d; 1H; J = 7.5 Hz), 8.08 (s; 2H), 8.02 ( d; 1H; J = 8.4 Hz), 7.83 (s; 1H), 7.63 (d; 1H; J = 8.4 Hz)? 7.55 (t; 3H; J = 7.5 Hz), 7.47 (d; 1H; J two 7.5 Hz), 7.37 (d; 1H; J = 8.4 Hz), 7.31 (s; 1H), 7.10 (t; 1H; J = 7.2 Hz), 7.00 (t; 1H; J = 7.2 Hz), 4.40 (m; 1H), 4.23 (m; 1H), 3.88 (m; 1H), 3.18 (m; 2H) ) Made from benzene. Example 365 (1S) -2- "5- (3-Ethyl-iso4-line-6-yl-V-pyridin-3-yloxy-VW1H-W-indol-3-ylmethyl-yl) -ethylamine MS ( DCI / NH3) m / e 423 (M + l) +; 1H NMR (300 MHz, D6 -DMSO) 5 = 11.04 • 292- 200301122 (285) (s; 1H), 9.61 (s; 1Η), 8 · 77 (s; 1H), 8.47 (s; 1Η), 8.45 (s; 1Η), 8.42 (d; 1H; J = 9.0 Hz), 8.20 (s; 2H), 8.14 ( d; 2H; J = 9.0 Hz), 8.03 (s; 2H)? 7.85 (s; 1H) 5 7.63 (d; 1H; J = 7.5Hz) 57.38 (d; 1H; J = 7.5 Hz), 7.30 (s LH), 7.10 (t; 1H: J = 7.5 Hz), 7.00 (t; 1H; J = 7.5 Hz), 4.40 (m; 1H), 4.22 (m; 1H), 3.88 (m; 1H), 3.18 (m; 2H)? 3.04 (q; 2H; J = 7.5 Hz), 1.37 (t; 3H; J = 7.5 Hz). Example 366 Zhao-a 3-ylmethyl V2- 『5- (3-port ratio Yodo-4-yl-Isokourine-6-based Vp ratio Yodo-3-

基氧基乙胺 MS (DCI/NH3) m/e 472 (M+l)+ ； 1 H NMR (300 MHz, D6 -DMSO) 5 = 11.04 (s ； 1H), 9.54 (s ； 1H), 8.93 (d ； 2H ； J=7.5 Hz), 8.87 (d ； 2H ； J=7.5 Hz), 8.83 (s ； lH)，8.70(s; 1H)，8.43 (s; 2H)，8.35 (d; 1H; J=8.4Hz)，8.09 (d; 2H; J=8.4Hz)， 7.84(s； lH),7.61(d； 1H； J=8.4 Hz), 7.38 (d； 1H； J=8.4 Hz), 7.25 (s； 1H), 7.12 (t； 1H； J=8.4 Hz), 7.03 (t ； 1H ； J=8.4 Hz), 4.45 (m ； 1H), 4.30 (m ； 1H),4.00 (m ； 1H), 3.30 (m ； 2H) 實例367 (lSV2-『5-(3-呋喃-2-基-異喳啉冬基）-吡啶-3-基氣基吲哚-3-Alkoxyethylamine MS (DCI / NH3) m / e 472 (M + 1) +; 1 H NMR (300 MHz, D6 -DMSO) 5 = 11.04 (s; 1H), 9.54 (s; 1H), 8.93 (d; 2H; J = 7.5 Hz), 8.87 (d; 2H; J = 7.5 Hz), 8.83 (s; lH), 8.70 (s; 1H), 8.43 (s; 2H), 8.35 (d; 1H; J = 8.4Hz), 8.09 (d; 2H; J = 8.4Hz), 7.84 (s; lH), 7.61 (d; 1H; J = 8.4 Hz), 7.38 (d; 1H; J = 8.4 Hz), 7.25 (s; 1H), 7.12 (t; 1H; J = 8.4 Hz), 7.03 (t; 1H; J = 8.4 Hz), 4.45 (m; 1H), 4.30 (m; 1H), 4.00 (m; 1H) , 3.30 (m; 2H) Example 367 (1SV2- [5- (3-furan-2-yl-isophosphorinyl) -pyridin-3-ylaminoindol-3-

基甲基乙胺 MS (DCI/NH3) m/e 461 (M+l)+ ； 1 H NMR (300 MHz, D6 -DMSO) δ = UM(s； lH)，9.39(s; lH)，8.74(s; 1H)，8.44 (s; 1H)，8.41 (s; 1H)，8.25 (d; 1H; J=8.4Hz)， 8.18 (m ; 3H)，8.00 (d ; 2H ; J=8.4 Hz), 7·89 (s ; 1H)，7.83 (s ; 1H)，7.63 (d ; 1H； J=8.4 Hz), 7.39 (d ； 1H ； J=8.4 Hz), 7.31 (s ； 1H), 7.18 (s ； 1H)，7.11 (t ; 1H ； J=8.4 Hz), 7.01 (t ； 1H ； J=8.4 Hz), 6.71 (s ； 1H), 4.40 (m ； 1H), 4.21 (m ; 1H)，3.88 (m ; 1H)，3.18 (m ; 2H) 實例368 -293 - 200301122Methylmethylethylamine MS (DCI / NH3) m / e 461 (M + l) +; 1 H NMR (300 MHz, D6 -DMSO) δ = UM (s; lH), 9.39 (s; lH), 8.74 (s; 1H), 8.44 (s; 1H), 8.41 (s; 1H), 8.25 (d; 1H; J = 8.4Hz), 8.18 (m; 3H), 8.00 (d; 2H; J = 8.4 Hz) , 7.89 (s; 1H), 7.83 (s; 1H), 7.63 (d; 1H; J = 8.4 Hz), 7.39 (d; 1H; J = 8.4 Hz), 7.31 (s; 1H), 7.18 ( s; 1H), 7.11 (t; 1H; J = 8.4 Hz), 7.01 (t; 1H; J = 8.4 Hz), 6.71 (s; 1H), 4.40 (m; 1H), 4.21 (m; 1H), 3.88 (m; 1H), 3.18 (m; 2H) Examples 368 -293-200301122

(286) nSM-ΠΗ-啕哚-3-基曱基）-2-「5-(3-笨基乙炔基-異口奎啉-6-基V吡啶- 3-基氧基乙胺 MS (DCI/NH3) m/e 495 (M+l)+ ； 1H NMR (300 MHz, D6-DMSO) 5 = 11.04 (s ； 1H)，9.41 (s; 1H)，8.73 (s; 1H)，8.45 (s; 1H)，8.35 (s; 1H)，8.31 (d; 1H; J=5.4 Hz)， 8.24 (s； 2H), 8.21(s； 1H), 8.07(d； 1H； J=5.4 Hz), 7.82 (s ； 1H), 7.65 m； 4H), 7.48 (m； 2H),7.39(d； 1H； J=5.4 Hz), 7.30 (s ； lH)?7.10(t； 1H； J=5.4 Hz), 7.00 (t； 1H； J=5.4 Hz), 4.40 (m ； 1H), 4.22 (m ； lH),4.13(m； lH),3.18(m； 2H). 實例369 (lS)-l-(lH-g弓丨口果-3-基甲基）-2-「5-(3-丙-1-決基-異口奎口林-6-基）-口比淀-3- 基氧基1-乙胺 MS (DCI/NH3) m/e 433 (M+l)+ ； 1H NMR (300 MHz, D6 -DMSO) 5 = 11.04 (s ； 1H)，9.32 (s; 1H)，8.71 (s; 1H)，8.43 (s; 1H)，8.28 (s; 1H)，8.25 (d; 1H; J=8.4 Hz)， 8.18 (s ； 2H), 8.02 (d ； 1H ； J=8.4 Hz), 7.99 (s ； 1H), 7.80 (s ； 1H), 7.62 (d ； 1H ； J=8.4 Hz), 7.38 (d ； 1H ； J=8.4 Hz), 730 (s ； lH),7.10(t； 1H ； J=8.4 Hz), 7.00 (t; 1H; J=8.4Hz)，4.40 (m; 1H)，4.21 (m; 1Η)，3·88(τη; 1H)，3.18 (m; 2H)，2.13 (s ； 3H). 實例370 (1S)-1-(1H-蜊嗓-3-基甲基）-2-「5-(3-乙烯基-異喹淋-6-基V吡啶-3-基氧基1-乙胺 MS (DCI/NH3) m/e 421 (M+l)+ ； 1 H NMR (300 MHz, D6 -DMSO) 5 = 11.04 (s ； lH)，9.36(s; 1H)，8.71 (s; 1H)，8.42 (s; 1H)，8.28 (s; 1H)，8.25 (d; 1H; J=9.0Hz)， 8.18 (s ； 2H), 8.00 (d ； 1H ； J=9.0 Hz), 7.85 (s ； 1H), 7.81 (s ； 1H), 7.63 (d ； 1H ； J=8.4 Hz), 7.38 (d ； 1H ； J=8.4 Hz), 7.29 (s ； 1H), 7.10 (t ； 1H ； J=8.4 Hz), 7.01 (t； 1H； J=8.4 Hz), 6.98 (dd； 1H； J=17.4Hz； J=12.0 Hz), 6.40 (d； 1H； J=17.4Hz), -294- (287) 5.50 (d ； 1H ； J=12.0 Hz), 4.40 (m ； 1H), 4.21 (m ； 1H), 3.88 (m ； 1H)5 3.18 (m； 2H). 實例371 nS)-6-{5-[2-胺基-3-ΠΗ-啕哚-3-基V丙氣基1-吡啶-3-基卜異4啉-3-曱腈(286) nSM-II-H-indol-3-ylfluorenyl) -2- "5- (3-benzylethynyl-isoquinolin-6-yl Vpyridin-3-yloxyethylamine MS ( DCI / NH3) m / e 495 (M + 1) +; 1H NMR (300 MHz, D6-DMSO) 5 = 11.04 (s; 1H), 9.41 (s; 1H), 8.73 (s; 1H), 8.45 ( s; 1H), 8.35 (s; 1H), 8.31 (d; 1H; J = 5.4 Hz), 8.24 (s; 2H), 8.21 (s; 1H), 8.07 (d; 1H; J = 5.4 Hz), 7.82 (s; 1H), 7.65 m; 4H), 7.48 (m; 2H), 7.39 (d; 1H; J = 5.4 Hz), 7.30 (s; lH)? 7.10 (t; 1H; J = 5.4 Hz) , 7.00 (t; 1H; J = 5.4 Hz), 4.40 (m; 1H), 4.22 (m; lH), 4.13 (m; lH), 3.18 (m; 2H). Example 369 (lS) -l- ( lH-g bow 丨 fruit-3-ylmethyl) -2- "5- (3-propan-1-decyl-isokouquelin-6-yl) -koubito-3-yloxy 1-Ethylamine MS (DCI / NH3) m / e 433 (M + l) +; 1H NMR (300 MHz, D6 -DMSO) 5 = 11.04 (s; 1H), 9.32 (s; 1H), 8.71 (s 1H), 8.43 (s; 1H), 8.28 (s; 1H), 8.25 (d; 1H; J = 8.4 Hz), 8.18 (s; 2H), 8.02 (d; 1H; J = 8.4 Hz), 7.99 (s; 1H), 7.80 (s; 1H), 7.62 (d; 1H; J = 8.4 Hz), 7.38 (d; 1H; J = 8.4 Hz), 730 (s; lH), 7.10 (t 1H; J = 8.4 Hz), 7.00 (t; 1H; J = 8.4Hz), 4.40 (m; 1H), 4.21 (m; 1Η), 3.88 (τη; 1H), 3.18 (m; 2H), 2.13 (s; 3H). Example 370 (1S) -1- (1H-clam-3-ylmethyl) -2- "5- (3-vinyl-isoquine-6-yl-V-pyridine-3 -Yloxy 1-ethylamine MS (DCI / NH3) m / e 421 (M + l) +; 1 H NMR (300 MHz, D6 -DMSO) 5 = 11.04 (s; lH), 9.36 (s; 1H ), 8.71 (s; 1H), 8.42 (s; 1H), 8.28 (s; 1H), 8.25 (d; 1H; J = 9.0Hz), 8.18 (s; 2H), 8.00 (d; 1H; J = 9.0 Hz), 7.85 (s; 1H), 7.81 (s; 1H), 7.63 (d; 1H; J = 8.4 Hz), 7.38 (d; 1H; J = 8.4 Hz), 7.29 (s; 1H), 7.10 (t; 1H; J = 8.4 Hz), 7.01 (t; 1H; J = 8.4 Hz), 6.98 (dd; 1H; J = 17.4Hz; J = 12.0 Hz), 6.40 (d; 1H; J = 17.4Hz ), -294- (287) 5.50 (d; 1H; J = 12.0 Hz), 4.40 (m; 1H), 4.21 (m; 1H), 3.88 (m; 1H) 5 3.18 (m; 2H). Example 371 nS) -6- {5- [2-Amino-3-ΠΗ-pyridin-3-yl V-propanyl 1-pyridin-3-yl-pyridin-4-line-3-phosphonitrile

實例371A (lSH2-f5-(3-氰基-異4啉-6-基V吡啶-3-基氧基哚-3-基甲基）-乙基1-胺甲基酸第三-丁酯所要之產物係經由以實例80E取代實例363B中之實例363A 而獲得。Example 371A (lSH2-f5- (3-cyano-iso4-line-6-ylVpyridin-3-yloxyindol-3-ylmethyl) -ethyl 1-aminomethyl acid tert-butyl ester The desired product was obtained by replacing Example 363A in Example 363B with Example 80E.

實例371B 【lS)-6-{5-『2-胺基-3-(111-口弓丨嗓-3-基）-丙氧基Ι-p比淀-3-基]•-異口奎g林-3-曱月膏所要之產物係經由以實例371A取代實例27C中之實例27B ，以三氟醋酸鹽獲得。MS(DCI/NH3)m/e420(M+l)+ ; iHNMR (300 MHz，D6-DMSO) 5 = 11·04 (s; 1H)，9·52 (s; 1H)，8.75 (s; 1H)，8·64 (s; 1H)， 8.47 (s ； 2H), 8.42 (d ； 1H ; J=6.0 Hz)，8.26 (m ; 3H)，7.84 (s ; 1H)，7.62 (d ; 1H； J=6.0Hz),7.38(d； 1H； J=6.0 Hz), 7.31 (s； lH),7.10(t； 1H； J=6.0 Hz), 7.00 (t ; 1H ; J=6.0 Hz)，4.40 (m ; 1H)，4.22 (m，1H)，3.88 (m ; 1H)，3.18 (m ; 2H). 實例372 (lS)-l-(lH-H丨嗓-3-基甲基）-2-(5-異口奎琳-6-基-6-乙缔基-p比淀-3-基氣基V乙胺所要之產物係經由以三丁基乙烯基錫取代實例364中之三丁基苯基錫，且以實例363A取代實例364中之實例§〇e ,以三氟醋酸鹽製成。MS(APCI)m/z420(M+l)+ ; iHNMRpOOMHz， CD3 〇D) 5 3.30 (m，2H)，3·98 (m，1H)，4.24 (dd，J=10.51，5·76 Hz，1H)，4·38 (dd，J= 200301122 (288) 10.51，3·05 Hz，1H)，5·39 (dd，J=10.85, 1.70 Hz, 1H)，6.24 (dd，J=16.95, 1.70 Hz, 1H)， 6.66 (dd，J=17.12, 10.68 Hz，1H)，7.00 (dd，J=6.78, 6·10 Hz，1H)，7.09 (t，J=7.63 Hz， 1H)，7.22 (s，1H)，7·35 (d，J=8· 14 Hz，1H)，7.40 (d，JN2.71 Hz，1H)，7.57 (d，J=7.80 Hz，1H)，7.95 (dd，J=8.48, 1.70 Hz，1H)，8.22 (s，1H)，8·45 (d，J=7.46 Hz，1H)，8·45 (s， 1H)，8·56 (d，J=8.81 Hz，1H)，8.64 (d，J=6.44 Hz，1H)，9.79 (s，1H); 對 C27H24N40.4TFA之分析計算值：C，47.96,3.22 ; Ν，6·39·實測值：C，48.02 ; H，3·00 ; N，6·07. 實例373 (lS)-2-(6-乙块基-5-異口奎淋-6-基-口比淀-3-基乳基）-1-(1Η-ρ引口果-3-基甲基V乙胺所要之產物係經由以三丁基乙炔基錫取代實例364中之丁基苯基錫，並以實例363Α取代實例364中之實例80Ε，以三氟醋酸鹽製成。MS(APCI)m/z419(M+l)+ ; iHNMRpOOMHACDsOD) δ 3·31 (m，2Η)，3.67 (s，1Η)，3.99 (m，1Η)，4.28 (dd，（J=10.74, 5.83 Ηζ，1Η)，4·42 (dd，JN10.74，3·07 Hz，1H)，7·00 (t，J=7.06 Hz，1H)，7·09 t，J=7.21 Hz，1H)，7.23 (s， 1H)，7·35 (d，J=8.29 Hz，1H)，7.55 (m，1H)，7·56 (d，J=7.98 Hz，1H)，8.19 (dd，J=8.59, 1.53 Hz，1H)，8.42 (s，2H)，8.47 (d，J=6.44 Hz，1H)，8.56 (d，J=8.59 Hz，1H)，8.63 (d， J=6.44 Hz，1H)，9.79 (s，1H);對 C2 7 H2 2 N4 Ο · 2·9 TFA 之分析計算值： C，52.59; Η，3·35; Ν，7·48·實測值：C，52.52 ; H，3.44; Ν，7·01· 實例374 (lS)-2-(6-咬喃-2-基-5-異峻〃林-6-基比咬-3-基乳基嗓-3-某甲基V乙胺Example 371B [lS) -6- {5- [2-Amino-3- (111-portal bow laryn-3-yl) -propoxyl-p biyodo-3-yl] • -Isoquinone The desired product of g Lin-3- 曱月月膏 was obtained by replacing Example 27B in Example 27C with Example 371A and using trifluoroacetate. MS (DCI / NH3) m / e420 (M + 1) +; iHNMR (300 MHz, D6-DMSO) 5 = 11.04 (s; 1H), 9.52 (s; 1H), 8.75 (s; 1H ), 8.64 (s; 1H), 8.47 (s; 2H), 8.42 (d; 1H; J = 6.0 Hz), 8.26 (m; 3H), 7.84 (s; 1H), 7.62 (d; 1H; J = 6.0Hz), 7.38 (d; 1H; J = 6.0 Hz), 7.31 (s; lH), 7.10 (t; 1H; J = 6.0 Hz), 7.00 (t; 1H; J = 6.0 Hz), 4.40 (m; 1H), 4.22 (m, 1H), 3.88 (m; 1H), 3.18 (m; 2H). Example 372 (lS) -l- (lH-H 丨 -3-ylmethyl) -2 -(5-Isoquinolin-6-yl-6-ethenyl-p-pyridine-3-ylamino V ethylamine The desired product is obtained by replacing tributyl in Example 364 with tributylvinyltin Phenyltin, and replaced with the example §〇e in Example 364 with Example 363A, made of trifluoroacetate. MS (APCI) m / z420 (M + 1) +; iHNMRpOOMHz, CD3 OD) 5 3.30 ( m, 2H), 3.98 (m, 1H), 4.24 (dd, J = 10.51, 5.76 Hz, 1H), 4.38 (dd, J = 200301122 (288) 10.51, 3.05 Hz, 1H ), 5.39 (dd, J = 10.85, 1.70 Hz, 1H), 6.24 (dd, J = 16.95, 1.70 Hz, 1H), 6.66 (dd, J = 17.12, 10.68 Hz, 1H), 7.00 (dd, J = 6.78, 6.10 Hz, 1H), 7.09 (t, J = 7.63 Hz, 1H), 7.22 (s, 1H), 7.35 (d, J = 8.14 Hz, 1H), 7.40 (d, JN2.71 Hz, 1H), 7.57 (d, J = 7.80 Hz, 1H ), 7.95 (dd, J = 8.48, 1.70 Hz, 1H), 8.22 (s, 1H), 8.45 (d, J = 7.46 Hz, 1H), 8.45 (s, 1H), 8.56 ( d, J = 8.81 Hz, 1H), 8.64 (d, J = 6.44 Hz, 1H), 9.79 (s, 1H); Analysis and calculation of C27H24N40.4TFA: C, 47.96, 3.22; Ν, 6.39 · Measured value: C, 48.02; H, 3.00; N, 6.07. Example 373 (lS) -2- (6-Ethyl-5-isoisoquine-6-yl-isopyridine-3 -Based lactyl) -1- (1Η-ρ-portol-3-ylmethyl V ethylamine The desired product is obtained by replacing the butylphenyltin in Example 364 with tributylethynyltin, and using the example 363A replaced Example 80E in Example 364 with trifluoroacetate. MS (APCI) m / z419 (M + 1) +; iHNMRpOOMHACDsOD) δ 3.31 (m, 2Η), 3.67 (s, 1Η), 3.99 (m, 1Η), 4.28 (dd, (J = 10.74, 5.83 Ηζ, 1Η), 4.42 (dd, JN10.74, 3.07 Hz, 1H), 7.0 (t, J = 7.06 Hz, 1H), 7.09 t, J = 7.21 Hz, 1H), 7.23 (s, 1H), 7.35 (d, J = 8.29 Hz, 1H), 7.55 (m, 1H), 7.56 (d, J = 7.98 Hz, 1H), 8.19 (dd, J = 8.59, 1.53 Hz, 1H), 8.42 (s, 2H), 8.47 (d, J = 6.44 Hz, 1H), 8.56 (d, J = 8.59 Hz, 1H), 8.63 (d, J = 6.44 Hz, 1H), 9.79 (s, 1H); Analytical calculated value for C2 7 H2 2 N4 0 · 2 · 9 TFA: C, 52.59; Η, 3.35; Ν, 7.48. Found: C, 52.52; H, 3.44; Ν, 7 · 01 · Example 374 (1S) -2- (6-octane-2-yl-5-isobutyrin-6-yl than bite-3-yllactyl-3-methyl Ethylamine

所要之產物係經由以三丁基乙決基錫取代實例364中之三丁基錫烷基呋喃，且以實例363A取代實例364中之實例8〇E -296- 200301122 (289) νΜΜΒΒΒνΒΡΟΒΒΒηΜΙΜβΒΒδΜβΚΒβΗΟΗΝβΙ ，以三氟醋酸鹽製成。MS (APCI) m/z 461 (M+lf ; 1 H NMR (300 MHz， CD3 OD) (5 3·30 (m，2H)，3.98 (m，1H)，4.25 (dd，J=10.51，5·76 Hz，1H)，4.40 (dd， J=10.51，3·05 Hz，1H)，6.39 (dd，J=3.39, 1.70 Hz，1H)5 6.44 (d，J=4.41 Hz，1H)，7.00 (dd，J=7.80, 7·12 Hz，1H)，7·09 (t，J=6.78 Hz，1H)，7·21 (s，1H)，7.28 (d，J=1.70 Hz， 1H)，7.37 (d，J=8.14 Hz，1H)，7·47 (d，J=2.71 Hz，1H)，7.57 (d，J=7.80 Hz，1H)，7.80 (dd，J=8.65, 1.53 Hz，1H)，8.21 (s，1H)，8.42 (d，J=6.78 Hz，1H)，8.46 (d，J=7.12 Hz， 1H)，8.48 (s，1H)，8.62 (d，J=6.44 Hz，1H)，9.77 (s，1H);對 C2 9 H2 4 N4 02 · 3.9TFA 之分析計算值：C，48.83 ; H，3.11 ; N，6.19.實測值：C，48.86 ; H，3.31 ;N，6.18. 實例375 (1S)-1-(1H-H|嗓-3-基甲基）-2-(5-異口奎琳-6-基-6-苯基乙块基-p比咬-3- 基氧基）-乙胺所要之產物係經由以三丁基（苯基乙炔基）锡取代實例364 中之三丁基苯基錫，且以實例363A取代實例364中之實例80E ，以三氟醋酸鹽製成。MS (APCI) m/z 495 (M+l)+ ; 1 H NMR (300 MHz， CD3 OD) δ 330 (m, 2H)? 4.02 (m, 1H)? 4.30 (dd, J=10.51, 5.76 Hz, 1H), 4.44 (dd, J= 10.51, 3.05 Hz, 1H)? 7.01 (t, J=7.46 Hz, 1H), 7.11 (t, J=7.46 Hz, 1H), 7.24 (s, 1H), 7.29 (m，5H)，7.36 (d，J=8.14 Hz，1H)，7·61 (d，J=2.71 Hz，1H)，7.59 (d，J=7.80 Hz， 1H), 8.24 (dd5 J=8.65, 1.53 Hz, 1H), 8.38 (d, J=6.44 Hz, 1H), 8.46 (d3 J=2.71 Hz, 1H), 8·46 (s，1H)，8.55 (d，J=8.81 Hz，1H)，8·62 (d，J=6.44 Hz，1H)，9.72 (s，1H): 實測值：C，59.61 ; H，4·04 ; N，7.36. 實例376 6-{5-丨(2S)-2-胺基-3-(lH-4l嗓-3-基）-丙氧基I-?比咬-3-基丨-異p奎淋-5-基胺 200301122 (290) 所要之產物係經由以5-胺基-6-溴基異喳啉取代實例32中之 6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 410 (M+l)+ ； 1 H NMR (300 ΜΗζ5 CD3 OD) δ 3.32 (m5 2H)? 4.00 (m, 1H)? 4.27 (dd, J= 10.51，5.76 Hz，1H)，4.44 (dd，J=10.51，3·39 Hz，1H)，7.01 (t，J=7.46 Hz，1H)，7.10 (t， J=7.46 Hz，1H)，7.24 (s，1H)，7.36 (d，J=7.80 Hz，1H)，7.59 (d，J=7.80 Hz，1H)，7.67 (d，J=8.14 Hz，1H)，7.73 (s，1H)，7·80 (d，J=8.48 Hz，1H) 8·45 (s，2H)，8.50 (d，J=The desired product was obtained by replacing tributylstannylfuran in Example 364 with tributylethinyl tin and replacing Example 8364 in Example 364 with Example 363A (E) 296- 200301122 (289) Made of salt. MS (APCI) m / z 461 (M + lf; 1 H NMR (300 MHz, CD3 OD) (5 3.30 (m, 2H), 3.98 (m, 1H), 4.25 (dd, J = 10.51, 5 76 Hz, 1H), 4.40 (dd, J = 10.51, 3.05 Hz, 1H), 6.39 (dd, J = 3.39, 1.70 Hz, 1H) 5 6.44 (d, J = 4.41 Hz, 1H), 7.00 (dd, J = 7.80, 7.12 Hz, 1H), 7.09 (t, J = 6.78 Hz, 1H), 7.21 (s, 1H), 7.28 (d, J = 1.70 Hz, 1H), 7.37 (d, J = 8.14 Hz, 1H), 7.47 (d, J = 2.71 Hz, 1H), 7.57 (d, J = 7.80 Hz, 1H), 7.80 (dd, J = 8.65, 1.53 Hz, 1H ), 8.21 (s, 1H), 8.42 (d, J = 6.78 Hz, 1H), 8.46 (d, J = 7.12 Hz, 1H), 8.48 (s, 1H), 8.62 (d, J = 6.44 Hz, 1H ), 9.77 (s, 1H); Analytical calculated value for C2 9 H2 4 N4 02 · 3.9TFA: C, 48.83; H, 3.11; N, 6.19. Found: C, 48.86; H, 3.31; N, 6.18 Example 375 (1S) -1- (1H-H | H-3-Methyl) -2- (5-Isoquinolin-6-yl-6-phenylethylblock-p specific bit-3 -Alkoxy) -ethylamine The desired product was obtained by replacing tributylphenyltin in Example 364 with tributyl (phenylethynyl) tin, and replacing Example 80E in Example 364 with Example 363A, and Fluoroacetic acid Made of salt. MS (APCI) m / z 495 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ 330 (m, 2H)? 4.02 (m, 1H)? 4.30 (dd, J = 10.51, 5.76 Hz, 1H), 4.44 (dd, J = 10.51, 3.05 Hz, 1H)? 7.01 (t, J = 7.46 Hz, 1H), 7.11 (t, J = 7.46 Hz, 1H), 7.24 (s, 1H), 7.29 (m, 5H), 7.36 (d, J = 8.14 Hz, 1H), 7.61 (d, J = 2.71 Hz, 1H), 7.59 (d, J = 7.80 Hz, 1H), 8.24 ( dd5 J = 8.65, 1.53 Hz, 1H), 8.38 (d, J = 6.44 Hz, 1H), 8.46 (d3 J = 2.71 Hz, 1H), 8.46 (s, 1H), 8.55 (d, J = 8.81 Hz, 1H), 8.62 (d, J = 6.44 Hz, 1H), 9.72 (s, 1H): Found: C, 59.61; H, 4.04; N, 7.36. Example 376 6- {5-丨 (2S) -2-amino-3- (lH-4l-3-olyl) -propoxy I-?-B-bite-3-yl 丨 -isop-quinucle-5-ylamine 200301122 (290) The desired product was prepared by replacing the 6-bromophthalimide in Example 32 with 5-amino-6-bromoisoxoline and using trifluoroacetate. MS (APCI) m / z 410 (M + l) +; 1 H NMR (300 μΗζ5 CD3 OD) δ 3.32 (m5 2H)? 4.00 (m, 1H)? 4.27 (dd, J = 10.51, 5.76 Hz, 1H ), 4.44 (dd, J = 10.51, 3.39 Hz, 1H), 7.01 (t, J = 7.46 Hz, 1H), 7.10 (t, J = 7.46 Hz, 1H), 7.24 (s, 1H), 7.36 (d, J = 7.80 Hz, 1H), 7.59 (d, J = 7.80 Hz, 1H), 7.67 (d, J = 8.14 Hz, 1H), 7.73 (s, 1H), 7.80 (d, J = 8.48 Hz, 1H) 8.45 (s, 2H), 8.50 (d, J =

6·78 Hz，1H)，8·66 (d，J=6.78 Hz，1H)，9.60 (s，1H);對 C2 5 H2 3 N5 O · 3.3TFA 之分析計算值：C，48.30 ; H，3·37 ; N，8.91.實測值：C，48.35 ; Η，3·44 ;N，8.91. 實例377 (lS)-l-(lH-巧丨哚-3-基甲基）-2-『5-(8-甲基-異崦啉-6-基V吡啶-3-基氧基1-乙胺所要之產物係經由以6-溴基-8-曱基-異喹啉取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 409 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) δ 2.91 (s, 3H), 3.32 (m, 2H), 4.02 (m,6.78 Hz, 1H), 8.66 (d, J = 6.78 Hz, 1H), 9.60 (s, 1H); Analytical calculated value for C2 5 H2 3 N5 O · 3.3TFA: C, 48.30; H, 3.37; N, 8.91. Found: C, 48.35; Rhenium, 3.44; N, 8.91. Example 377 (lS) -l- (lH-Carloindol-3-ylmethyl) -2- " The desired product of 5- (8-methyl-isofluorin-6-ylpyridin-3-yloxy1-ethylamine was obtained by substituting 6-bromo-8-fluorenyl-isoquinoline in Example 32 6-Bromophthalimide, made from trifluoroacetate. MS (APCI) m / z 409 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 2.91 (s , 3H), 3.32 (m, 2H), 4.02 (m,

1H)5 4.32 (dd? 1=10.51, 5.76 Hz, 1H), 4.47 (dd3 J=10.51, 3.39 Hz, 1H)? 7.02 (t, J- 7.46 Hz，1H)，7.11 (t，J=7.63 Hz，1H)，7·25 (s，1H)，7.37 (d，J=8.14 Hz，1H)，7·60 (d， J=8.14 Hz，1H)，7.91 (dd，J=8.31，4·92 Hz，1H)，7·96 (d，J=1.70 Hz，1H)，8.15 (s，1H), 8.31 (d，J=2.03 Hz，1H)，8·46 (s，1H)，8.74 (s，1H)，8.87 (dd，J=8.48, 1·70 Hz，1H)， 9.08(dd，J=4.92，1.53Hz，lH);對 C26H24N40.3.5TFA之分析計算值： C，49.08 ; H，3·43 ; N，6·94·實測值：C，49·23 ; H，3·24 ; N，6·87· 實例378 (lSV2-[5-(4-氣-嘍吩并『2,3-cl吡啶-2-基）-吡啶-3-某氣基哚- 3-基甲基V乙胺 -298 - 200301122 (291) 標題化合物係經由以4-氯基嘍吩并[2,3-c]吡啶取代實例38 中之嘧吩并[2,3-c]吡啶而製成。MS(APCI)m/z435 (M+l)+ ; iHNMR (300 MHz，CD3 OD) 5 3.31 (m，2H)，4.01 (m，1H)，4·29 (dd，J二 10.51，5.76 Hz，1H)， 4.44 (dd，J=10.51，3.05 Hz，1H)，7.04 (t，J=8.14 Hz, 1H)，7.12 (t，J=6.95 Hz，1H)， 7.25 (s，1H)，7·39 (d，J=8.14 Hz，1H)，7.61 (d，J=7.80 Hz，1H)，7.84 (t，J=2.71 Hz, 1H)，8.04 (s，1H)，8.42 (d，J=2.03 Hz，1H)，8.51 (s，1H)，8.72 (s，1H)，9.13 (s，1H); 對（：231119〇>^〇3.2.8丁?入之分析計算值：0：，45.55;11，2.91;凡7.43· 實測值：C，45.42 ; Η，2·70 ; N，7.28. 實例379 (lS)-l-(lH-啕哚-3-基甲基）-245-(4-笨基-嘍吩并「2,3-cl吡啶-2-基）-吡症-3-基乳基V乙胺標題化合物係經由以4-苯基嘍吩并[2,3-c]吡啶取代實例38 中之嘍吩并[2,3-c]吡啶而製成。MS(APCI)m/z477(M+l)+ ; iHNMR (300 MHz，CD3 OD) 5 3·31 (m，2H)，4.00 (m，1H)，4.26 (dd，J=10.51，5.76 Hz，1H)， 4.41 (dd，J=10.51，3.39 Hz，1H)，6.99 (t，J=6.95 Hz，1H)，7.10 (t，J=7.12 Hz，1H)， 7.22 (s, 1H), 7.36 (d, J=7.80 Hz, 1H)5 7.57 (d, J=7.80 Hz, 1H), 7.65 (m, 3H), 7.73 (t5 JN2.03 Hz, 1H)，7.76 (d，J=1.70 Hz，1H)，7.84 (m，1H)，8.11 (s，1H)，8.46 (s，1H)， 8.62 (s，1H)，8.74 (s，1H)，9.52 (s，1H);對 C29H24N4OS · 2.8TFA 之分析計算值：C，52.22; Η，3·39; Ν，7·04·實測值：C，52.11; Η，3·13; Ν，6·91· 實例380 (1SM-(1H-口弓1嗓-3-基甲基V2-『5-(4-笨氧基-口塞吩并r2.3-c扣比症-2-基）- 哄啶各基氧基1-乙胺標題化合物係經由以4-苯氧基喧吩并[2,3-c>比啶取代實例 38 中之噻吩并[2,3-c]吡啶而製成。MS(APCI)m/z493 (M+l)+ ; (292)1H) 5 4.32 (dd? 1 = 10.51, 5.76 Hz, 1H), 4.47 (dd3 J = 10.51, 3.39 Hz, 1H)? 7.02 (t, J- 7.46 Hz, 1H), 7.11 (t, J = 7.63 Hz , 1H), 7.25 (s, 1H), 7.37 (d, J = 8.14 Hz, 1H), 7.60 (d, J = 8.14 Hz, 1H), 7.91 (dd, J = 8.31, 4.92 Hz, 1H), 7.96 (d, J = 1.70 Hz, 1H), 8.15 (s, 1H), 8.31 (d, J = 2.03 Hz, 1H), 8.46 (s, 1H), 8.74 (s , 1H), 8.87 (dd, J = 8.48, 1.70 Hz, 1H), 9.08 (dd, J = 4.92, 1.53Hz, lH); Analytical calculations for C26H24N40.3.5TFA: C, 49.08; H, 3.43; N, 6.94 · Measured values: C, 49 · 23; H, 3.24; N, 6.87 · Example 378 (lSV2- [5- (4-Ga-fluorene and "2, 3-cl pyridin-2-yl) -pyridine-3-a certain indolyl-3-ylmethyl Vethylamine-298-200301122 (291) The title compound is obtained via 4-chlorofluoreno [2,3 -c] pyridine was prepared by substituting the pyrido [2,3-c] pyridine in Example 38. MS (APCI) m / z435 (M + 1) +; iHNMR (300 MHz, CD3 OD) 5 3.31 (m , 2H), 4.01 (m, 1H), 4.29 (dd, J 2 10.51, 5.76 Hz, 1H), 4.44 (dd, J = 10.51, 3.05 Hz, 1H), 7.04 (t, J = 8.14 Hz, 1H), 7.12 (t, J = 6.95 Hz, 1H), 7.25 ( s, 1H), 7.39 (d, J = 8.14 Hz, 1H), 7.61 (d, J = 7.80 Hz, 1H), 7.84 (t, J = 2.71 Hz, 1H), 8.04 (s, 1H), 8.42 (d, J = 2.03 Hz, 1H), 8.51 (s, 1H), 8.72 (s, 1H), 9.13 (s, 1H); Analysis of (: 231119〇 > ^ 〇3.2.8) Calculated values: 0 :, 45.55; 11, 2.91; Where 7.43 · Found: C, 45.42; H2, 2.70; N, 7.28. Example 379 (lS) -l- (lH-oxindole-3-ylmethyl) ) -245- (4-benzyl-fluoreno "2,3-clpyridin-2-yl) -pyridin-3-yllactyl V ethylamine The title compound is [2,3-c] pyridine was prepared in place of the fluoreno [2,3-c] pyridine in Example 38. MS (APCI) m / z477 (M + 1) +; iHNMR (300 MHz, CD3 OD) 5 3.31 (m, 2H), 4.00 (m, 1H), 4.26 (dd, J = 10.51, 5.76 Hz, 1H), 4.41 (dd, J = 10.51, 3.39 Hz, 1H), 6.99 (t, J = 6.95 Hz, 1H), 7.10 (t, J = 7.12 Hz, 1H), 7.22 (s, 1H), 7.36 ( d, J = 7.80 Hz, 1H) 5 7.57 (d, J = 7.80 Hz, 1H), 7.65 (m, 3H), 7.73 (t5 JN2.03 Hz, 1H), 7.76 (d, J = 1.70 Hz, 1H ), 7.84 (m, 1H), 8.11 (s, 1H), 8.46 (s, 1H), 8.62 (s, 1H), 8.74 (s, 1H), 9.52 (s, 1H); for C29H24N4OS · 2.8TFA Analytical calculated value: C, 52.22; Η, 3.39; Ν, 7.04. Measured value: C, 52.11; Η, 3.13; Ν, 6.91. Example 380 (1SM- (1H- 口弓 1 3--3-methylmethyl V2- "5- (4-benzyloxy-orthopheno-r2.3-c-bipyron-2-yl)-oxidinyloxy 1-ethylamine title compound system Prepared by replacing the thieno [2,3-c] pyridine in Example 38 with 4-phenoxynobenzo [2,3-c> pyridine. MS (APCI) m / z493 (M + 1) +; (292)

1 H NMR (300 MHz，CD3 0D) δ 3·30 (m5 2H)，4·01 (m，1H)，4·27 (dd，J=10.51， 5·76 Hz，1H)，4.42 (dd，J=10.51，3.05 Hz, 1H)，7·03 (t，J=7.46 Hz，1H)，7.11 (t，J= 7.46 Hz，1H)，7.24 (s，1H)，7.25 (d，JN8.82 Hz，1H)，7.33 (t，J=7.46 Hz，2H)，7.38 (d， J=7.80 Hz，1H)，7.52 (t，J=7.97 Hz，2H)，7.60 (d，J=7.80 Hz，·1Η)，7.85 (s，1H)，8.00 (s，1H)，8·16 (s，1H)，8.44 (d，J=2.03 Hz，1H)，8.72 (s，1H)，9.17 (s，1H). 實例381 (lS)-l-(lH-Hl 口朵-3-基甲基）-2-[5-(4-乙烯基-p塞吩并 |~2.3-cV比淀-2-基1 H NMR (300 MHz, CD3 0D) δ 3.30 (m5 2H), 4.01 (m, 1H), 4.27 (dd, J = 10.51, 5.76 Hz, 1H), 4.42 (dd, J = 10.51, 3.05 Hz, 1H), 7.03 (t, J = 7.46 Hz, 1H), 7.11 (t, J = 7.46 Hz, 1H), 7.24 (s, 1H), 7.25 (d, JN8.82 Hz, 1H), 7.33 (t, J = 7.46 Hz, 2H), 7.38 (d, J = 7.80 Hz, 1H), 7.52 (t, J = 7.97 Hz, 2H), 7.60 (d, J = 7.80 Hz, · 1Η), 7.85 (s, 1H), 8.00 (s, 1H), 8.16 (s, 1H), 8.44 (d, J = 2.03 Hz, 1H), 8.72 (s, 1H), 9.17 (s, 1H). Example 381 (lS) -l- (lH-Hl oxo-3-ylmethyl) -2- [5- (4-vinyl-p-thiophene | ~ 2.3-cV 比淀 -2- base

口比淀-3-基氧基1-乙胺實例381A (lSM2-『5-(4-氣吩并f2,3-cl吡啶-2-基）-吡啶-3-基氫某1-H1H-吲哚-3-某甲基乙基1-胺曱基酸第三-丁酷標題化合物係經由以4-氯基嘧吩并[2,3-c]吡啶取代實例38 中之嘧吩并[2,3-cH 啶而製成。MS(APCI)m/z 535 (M+l)+.Example 381A (1SM2- "5- (4-Gapheno f2,3-cl pyridin-2-yl) -pyridin-3-yl hydrogen 1-H1H- The indole-3-some methylethyl 1-aminofluorenic acid tertiary-butanoic acid title compound is obtained by substituting the 4-pyrimido [2,3-c] pyridine in Example 38 for the pyrido [ 2,3-cH pyridine. MS (APCI) m / z 535 (M + l) +.

實例381B (18)-{1-(111-口?1 嗓-3-基甲基）·2-[5-(4-乙烯基塞吩并「2,3-cl口比症-2-基）-吡啶-3-基氧基1-乙基丨-胺甲某醢第二-丁酯於25毫升RBF中，裝填實例381A(102毫克，0.19毫莫耳）、 Pd2(dba)3(18毫克，0.019毫莫耳）及2-二環己基膦基-2，-(N，N-二曱胺基）聯苯（15毫克’ 〇·〇38毫莫耳），並以n2滌氣。經由注射為添加供水DMF (5¾升）、二丁基乙缔基錫（hi微升’ 〇·38毫莫耳）及Et3N (80微升）。將此溶液以N2再滌氣一次，並於70 °C下加熱20小時。冷卻後，添加醋酸乙酯（5〇毫升）。將混合物以鹽水（50毫升）及水（5〇 ί:升）洗滌。使醋酸乙g旨溶液濃縮，並藉急驟式層析（A: 2: 1 EtOAc/己烷，於a中之0-15% CH3OH) 200301122 (293) 分離殘留油，而得所要之產物（72毫克，72% )。MS (APCI) m/z 527 (M+l)+ ·Example 381B (18)-{1- (111-Methyl-3-ylmethyl) · 2- [5- (4-vinylthiophene "2,3-cl Methylpyridin-2-yl ) -Pyridin-3-yloxy 1-ethyl 丨 -carbamidine second-butyl ester in 25 ml of RBF, filled with Example 381A (102 mg, 0.19 mmol), Pd2 (dba) 3 (18 Mg, 0.019 millimoles) and 2-dicyclohexylphosphino-2,-(N, N-diamidino) biphenyl (15 mg '0.038 millimoles), and was purged with n2. Water was added via injection to DMF (5¾ liters), dibutylethylene tin (hi microliters' 0.38 mmol), and Et3N (80 microliters). This solution was repurified with N2 once, and Heated at 70 ° C for 20 hours. After cooling, ethyl acetate (50 ml) was added. The mixture was washed with brine (50 ml) and water (50 liter: liter). The ethyl acetate solution was concentrated and borrowed. Flash chromatography (A: 2: 1 EtOAc / hexane, 0-15% CH3OH in a) 200301122 (293) The residual oil was separated to give the desired product (72 mg, 72%). MS (APCI) m / z 527 (M + l) +

實例381C (1SM-(1H-吲哚-3-基曱基）-245-(4-乙烯某-口塞吩并f2,3-cl吡啶-2-基—)- p比淀-3-基氧基1·乙胺所要之產物係經由以實例381B取代實例2?C中之實例27B ，以三氟醋酸鹽製成。MS(APCI)m/z427(M+l)+; iHNMRpOOMHz， CD3 OD) δ 3.32 (m, 2H), 4.03 (m, 1H), 4.30 (dd, J=10.51, 5.76 Hz, 1H), 4.46 (dd, J=10.51? 3.39 Hz, 1H), 5.84 (d, J=11.19 Hz, 1H), 6.26 (d, J=17.29 Hz, 1H), 7.03 (t, J= 7.46 Hz, 1H), 7.12 (t5 J=7.63 Hz, 1H), 725 (s, 1H), 7.35 (d, J=10.85 Hz, 1H), 7.41 (d, J=10.85 Hz，1H)，7.60 (d，JM7.80 Hz，1H)，7·90 (m，1H)，8.44 (s，1H)，8.49 (d，J=2.37 Hz，1H)，8.79 (s，2H)，9.42 (s，1H);對 C2 5 H2 2 N4 OS · 3·2 TFA 之分析計算值：C，47.65 ; H，3.21; Ν，7·08.實測值：C，47.74; Η，3·13; Ν，6·96· 實例382 (lSV2-「5-(4-乙基吩并f2,3-c>比啶-2-基V吡啶-3-基氣基1-1-ΠΗ4Ι 哚各基曱基乙胺在氮氣下，於實例381A (50毫克，0.063毫莫耳）在曱醇（4毫升）中之溶液内，添加三乙胺（56微升）與10% Pd/C (20毫克）。將此懸浮液以H2(氣瓶）滌氣，並於室溫下攪拌6小時。將固體物質濾出。使濾液濃縮，並使殘留物藉HPLC純化 (Zorbax，C-18,250x2.54 管柱，流動相 A: H20 中之 0.1% tfA; B: CH3CN 中之0.1% TFA ; 0-100%梯度液），提供標題化合物（37.2毫克， 74% )。MS(APCI)m/z429(M+l)+ ; 1H NMR (300 MHz, CD3 OD) 5 1.46 (t, J=7.46 Hz, 3H), 3.23 (q? J=7.46 Hz, 2H), 3.36 (m, 2H), 4.03 (m3 1H), 4.31 (dd, J=10.5 200301122Example 381C (1SM- (1H-Indol-3-ylfluorenyl) -245- (4-vinyl-orthophenof2,3-clpyridin-2-yl-)-p-pyridol-3-yl The desired product of oxy 1 · ethylamine was prepared by replacing Example 27B in Example 2? C with Trifluoroacetate with Example 381B. MS (APCI) m / z427 (M + 1) +; iHNMRpOOMHz, CD3 OD ) δ 3.32 (m, 2H), 4.03 (m, 1H), 4.30 (dd, J = 10.51, 5.76 Hz, 1H), 4.46 (dd, J = 10.51? 3.39 Hz, 1H), 5.84 (d, J = 11.19 Hz, 1H), 6.26 (d, J = 17.29 Hz, 1H), 7.03 (t, J = 7.46 Hz, 1H), 7.12 (t5 J = 7.63 Hz, 1H), 725 (s, 1H), 7.35 ( d, J = 10.85 Hz, 1H), 7.41 (d, J = 10.85 Hz, 1H), 7.60 (d, JM7.80 Hz, 1H), 7.90 (m, 1H), 8.44 (s, 1H), 8.49 (d, J = 2.37 Hz, 1H), 8.79 (s, 2H), 9.42 (s, 1H); Analysis and calculation of C2 5 H2 2 N4 OS · 3.2 TFA: C, 47.65; H, 3.21 N, 7.08. Found: C, 47.74; H3, 3.13; N, 6.96. Example 382 (1SV2- "5- (4-ethylphenof2,3-c > Bipyridine- 2-yl-V-pyridin-3-ylamino-l-l-IIΗ4I indolyl fluorenylethylamine under nitrogen in a solution of Example 381A (50 mg, 0.063 mmol) in methanol (4 ml) , Add triethylamine (56 μl) and 10% Pd / C (20 mg). The suspension was purged with H2 (gas cylinder) and stirred at room temperature for 6 hours. The solid material was filtered off. The filtrate Concentrate and purify the residue by HPLC (Zorbax, C-18, 250x2.54 column, mobile phase A: 0.1% tfA in H20; B: 0.1% TFA in CH3CN; 0-100% gradient), provided Title compound (37.2 mg, 74%). MS (APCI) m / z429 (M + 1) +; 1H NMR (300 MHz, CD3 OD) 5 1.46 (t, J = 7.46 Hz, 3H), 3.23 (q? J = 7.46 Hz, 2H), 3.36 (m, 2H), 4.03 (m3 1H), 4.31 (dd, J = 10.5 200301122

(294) 1，5.76 Hz，1H)，4.47 (dd，J=10.51，3·39 Hz，1H)，7·02 (t，J=7.46 Hz，1Η)，7·12 (t，J= 7·46 Hz，1H)，7.25 (s，1H)，7·38 (d，J=8· 14 Hz，1H)，7.60 (d，J=7.80 Hz，1H)，7.92 (t， J=2.03 Hz, 1H), 8.39 (s5 1H), 8.49 (s, 1H), 8.49 (d, J=3.05 Hz, 1H), 8.81 (d, J=1.70 Hz，1H)，9·45 (s，1H);對 C2 5 H24N4 OS · 3.3 TFA 之分析計算值：C，47.16 ;H，3·42 ; N，6·96·實測值：C，47·03 ; H，3·34 ; N，6.96. 實例383(294) 1, 5.76 Hz, 1H), 4.47 (dd, J = 10.51, 3.39 Hz, 1H), 7.02 (t, J = 7.46 Hz, 1Η), 7.12 (t, J = 7 46 Hz, 1H), 7.25 (s, 1H), 7.38 (d, J = 8 · 14 Hz, 1H), 7.60 (d, J = 7.80 Hz, 1H), 7.92 (t, J = 2.03 Hz , 1H), 8.39 (s5 1H), 8.49 (s, 1H), 8.49 (d, J = 3.05 Hz, 1H), 8.81 (d, J = 1.70 Hz, 1H), 9.45 (s, 1H); Analysis and calculation of C2 5 H24N4 OS · 3.3 TFA: C, 47.16; H, 3.42; N, 6.96 · Found: C, 47 · 03; H, 3.34; N, 6.96. Example 383

(lS)-(2-{5-[2-胺基-3-(lH-4|嗓-3-基）-丙氧基l-τ?比咬-3-基丨塞吩并「2,3-cV比淀-4-基）-笨基-胺實例383A (1S)-{1-(1H-吲哚-3-基甲基）-245-(4-苯某胺基-口塞吩并f2,3-cl吡啶-2-基）-吡啶-3-基氧基1-乙基μ胺甲某酸第三-丁酯於25毫升RBF中，裝填實例381Α(100毫克，0.186毫莫耳）、 Pd2(dba)3(17毫克，0.0186毫莫耳）及氯化ι，3-雙（2,6-二-異-丙基苯基）咪銼（Nolan配位體）(16毫克，〇·〇372毫莫耳），並以n2滌氣。經由注射器添加無水二氧陸圜（3毫升）、苯胺（21毫克， 0.224毫莫耳）及第三-丁醇鉀（在THF中之1.0 Μ溶液，0.279毫升）。將此溶液以Ν2再滌氣一次，並於i〇〇°c下加熱20小時。於冷卻後，添加醋酸乙醋（50毫升），並將混合物以鹽水（50 毫升）及水洗滌。使EtOAc溶液濃縮，並藉急驟式層析（於己烷中之30-80% EtOAc)分離殘留物，提供所要之產物（34毫克，31%)。MS(APCI)m/z 592 (M+l)+·(lS)-(2- {5- [2-Amino-3- (lH-4 | H-3-))-propoxyl-τ? biphenyl-3-yl Example of 3-cV Biyodo-4-yl) -benzyl-amine 383A (1S)-{1- (1H-indole-3-ylmethyl) -245- (4-phenylamino Benzene f2,3-cl pyridin-2-yl) -pyridin-3-yloxy 1-ethyl μ carbamic acid tertiary-butyl ester in 25 ml of RBF, filled with Example 381A (100 mg, 0.186 mmol) (Ear), Pd2 (dba) 3 (17 mg, 0.0186 mmol) and chloro, 3-bis (2,6-di-iso-propylphenyl) imid (Nolan ligand) (16 mg , 0.0372 millimoles), and scrubbing with n2. Anhydrous dioxan (3 mL), aniline (21 mg, 0.224 millimoles), and potassium tert-butoxide (in THF) were added via a syringe. 1.0 M solution, 0.279 ml). This solution was re-washed with N2 and heated at 100 ° C for 20 hours. After cooling, ethyl acetate (50 ml) was added, and the mixture was washed with brine (50 ml). 50 ml) and water. The EtOAc solution was concentrated and the residue was separated by flash chromatography (30-80% EtOAc in hexanes) to provide the desired product (34 mg, 31%). MS (APCI) m / z 59 2 (M + l) + ·

±J1383B 胺基-3-ΠΗ-β!哚-3—-基V丙氧基i-吡啶各某卜塞吩并[~2,3-cl吡啶-4-基笨某-胺 -302- 2 2± J1383B Amino-3-ΠΗ-β! Indole-3 —-yl V propoxy i-pyridine each phenpheno [~ 2,3-cl pyridin-4-ylbenzyl-amine-302- 2 2

(295) 所要之產物係經由以實例383A取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 492 (M+l)+ ; 1 H NMR (300 MHz， DMSO-d6) 5 3·19 (d，JN7.12 Ηζ，2Η)，3·88 (m，1Η)，4·20 (dd，J=10.51，5·42 Ηζ，1Η)， 4·38 (d，J=10.51 Hz，1H)，7.01 (t，J=7.46 Hz，1H)，7.11 (m，3H)，7.38 (m，6H)，7.62 (d， J=8.14 Hz5 1H), 7.78 (s, 1H), 8.22 (s, 2H), 8.29 (s, 1H), 8.47 (s5 1H), 8.74 (s, 1H), 8.98 (s，1H)，9.06 (s，1H)，11.04 (s，1H);對 C29H25N5OS · 3 TFA 之分析計算值·· C，50.42; Η，3·39; Ν，8.40·實測值：C，50.40; Η，3·58; Ν，8·23· 實例384 5-{5-『(25)-2-胺基-3-(111-巧哚-3-基）-丙氣基1-吡啶-3-基}-3,3-二氟-1,3- 二氫-沔1嗓-2-酮所要之產物係經由以5-溴基-3,3-二氟-1,3-二氫-吲哚-2-酮，取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 435 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) 5 3·36 (m，2Η)， 4·01 (m，1Η)，4.26 (dd，J=10.51，5·76 Ηζ，1Η)，4·43 (dd, J=10.51，3·05 Ηζ，1Η)，7·03 (t, J=7.46 Hz, 1H)3 7.13 (t5 J=7.46 Hz, 2H), 7.24 (s, 1H), 7.39 (d, J=8.14 Hz, 1H), 7.60 (d，J=8.14 Hz，1H)，7.79 (m，2H)，7.90 (d，J=l.70 Hz，1H)，8.36 (d，J二2.03 Hz， 1H)，8.56 (s，1H);對 C2 4 H2 〇 F2 N4 02 · 2.5 TFA 之分析計算值：C，48.41 ；Η, 3·15 ; Ν，7·79·實測值：C, 48.66 ; H，3.20 ; N，7.82. 實例385 6-{5-f(2SV2-胺基哚-3-基）-丙氧基V吡啶-3-基}-3H-吟唑并『4,5-bl吡啶-2-酮所要之產物係經由以6-溴基-3H-哼唑并[4,5-b]吡啶-2-酮，取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS(APCI)m/z402(M+l)+ ; 1H NMR (300 MHz, CD3 OD) δ 334(m52H), - 303 - (296)(295) The desired product was prepared by replacing Example 27B in Example 27C with Example 383A and using trifluoroacetate. MS (APCI) m / z 492 (M + l) +; 1 H NMR (300 MHz, DMSO-d6) 5 3 · 19 (d, JN7.12 Ηζ, 2Η), 3.88 (m, 1Η), 4.20 (dd, J = 10.51, 5.42 Ηζ, 1Η), 4.38 (d, J = 10.51 Hz, 1H), 7.01 (t, J = 7.46 Hz, 1H), 7.11 (m, 3H) , 7.38 (m, 6H), 7.62 (d, J = 8.14 Hz5 1H), 7.78 (s, 1H), 8.22 (s, 2H), 8.29 (s, 1H), 8.47 (s5 1H), 8.74 (s, 1H), 8.98 (s, 1H), 9.06 (s, 1H), 11.04 (s, 1H); C29H25N5OS · 3 TFA analysis calculated value · C, 50.42; Η, 3.39; Ν, 8.40 · Measured Value: C, 50.40; Hf, 3.58; N, 8.23. Example 384 5- {5-『(25) -2-Amino-3- (111-carolin-3-yl) -propane gas 1-pyridin-3-yl} -3,3-difluoro-1,3-dihydro-fluorenone-1-2-one is the desired product via 5-bromo-3,3-difluoro-1 , 3-Dihydro-indole-2-one, instead of 6-bromophthalimide in Example 32, and made of trifluoroacetate. MS (APCI) m / z 435 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 3.36 (m, 2Η), 4.01 (m, 1Η), 4.26 (dd, J = 10.51, 5.76 Ηζ, 1Η), 4.43 (dd, J = 10.51, 3.05 Ηζ, 1Η), 7.03 (t, J = 7.46 Hz, 1H) 3 7.13 (t5 J = 7.46 Hz, 2H), 7.24 (s, 1H), 7.39 (d, J = 8.14 Hz, 1H), 7.60 (d, J = 8.14 Hz, 1H), 7.79 (m, 2H), 7.90 (d, J = l.70 Hz, 1H), 8.36 (d, J 2.03 Hz, 1H), 8.56 (s, 1H); Analytical calculated values for C2 4 H2 〇F2 N4 02 · 2.5 TFA: C, 48.41; Η, 3.15; Ν, 7.79. Found: C, 48.66; H, 3.20; N, 7.82. Example 385 6- {5-f (2SV2-aminoindol-3-yl) -propoxy Vpyridin-3-yl } -3H-indazolo [4,5-blpyridin-2-one The desired product was substituted with 6-bromo-3H-humazolo [4,5-b] pyridin-2-one, replacing Example 32 The 6-bromophthalimide is made from trifluoroacetate. MS (APCI) m / z402 (M + 1) +; 1H NMR (300 MHz, CD3 OD) δ 334 (m52H),-303-(296)

4·00 (m，1H)，4.28 (dd，J=10.51，5.76 Ηζ，1Η)，4·42 (dd，J=10.51，3.05 Hz，1H)，7·02 (t，J=7.46 Hz，1H)，7.12 (t，J=7.63 Hz，1H)，7.23 (s，1H)，7·38 (d，J=8.14 Hz，1H)，4.00 (m, 1H), 4.28 (dd, J = 10.51, 5.76 Ηζ, 1Η), 4.42 (dd, J = 10.51, 3.05 Hz, 1H), 7.02 (t, J = 7.46 Hz, 1H), 7.12 (t, J = 7.63 Hz, 1H), 7.23 (s, 1H), 7.38 (d, J = 8.14 Hz, 1H),

7.59 (d，J=7.80 Hz，1H)，7.74 (d，J=1.70 Hz，1H)，7.83 (d，J=1.70 Hz，1H)，8·33 (d， J=2.03 Hz，1H)，8·38 (d，J=2.37 Hz，1H)，8.55 (s，1H);對 C2 2 9N5 03 · 2.6TFA 之分析計算值：C，46.81 ; H，3·12 ; N，10.04.實測值：C，46.67 ; H，2.98 ;N，9.89. 實例3867.59 (d, J = 7.80 Hz, 1H), 7.74 (d, J = 1.70 Hz, 1H), 7.83 (d, J = 1.70 Hz, 1H), 8.33 (d, J = 2.03 Hz, 1H), 8 · 38 (d, J = 2.37 Hz, 1H), 8.55 (s, 1H); Analysis and calculation of C2 2 9N5 03 · 2.6TFA: C, 46.81; H, 3.12; N, 10.04. Measured value : C, 46.67; H, 2.98; N, 9.89. Example 386

Nl-(5-異4啉-6-基-吡啶：基V乙烷-1,2-二胺Nl- (5-iso4-line-6-yl-pyridine: yl V ethane-1,2-diamine

實例386A 「2-(5-溴-吡啶-3-基胺基V乙基1-胺甲基酸第三-丁酯於50毫升RBF中，裝填3,5-二溴基吡啶（3.70克，15.6毫莫耳）、N-(2-胺基乙基）胺基甲酸第三-丁酯（2.50克，15.6毫莫耳）、 Pd2(dba)3(714 毫克，0.78 毫莫耳）、（R)-BINAP(1.46 克，2·34 莫耳）及Cs2C03(7.62克，23.4毫莫耳），並以Ν2滌氣。經由注射器添加無水曱苯（120毫升）。將此溶液以Ν2再滌氣一次，並於1〇〇 °C下加熱過夜。於冷卻後，添加醋酸乙酯（500毫升），並將混合物以水洗滌。使EtOAc溶液濃縮，並藉急驟式層析（於己烷中之20-80% EtOAc)分離殘留物，提供所要之產物（2.1克，43%)。MS(DCI)m/z316,318(M+l)+·Example 386A "3- (5-Bromo-pyridin-3-ylamino Vethyl 1-aminomethyl acid tert-butyl ester) In 50 ml of RBF, 3,5-dibromopyridine (3.70 g, 15.6 millimoles), N- (2-aminoethyl) aminocarboxylic acid tert-butyl ester (2.50 g, 15.6 millimoles), Pd2 (dba) 3 (714 mg, 0.78 millimoles), ( R) -BINAP (1.46 g, 2.34 mol) and Cs2C03 (7.62 g, 23.4 mmol) and purged with N2. Anhydrous toluene (120 ml) was added via syringe. Once, and heated at 100 ° C. overnight. After cooling, ethyl acetate (500 ml) was added and the mixture was washed with water. The EtOAc solution was concentrated and subjected to flash chromatography (in hexanes). (20-80% EtOAc) to isolate the residue to provide the desired product (2.1 g, 43%). MS (DCI) m / z 316,318 (M + 1) + ·

實例386B 「2-(5-異4啉各基吡啶-3-基胺某V乙基1-胺甲基酸第三-丁酯所要之產物係經由以實例386A取代實例2%中之實例2八而製成。MS(APCI)m/z365 (M+l)+.Example 386B "2- (5-Iso-4-lineylpyridin-3-ylamine, some Vethyl 1-aminomethyl acid tert-butyl ester. The desired product is obtained by replacing Example 2 in Example 2% with Example 386A. Made from eight. MS (APCI) m / z365 (M + l) +.

實例386C (297)Example 386C (297)

Nl-(5-異4淋-6-基-吡啶-3-基乙檢.-1.2-二fe 所要之產物係經由以實例386B取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 265 (M+l)+; 1 H NMR (300 MHz， CD3 OD) δ 3.26 (t, J=5.76 Hz, 2H), 3.70 (t, J=5.76 Hz, 2H), 8.10 (s5 1H), 8.25 (s, 1H)，8·33 (d，J=8.82 Hz，1H)，8.45 (d，J=6.44 Hz，1H)，8.56 (s，1H)，8.63 (m，3H)， 9.76 (s，1H). 實例387 基-2-續酸（2-胺基基）-(5-異p奎g林-6-基比咬-3-基）-醯胺Nl- (5-Iso-4-L--6-yl-pyridin-3-yl). The desired product was made by replacing Example 27B in Example 27C with Example 386B and using trifluoroacetate. MS (APCI) m / z 265 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ 3.26 (t, J = 5.76 Hz, 2H), 3.70 (t, J = 5.76 Hz, 2H), 8.10 (s5 1H), 8.25 (s, 1H), 8.33 (d, J = 8.82 Hz, 1H), 8.45 (d, J = 6.44 Hz, 1H), 8.56 (s, 1H), 8.63 (m, 3H), 9.76 (s, 1H). Example 387 Amino-2-contanoic acid (2-amino)-(5-iso-p-glycin-6-yl than sulfan-3-yl) -fluorenamine

實例387A (2-「(5-異4啉各基-吡啶二3-基Μ蓁-2-磺醯某胺基1-乙基卜胺甲某酸第三-丁酯在室溫下，於實例386Β (70毫克，〇·192毫莫耳）在吡啶（3毫升）中之溶液内，添加氯化2-莕磺醯（87毫克，0.384毫莫耳）。將所形成之黃色溶液於室溫下攪拌15小時。在減壓下移除吡啶，並使殘留油藉急驟式層析（於2 : 1 EtOAc /己烷中之0-15% CH3OH)純化，提供所要之產物（69毫克，65% )。 MS (APCI) m/z 555 (M+l)+.Example 387A (2-"(5-Iso-4lineyl-yl-pyridinedi3-yl M 蓁 -2-sulfosulfanylamino 1-ethylpyridinecarboxylic acid tertiary-butyl ester at room temperature, at Example 386B (70 mg, 0.292 mmol) in a solution of pyridine (3 ml) was added with 2-sulfenamidine chloride (87 mg, 0.384 mmol). The resulting yellow solution was placed in a chamber Stir for 15 hours at room temperature. Pyridine was removed under reduced pressure and the residual oil was purified by flash chromatography (0-15% CH3OH in 2: 1 EtOAc / hexane) to provide the desired product (69 mg, 65%). MS (APCI) m / z 555 (M + l) +.

實例387B 玄-2-碚酸（2-胺基-乙基M5-異4啉-6-基-吡啶-3-基醯胺所要之產物係經由以實例387B取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 455 (M+l)+; 1H NMR (300 MHz， CD3 〇D) δ 3.17 (t, J=5.76 Hz, 2H), 4.09 (t5 J=5.43 Hz, 2H), 7.66 (t, J=6.78 Hz, 1H), 7.75 (t，J=7.46 Hz，1H)，7.99 (m，2H)，8·06 (m，3H)，8.13 (d，J=8.82 Hz，1H)，8·26 (m， 2H)，8.31 (s，1H)，8.47 (d，J=8.48 Hz，1H)，8.59 (m，2H)，9.08 (d，J=2.03 Hz，1H)， (298) 9.69 (s，1H). 實例388 黧-1-碏酸（2-胺基-乙基M5-異4啉-6-基-外1：啶-3-基）-醯嚴_ 所要之產物係經由以1-莕磺醯氯取代實例387中之氯化2-莕磺醯，以三氟醋酸鹽製成。MS(APCI)m/z455 (M+l)+ ; iHNMR (300 MHz, CD3 OD) δ 3.14 (t, J=5.76 Hz, 2H), 4.04 (t, J=5.76 Hz, 2H), 7.33 (t, J= 7·46 Hz，1H)，7·51 (t，J=7.12 Hz，1H)，7.70 (t，J=8.14 Hz，1H)，7.85 (t，J=2.20 Hz， 1H)，7.92 (dd，J=8.48, 1.70 Hz，1H)，8.04 (dd，J=8.31，3·56 Hz，2H)，8.15 (s，1H)， 8.29 (d, J=4.75 Hz, 1H), 8.31 (d, J=5.42 Hz, 2H), 8.47 (d, J=8.48 Hz, 1H), 8.60 (d, J= 6.44 Hz, 1H), 8.63 (d, J=237 Hz, 1H), 9.03 (d5 J=2.03 Hz, 1H), 9.67 (s3 1H). 實例389 5-二甲胺基-奈-1-石黃酸（2-胺基-乙基）-(5-異口套口林-6-基-口比症-3-基）· 醯胺所要之產物係經由以氯化5-二甲胺基莕磺醯取代實例387 中之氯化2-莕磺醯，以三氟醋酸鹽製成。MS(APCI)m/z498 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) δ 2·81 (s，6H)，3.16 (d，J=5.76 Hz，2H)， 4.06 (d，J=5.76 Hz，2H)，7.16 (d，J=7.12 Hz，1H)，7.25 (t，J=7.80 Hz，1H)，7.67 (dd， J=8.48, 7.80 Hz, 1H)5 7.75 (d, J=8.48 Hz, 1H), 7.85 (t5 J=2.20 Hz, 1H), 7.98 (dd, J= 8·48, 1·70 Hz, 1H)，8.29 (d，J=7.12 Hz，1H)，8·30 (s，1H)，8.43 (d，>6.44 Hz，1H)， 8.53 (d，J=8.82 Hz，1H)，8.64 (m，3H)，9.03 (d，J=2.03 Hz，1H)，9.76 (s，1H); 對 C28H27N502S.4TFA之分析計算值：C，45.34 ; Η，3·28 ; Ν，7·34· 實測值：C，45.28 ; Η，3·11 ; Ν，7·23· 實例390 口奎淋-5-續敗（2-胺基-乙基）-(5-異邊〃林-6-基-ρ比淀-3-基）-酿胺 (299) 所要之產物係經由以氯化8-喹_淋磺醯取代實例387中之氯化2-莕磺醯，以三氟醋酸鹽製成。MS(APCI)m/z456(M+l)+ ; 1 H NMR (300 MHz, CD3 OD) 5 3.29 (t，J=5.43 Hz，2H)，4.57 (t，J=5.43 Hz，2H)， 7.65 (t，J=7.46 Hz，1H)，7.76 (dd，J=8.48, 4·41 Hz，1H)，8.12 (dd，J=8.48, 1·70 Hz， 1H)，8.18 (t，J=2.03 Hz，1H)，8.29 (s，1H)，8.31 (d，J=7.12 Hz，1H)，8·33 (dd，J=7.46， 1·36 Hz，1H)，8.41 (s，1H)，8.42 (d，J=7.80 Hz，1H)，8.55 (d，J=8.82 Hz，1H)，8.56 (dd， J=8.31，1.87 Hz，1H)，8.62 (d，J=6.44 Hz，1H)，8.95 (d，J=l.70 Hz，1H)，9·08 (dd，J= 4.41，1·70 Hz，1H)，9.74 (s，1H);對 C2 5 H2 ! N5 02 S · 3.3TFA 之分析計算值·· C，45.63 ; Η，2·94; Ν，8·42·實測值：C，45.70 ; Η，2·64; Ν，8·18· 實例391 聯苯基斗磺酸（2-胺基-乙基Μ5-異4啉-6-基-说啶-3-基V醯胺所要之產物係經由以氯化聯苯基-4-磺醯取代實例387中之氯化2-莕磺醯，以三氟醋酸鹽製成。MS(APCI)m/z481 (M+l)+ ；1 H NMR (300 MHz, CD3 OD) 6 3.16 (t, J=5.76 Hz, 2H), 4.10 (t, J=5.76 Hz, 2H), 7.49 (m, 3H), 7.68 (d, J=8.14 Hz, 2H), 7.72 (d, J=8.82 Hz, 2H), 7.89 (d, J=8.48 Hz, 2H)，8.07 (t，J=2.03 Hz，1H)，8.22 (dd，J=8.48, 1.70 Hz，1H)，8.29 (d，J=6.44 Hz，1H)， 8.45 (s, 1H), 8.53 (d, J=8.82 Hz, 1H), 8.57 (d5 J=6.44 Hz, .1H), 8.63 (d, J=2.03 Hz, 1H)，9.10 (d，J=1.70 Hz，1H)，9.72 (s，1H);對 C28H24N402S · 3.1TFA 之分析計算值：C，49.25 ; H，3·27 ; N，6·72·實測值：C，49.20 ; H，3.24 ; N, 6.62. 實例392 1-甲基-1H-味峻-4-續酸（2-胺基-乙基）-(5-異峻琳-6-基比淀-3-基）- 醯胺所要之產物係經由以氯化1-甲基咪唑-4-磺醯取代實例387 200301122Example 387B Mesano-2-acetic acid (2-amino-ethyl M5-iso4-line-6-yl-pyridin-3-ylfluorenamine) The desired product was obtained by replacing Example 27B in Example 27C with Example 387B, and Made of trifluoroacetate. MS (APCI) m / z 455 (M + l) +; 1H NMR (300 MHz, CD3 〇D) δ 3.17 (t, J = 5.76 Hz, 2H), 4.09 (t5 J = 5.43 Hz, 2H), 7.66 (t, J = 6.78 Hz, 1H), 7.75 (t, J = 7.46 Hz, 1H), 7.99 (m, 2H), 8.06 (m, 3H), 8.13 (d, J = 8.82 Hz, 1H), 8.26 (m, 2H), 8.31 (s, 1H), 8.47 (d, J = 8.48 Hz, 1H), 8.59 (m, 2H), 9.08 (d, J = 2.03 Hz, 1H), (298) 9.69 (s, 1H). Example 388 fluoren-1-ylacetate (2-amino-ethyl M5-iso4line-6-yl-exo: pyridin-3-yl) -醯严 _ The desired product was prepared by substituting 1-sulfoniumsulfonium chloride for 2-sulfoniumsulfonium chloride in Example 387 and using trifluoroacetate. MS (APCI) m / z455 (M + 1) + ; iHNMR (300 MHz, CD3 OD) δ 3.14 (t, J = 5.76 Hz, 2H), 4.04 (t, J = 5.76 Hz, 2H), 7.33 (t, J = 7.46 Hz, 1H), 7 · 51 (t, J = 7.12 Hz, 1H), 7.70 (t, J = 8.14 Hz, 1H), 7.85 (t, J = 2.20 Hz, 1H), 7.92 (dd, J = 8.48, 1.70 Hz, 1H), 8.04 (dd, J = 8.31, 3.56 Hz 2H), 8.15 (s, 1H), 8.29 (d, J = 4.75 Hz, 1H), 8.31 (d, J = 5.42 Hz, 2H), 8.47 (d, J = 8.48 Hz, 1H), 8.60 (d, J = 6.44 Hz, 1H), 8.63 (d, J = 237 Hz, 1H), 9.03 (d5 J = 2.03 Hz, 1H), 9.67 (s3 1H). Example 389 5-dimethylamino-naphthalene-1- Luteinic acid (2-Amino-ethyl)-(5-Iso-Mortal-6-yl-Oxyl-3-yl) · The desired product of amidine is via 5-dimethylamine chloride The sulfenylsulfonium chloride was substituted for the 2-sulfenylsulfonium chloride in Example 387 and was made from trifluoroacetate. MS (APCI) m / z498 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) δ 2.81 (s, 6H), 3.16 (d, J = 5.76 Hz, 2H), 4.06 (d, J = 5.76 Hz, 2H), 7.16 (d, J = 7.12 Hz, 1H), 7.25 (t, J = 7.80 Hz, 1H), 7.67 (dd, J = 8.48, 7.80 Hz, 1H) 5 7.75 (d, J = 8.48 Hz, 1H), 7.85 (t5 J = 2.20 Hz, 1H), 7.98 (dd, J = 8.48, 1.70 Hz, 1H), 8.29 (d, J = 7.12 Hz, 1H), 8.30 (s, 1H), 8.43 (d, > 6.44 Hz, 1H), 8.53 (d, J = 8.82 Hz, 1H), 8.64 (m, 3H), 9.03 (d, J = 2.03 Hz, 1H), 9.76 (s, 1H); Analytical calculation for C28H27N502S.4TFA: C, 45.34; Η, 3 · 28; Ν, 7.34 ·, measured: C, 45.28; Η , 3 · 11; Ν, 7 · 23 · Example 390 Koulyin-5-continuous failure (2-amino-ethyl)-(5-isoimazalin-6-yl-p-pyridol-3-yl ) -Fermenting amine (299) The desired product was prepared by replacing 8-quinosulfonium chloride with 2-fluorenylsulfonium chloride in Example 387 with trifluoroacetate. MS (APCI) m / z456 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 5 3.29 (t, J = 5.43 Hz, 2H), 4.57 (t, J = 5.43 Hz, 2H), 7.65 (t, J = 7.46 Hz, 1H), 7.76 (dd, J = 8.48, 4.41 Hz, 1H), 8.12 (dd, J = 8.48, 1.70 Hz, 1H), 8.18 (t, J = 2.03 Hz, 1H), 8.29 (s, 1H), 8.31 (d, J = 7.12 Hz, 1H), 8.33 (dd, J = 7.46, 1.36 Hz, 1H), 8.41 (s, 1H), 8.42 (d, J = 7.80 Hz, 1H), 8.55 (d, J = 8.82 Hz, 1H), 8.56 (dd, J = 8.31, 1.87 Hz, 1H), 8.62 (d, J = 6.44 Hz, 1H), 8.95 (d, J = 1.70 Hz, 1H), 9.08 (dd, J = 4.41, 1.70 Hz, 1H), 9.74 (s, 1H); for C2 5 H2! N5 02 S · 3.3TFA Analytical calculated values ·· C, 45.63; Η, 2.94; Ν, 8.42 · Measured values: C, 45.70; Η, 2.64; Ν, 8.18 · Example 391 Biphenyl sulfonic acid (2 -Amino-Ethyl M5-Iso-4-line-6-yl-Supridin-3-yl Vyridamine The desired product is obtained by substituting the 2-chloro-2-biphenyl-4-sulfonyl chloride in Example 387 for 2- Sulfasulfonium, made from trifluoroacetate. MS (APCI) m / z481 (M + l) +; 1 H NMR (300 MHz, CD3 OD) 6 3.16 (t, J = 5.76 Hz, 2H), 4.10 (t, J = 5.76 Hz, 2H), 7.49 (m, 3H), 7.68 (d, J = 8.14 Hz, 2H), 7.72 (d, J = 8.82 Hz, 2H), 7.89 (d, J = 8.48 Hz, 2H), 8.07 (t, J = 2.03 Hz, 1H), 8.22 ( dd, J = 8.48, 1.70 Hz, 1H), 8.29 (d, J = 6.44 Hz, 1H), 8.45 (s, 1H), 8.53 (d, J = 8.82 Hz, 1H), 8.57 (d5 J = 6.44 Hz , .1H), 8.63 (d, J = 2.03 Hz, 1H), 9.10 (d, J = 1.70 Hz, 1H), 9.72 (s, 1H); Analytical calculation for C28H24N402S · 3.1TFA: C, 49.25; H, 3.27; N, 6.72. Found: C, 49.20; H, 3.24; N, 6.62. Example 392 1-methyl-1H-weijun-4-contanoic acid (2-amino-ethyl )-(5-isojunline-6-ylpyridin-3-yl) -fluorenamine The desired product is obtained by substituting 1-methylimidazole-4-sulfonium chloride for example 387 200301122

(300) 中之氯化2-莕磺醯，以三氟醋·酸鹽製成。MS(APCI)m/z409 (M+l)+ ； 1 H NMR (300 MHz, CD3 OD) 5 3.19 (t5 J=5.59 Hz, 2H), 3.77 (s5 3H), 4.18 (t，J=5.59 Hz，2H)，7.71 (s，1H)，7.89 (s，1H)，8.31 (m，2H)，8·50 (d，J=6.44 Hz， 1H)，8.57 (d，J=8.14 Hz，1H)，8.59 (s，1H)，8.62 (d，J=8.48 Hz，1H)，8.64 (d，J=6,44 Hz，1H)，9.07 (d，J=2.03 Hz，1H)，9.78 (s，1H);對 C2 〇 H2 〇N6 02 S · 3.8 TFA 之分析計算值：C，39.38 ; H，2.85 ; N，9.98·實測值：C，39.35 ; H，2.73 ;N，9.79.(300) 2-sulfenium chloride is made of trifluoroacetic acid. MS (APCI) m / z409 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) 5 3.19 (t5 J = 5.59 Hz, 2H), 3.77 (s5 3H), 4.18 (t, J = 5.59 Hz , 2H), 7.71 (s, 1H), 7.89 (s, 1H), 8.31 (m, 2H), 8.50 (d, J = 6.44 Hz, 1H), 8.57 (d, J = 8.14 Hz, 1H) , 8.59 (s, 1H), 8.62 (d, J = 8.48 Hz, 1H), 8.64 (d, J = 6, 44 Hz, 1H), 9.07 (d, J = 2.03 Hz, 1H), 9.78 (s, 1H); Analytical calculated value for C2 0H2 0N6 02 S · 3.8 TFA: C, 39.38; H, 2.85; N, 9.98. Found: C, 39.35; H, 2.73; N, 9.79.

實例393 3-胺基-2-[5-(3-甲基-1H-41峻-5-基）比咬-3-基氧基1-丙-1-醇Example 393 3-Amino-2- [5- (3-methyl-1H-41a-5-yl) -ratio-3-yloxy1-propan-1-ol

實例393A 第三-丁基-二甲基-碎烷基氣基V2-#垔基-丙基1-胺甲基酸第三-丁酯於N-(2,3-二羥基丙基）胺基甲酸第三-丁酯（9.0克，47毫莫耳）在Ci^Cl2 (75毫升）中之溶液内，添加氯化第三-丁基二甲基矽烷（7·80克，51.7毫莫耳）、三乙胺（7.86毫升，56.4毫莫耳）及 DMAP (230毫克）。將此溶液於室溫下攪拌過夜。以CH2Cl2(5〇毫升）稀釋後，將溶液以水洗滌（2x100亳升），以MgS04脫水鲁乾燥及濃縮。於真空下藉矽藻土蒸餾殘留油，而得所要之產物（13.6 克，95%)。MS(DCI)m/z306(M+l)+.Example 393A Third-butyl-dimethyl-crucylalkylamino V2- # fluorenyl-propyl 1-aminomethyl acid third-butyl ester in N- (2,3-dihydroxypropyl) amine Tertiary-butyl carbamate (9.0 g, 47 mmol) In a solution of Ci ^ Cl2 (75 ml), tertiary-butyl dimethyl silane (7.80 g, 51.7 mmol) was added Ear), triethylamine (7.86 ml, 56.4 mmol) and DMAP (230 mg). This solution was stirred at room temperature overnight. After diluting with CH2Cl2 (50 ml), the solution was washed with water (2 x 100 ml), dried over MgS04, and concentrated. The residual oil was distilled under diatomaceous earth under vacuum to obtain the desired product (13.6 g, 95%). MS (DCI) m / z306 (M + 1) +.

實例393BExample 393B

IgiL5-漠4啶-3-基氧j 第三-丁基-二甲基-碎基氧某）_兩胺甲基酸第三-丁酯於100毫升RBF中’裝填3-溴基-5-經基峨淀（949毫克，5.45毫莫耳）、實例393Α(2·0克，6.45毫莫耳）及ph3P(i.72克，6 54毫 -308- (301) 莫耳），並以氮滌氣。於0°c下添加THF (22毫升）。在0°C下攪拌10分鐘後，經由注射器添加DEAD (1.03毫升，6.54毫莫耳）。將反應混合物於〇°C下攪拌1小時，並在室溫下過夜。使反應混合物濃縮，並藉急驟式層析（於己烷中之5-30% EtOAc) 分離殘留物，提供所要之產物（1.76克，70% )。MS (DCI)m/z 461， 463 (Μ+1)+·IgiL5- Molyl-4pyridin-3-yloxy j tert-butyl-dimethyl-branthyloxy)-Diamine methyl acid tert-butyl ester in 100 ml RBF 'filled with 3-bromo-5 -Via Jiedian (949 mg, 5.45 mmol), Example 393A (2.0 g, 6.45 mmol) and ph3P (i. 72 g, 6 54 mmol-308- (301) Mol), and Purify with nitrogen. THF (22 mL) was added at 0 ° C. After stirring at 0 ° C for 10 minutes, DEAD (1.03 ml, 6.54 mmol) was added via a syringe. The reaction mixture was stirred at 0 ° C for 1 hour and overnight at room temperature. The reaction mixture was concentrated and the residue was separated by flash chromatography (5-30% EtOAc in hexanes) to provide the desired product (1.76 g, 70%). MS (DCI) m / z 461, 463 (Μ + 1) + ·

實例393C 545-Γ2-第三-丁氧羰基胺基-1-(第三-丁基-二甲基-矽烷基氧基甲基乙氧基1-吡啶-3-基丨-3-甲基-吲唑小羧酸第三丁酯於100毫升RBF中，裝填實例39犯（L60克，3·47毫莫耳）、實例 203B(L37 克，3.47 毫莫耳）' pd2(dba)3(318 毫克，0.347 毫莫耳）及三-鄰-甲苯基膦（318毫克），並以N2滌氣。經由注射器添加無水DMF (50毫升）與Et3N (1.45毫升）。將此溶液以N2再滌氣一次，並於75°C下加熱5小時。於冷卻後，添加醋酸乙酯 (200毫升）。將混合物以鹽水（250毫升）及水（250毫升）洗滌。使醋酸乙醋〉容液濃縮’並藉急驟式層析（於己燒中之20-60% EtOAc)分離殘留油，而得所要之產物（ι·51克，71% )。MS (DCI) m/z 613 (M+l)+.Example 393C 545-Γ2-Third-butoxycarbonylamino-1- (third-butyl-dimethyl-silyloxymethylethoxy 1-pyridin-3-yl 丨 -3-methyl -Indazole tributyl tricarboxylic acid in 100 ml of RBF, filled with Example 39 (L60 g, 3.47 mmol), Example 203B (L37 g, 3.47 mmol) 'pd2 (dba) 3 ( 318 mg, 0.347 mmol) and tri-o-tolylphosphine (318 mg), and purged with N2. Anhydrous DMF (50 ml) and Et3N (1.45 ml) were added via a syringe. This solution was then washed with N2 Air once and heat at 75 ° C for 5 hours. After cooling, ethyl acetate (200 ml) was added. The mixture was washed with brine (250 ml) and water (250 ml). Ethyl acetate> the solution was concentrated 'And separated the residual oil by flash chromatography (20-60% EtOAc in hexane) to give the desired product (ι · 51 g, 71%). MS (DCI) m / z 613 (M + l ) +.

實例393D 弟二-丁一乳魏基胺基-1-輕甲基-乙氧盖比咬各基1-3-甲某土弓丨唑-1-羧酸第三-丁酉§_ 在室溫下’於實例393C(1.122克，1.83亳莫耳）在THF(20毫升）中之）谷液内’添加TBAF (1.92愛升將此溶液於室溫下攪拌1小時，及濃縮。藉急驟式層析（於2 : 1 Et〇Ac /己垸中 200301122 (302) 之0-15% CH2 OH)分離殘留油，而得標題化合物（0.82克，90% ) 。MS(DCI)m/z499(M+l)+·Example 393D Brother di-butyrolactamylamino-1-light methyl-ethoxygabitol bite each base 1-3-methyl certain archer azole-1-carboxylic acid tertiary-butyrate §_ at room temperature Next, in Example 393C (1.122 g, 1.83 mol) in THF (20 ml)), add TBAF (1.92 liters). This solution was stirred at room temperature for 1 hour, and concentrated. By flash method Chromatography (0-1: 15% CH2OH of 20030122 (302) in 2: 1 EtAc / hexane) to separate the residual oil to give the title compound (0.82 g, 90%). MS (DCI) m / z499 ( M + l) + ·

實例393E 3-胺基-2-「5-(3-甲基-1H-喇唑-5-基V吡啶-3-基氣某1-丙小醇所要之產物係經由以實例39犯取代實例27C中之實例27B ，以 HC1 鹽製成。MS(APCI)m/z299(M+l)+ ; 1H NMR (300 MHz， DMSO-d6) 5 2·58 (s，3H)，3.26 (m，2H)，3.68 (dd，J=12.21，5.09 Hz，1H)，3.75 (dd，Example 393E 3-Amino-2- "5- (3-methyl-1H-razol-5-yl Vpyridin-3-yl gas The desired product of 1-propanol is substituted by the example in Example 27B in 27C, made from HC1 salt. MS (APCI) m / z299 (M + 1) +; 1H NMR (300 MHz, DMSO-d6) 5 2 · 58 (s, 3H), 3.26 (m, 2H), 3.68 (dd, J = 12.21, 5.09 Hz, 1H), 3.75 (dd,

J=12.54, 4.75 Hz, 1H), 5.05 (m, J=4.07 Hz, 1H), 7.62 (d, J=8.81 Hz, 1H), 7.85 (dd, J= 8.81, 1.70 Hz, 1H), 8.35 (s, 4H), 8.52 (s, 1H), 8.64 (d, J=2.37 Hz? 1H), 8.90 (s? 1H)；對 C16H18N402 .3.2HC1之分析計算值：C，46.31; H，5.15; Ν，13·50· 實測值：C，46.46 ; Η，5·12 ; N，13.42. 實例394 }「5-(3-甲基-ΙΗ-Κ丨咬-5-基比淀-3-基氧基1-3-笨氧基-丙胺J = 12.54, 4.75 Hz, 1H), 5.05 (m, J = 4.07 Hz, 1H), 7.62 (d, J = 8.81 Hz, 1H), 7.85 (dd, J = 8.81, 1.70 Hz, 1H), 8.35 ( s, 4H), 8.52 (s, 1H), 8.64 (d, J = 2.37 Hz? 1H), 8.90 (s? 1H); Analysis and calculation of C16H18N402.3.2HC1: C, 46.31; H, 5.15; Ν , 13.50 · Measured value: C, 46.46; Hf, 5.12; N, 13.42. Example 394} "5- (3-Methyl-lΗ-K 丨 B-5-ylpyridine-3-yloxy 1-3-benzyloxy-propylamine

實例394A 第三-丁氣赛某脖基小笨氧基甲基-乙氫基吡啶各基1-3-甲基^1唑小羧酸第三-丁酯於25毫升RBF中，裝填酚02毫克，0·45毫莫耳）、實例393D.(150 鲁毫克，0.3毫莫耳）及ph3p (142毫克，0.54毫莫耳），並以氮滌氣。於0°C下添加THF (4毫升）。在0°C下攪拌10分鐘後，經由注射器添加DEAD (85微升，’ 0.54毫莫耳）。將反應混合物於〇 °C下搅摔1小時’並在室溫下過夜。使反應混合物濃縮，並藉急驟式層析（於己烷中之20-60% EtOAc)分離殘留物，提供所要之產物（I63 毫克，％% )。MS (DCI) m/z 575 (M+l)+ ·Example 394A The third-butanyl group is a stubyloxymethyl-ethylhydropyridine group, each of which is 1-3-methyl ^ 1azole small carboxylic acid tertiary-butyl ester in 25 ml of RBF, filled with phenol 02 (Mg, 0.45 mmol), Example 393D. (150 mg, 0.3 mmol) and ph3p (142 mg, 0.54 mmol), and purged with nitrogen. THF (4 mL) was added at 0 ° C. After stirring at 0 ° C for 10 minutes, DEAD (85 µl, '0.54 mmol) was added via a syringe. The reaction mixture was stirred at 0 ° C for 1 hour 'and overnight at room temperature. The reaction mixture was concentrated and the residue was separated by flash chromatography (20-60% EtOAc in hexanes) to provide the desired product (I63 mg, %%). MS (DCI) m / z 575 (M + l) +

實例394B -310- 200301122 (303)Example 394B -310- 200301122 (303)

2-「5-(3-甲某-1H-W唑-5-基V吡啶-3-基氲基1-3-笨氣基-丙胺所要之產物係經由以實例394A取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 375 (M+l)+ ; 1 H NMR (300 MHz， CD3 OD) (5 2.62 (s，3Η)，3·58 (d，J=5.76 Ηζ，2Η)，4.34 (dd，J=11.19, 5·09 Ηζ，·1Η)， 4.42 (dd，J=11.19, 3·73 Hz，1H)，5·33 (m，1H)，6.94 (m，3H)，7·26 (dd，JN8.81，7.46 Hz，2H)，7.62 (d，J=7.80 Hz，1H)，7·72 (dd，J=8.81，1.70 Hz，1H)，8·09 (s，1H)，8.27 (s， 1H)，8.52 (d，J=2.37 Hz，1H)，8.75 (d，J=1.36 Hz，1H);對 C2 2 H2 2 N4 02 · 2TFA 之分析計算值：C，51.83 ; H，4.02 ; N，9.30.實測值：C，51.97 ; H，3.97 ;N，9.41. 實例3952-``5- (3-methyl-1H-Wazole-5-yl Vpyridin-3-ylfluorenyl 1-3-benzyl-propylamine The desired product is obtained by replacing the example in Example 27C with Example 394A 27B, made of trifluoroacetate. MS (APCI) m / z 375 (M + 1) +; 1 H NMR (300 MHz, CD3 OD) (5 2.62 (s, 3Η), 3.58 (d, J = 5.76 Ηζ, 2Η), 4.34 (dd, J = 11.19, 5.09 Ηζ, · 1Η), 4.42 (dd, J = 11.19, 3.73 Hz, 1H), 5.33 (m, 1H), 6.94 (m, 3H), 7.26 (dd, JN8.81, 7.46 Hz, 2H), 7.62 (d, J = 7.80 Hz, 1H), 7.72 (dd, J = 8.81, 1.70 Hz, 1H) , 8.09 (s, 1H), 8.27 (s, 1H), 8.52 (d, J = 2.37 Hz, 1H), 8.75 (d, J = 1.36 Hz, 1H); for C2 2 H2 2 N4 02 · 2TFA Analytical calculated values: C, 51.83; H, 4.02; N, 9.30. Found: C, 51.97; H, 3.97; N, 9.41. Example 395

2-「5-(3-甲基-1H-吲唑-5-基）-吡啶-3-基氧基1各(茬-2-基氣基丙胺所要之產物係經由以2-莕酚取代實例394中之酚，以三氟醋酸鹽製成。MS(APCI)m/z425 (M+l)+ ; 1HNMR(300MHz，CD3OD) δ 2.56 (s，3H)，3.62 (d，J=5.76 Hz，2H)，4.47 (dd，J=11.19, 5.09 Hz，1H)，4.56 (dd，J= 11.19, 3·73 Hz，1H)，5·36 (m，1H)，7.08 (dd，J=8.98, 2.54 Hz，1H)，7.28 (m，1H)，7·33 (d，J=8.14 Hz，1H)，7.40 (t，J=8.14 Hz，1H)，7·54 (d，J=8.48 Hz，1H)，7·62 (dd，J= 10.17, 1·70 Hz，1H)，7.71 (d，J=8.14 Hz，1H)，7.72 (d，J=2.03 Hz，1H)，7.74 (s，1H)， 8.00 (s，1H)，8.11 (m，1H)，8·50 (d，J=2.37 Hz，1H)，8.68 (d，J=1.36 Hz，1H); 對 C26H24N402 .2.8TFA之分析計算值：C，51.03; Η，3·63; Ν，7·53· 實測值：C，51.18 ; H，3·47 ; N，7.55. 實例396 3-(聯本 -4-基氧基V2-f5-(3-甲基-lH-Hl峻-5-基比症-3-基氧基V丙胺所要之產物係經由以4-苯基酚取代實例394中之酚，以三氟醋酸鹽製成。MS (APCI) m/z 452 (M+l)+ ; 1 H NMR (300 MHz，CD3 OD) -311 - (304)2- "5- (3-Methyl-1H-indazol-5-yl) -pyridin-3-yloxy 1 (each 2-ylaminopropylamine desired product is substituted by 2-fluorenol The phenol in Example 394 was made from trifluoroacetate. MS (APCI) m / z425 (M + 1) +; 1HNMR (300MHz, CD3OD) δ 2.56 (s, 3H), 3.62 (d, J = 5.76 Hz , 2H), 4.47 (dd, J = 11.19, 5.09 Hz, 1H), 4.56 (dd, J = 11.19, 3.73 Hz, 1H), 5.36 (m, 1H), 7.08 (dd, J = 8.98 , 2.54 Hz, 1H), 7.28 (m, 1H), 7.33 (d, J = 8.14 Hz, 1H), 7.40 (t, J = 8.14 Hz, 1H), 7.54 (d, J = 8.48 Hz , 1H), 7.62 (dd, J = 10.17, 1.70 Hz, 1H), 7.71 (d, J = 8.14 Hz, 1H), 7.72 (d, J = 2.03 Hz, 1H), 7.74 (s, 1H), 8.00 (s, 1H), 8.11 (m, 1H), 8.50 (d, J = 2.37 Hz, 1H), 8.68 (d, J = 1.36 Hz, 1H); Analysis of C26H24N402 .2.8TFA Calculated: C, 51.03; Η, 3.63; Ν, 7.53. Found: C, 51.18; H, 3.47; N, 7.55. Example 396 3- (biben-4-yloxy V2 The desired product of -f5- (3-methyl-lH-Hl Jun-5-ylpyridin-3-yloxy V propylamine is obtained by replacing the phenol in Example 394 with 4-phenylphenol, and trifluoroacetate Made of. MS (APCI) m / z 452 (M + l) +; 1 H NMR (300 MHz, CD3 OD) -311-(304)

5 2.57 (s，3H)，3.58 (d，J=6.10 Hz，2H)，4.39 (dd，J=11.19, 5.09 Hz，1H)，4.47 (dd，J= 11.53, 3.73 Hz，1H)，5.30 (m5 1H)，6.99 (d，J=8.81 Hz，2H)，7.27 (d，J=7.12 Hz，1H)， 7·36 (t，J=7.46 Hz，2H)，7.51 (m，4H)，7.57 (d，J=8.48 Hz，1H)，7.67 (dd，J=8.81，1.70 Hz，1H)，8.03 (s，1H)，8.09 (dd，J=4.41，2·37 Hz，1H)，8.49 (d，J=2.37 Hz，1H)，8.69 (s， 1H);對 C28H26N402 ·3·2ΤΡΑ 之分析計算值：C，5〇.67; Η，3·61; Ν，6·87· 實測值：C，50.77 ; Η，3·51 ; Ν，6.64. 實例397 2-「5-(3-甲基-ΠΊ』引嗅-5-基）-外匕咬-3-基乳基1-3-(口奎淋-7-基氣基）-丙胺所要之產物係經由以7-經基喹淋取代實例394中之酚，以三氟醋酸鹽製成。MS (APCI) m/z 426 (M+l)+; 1 H NMR (300 MHz，CD3 OD) δ 2.59 (s，3H)，3.64 (d，J=5.76 Hz，2H)，4.62 (dd，J=l〇.85, 5·09 Hz，1H)，4.70 (d， 11.19 Hz, 1H)5 5.42 (m, 1H), 7.50 (dd, J=9.32, 2.20 Hz, 1H), 7.58 (dd, J=5.26, 3.22 Hz，2H)，7.69 (d，J=8.48 Hz，1H)，7.78 (dd，J=8.14, 5.43 Hz, 1H)，8.03 (s，1H)，8.07 (s， 1H)，8.16 (d，J=9.16 Hz，1H)，8.47 (s，1H)，8.67 (s，1H)，8.88 (d，J=8.14 Hz，1H)，8.98 (d，J=4.41Hz，lH);對 C25H23N502 . 3.9TFA之分析計算值：C，45.27 ;Η，3·12; N，8.05.實測值：C，45.26 ; Η，3·05; N，7.92. 實例398 2~T5-(3-甲基-ΙΗ-口弓丨咬-5-基）-π比症-3-基氧基比淀-4-基氣某）-丙胺所要之產物係經由以4- #至基吡啶取代實例394中之酚，以 HC1 鹽製成。MS (APCI) m/z 376 (M+l)+ ; 1 H NMR (300 MHz, DMSO-d6) δ 2·58 (s，3H)，3·40 (br s，2H)，4.75 (d，J=11.87 Hz，1H)，4.85 (d，J=ll.49 Hz，1H)， 5.61 (m，1H)，7·59 (m，2H)，7·86 (d，J=8.82 Hz，1H)，8.37 (s，1H)，8·56 (s，1H)，8.66 (s，1H)，8.73 (s，2H)，8.79 (s，1H)，8.81 (s，m)，8.92 (s，1H);對 C2 i H2 i N5 02 · 4.5 HC1 之分析計算值：C，46·75 ; H，4·76 ; N，12.98.實測值：c，46.77 (305) ；Η, 4.41； N, 12.83. 實例399 245-(3-甲基-1H-W唑-5-基V吡啶-3-基氣基1-3-(苯小基氣基V丙胺所要之產物係經由以1-莕酚取代實例394中之酚，以三氟醋酸鹽製成。MS(APCI)m/z426(M+l)+ ; iHNMROOOMHiCDsOD) 5 3.34 (s，3H)，3.65 (d，J=5.76 Hz，2H)，4·57 (m，2H)，5·49 (m，1H)，6·97 (d，J=7.46 Hz，1H)，7.23 (t，JK7.63 Hz，1H)，7.37 (d，J=7.46 Hz，1H)，7.41 (d，J=8.82 Hz，1H)， 7.44 (d5 J=8.48 Hz, 1H), 7.56 (s, 2H), 7.74 (d, J=8.48 Hz, 1H), 7.84 (d, J=7.80 Hz, 1H)，7.92 (s，1H)，8·15 (s，1H)，8.50 (d，J=2.03 Hz，1H)，8.65 (s，1H); 對匸2611241^4〇2.3.1丁?八之分析計算值：（：，49/71;11，3.51;凡7.20· 實測值·· C，49.70 ; H，3.47; N，7.07. 實例400 3-{(2S)-2-胺基-345-(3-甲基-1H-㈤唑-5-基）-吡啶-3-基氧基1-丙基}-5 2.57 (s, 3H), 3.58 (d, J = 6.10 Hz, 2H), 4.39 (dd, J = 11.19, 5.09 Hz, 1H), 4.47 (dd, J = 11.53, 3.73 Hz, 1H), 5.30 ( m5 1H), 6.99 (d, J = 8.81 Hz, 2H), 7.27 (d, J = 7.12 Hz, 1H), 7.36 (t, J = 7.46 Hz, 2H), 7.51 (m, 4H), 7.57 (d, J = 8.48 Hz, 1H), 7.67 (dd, J = 8.81, 1.70 Hz, 1H), 8.03 (s, 1H), 8.09 (dd, J = 4.41, 2.37 Hz, 1H), 8.49 ( d, J = 2.37 Hz, 1H), 8.69 (s, 1H); Analytical calculated value for C28H26N402 · 3 · 2TPA: C, 5〇.67; Η, 3.61; Ν, 6.87 · Measured value: C, 50.77; hydrazone, 3.51; N, 6.64. Example 397 2- "5- (3-methyl-ΠΊ" olfactory-5-yl) -exobital-3-yllactyl1-3- (Kou Kuilin-7-base gas group)-The desired product of propylamine is made by substituting the phenol in Example 394 with 7-methylquinone and using trifluoroacetate. MS (APCI) m / z 426 (M + l) +; 1 H NMR (300 MHz, CD3 OD) δ 2.59 (s, 3H), 3.64 (d, J = 5.76 Hz, 2H), 4.62 (dd, J = 1.85, 5.09 Hz , 1H), 4.70 (d, 11.19 Hz, 1H) 5 5.42 (m, 1H), 7.50 (dd, J = 9.32, 2.20 Hz, 1H), 7.58 (dd, J = 5.26, 3.22 Hz, 2H), 7.69 (d, J = 8.48 Hz 1H), 7.78 (dd, J = 8.14, 5.43 Hz, 1H), 8.03 (s, 1H), 8.07 (s, 1H), 8.16 (d, J = 9.16 Hz, 1H), 8.47 (s, 1H), 8.67 (s, 1H), 8.88 (d, J = 8.14 Hz, 1H), 8.98 (d, J = 4.41Hz, lH); Analytical calculation for C25H23N502. 3.9TFA: C, 45.27; Η, 3.12 N, 8.05. Measured value: C, 45.26; Η, 3.05; N, 7.92. Example 398 2 ~ T5- (3-methyl-lΗ-oral arch 丨 bite-5-yl) -π ratio syndrome- The desired product of 3-yloxy than dian-4-yl gas) -propylamine was prepared by replacing the phenol in Example 394 with 4- # to ylpyridine and using the HC1 salt. MS (APCI) m / z 376 (M + l) +; 1 H NMR (300 MHz, DMSO-d6) δ 2.58 (s, 3H), 3.40 (br s, 2H), 4.75 (d, J = 11.87 Hz, 1H), 4.85 (d, J = ll.49 Hz, 1H), 5.61 (m, 1H), 7.59 (m, 2H), 7.86 (d, J = 8.82 Hz, 1H ), 8.37 (s, 1H), 8.56 (s, 1H), 8.66 (s, 1H), 8.73 (s, 2H), 8.79 (s, 1H), 8.81 (s, m), 8.92 (s, 1H); Analytical calculation for C2 i H2 i N5 02 · 4.5 HC1: C, 46 · 75; H, 4.76; N, 12.98. Found: c, 46.77 (305); Η, 4.41; N, 12.83. Example 399 245- (3-Methyl-1H-Wazole-5-yl Vpyridin-3-ylamino 1- 3- (benzene small arylamino V propylamine) The desired product is Replaced the phenol in Example 394 with trifluoroacetate. MS (APCI) m / z426 (M + 1) +; iHNMROOOMHiCDsOD) 5 3.34 (s, 3H), 3.65 (d, J = 5.76 Hz, 2H) , 4.57 (m, 2H), 5.49 (m, 1H), 6.97 (d, J = 7.46 Hz, 1H), 7.23 (t, JK7.63 Hz, 1H), 7.37 (d, J = 7.46 Hz, 1H), 7.41 (d, J = 8.82 Hz, 1H), 7.44 (d5 J = 8.48 Hz, 1H), 7.56 (s, 2H), 7.74 (d, J = 8.48 Hz, 1H), 7.84 (d, J = 7.80 Hz, 1H), 7.92 (s, 1H), 8.15 (s, 1H), 8.5 0 (d, J = 2.03 Hz, 1H), 8.65 (s, 1H); Analytical calculations for 匸 2611241 ^ 4〇2.3.1 Ding? Ba: (:, 49/71; 11, 3.51; Where 7.20 · Found: C, 49.70; H, 3.47; N, 7.07. Example 400 3-{(2S) -2-amino-345- (3-methyl-1H-oxazol-5-yl) -pyridine- 3-yloxy 1-propyl}-

1H-W 哚-5-醇實例400A (2SV2-第三-丁氧羰基胺基-3-(5-羥基-1H-吲哚-3-基）-丙酸甲酯於BOC-5-羥基-色胺酸（5.9克，18·4毫莫耳）與碘甲烷（3.43毫升）在DMF (80毫升）中之溶液内，添加粉末狀KHC03 (3·68克）。將反應混合物於室溫下攪拌4小時。添加EtOAc (500毫升），並將混合物以鹽水（5〇〇毫升）及水（500毫升）洗滌。使有機相濃縮，並將殘留油以CH2C12(20毫升）研製。藉過濾收集所形成之白色固體，以CH2C12(20毫升）洗滌並乾燥’而得所要之產物（4.48 克，73% )。MS(DCI)m/z335Example of 1H-W indole-5-ol 400A (2SV2-third-butoxycarbonylamino-3- (5-hydroxy-1H-indol-3-yl) -propionic acid methyl ester in BOC-5-hydroxy- To a solution of tryptophan (5.9 g, 18.4 mmol) and methyl iodide (3.43 ml) in DMF (80 ml) was added powdered KHC03 (3.68 g). The reaction mixture was allowed to stand at room temperature. Stir for 4 hours. EtOAc (500 mL) is added and the mixture is washed with brine (500 mL) and water (500 mL). The organic phase is concentrated and the residual oil is triturated with CH2C12 (20 mL). Collect by filtration The white solid formed was washed with CH2C12 (20 ml) and dried to give the desired product (4.48 g, 73%). MS (DCI) m / z335

實例400B 200301122Example 400B 200301122

(306) 氧羰基胺基各『5-(第三-丁基-二甲基-矽烷基 ΜΗ-叫1嗓-3-基1-丙酸甲酯在室溫下，於實例4〇〇Α (1·20克，3.59毫莫耳）在DMF (20亳升）中之溶液内，添加氯化第三-丁基二甲基矽烷（649毫克，4 3 毫莫耳）、咪唑（293毫克，4.3毫莫耳）及DMAP (50毫克）。將反應混合物於室溫下攪拌16小時。添加EtOAc (100毫升），並將混合物以鹽水（100毫升）及水（100毫升）洗滌。使有機相濃縮’並使殘留油藉急騾式層析（於己烷中之10-40% EtOAc)純化’獲得所要之產物（1.6 克，1〇〇% )。MS(DCI)m/z466(M+18)+·(306) oxycarbonylamino groups each of 5- (tertiary-butyl-dimethyl-silylmethyl) -called 1-methyl-3-yl 1-propionic acid methyl ester at room temperature in Example 400A (1.20 g, 3.59 mmol) in a solution in DMF (20 ml) added tertiary-butyldimethylsilyl chloride (649 mg, 4 3 mmol), imidazole (293 mg , 4.3 mmol) and DMAP (50 mg). The reaction mixture was stirred at room temperature for 16 hours. EtOAc (100 ml) was added and the mixture was washed with brine (100 ml) and water (100 ml). Organic The phases were concentrated 'and the residual oil was purified by flash chromatography (10-40% EtOAc in hexanes) to obtain the desired product (1.6 g, 100%). MS (DCI) m / z466 (M +18) + ·

實例400C (lSHgj>(第三-丁某-二甲基-矽烷基氣基y1H•吲哚各某]小羥甲基-乙基丨-胺甲基酸第三-丁酯在室溫下，於實例400B (1.50克，3.3毫莫耳）在THF (15毫升）中之溶液内，慢慢以數份添加LiAIH4粉末（127毫克，3.3毫莫耳）。於添加後，反應混合物轉化成黏性，並停止攪拌。Example 400C (lSHgj) (Third-Butyl-dimethyl-silylyl y1H • indole each) Small methylol-ethyl 丨 -aminomethyl acid tert-butyl ester at room temperature, In a solution of Example 400B (1.50 g, 3.3 mmol) in THF (15 ml), slowly add LiAIH4 powder (127 mg, 3.3 mmol) in several portions. After the addition, the reaction mixture was converted to a viscous And stop stirring.

混合物之溫度上升至〜50°C。添加醚（30毫升），並將混合物攪拌20分鐘。慢慢添加甲醇（2毫升）與稀HC1，並將混合物以醚萃取。將有機相以水洗滌及濃縮。藉急騾式層析（於己烷中之20-60% EtOAc)分離殘留物，而得所要之產物（982毫克，70%)。MS(DCI)m/z421(M+l)+·The temperature of the mixture rose to ~ 50 ° C. Ether (30 ml) was added and the mixture was stirred for 20 minutes. Methanol (2 ml) and dilute HC1 were slowly added, and the mixture was extracted with ether. The organic phase was washed with water and concentrated. The residue was separated by flash chromatography (20-60% EtOAc in hexanes) to give the desired product (982 mg, 70%). MS (DCI) m / z421 (M + l) + ·

實例400D (lSW2-(5->臭-p比咬-3-基氧基第三-丁基-二甲基-玲fe基氧多V1H-H丨嗓-3-基甲基1-乙基卜胺甲基酸第三-丁酉旨於100毫升RBF中，裝填3-溴基-5-輕基吡啶（432毫克，2.48毫 -314- 200301122 (307) 莫耳）、實例400C (950毫克，2·26亳莫耳）及Ph3P (711毫克，2·71 亳莫耳），並以氮滌氣。於〇°C下添加THF (15毫升）。在0°C下攪拌10分鐘後，經由注射器添加DEAD (427微升，2.71毫莫耳）。將反應混合物於0°C下攪拌1小時，並在室溫下過夜。使反應混合物濃縮，並藉急驟式層析（於己烷中之10-50% EtOAc) 分離殘留物，提供所要之產物（1.05克，80% )。MS (APO〇 m/z 576, 578 (M+l)+ ·Example 400D (lSW2- (5- > odor-p is more than 1--3-yloxy tertiary-butyl-dimethyl-lingeryl-oxyl V1H-H) The tertiary butylamine methyl acid was prepared in 100 ml of RBF and filled with 3-bromo-5-light pyridine (432 mg, 2.48 mmol-314- 200301122 (307) mole), Example 400C (950 mg , 2.26 μmol) and Ph3P (711 mg, 2.71 μmol) and purged with nitrogen. THF (15 ml) was added at 0 ° C. After stirring at 0 ° C for 10 minutes, DEAD (427 μl, 2.71 mmol) was added via syringe. The reaction mixture was stirred at 0 ° C. for 1 hour and overnight at room temperature. The reaction mixture was concentrated and subjected to flash chromatography (in hexanes). (10-50% EtOAc) separated the residue to provide the desired product (1.05 g, 80%). MS (APOm / z 576, 578 (M + 1) + ·

實例400E 5-(5-丨(2S)-2-第二-丁氧魏基胺基-3-『5-(第三-丁基-二甲基-碎jt充基氣基嗓-3-基V丙氧基丨-η比淀-3-基V3-甲基-Hi峻-1-複酸第三-丁酯所要之產物係經由以實例400D取代實例2〇3C中之實例202A 而製成。MS (DCI) m/z 728 (M+l)+ ·Example 400E 5- (5- 丨 (2S) -2-Second-butoxybenzylamino-3- "5- (Third-butyl-dimethyl-branched jt-based gas-based radical-3- The desired product of the radical Vpropoxy 丨 -η than 3-Yodo-3-yl V3-methyl-His-1-multicarboxylic acid tert-butyl ester was prepared by replacing Example 202A in Example 203C with Example 400D Success. MS (DCI) m / z 728 (M + l) + ·

實例400F 5-{5-f(2SV2-第三-丁乳藏基胺基-3-(5-¾基-1H-1^丨嗓-3-基）-丙氧基外匕啶各基丨各甲基唑小羧酸第三-丁酯在室溫下，於實例400Ε (850毫克，1.17毫莫耳）在THF (10毫 ® 升）中之溶液内，添加TBAF (1.28毫升，1·28毫莫耳）。將此溶液於室溫下攪拌2小時，及濃縮。使殘留油藉急驟式層析（於2 ·· 1 EtOAc /己烷中之0-15% CH3OH)純化，而得所要之產物（530 毫克，74%)。MS(DCI)m/z614(M+l)+·Example 400F 5- {5-f (2SV2-Third-Butylsuccinylamino-3- (5-¾yl-1H-1 ^ 丨 -3-yl) -propoxy exotridinyl group 丨Each methylazole tricarboxylic acid tert-butyl ester was added to a solution of Example 400E (850 mg, 1.17 mmol) in THF (10 mmol® liter) at room temperature, and TBAF (1.28 ml, 1 ·· 28 mmol). The solution was stirred at room temperature for 2 hours and concentrated. The residual oil was purified by flash chromatography (0-1.5% CH3OH in 2 · 1 EtOAc / hexane) to obtain The desired product (530 mg, 74%). MS (DCI) m / z614 (M + 1) + ·

實例400G 3-{(2S)-2-胺基-345-(3-甲基丨吐-5-基比咬-3-基氧某1·丙基}· 1HW1 哚-5-醇 -315- (308) 所要之產物係經由以實例400F取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS(APCI)m/z414(M+l)+; iHNMRpOOMHz， CD3 OD) (5 2.63 (s, 3H), 3.25 (dd, J=7.12, 2.37 Hz, 2H), 3.98 (m, 1H), 4.35 (dd, J= 10·51，5.76 Hz，1H)，4.48 (dd，J=10.51，3·39 Hz，1H)，6.70 (dd，J=8.48, 2.37 Hz，1H)， 6·93 (d，J=2.03 Hz，1H)，7.18 (s，1H)，7·20 (d，J=8.48 Hz，H)，7.63 (d，J=8.81 Hz，1H)， 7.71 (dd，J=8.81，2.03 Hz，1H)，8·11 (m，2H)，8·41 (d，J=2.37 Hz，1H)，8.74 (d，J= 1.70Hz，1H);對 C24H23N502 ·3·7ΤΡΑ之分析計算值：C，45.15; Η，3·22 ;N，8.38.實測值：C，45.15 ; H，3.45; Ν，8·43· 實例401 gSH-(5-甲氧基-1H-W哚各基曱基）-245-(3-甲基-1H-峭唑-5-某V吡Example 400G 3-{(2S) -2-Amino-345- (3-methyl 丨 T-5-yl than bit-3-yloxy-1 · propyl} · 1HW1 indol-5-ol-315- (308) The desired product was made from trifluoroacetate by replacing Example 27B in Example 27C with Example 400F. MS (APCI) m / z414 (M + 1) +; iHNMRpOOMHz, CD3 OD) (5 2.63 ( s, 3H), 3.25 (dd, J = 7.12, 2.37 Hz, 2H), 3.98 (m, 1H), 4.35 (dd, J = 10.51, 5.76 Hz, 1H), 4.48 (dd, J = 10.51, 3.39 Hz, 1H), 6.70 (dd, J = 8.48, 2.37 Hz, 1H), 6.93 (d, J = 2.03 Hz, 1H), 7.18 (s, 1H), 7.20 (d, J = 8.48 Hz, H), 7.63 (d, J = 8.81 Hz, 1H), 7.71 (dd, J = 8.81, 2.03 Hz, 1H), 8.11 (m, 2H), 8.41 (d, J = 2.37 Hz, 1H), 8.74 (d, J = 1.70Hz, 1H); Analysis and calculation of C24H23N502 · 3. · 7TPA: C, 45.15; Η, 3.22; N, 8.38. Measured value: C, 45.15; H, 3.45; N, 8.43. Example 401 gSH- (5-methoxy-1H-W indolyl fluorenyl) -245- (3-methyl-1H-andolazole-5-a certain pyridine

淀-3-基氧基1-乙胺實例401A g^5-[(2S)-2-第三-丁氧羰基胺某-3-(5-曱氫基-1H-吲哚-3-某V丙氧基症,.-3-基卜3-甲基-K1唑-1—教酸第三-丁酯於25毫升RBF中，裝填實例400F (100毫克，0.163毫莫耳）與 Ph3 P (85毫克’ 0.325毫莫耳），並以氮滌氣。於〇°c下添加THF (4 毫升）與甲醇（14微升）。在〇。(：下攪拌1〇分鐘後，經由注射器添加DEAD (51微升，0.325毫莫耳）。將反應混合物於π下攪拌1小時，並在室溫下度過週末。使反應混合物濃縮，並藉急驟式層析（於己烷中之50-80% Et〇Ac)分離殘留物，提供所要之產物（33毫克，32% )。Ms心628 (M+1)+Example of yt-3-yloxy 1-ethylamine 401A g ^ 5-[(2S) -2-Third-butoxycarbonylamine some-3- (5-fluorenyl-1H-indole-3-some V-propoxy disease, .3-kib 3-methyl-K1azole-1-tau-acid tert-butyl ester in 25 ml of RBF, filled with Example 400F (100 mg, 0.163 mmol) and Ph3 P (85 mg '0.325 mmol) and purged with nitrogen. THF (4 ml) and methanol (14 μl) were added at 0 ° C. After stirring at 0 ° C: for 10 minutes, add via syringe DEAD (51 μl, 0.325 mmol). The reaction mixture was stirred at π for 1 hour and spent the weekend at room temperature. The reaction mixture was concentrated and subjected to flash chromatography (50- 80% Et. Ac) separated the residue to provide the desired product (33 mg, 32%). Ms Heart 628 (M + 1) +

實例401B 胆)-1-(5-甲一氧基」复座各基甲D-2-『5-(3-甲基-1Η-Θ1唑-5·基V吡毽-3-基氣某1-λ栌 200301122 (309) 所要之產物係經由以實例4〇1Α取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) ιώ/ζ 428 (M+l)+ ; 1 H NMR (300 MHz， CD3 OD) (5 2·62 (s，3Η)，3·33 (m，2Η)，3.70 (s，3Η), 3.98 (m，1Η)，4.32 (dd，J=10.51， 5.42 Hz，1H)，4.45 (dd，J=10.51，3·05 Hz，1H)，6.78 (dd，J=8.81，2.37 Hz，1H)，7·05 (d， J=2.03 Hz，1H)，7·21 (s，1H)，7·27 (d，J=8.81 Hz，1H)，7.60 (d，J=7.80 Hz，1H)，7.67 (dd，J=8.81，1.70 Hz，1H)，7.91 (m，1H)，8·03 (s，1H)，8.35 (d，J=2.03 Hz，1H)，8.65 (s， 1H).Example 401B bile) -1- (5-methylmonooxy) compound D-2- "5- (3-methyl-1Η-Θ1azole-5 · yl V pyridin-3-yl 1-λ 栌 200301122 (309) The desired product was made from trifluoroacetate by substituting Example 27B in Example 27C with Example 401A. MS (APCI) ιώ / ζ 428 (M + l) +; 1 H NMR (300 MHz, CD3 OD) (5 2.62 (s, 3Η), 3.33 (m, 2Η), 3.70 (s, 3Η), 3.98 (m, 1Η), 4.32 (dd, J = 10.51 , 5.42 Hz, 1H), 4.45 (dd, J = 10.51, 3.05 Hz, 1H), 6.78 (dd, J = 8.81, 2.37 Hz, 1H), 7.05 (d, J = 2.03 Hz, 1H) , 7.21 (s, 1H), 7.27 (d, J = 8.81 Hz, 1H), 7.60 (d, J = 7.80 Hz, 1H), 7.67 (dd, J = 8.81, 1.70 Hz, 1H), 7.91 (m, 1H), 8.03 (s, 1H), 8.35 (d, J = 2.03 Hz, 1H), 8.65 (s, 1H).

(1S)-H5-乙氣基-1H-吲哚-3-基甲基）-2-『5-(3-甲基-1H-蜊唑-5-基V吡咬-3-基乳基1-乙胺所要之產物係經由以乙醇取代實例401中之甲醇，以三氟醋酸鹽製成。MS(APCI)m/z442(M+l)+ ; hNMRpOOMHiCDsOD)(1S) -H5-Ethylamino-1H-indol-3-ylmethyl) -2- "5- (3-methyl-1H-lamazol-5-yl Vpyridin-3-yllactyl The desired product of 1-ethylamine was prepared from trifluoroacetate by replacing the methanol in Example 401 with ethanol. MS (APCI) m / z442 (M + 1) +; hNMRpOOMHiCDsOD)

δ 1.26 (t, J=6.95 Hz, 3H), 2.62 (s5 3H), 3.35 (m, 2H), 3.86 (q, J=7.12 Hz, 2H), 3.95 (m，1H)，4.32 (dd，JN10.51，5.42 Hz, 1H), 4.45 (dd，J=10.51，3.39 Hz，1H)，6.78 (dd， J=8.82, 2.37 Hz, 1H), 7.02 (d5 J=2.37 Hz, 1H), 7.21 (s3 1H), 7.26 (d, J=8.81 Hz, 1H), 7·61 (d，J=9.49 Hz，·1Η)，7.68 (d，J=8.81 Hz，1H)，7.97 (s，1H)，8·05 (s，1H)，8·37 (d， J=2.37 Hz, 1H), 8.68 (d, J=1.36 Hz, 1H)；對 C2 6H2 7N5 02 · 3·2 TFA 之分析計算值：C，48·26; H，3·77; Ν，8·68·實測值：C，48.14; Η，3·60; N，8.45. 實例403 (1SVH5-丁氧基-1H-啕哚-3-基甲基）-245-(3-甲基-1H-⑼唑-5-基V吡啶-3-基氣基1-乙胺所要之產物係經由以正-丁醇取代實例401中之甲醇，以三氟醋酸鹽製成。MS(APCI)m/z470(M+l)+ ; iHNMRpOOMHz， CD3 OD) δ 0.87 (t，J=7.36 Hz，3H)，L37 (m，2H)，1·59 (m，2H)，2·61 (s，3H)，3·29 -317- 200301122 (310) (m，2H)，3·81 (m，2H)，3·97 (s，1H)，4.35 (dd，J=10.13, 4.91 Hz，1H)，4.46 (d，J=7.98 Hz，1H)，6.76 (d，J=8.59 Hz，1H)，7.01 (s，1H)，7·21 (s，1H)，7.25 (d，J=8.59 Hz，1H)， 7.61 (d，J=8.59 Hz，1H)，7.68 (d，J=8.59 Hz，1H)，8.06 (s，2H)，8.38 (s，1H)，8.71 (s， 1H);對 C28H31N502 .2.8TFA 之分析計算值：C，51.16; Η，4·32; N，8.88. 實測值：C，51.36 ; Η，4·51; N，8.99· 實例404δ 1.26 (t, J = 6.95 Hz, 3H), 2.62 (s5 3H), 3.35 (m, 2H), 3.86 (q, J = 7.12 Hz, 2H), 3.95 (m, 1H), 4.32 (dd, JN10 .51, 5.42 Hz, 1H), 4.45 (dd, J = 10.51, 3.39 Hz, 1H), 6.78 (dd, J = 8.82, 2.37 Hz, 1H), 7.02 (d5 J = 2.37 Hz, 1H), 7.21 ( s3 1H), 7.26 (d, J = 8.81 Hz, 1H), 7.61 (d, J = 9.49 Hz, · 1Η), 7.68 (d, J = 8.81 Hz, 1H), 7.97 (s, 1H), 8 · 05 (s, 1H), 8.37 (d, J = 2.37 Hz, 1H), 8.68 (d, J = 1.36 Hz, 1H); Analysis and calculation of C2 6H2 7N5 02 · 3 · 2 TFA: C, 48 · 26; H, 3.77; Ν, 8.68 · Found: C, 48.14; Hf, 3.60; N, 8.45. Example 403 (1SVH5-butoxy-1H-pyridin-3 -Methyl) -245- (3-methyl-1H-oxazol-5-yl Vpyridin-3-ylamino 1-ethylamine The desired product is obtained by replacing the methanol in Example 401 with n-butanol , Made of trifluoroacetate. MS (APCI) m / z470 (M + 1) +; iHNMRpOOMHz, CD3 OD) δ 0.87 (t, J = 7.36 Hz, 3H), L37 (m, 2H), 1 · 59 (m, 2H), 2.61 (s, 3H), 3.29 -317- 200301122 (310) (m, 2H), 3.81 (m, 2H), 3.97 (s, 1H), 4.35 (dd, J = 10.13, 4.91 Hz, 1H), 4.46 (d, J = 7. 98 Hz, 1H), 6.76 (d, J = 8.59 Hz, 1H), 7.01 (s, 1H), 7.21 (s, 1H), 7.25 (d, J = 8.59 Hz, 1H), 7.61 (d, J = 8.59 Hz, 1H), 7.68 (d, J = 8.59 Hz, 1H), 8.06 (s, 2H), 8.38 (s, 1H), 8.71 (s, 1H); Analysis and calculation of C28H31N502 .2.8TFA : C, 51.16; Η, 4.32; N, 8.88. Found: C, 51.36; Η, 4.51; N, 8.99. Example 404

(lSVl-(5-異丙氧基-1H-吲哚-3-基甲基V2-「5-(3-甲基-1H-吲唑-5-基V(1SVl- (5-isopropoxy-1H-indol-3-ylmethyl V2- "5- (3-methyl-1H-indazol-5-yl V

口比淀-3-基氣基V乙胺所要之產物係經由以異丙醇取代實例401中之甲醇，以三氟醋酸鹽製成。MS (APCI) m/z 456 (M+l)+ ; 1 H NMR (400 MHz，CD3 OD) 5 1.18 (m，6H)，2.61 (s，3H)，3·30 (m，2H)，3·97 (s，1H)，4.38 (m，2H)，4.48 (d，J= 8.29 Hz, 1H), 6.77 (d, J=7.98 Hz, 1H), 7.07 (s, 1H), 7.23 (s, 1H), 7.26 (d, J=8.90 Hz, 1H)，7.61 (d，J二8.90 Hz，1H)，7·69 (d，JN8.59 Hz，1H)，8·08 (s，1H)，8.12 (s，1H)， 8.42 (s，1H)，8.74 (s，1H);對 C2 7 H2 9N5 02 · 3.2 TFA 之分析計算值：C， 48·90; H，3·96; N，8.54·實測值：C，48.93 ; H，3·88; Ν，8·55· 實例405The desired product was prepared by using isopropyl alcohol instead of the methanol in Example 401 and trifluoroacetate. MS (APCI) m / z 456 (M + l) +; 1 H NMR (400 MHz, CD3 OD) 5 1.18 (m, 6H), 2.61 (s, 3H), 3.30 (m, 2H), 3 · 97 (s, 1H), 4.38 (m, 2H), 4.48 (d, J = 8.29 Hz, 1H), 6.77 (d, J = 7.98 Hz, 1H), 7.07 (s, 1H), 7.23 (s, 1H), 7.26 (d, J = 8.90 Hz, 1H), 7.61 (d, J = 8.90 Hz, 1H), 7.69 (d, JN 8.59 Hz, 1H), 8.08 (s, 1H), 8.12 (s, 1H), 8.42 (s, 1H), 8.74 (s, 1H); Analytical calculations for C2 7 H2 9N5 02 · 3.2 TFA: C, 48 · 90; H, 3.96; N, 8.54 Measured value: C, 48.93; H, 3.88; Ν, 8.55. Example 405

3-(lH-g?| 嗓-3-基）-2-[5-(3-甲基嗅-5-基）-p比淀-3-基氧基 1-丙-1-醇3- (lH-g? | Homo-3-yl) -2- [5- (3-methylol-5-yl) -p ratio lake-3-yloxy 1-propan-1-ol

實例405A 2-(5->臭-外1：咬-3-基乳基）-3-(1Η·Ηΐ嘴-3-基）-丙酸曱酉旨於100毫升RBF中，裝填3-溴基-5-羥基吡啶（1.67克，9.58毫莫耳）’ 2-起基-3-(111-41嗓-3-基）-丙酸曱g旨（2.1克，9.58毫莫耳），其係根據文獻方法（Μ· Ε· Jung 等人，j. 〇rg. Chem. 1999, 64, 2976)合成而得，及Ph3P (3.01克，11·5毫莫耳），並以氮務氣。於〇°C 下添加THF (40毫升）。在0°C下檟:拌1〇分鐘後，經由注射器 -318- (311) 添加DEAD (1.81毫升，11.5毫莫耳）。將反應混合物於0°C下攪拌1小時，並在室温下過夜。使反應混合物濃縮，並藉急驟式層析（於己烷中之20·60% Et0Ac)分離殘留物，提供所要之產物（3.4 克，94% )。MS(DCI) m/z375,377 (M+l)+·Example 405A 2- (5- > Odor-external 1: bite-3-yllactyl) -3- (1Η · Η 嘴 -3-yl) -propionic acid was prepared in 100 ml of RBF, and filled with 3- Bromo-5-hydroxypyridine (1.67 g, 9.58 mmol)-2-methyl-3- (111-41 carb-3-yl) -propionate g (2.1 g, 9.58 mmol), It was synthesized according to literature methods (M.E. Jung et al., J. Org. Chem. 1999, 64, 2976), and Ph3P (3.01 g, 11.5 mmol) with nitrogen gas . THF (40 mL) was added at 0 ° C. At 0 ° C: After mixing for 10 minutes, DEAD (1.81 ml, 11.5 mmol) was added via syringe -318- (311). The reaction mixture was stirred at 0 ° C for 1 hour and overnight at room temperature. The reaction mixture was concentrated and the residue was separated by flash chromatography (20.60% EtoAc in hexane) to provide the desired product (3.4 g, 94%). MS (DCI) m / z375,377 (M + l) + ·

實例405B 2-(5-溴-ρ比症-3-基氧基V3-(lH-4丨味-3-基）-丙-1-醇在室溫下，於實例405A (3.2克，8.5毫莫耳）在THF (20毫升）與醚（30毫升）中之溶液内，慢慢以數份添加LiAlH4粉末（323 毫克，8.5毫莫耳）。當添加LAH時，大量固體物質自溶液沉澱，且溫度上升至約40°C。慢慢添加水（2毫升）與稀HC1 ，並將混合物以NaHC03中和，且以醋酸乙酯萃取。將有機相以水洗滌，及濃縮。藉急驟式層析（於己烷中之20-80% EtOAc) 分離殘留物，而得所要之產物（1.24克，42% )。MS (DCI) m/z 347， 349 (M+l)+.Example 405B 2- (5-Bromo-rhobiazyl-3-yloxy V3- (lH-4 丨 taste-3-yl) -propan-1-ol at room temperature in Example 405A (3.2 g, 8.5 LiAlH4 powder (323 mg, 8.5 mmol) was slowly added in several portions to a solution in THF (20 ml) and ether (30 ml). When LAH was added, a large amount of solid matter precipitated from the solution And the temperature rose to about 40 ° C. Water (2 ml) and dilute HC1 were slowly added, and the mixture was neutralized with NaHC03 and extracted with ethyl acetate. The organic phase was washed with water and concentrated. By flash Chromatography (20-80% EtOAc in hexanes) separated the residue to give the desired product (1.24 g, 42%). MS (DCI) m / z 347, 349 (M + 1) +.

實例405C 5-{5-「l-羥甲基-2-(1Η-吲哚-3-基V乙氣某1-吡啶各基丨各甲基唑- 1-羧酸第三-丁酯於50毫升RBF中，裝填實例405Β (580毫克，1.67毫莫耳）、實例 203Β(660 毫克，1·67 毫莫耳）、pd2(dba)3(153 毫克，0.167 毫莫耳）及三-鄰-曱苯基膦（153毫克），並以n2滌氣。經由注射器添加無水DMF (22毫升）與Et3N (0.698毫升）。將此溶液以N2 再滌氣一次’並在70°C下加熱15小時。於冷卻後，添加醋酸乙醋（100毫升）。將混合物以鹽水（1〇〇毫升）及水（100毫升）洗滌。使醋酸乙酯溶液濃縮，並藉急驟式層析（於2 : 1 EtOAc (312)Example 405C 5- {5-``l-Hydroxymethyl-2- (1'-indol-3-yl V ethyl gas, 1-pyridine groups, each methylazole- 1-carboxylic acid tert-butyl ester in In 50 ml of RBF, fill with Example 405B (580 mg, 1.67 mmol), Example 203B (660 mg, 1.67 mmol), pd2 (dba) 3 (153 mg, 0.167 mmol) and tri-neighbor -Phenylphosphine (153 mg) and scrubbing with n2. Anhydrous DMF (22 ml) and Et3N (0.698 ml) were added via syringe. This solution was purged with N2 again and heated at 70 ° C for 15 Hours. After cooling, ethyl acetate (100 mL) was added. The mixture was washed with brine (100 mL) and water (100 mL). The ethyl acetate solution was concentrated and subjected to flash chromatography (2: 1 EtOAc (312)

/己烷中之〇-15% CH2 OH)分離殘留油’而得所要之產物（656 毫克，79% )。MS(APCI)m/z499(M+l)+·(0-15% CH2OH in hexanes) to separate the residual oil 'to obtain the desired product (656 mg, 79%). MS (APCI) m / z499 (M + l) + ·

實例405D 3-(lH-Hl 嗓-3-基）-2-[5-(3-甲基-ΙΗ-βΙ 峻-5-基比咬-3-基氧基 1-丙-1-醇所要之產物係經由以實例4〇5C取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 399 (M+l)+ ; 1 H NMR (400 MHz， CD3 OD) δ 2.56 (s, 3H), 3.09 (dd, J=14.73, 8.90 Hz, 1H), 3.19 (dd5 J=15.04, 3.99 Hz, 1H)，3.85 (dd，J=12.12, 6·60 Hz，1H)，3.92 (m，1H)，4.99 (m，1H)，6.97 (dd，J=6.14， 3.07 Hz，2H)，7.07 (s，1H)，7.16 (m，1H)，7·25 (dd，J=8.75, 1·38 Hz，1H)，7.49 (d，J= 8·90 Hz，1H)，7.57 (dd，J=6.14, 2·76 Hz，1H)，7.84 (d，J=10.43 Hz，2H)，8·14 (s，1H)， 8.38(s，lH);對 C24H22N402 .UTFA 之分析計算值：C，55.56; Η，4·03 ;N，9.46.實測值：C，55.69 ; H，4·02 ; N，9.58. 實例406 3-(lH-^[哚-3-基）-245-(3-甲基-1H-W唑-5-基V吡啶-3-基氧基1-丙胺Example 405D 3- (lH-Hl-3-yl) -2- [5- (3-methyl-lΗ-βl) Jun-5-yl is more desirable than 3-methyloxyl-propan-1-ol The product was made from trifluoroacetate by replacing Example 27B in Example 27C with Example 40C. MS (APCI) m / z 399 (M + 1) +; 1 H NMR (400 MHz, CD3 OD) δ 2.56 (s, 3H), 3.09 (dd, J = 14.73, 8.90 Hz, 1H), 3.19 (dd5 J = 15.04, 3.99 Hz, 1H), 3.85 (dd, J = 12.12, 6.60 Hz, 1H) , 3.92 (m, 1H), 4.99 (m, 1H), 6.97 (dd, J = 6.14, 3.07 Hz, 2H), 7.07 (s, 1H), 7.16 (m, 1H), 7.25 (dd, J = 8.75, 1.38 Hz, 1H), 7.49 (d, J = 8.90 Hz, 1H), 7.57 (dd, J = 6.14, 2.76 Hz, 1H), 7.84 (d, J = 10.43 Hz, 2H), 8.14 (s, 1H), 8.38 (s, lH); Analytical calculated value for C24H22N402.UTFA: C, 55.56; Η, 4.03; N, 9.46. Found: C, 55.69; H , 4.02; N, 9.58. Example 406 3- (lH-^ [indol-3-yl) -245- (3-methyl-1H-Wazole-5-yl Vpyridin-3-yloxy 1 -Propylamine

實例406A 疊氮基甲基-2-(lH^l哚-3-基V乙氣基1-吡啶-3-基}-3-甲基-吲唑-l-藉酸第三-丁酯於50毫升RBF中，裝填實例405C (580毫克，1.16毫莫耳）與 Pl^P (456毫克，1.74毫莫耳），並以氮滌氣。於〇。〇下添加THF (14 毫升），接著添加DPPA (375微升，1.74毫莫耳）。在〇°C下攪拌 1分鐘後，經由注射器添加DEAD (274微升1.74毫莫耳）。將反應混合物於〇°C下攪拌〇·5小時，並在室溫下過夜。使反應混合物濃縮，並藉急騾式層析（於己燒中之20-80% EtOAc)分離殘留物，提供所要之產物（534毫克，87% )。MS (APCI) m/z 524 -320- (313) (M+l)'Example 406A Azidomethyl-2- (lH ^ l indol-3-yl V ethylamino 1-pyridin-3-yl) -3-methyl-indazole-l-boronic acid tert-butyl ester In 50 ml of RBF, Example 405C (580 mg, 1.16 mmol) and Pl ^ P (456 mg, 1.74 mmol) were charged and purged with nitrogen. THF (14 ml) was added at 0.0%, then Add DPPA (375 μl, 1.74 mmol). After stirring at 0 ° C for 1 minute, add DEAD (274 μl 1.74 mmol) via syringe. Stir the reaction mixture at 0.5 ° C for 0.5 hour And overnight at room temperature. The reaction mixture was concentrated and the residue was separated by flash chromatography (20-80% EtOAc in hexane) to provide the desired product (534 mg, 87%). MS ( APCI) m / z 524 -320- (313) (M + l) '

實例406B 5-{5-fl-胺基甲基丨嗓-3-基）-乙氣某1-p比淀-3-基丨-3-甲基峻-1-#酸第三-丁酯在氮氣下，於實例406A (480毫克）在乙醇中之溶液内，添加10% Pd/C (160毫克）。將此懸浮液以氫滌氣（3次），並於氫（氣瓶）下攪拌4小時。將固體物質濾出，並使濾液濃縮，而得所要之產物（443 毫克，97% )。MS (APCI) ιώ/ζ 498 (M+l)+.Example 406B 5- {5-fl-Aminomethyl-1-Hy-3-yl) -ethyl To a solution of Example 406A (480 mg) in ethanol under nitrogen was added 10% Pd / C (160 mg). The suspension was purged with hydrogen (3 times) and stirred under hydrogen (gas cylinder) for 4 hours. The solid material was filtered off, and the filtrate was concentrated to obtain the desired product (443 mg, 97%). MS (APCI) ιώ / ζ 498 (M + l) +.

實例406C 3-(1Η-吲哚-3-基）-245-(3-甲基-1H-吲唑-5-某V毗啶-3-基氧基1-丙胺所要之產物係經由以實例406B取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 398 (M+l)+ ; 1H NMR (300 MHz， CD3 OD) 5 2.62 (s5 3H), 3.29 (m, 2H), 3.40 (dd5 J=13.56, 9.15 Hz, 1H), 3.53 (dd, J= 13.90, 2·71 Hz，1H)，5.32 (m，1H)，7.03 (m，2H)，7·14 (s，1H)，7.20 (dd，J=6.27, 2·54 Hz, 1H), 7.28 (dd, J=8.81, 1.70 Hz, 1H), 7.55 (d, J=8.48 Hz, 1H), 7.59 (dd, J=6.10, 2·37 Hz，1H)，7.80 (s，1H)，7.85 (s，1H)，8.22 (d，J=2.37 Hz，1H)，8·47 (s，1H); 對匸241123^〇*3.3丁?八之分析計算值：€：，47.50;11，3.43;凡9.05· 實測值：C，47.41 ; H，3.71; N，9.11. 實例407 茬-2-磺酸（2-胺基-乙基M5-(3-甲基-1H-吲唑：基V吡嘧-3-某1-醯胺Example 406C 3- (1H-indol-3-yl) -245- (3-methyl-1H-indazole-5-a certain pyridin-3-yloxy 1-propylamine 406B replaces Example 27B in Example 27C and is made of trifluoroacetate. MS (APCI) m / z 398 (M + 1) +; 1H NMR (300 MHz, CD3 OD) 5 2.62 (s5 3H), 3.29 ( m, 2H), 3.40 (dd5 J = 13.56, 9.15 Hz, 1H), 3.53 (dd, J = 13.90, 2.71 Hz, 1H), 5.32 (m, 1H), 7.03 (m, 2H), 7 · 14 (s, 1H), 7.20 (dd, J = 6.27, 2.554 Hz, 1H), 7.28 (dd, J = 8.81, 1.70 Hz, 1H), 7.55 (d, J = 8.48 Hz, 1H), 7.59 (dd, J = 6.10, 2.37 Hz, 1H), 7.80 (s, 1H), 7.85 (s, 1H), 8.22 (d, J = 2.37 Hz, 1H), 8.47 (s, 1H); Analytical calculations for 匸 241123 ^ 〇 * 3.3 丁? 8: €: 47.50; 11, 3.43; Where 9.05. Found: C, 47.41; H, 3.71; N, 9.11. Example 407 Stub-2-sulfonic acid (2-Amino-ethyl M5- (3-methyl-1H-indazol: yl V-pyrimidin-3-some 1-fluorenamine

實例407A 臭-τ7比淀-3-基）-(奈-2-橫酸基）-胺基V乙基丨-胺甲基酸第三- 丁酯在室溫下，於實例386Α (50毫克，0.158毫莫耳）在吡啶（2毫 ^ w U. (314) 升）中《落液内，添加氯化莕磺醯（72毫克，〇·316毫莫耳）。於1：溫下將所形成之黃色溶液攪拌15小時。經由以氮起泡’移除ρ比呢’並使殘留黃色固體藉急驟式層析（於己烷中之30-60% EtOAc)純化成所要之產物（81毫克，1〇〇% )。MS (DCI) m/z 506, 508 (M+l)+ ·Example 407A odorant-τ7-Hydroxy-3-yl)-(naphthalene-2-transacid) -amino Vethyl 丨 -aminomethyl acid tert-butyl ester at room temperature in Example 386A (50 mg (0.158 mmol) in pyridine (2 mmol ^ U. (314) liters) "Into the liquid, sulfonium sulfonium chloride (72 mg, 0.316 mmol) was added. The yellow solution formed was stirred at 1:15 for 15 hours. The desired product (81 mg, 100%) was purified by bubbling with nitrogen 'removing the pbyline' and residing the remaining yellow solid by flash chromatography (30-60% EtOAc in hexanes). MS (DCI) m / z 506, 508 (M + l) +

實例407BExample 407B

甲基-1H-W峻全基吡啶·3·基_2·讀醯基胺基乙某 Ιιϋ-i基酸第三-丁酯Methyl-1H-W allylpyridine · 3 · yl_2 · reading aminoamino ethyl Ιια-i-acid tert-butyl ester

於25毫升RBF中，裝填實例4〇7A(78毫克，0154毫莫耳）、實例2〇3B(45毫克，〇·ΐ54毫莫耳）、哗⑽咖^4毫克，0 0154毫莫耳）及三-鄰-甲苯基膦（14毫克），並以n2滌氣。經由注射器添加無水DMF (4毫升）與Et3N (64微升）。將此溶液以N2再滌氣一次，並在70°C下加熱15小時。於冷卻後，添加醋酸乙酯（50毫升）。將混合物以鹽水（5〇毫升）及水（50毫升）洗滌。使醋酸乙酯溶液濃縮，並藉急驟式層析（A : 2 : 1 EtOAc / 己烷，0-15% CH3OH/A)分離殘留油，而得所要之產物（54毫克，63%)。MS(APCI)m/z 558 (M+l)+·In 25 ml of RBF, Example 407A (78 mg, 0154 mmol) was charged, Example 203B (45 mg, 0.45 mmol), and Café ^ 4 mg, 0 0154 mmol. And tri-o-tolylphosphine (14 mg), and purged with n2. Anhydrous DMF (4 mL) and Et3N (64 μl) were added via a syringe. This solution was re-gased with N2 and heated at 70 ° C for 15 hours. After cooling, ethyl acetate (50 ml) was added. The mixture was washed with brine (50 ml) and water (50 ml). The ethyl acetate solution was concentrated and the residual oil was separated by flash chromatography (A: 2: 1 EtOAc / hexane, 0-15% CH3OH / A) to give the desired product (54 mg, 63%). MS (APCI) m / z 558 (M + l) + ·

實例407C 茗-2-磺酸（2-胺基-乙基M5-(3-甲基-1H-吲唑-5-基吡啶-3-基1-醯胺所要之產物係經由以實例407B取代實例27C中之實例27B ，以三氟醋酸鹽製成。MS (APCI) m/z 458 (M+l)+ ; 1H NMR (300 MHz， CD3 0D) δ 2.50 (s，3H)，3.14 (t，J=5.59 Hz，2H)，4·06 (t，J=5.59 Hz，2H)，7·48 (m， 2H)，7.66 (m，2H)，7·74 (d，J=8.14 Hz，1H)，7·77 (d，J=8.14 Hz，1H)，7.80 (t，J=2.03 Hz, 1H), 8.02 (d, J=8.14 Hz, 1H), 8.06 (d, J=8.48 Hz, 1H), 8.14 (d, J=8.48 Hz, 1H), -322- 200301 (315) 8·28 (s，1H)，8·47 (d，J=2.37 Hz，1H)，8.92 (d，J=1.70 Hz，1H);對 C2 5 H2 3 N5 02 S • 3.3TFA 之分析計算值：C，45.52 ; H，3.18 ; N，8.40·實測值：C，45.42 ;H，3·13; N，8.43. 實例408 聯茉某-4-磺酸（2-胺基-乙基M5-(3-甲基-1H-吲唑-5-基V吡啶-3：^^ 醯胺Example 407C fluorene-2-sulfonic acid (2-amino-ethyl M5- (3-methyl-1H-indazol-5-ylpyridin-3-yl1-fluorenylamine) The desired product was substituted by Example 407B Example 27B in Example 27C, made from trifluoroacetate. MS (APCI) m / z 458 (M + 1) +; 1H NMR (300 MHz, CD3 0D) δ 2.50 (s, 3H), 3.14 (t , J = 5.59 Hz, 2H), 4.06 (t, J = 5.59 Hz, 2H), 7.48 (m, 2H), 7.66 (m, 2H), 7.74 (d, J = 8.14 Hz, 1H), 7.77 (d, J = 8.14 Hz, 1H), 7.80 (t, J = 2.03 Hz, 1H), 8.02 (d, J = 8.14 Hz, 1H), 8.06 (d, J = 8.48 Hz, 1H), 8.14 (d, J = 8.48 Hz, 1H), -322- 200301 (315) 8 · 28 (s, 1H), 8.47 (d, J = 2.37 Hz, 1H), 8.92 (d, J = 1.70 Hz, 1H); Analytical calculated value for C2 5 H2 3 N5 02 S • 3.3TFA: C, 45.52; H, 3.18; N, 8.40 · Measured value: C, 45.42; H, 3.13; N, 8.43. Example 408 Diazine-4-sulfonic acid (2-amino-ethyl M5- (3-methyl-1H-indazol-5-yl Vpyridine-3: ^ amine)

所要之產物係經由以氯化4-聯苯基磺醯取代實例407中之氯化2-莕磺醯，以三氟醋酸鹽製成。MS (APCI) m/z484 (M+l)+ ; 1 H NMR (300 MHz, DMSO-d6) δ 2.42 (s，3H)，2.96 (m，2H)，3.95 (m，2H)，7·54 (m，4H)，7.69 (d，J=8.48 Hz，2H)，7.77 (d，JN7.12 Hz，2H)，7.95 (m，5H)，8·45 (s，1H)， 8.98 (s，1H);對 C2 7 H2 5 N5 02 S · 1.3TFA 之分析計算值：C，56.27; H，4.20 ;N，11.08.實測值：C，56.00 ; H，4.21 ; N，10.87. 實例409 5-{5-「(2S)-2-胺基-3-ΠΗ-吲哚-3-基V丙氣基1-吡啶-3-基}-3-亞異丙某-1，3-二氫^?1哚-2-酮The desired product was prepared by substituting 4-biphenylsulfonium chloride for 2-sulfonium chloride in Example 407 and trifluoroacetate. MS (APCI) m / z484 (M + l) +; 1 H NMR (300 MHz, DMSO-d6) δ 2.42 (s, 3H), 2.96 (m, 2H), 3.95 (m, 2H), 7.54 (m, 4H), 7.69 (d, J = 8.48 Hz, 2H), 7.77 (d, JN7.12 Hz, 2H), 7.95 (m, 5H), 8.45 (s, 1H), 8.98 (s, 1H); Analytical calculation for C2 7 H2 5 N5 02 S · 1.3TFA: C, 56.27; H, 4.20; N, 11.08. Found: C, 56.00; H, 4.21; N, 10.87. Example 409 5- {5-"(2S) -2-Amino-3-ΠΗ-indole-3-yl V-propanyl 1-pyridin-3-yl} -3-isopropylidene-1,3-dihydro ^ ? 1 indol-2-one

所要之化合物係經由以5-溴基各亞異丙基-1，3-二氫哚-2-酮（L· Sun 等人，J· Med· Chem·，1998, 41，2588)，取代實例 32 中之 6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。1HNMR(400MHz， CD3 OD) δ ppm 2.47 (s, 3H), 2.60 (s, 3H), 3.31 (m, 2H), 4.01 (m, 1H)5 4.34 (dd, J= 10.43, 5.83 Hz, 1H), 4.47 (dd, J=10.43, 3.38 Hz, 1H), 7.01 (t, J=7.06 Hz, 1H), 7.04 (d, J=7.98 Hz, 1H), 7.12 (t5 J=7.06 Hz, 1H), 7.24 (s, 1H), 7.38 (d, J=8.29 Hz, 1H), 7.50 (dd, J=7.98, 1.84 Hz5 1H), 7.58 (d, J=7.98 Hz, 1H), 7.79 (d? J=1.53 Hz, 1H), 7.97 (d, >1.84沿，111)，8.37(5，1印，8.63(5，111);對（：271126^02之分析計算值 :C，52.14 ; H，3.88; N，7.51.實測值·· C，52.19 ; H，3·67; N，7.42. -323 - (316) 實例4ί〇 5-{5-『(2SV2-胺基-3-ΠΗ-啕哚-3-某V丙氧基1-吡啶-3-某丨-3-(1Η-咪唑冬基亞甲基）-1，3-二乳-ρ?|嗓-2-酉同所要之化合物係經由以5-溴基-3-(1Η-咪唑-2-基亞甲基）-1，3-二氫-41 哚-2-酮（L· Sun 等人，J· Med. Chem.，1998, 41，2588.)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (DCI/NH3) m/z 477 (M+l)+; 1H NMR (500 MHz，CD3 OD) (5 ppm 3·31 (m，2H)，4·04 (m，1H)， 4.37 (dd，J=10.45, 5.77 Hz，1H)，4·50 (dd，J=10.29, 3.12 Hz，1H)，7·02 (t，J=7.49 Hz， 1H), 7.11 (d, J=7.49 Hz, 1H), 7.13 (m, 1H), 7.25 (s, 1H), 7.38 (d, J=8.11 Hz, 1H), 7.60 (d，J=7.80 Hz，1H)，7.72 (d，J=8.11 Hz，1H)，7.77 (s，2H)，7·85 (s，1H)，8.02 (s， 1H)，8.13 (s，1H)，8·42 (s，1H)，8.67 (s，1H). 實例411 5-{5-『2-胺基吲哚-3-基）-丙氧基1-吡啶-3-某P3-吡啶-2-基亞甲基-1,3-二氫哚-2-酮所要之化合物係經由以5-溴基各吡啶-2-基亞甲基-1，3-二氫-㈣哚-2-酮（L· Sun 等人，J· Med· Chem·，1998, 41，2588·)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (DCI/NH3) m/z 488 (M+l)+; 1H NMR (500 MHz, CD3 OD) (5 ppm 3·32 (m，2H)，4.02 (m，1H)， 4·34 (dd，J=10.61，5·62 Hz，1H)，4.47 (dd，J=10.45, 3·28 Hz，1H)，7.03 (t，J=7.02 Hz， 1H)，7.13 (m，1H)，7·19 (d，J=8.11 Hz，1H)，7·25 (s，1H)，7.38 (d，J=8.42 Hz，1H)， 7.60 (d，J=7.80 Hz，1H)，7.76 (dd，J=8.11，1.87 Hz，1H)，7·94 (dd，J=2.50, 1.87 Hz， 1H)，8.14 (m，1H)，8.17 (s，1H)，8.26 (d，J=1.56 Hz，1H)，8.38 (d，J=7.80 Hz，1H)， 8.41 (s，1H)，8.66 (s，1H)，8.72 (m，1H)，9.08 (dd，J=5.62, 1·56 Hz，1H); 對 C3〇H25N502之分析計算值：C，47.41 ; H，3,02 ; Ν，7·16.實測值 0301122 (317) ：C, 47.40 ； H, 2.93 ； N, 6.98. 實例412 5-{5-f(2S)-2-胺基-3-(lH-沔丨哚-3-基丙氧基1-吡畦-3-某}-3-呋喃-2-基亞甲基-U-二氫-啕哚-2-酮所要之化合物係經由以5-溴基-3-呋喃-2-基亞甲基-1，3-二氫-吲哚-2-酮（L. Sun 等人，J· Med· Chem·，1998, 41，2588)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (DCI/NH3) m/z 477 (M+l)+; 1 H NMR (500 MHz，CD3 OD) 5 ppm 3.34 (m，4H)，4·06 (m，2H)， 4.37 (dd，JN10.45, 5.77 Hz，2H)，4.51 (dd，J=10.45, 3·28 Hz，·2Η)，6.68 (dd，J=3.28， 1.40 Hz, 1H), 6.72 (dd, J=3.59, 1.72 Hz, 1H), 7.02 (t5 J=7.64 Hz, 2H)? 7.05 (d, J=8.11 Hz，2H)，7·12 (m，3H)，7.26 (s，1H)，7.27 (s，1H)，7.38 (d，J=8.11 Hz，2H)，7.43 (s， 1H), 7.55 (d, J=1.87 Hz, 1H), 7.58 (dd, J=8.11, 1.87 Hz, 1H), 7.61 (d, J=7.80 Hz, 2H), 7.73 (s，1H)，7.77 (d，J=1 ·56 Hz，1H)，7.85 (d，J=1 ·87 Hz，1H)，7.97 (d，J=1.56 Hz，1H )，8·06 (d，J=4.37 Hz，1H)，8.15 (d，J=1.87 Hz，1H)，8.30 (d，J=3.43 Hz，1H)，8.44 (m， 2H)，8.69(s，lH).8.73(d，J=1.87Hz，2H);對 C29H24N403之分析計算值 :C，50.33 ; H，3.24; Ν，6·61·實測值：C，50.30; Η，3·12; N，6.65. 實例413 5-{5-f(2SV2-胺基-3-(1Η-吲哚-3-基）-丙氧基1-吡啶各基丨-3-(5-甲基-呋喃-2·基亞甲基1,3-二乳弓1嗓-2-嗣所要之化合物係經由以5-溴基-3-(5-甲基-呋喃-2-基亞甲基）-1，3-二氫-啕哚-2-酮（1^.51111等人，】.1^丄0^111.，1998,41，2588)，取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。 MS(DCI/NH3)m/z477(M+l)+ ； 1 H NMR (500 MHz, CD3 OD) 6 ppm 2.41 (s, 3H)，3.32 (m，2H)，（4.02 (m，1H)，4·31 (dd，J=10.45, 5·77 Hz，1H)，4·45 (dd，J=10.45, -325 - 200301122The desired compound is substituted by 5-bromoisopropylidene-1,3-dihydroindol-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588) 6-bromophthalimide of 32 is made of trifluoroacetate. 1HNMR (400MHz, CD3 OD) δ ppm 2.47 (s, 3H), 2.60 (s, 3H), 3.31 (m, 2H), 4.01 (m, 1H) 5 4.34 (dd, J = 10.43, 5.83 Hz, 1H) , 4.47 (dd, J = 10.43, 3.38 Hz, 1H), 7.01 (t, J = 7.06 Hz, 1H), 7.04 (d, J = 7.98 Hz, 1H), 7.12 (t5 J = 7.06 Hz, 1H), 7.24 (s, 1H), 7.38 (d, J = 8.29 Hz, 1H), 7.50 (dd, J = 7.98, 1.84 Hz5 1H), 7.58 (d, J = 7.98 Hz, 1H), 7.79 (d? J = 1.53 Hz, 1H), 7.97 (d, > 1.84 edge, 111), 8.37 (5, 1 mark, 8.63 (5, 111); Analytical calculation for (: 271126 ^ 02: C, 52.14; H, 3.88 N, 7.51. Measured value · C, 52.19; H, 3.67; N, 7.42. -323-(316) Example 4 ί〇5- {5-『(2SV2-Amino-3-ΠΗ-fluorene) -3-A certain V propoxyl 1-pyridine-3- Some 丨 -3- (1Η-imidazolylmethylene) -1,3-dilactate-ρ? | Via 5-bromo-3- (1'-imidazol-2-ylmethylene) -1,3-dihydro-41 indol-2-one (L. Sun et al., J. Med. Chem., 1998 , 41, 2588.), instead of 6-bromophthalimide in Example 32, made of trifluoroacetate. MS (DCI / NH3) m / z 477 (M + l) +; 1H NMR (500 MHz, CD3 OD) (5 ppm 3.31 (m, 2H), 4 · 04 (m, 1H), 4.37 (dd, J = 10.45, 5.77 Hz, 1H), 4.50 (dd, J = 10.29, 3.12 Hz, 1H), 7.02 (t, J = 7.49 Hz, 1H) , 7.11 (d, J = 7.49 Hz, 1H), 7.13 (m, 1H), 7.25 (s, 1H), 7.38 (d, J = 8.11 Hz, 1H), 7.60 (d, J = 7.80 Hz, 1H) , 7.72 (d, J = 8.11 Hz, 1H), 7.77 (s, 2H), 7.85 (s, 1H), 8.02 (s, 1H), 8.13 (s, 1H), 8.42 (s, 1H ), 8.67 (s, 1H). Example 411 5- {5- [2-Aminoindole-3-yl) -propoxy1-pyridine-3-P3-pyridin-2-ylmethylene- The desired compound for 1,3-dihydroindole-2-one is via 5-bromopyridin-2-ylmethylene-1,3-dihydro-pyridin-2-one (L. Sun et al. , J. Med. Chem., 1998, 41, 2588.), instead of 6-bromophthalimide in Example 32, made of trifluoroacetate. MS (DCI / NH3) m / z 488 (M + l) +; 1H NMR (500 MHz, CD3 OD) (5 ppm 3.32 (m, 2H), 4.02 (m, 1H), 4.34 (dd , J = 10.61, 5.62 Hz, 1H), 4.47 (dd, J = 10.45, 3.28 Hz, 1H), 7.03 (t, J = 7.02 Hz, 1H), 7.13 (m, 1H), 7 · 19 (d, J = 8.11 Hz, 1H), 7.25 (s, 1H), 7.38 (d, J = 8.42 Hz, 1H), 7.60 (d, J = 7.80 Hz, 1H), 7.76 (dd, J = 8.11, 1.87 Hz, 1H), 7.94 (dd, J = 2.50, 1.87 Hz, 1H), 8.14 (m, 1H), 8.17 (s, 1H), 8.26 (d, J = 1.56 Hz, 1H) , 8.38 (d, J = 7.80 Hz, 1H), 8.41 (s, 1H), 8.66 (s, 1H), 8.72 (m, 1H), 9.08 (dd, J = 5.62, 1.56 Hz, 1H); Analytical calculated values for C3OH25N502: C, 47.41; H, 3, 02; N, 7.16. Found 0301122 (317): C, 47.40; H, 2.93; N, 6.98. Example 412 5- {5 -f (2S) -2-amino-3- (lH- 沔丨 indol-3-ylpropoxy 1-pyridin-3-some} -3-furan-2-ylmethylene-U-di The desired compound for hydrogen-oxolin-2-one is via 5-bromo-3-furan-2-ylmethylene-1,3-dihydro-indole-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing the 6-bromo group in Example 32 Dimethyimine, made from trifluoroacetate. MS (DCI / NH3) m / z 477 (M + l) +; 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.34 (m, 4H), 4 · 06 (m, 2H), 4.37 (dd, JN10.45, 5.77 Hz, 2H), 4.51 (dd, J = 10.45, 3.28 Hz, · 2Η), 6.68 (dd, J = 3.28, 1.40 Hz , 1H), 6.72 (dd, J = 3.59, 1.72 Hz, 1H), 7.02 (t5 J = 7.64 Hz, 2H)? 7.05 (d, J = 8.11 Hz, 2H), 7.12 (m, 3H), 7.26 (s, 1H), 7.27 (s, 1H), 7.38 (d, J = 8.11 Hz, 2H), 7.43 (s, 1H), 7.55 (d, J = 1.87 Hz, 1H), 7.58 (dd, J = 8.11, 1.87 Hz, 1H), 7.61 (d, J = 7.80 Hz, 2H), 7.73 (s, 1H), 7.77 (d, J = 1 · 56 Hz, 1H), 7.85 (d, J = 1 · 87 Hz, 1H), 7.97 (d, J = 1.56 Hz, 1H), 8.06 (d, J = 4.37 Hz, 1H), 8.15 (d, J = 1.87 Hz, 1H), 8.30 (d, J = 3.43 Hz, 1H), 8.44 (m, 2H), 8.69 (s, 1H). 8.73 (d, J = 1.87Hz, 2H); Analytical calculated value for C29H24N403: C, 50.33; H, 3.24; Ν, 6 · 61 · Found: C, 50.30; Hf, 3.12; N, 6.65. Example 413 5- {5-f (2SV2-amino-3- (1H-indol-3-yl) -propoxy 1-pyridine groups-3--3- (5-methyl-furan-2-ylmethylene 1,3-dilactate The desired compound is obtained via 5-bromo-3- (5-methyl-furan-2-ylmethylene) -1,3-dihydro-oxolin-2-one (1 ^. 51111 et al., 1 ^ 丄 0 ^ 111., 1998, 41, 2588), instead of 6-bromophthalimide in Example 32, and made of trifluoroacetate. MS (DCI / NH3) m / z477 (M + 1) +; 1 H NMR (500 MHz, CD3 OD) 6 ppm 2.41 (s, 3H), 3.32 (m, 2H), (4.02 (m, 1H), 4 · 31 (dd, J = 10.45, 5.77 Hz, 1H), 4 · 45 (dd, J = 10.45, -325-200301122

MWBSffiWMIWWBWKBtSI (318) 3·28 Hz，1H)，6·38 (dd，J=3.43, 0·94 Hz，1H)，7:03 (m，3H)，7·12 (t，J=7.18 Hz，1H)， 7·24 (s，1H)，7.37 (s，1H)，7.38 (d，J=8.11 Hz，1H)，7.54 (dd，J=8.11，1·87 Hz，1H)， 7.60 (d，J=8.11 Hz，1H)，7.90 (dd，J=2.50, 1·87 Hz，1H)，8·38 (s，1H)，8.64 (s，1H)， 8.73(s，lH);對 C30H26N4O3之分析計算值：C，49.59; Η，3·31; Ν，6·22· 實測值：C，4990 ; Η，3·18 ; Ν，6.10· 實例414 5-{5-『(28)-2-胺基-3-(111-吲哚-3-基）-丙氣基1-吡啶-3-基}-3-(4,5-二甲基-口夫喃-2-基亞甲基）-1,3-二氮-口弓1嗓-2-酉同所要之化合物係經由以5-溴基各(4,5-二甲基-呋喃-2-基亞甲基）-1，3-二氫丨哚-2-酮（L· Sun 等人，J· Med· Chem·，1998, 41, 2588)，取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS(DCI/NH3)m/z 505 (M+l)+ ; 1 H NMR (500 MHz, CD3 OD) δ ppm 1.99 (s，3H)，2.27 (s，3H)，3·34 (m，2H)，4·06 (m，1H)，4.37 (dd，J=10.45, 5.77 Hz，1H)， 4·51 (dd，J=10.45, 3·28 Hz，1H)，6.82 (s，1H)，6.99 (d，J=8.42 Hz，1H)，7·03 (t，J= 7.02 Hz, 1H), 7.13 (t, J=7.02 Hz, 1H), 7.21 (s, 1H), 7.27 (s, 1H), 7.39 (d5 J=8.11 Hz, 1H)，7.52 (dd，J=8.11，L87 Hz，1H)，7.61 (d，J=8.11 Hz，1H)，8.05 (s，1H)，8·45 (s， 1H)，8·62 (d，J=l_56 Hz，1H)，8.66 (s，1H);對 C3 丨 H2 8 N4 03 之分析計算值： C，52.92 ; Η，3·73; Ν，6·71·實測值：C，52.90 ; Η，3·45; Ν，6·97· 實例415 5-{5-〖(2S)-2-胺基-3-(1Η-啕哚各基V丙氧基V吡啶-3-基卜3-ρ塞吩-2-基亞甲基·1，3_二乳-口弓1 口呆-2-酉同所要之化合物係經由以5-溴基-3-嘍吩-2-基亞甲基-1，3-二氫-吲哚-2-酮（L· Sun 等人，J· Med· Chem·，1998, 41，2588)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z -326- (319) 493 (M+1)+ ； 1HNMR(500MHz，CD3OD) 5 ppm3.32(m，4H)，4.03(m，2H)， 4.30 (dd，J=10.45, 5·77 Hz，1H)，4.35 (dd，J=10.61，5·93 Hz，1H)，4·44 (dd，J=10.29， 3.12 Hz，1H)，4.48 (dd，J=10.61，3.12 Hz，1H)，7·02 (m，2H)，7.04 (s，1H)，7.06 (d， 0.94 Hz，1H)，7·08 (d，J=8.11 Hz, 1H)，7.14 (t，J=7.49 Hz，2H)，7·20 (dd，J=4.99, 3.74 Hz，1H)，7·23 (d，J=1.25 Hz，1H)，7.24 (s，1H)，7.26 (m，1H)，7.37 (s，1H)，7·39 (d，J= 8.11 Hz，1H)，7.53 (dd，J=8.11，1·87 Hz，1H)，7·56 (dd，J=8.11，1·56 Hz，1H)，7.59 (s， 1H)，7.61 (d，J=7.80 Hz，1H)，7.71 (d，J=2.50 Hz，1H)，7.74 (d，J=5.30 Hz，1H)，7.79 (d，JN4.99 Hz，1H)，7·92 (s，1H)，7.93 (s，1H)，7.96 (s，1H)，7.98 (d，J=1.56 Hz，1H)， 8·09 (s，1H)，8·37 (s，2H)，8.48 (d，J=1.56 Hz，1H)，8.56 (s，1H)，8.65 (s，1H)；對 C29H24N402S 之分析計算值：C，50.37 ; H，3.26 ; N，6.71.實測值：C5 50.52 ； H, 3.45 ； N5 6.84. (A-441246)實例 416 5-{5-「(2SV2-胺基-3-ΠΗ-吲哚-3-基V丙氧基1-吡啶-3-基V3-(l-甲基-1H- 口比哈-2·基亞甲基)-1,3--- ^ _口亏1 口朱-2-酉同所要之化合物係經由以5-溴基-3-(1-甲基-1H-吡咯-2-基亞甲基）-1，3-二氫丨哚-2-酮（L. Sun 等人，J· Med· Chem.，1998, 41，2588)，取代實例32中之6-溴基鄰苯二曱醯亞胺，以三氟醋酸鹽製成。MS(APCI)m/z490(M+l)+ ; 1H NMR (500 MHz, CD3 OD) δ ppm 3.32 (m, 4H)，3.81 (s，3H)，3.89 (s，3H)，4·03 (m，2H)，4.30 (dd，J=10.61，5·93 Hz，1H)，4.37 (dd，J=10.61，5·93 Hz，1H)，4.44 (dd，J=10.45, 3·28 Hz，1H)，4.50 (dd，J=10.29, 3.12 Hz，1H)，6·28 (m，2H)，7.02 (m，3H)，7·07 (m，3H)，7.12 (m，2H)，7.19 (d，J=3.74 Hz， 1H)，7·24 (s，1H)，7·26 (s，1H)，7.38 (d，J=8.11 Hz，1H)，7·39 (d，J=8.11 Hz，1H)， 7.46 (dd，J=8.11，1.87 Hz，1H)，7.50 (dd，J=8.27, 1·72 Hz，1H)，7.59 (d，J=7.80 Hz， 1H)，7.61 (d，J=8· 11 Hz，1H)，7·70 (s，1H)，7.74 (s，1H)，7.86 (s，1H)，7.98 (d，J=1.87 (320)MWBSffiWMIWWBWKBtSI (318) 3.28 Hz, 1H), 6.38 (dd, J = 3.43, 0.994 Hz, 1H), 7:03 (m, 3H), 7.12 (t, J = 7.18 Hz, 1H), 7.24 (s, 1H), 7.37 (s, 1H), 7.38 (d, J = 8.11 Hz, 1H), 7.54 (dd, J = 8.11, 1.87 Hz, 1H), 7.60 (d , J = 8.11 Hz, 1H), 7.90 (dd, J = 2.50, 1.87 Hz, 1H), 8.38 (s, 1H), 8.64 (s, 1H), 8.73 (s, lH); for C30H26N4O3 Analytical calculated value: C, 49.59; Η, 3.31; Ν, 6.22 · Measured value: C, 4990; Η, 3 · 18; Ν, 6.10 · Example 414 5- {5-『(28)- 2-Amino-3- (111-indole-3-yl) -propanyl 1-pyridin-3-yl} -3- (4,5-dimethyl-oxan-2-ylmethylene ) -1,3-diazepine-oral arch 1-2-methyl, and the desired compound is via 5-bromo (4,5-dimethyl-furan-2-ylmethylene) -1 3-dihydroindol-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6-bromophthalimide in Example 32, with Made from trifluoroacetate. MS (DCI / NH3) m / z 505 (M + l) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 1.99 (s, 3H), 2.27 (s, 3H), 3.34 (m, 2H ), 4.06 (m, 1H), 4.37 (dd, J = 10.45, 5.77 Hz, 1H), 4.51 (dd, J = 10.45, 3.28 Hz, 1H), 6.82 (s, 1H), 6.99 (d, J = 8.42 Hz, 1H), 7.03 (t, J = 7.02 Hz, 1H), 7.13 (t, J = 7.02 Hz, 1H), 7.21 (s, 1H), 7.27 (s, 1H ), 7.39 (d5 J = 8.11 Hz, 1H), 7.52 (dd, J = 8.11, L87 Hz, 1H), 7.61 (d, J = 8.11 Hz, 1H), 8.05 (s, 1H), 8.45 ( s, 1H), 8.62 (d, J = l_56 Hz, 1H), 8.66 (s, 1H); Analytical calculated values for C3 丨 H2 8 N4 03: C, 52.92; Η, 3.73; Ν, 6.71 · Measured values: C, 52.90; H3, 3.45; N, 6.97. Example 415 5- {5-〖(2S) -2-Amino-3- (1H-oxindole group V Propoxy V-pyridin-3-ylbu 3-p-sephen-2-ylmethylene · 1,3-dilactate-oral arch 1 oral-2-en with the desired compound via 5-bromo -3-fluoren-2-ylmethylene-1,3-dihydro-indole-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), instead of Example 32 6-bromophthalimide is made from trifluoroacetate. MS (APCI ) m / z -326- (319) 493 (M + 1) +; 1HNMR (500MHz, CD3OD) 5 ppm3.32 (m, 4H), 4.03 (m, 2H), 4.30 (dd, J = 10.45, 5 77 Hz, 1H), 4.35 (dd, J = 10.61, 5.93 Hz, 1H), 4.44 (dd, J = 10.29, 3.12 Hz, 1H), 4.48 (dd, J = 10.61, 3.12 Hz, 1H), 7.02 (m, 2H), 7.04 (s, 1H), 7.06 (d, 0.94 Hz, 1H), 7.08 (d, J = 8.11 Hz, 1H), 7.14 (t, J = 7.49 Hz, 2H), 7.20 (dd, J = 4.99, 3.74 Hz, 1H), 7.23 (d, J = 1.25 Hz, 1H), 7.24 (s, 1H), 7.26 (m, 1H), 7.37 (s, 1H), 7.39 (d, J = 8.11 Hz, 1H), 7.53 (dd, J = 8.11, 1.87 Hz, 1H), 7.56 (dd, J = 8.11, 1.56 Hz , 1H), 7.59 (s, 1H), 7.61 (d, J = 7.80 Hz, 1H), 7.71 (d, J = 2.50 Hz, 1H), 7.74 (d, J = 5.30 Hz, 1H), 7.79 (d , JN4.99 Hz, 1H), 7.92 (s, 1H), 7.93 (s, 1H), 7.96 (s, 1H), 7.98 (d, J = 1.56 Hz, 1H), 8.09 (s, 1H), 8.37 (s, 2H), 8.48 (d, J = 1.56 Hz, 1H), 8.56 (s, 1H), 8.65 (s, 1H); Analysis and calculation of C29H24N402S: C, 50.37; H , 3.26; N, 6.71. Found: C5 50.52; H, 3.45; N5 6.84. (A-4412 46) Example 416 5- {5-`` (2SV2-Amino-3-ΠΗ-indole-3-yl Vpropoxy 1-pyridin-3-yl V3- (l-methyl-1H- -2 · Methylene group) -1,3 --- ^ 口 1 口 Zhu-2- 酉 and the desired compound are via 5-bromo-3- (1-methyl-1H-pyrrole- 2-Methylene) -1,3-dihydroindol-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing the 6-bromo group in Example 32 O-Phenylenediimide, made from trifluoroacetate. MS (APCI) m / z490 (M + 1) +; 1H NMR (500 MHz, CD3 OD) δ ppm 3.32 (m, 4H), 3.81 (s, 3H), 3.89 (s, 3H), 4.03 ( m, 2H), 4.30 (dd, J = 10.61, 5.93 Hz, 1H), 4.37 (dd, J = 10.61, 5.93 Hz, 1H), 4.44 (dd, J = 10.45, 3.28 Hz, 1H), 4.50 (dd, J = 10.29, 3.12 Hz, 1H), 6.28 (m, 2H), 7.02 (m, 3H), 7.07 (m, 3H), 7.12 (m, 2H), 7.19 (d, J = 3.74 Hz, 1H), 7.24 (s, 1H), 7.26 (s, 1H), 7.38 (d, J = 8.11 Hz, 1H), 7.39 (d, J = 8.11 Hz, 1H), 7.46 (dd, J = 8.11, 1.87 Hz, 1H), 7.50 (dd, J = 8.27, 1.72 Hz, 1H), 7.59 (d, J = 7.80 Hz, 1H), 7.61 (d , J = 8.11 Hz, 1H), 7.70 (s, 1H), 7.74 (s, 1H), 7.86 (s, 1H), 7.98 (d, J = 1.87 (320)

Hz，1H)，8·08 (s，1H)，8.30 (dd，J=4.37, 1·56 Hz，1H)，8·34 (d，J=1.56 Hz，1H)，8.38 (s，2H)，8.57 (s，1H)，8.73 (s，1H);對 C3 〇 H2 7 N5 02 之分析計算值：C，55.28 ;H，3·93 ; N，9·32·實測值·· C，55.32 ; H，3·57 ; N，9.08 實例417 5-{54(2SV2-胺基-3-ΠΗ-吲哚-3-基）-丙氧基 1-吡啶-3-某}-3-(lH-口弓 1 哚-3- 基亞甲基VU-二氫，哚-2-酮所要之化合物係經由以5-溴基-3-(1Η-吲哚-3-基亞甲基）-1.3-二氫-吲哚-2-酮（L. Sun 等人，J. Med· Chem·，1998, 41，2588)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 526 (M+l)+ ； 1 H NMR (500 MHz, CD3 OD) δ ppm 3.32 (m5 4H), 4.05 (m, 2H), 4.15 (m, 1H), 4.25 (m, 1H), 4.38 (d, J=5.93 Hz, 1H), 4.49 (dd, J=10.29, 3.12 Hz, 1H), 7.02 (m, 2H), 7.06 (m, 1H), 7.09 (m, 2H), 7.14 (t, J=7.64 Hz, 2H), 7.23 (m, 4H), 7.28 (s，1H)，7.39 (m，2H)，7.43 (d，J=4.99 Hz，1H)，7.47 (m，4H)，7·56 (d，J=8.11 Hz，1H)， 7.59 (s，1H)，7.63 (d，J=8.11 Hz，2H)，8.01 (m，2H)，8·06 (d，J=1.56 Hz，1H)，8.12 (s， 2H)，8·24 (s，1H)，8.28 (s，1H)，8.35 (s，2H)，8.72 (s，1H)，9.40 (s，1H); 對 C33H27N502之分析計算值：C，53.99 ; Η，3·48 ; Ν，8·07·實測值 :C，54·27 ; Η，3·64 ; Ν，7.84 實例418 5-{5-|Y2SV2-胺基口引口呆-3-基）-丙乳基 1-口比症-3-基}-3-(1-表基-1Η-吡咯-3-基亞甲基VI,3-二氫-吲哚-2-酮所要之化合物係經由以5-溴基-3-(2,5-二甲基小苯基-ΙΗ-吡咯-3-基亞甲基）-1，3-二氫-吲哚-2-酮（L.Sim 等人，J.Med.Chem.，1998,41， 2588)，取代實例32中之6-溴基鄰苯二曱醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 580 (M+l)+; 1 H NMR (500 MHz，CD3 OD) 6 ppm 200301122Hz, 1H), 8.08 (s, 1H), 8.30 (dd, J = 4.37, 1.56 Hz, 1H), 8.34 (d, J = 1.56 Hz, 1H), 8.38 (s, 2H) , 8.57 (s, 1H), 8.73 (s, 1H); Analytical calculated values for C3 0H2 7 N5 02: C, 55.28; H, 3.93; N, 9.32 · Measured value · C, 55.32 ; H, 3.57; N, 9.08 Example 417 5- {54 (2SV2-Amino-3-Πfluorene-indol-3-yl) -propoxy 1-pyridine-3-some} -3- (lH -Oral arch 1 Indole-3-ylmethylene VU-dihydro, indole-2-one The desired compound is via 5-bromo-3- (1Η-indol-3-ylmethylene) -1.3 -Dihydro-indole-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6-bromophthalimide in Example 32 with three Made of fluoroacetate. MS (APCI) m / z 526 (M + l) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 3.32 (m5 4H), 4.05 (m, 2H), 4.15 (m, 1H), 4.25 (m, 1H), 4.38 (d, J = 5.93 Hz, 1H), 4.49 (dd, J = 10.29, 3.12 Hz, 1H), 7.02 (m, 2H), 7.06 (m, 1H), 7.09 (m, 2H), 7.14 (t, J = 7.64 Hz, 2H), 7.23 (m, 4H), 7.28 (s, 1H), 7.39 (m, 2H), 7.43 (d, J = 4.99 Hz, 1H ), 7.47 (m, 4H), 7.56 (d, J = 8.11 Hz, 1H), 7.59 (s 1H), 7.63 (d, J = 8.11 Hz, 2H), 8.01 (m, 2H), 8.06 (d, J = 1.56 Hz, 1H), 8.12 (s, 2H), 8.24 (s, 1H ), 8.28 (s, 1H), 8.35 (s, 2H), 8.72 (s, 1H), 9.40 (s, 1H); Analysis and calculation of C33H27N502: C, 53.99; Η, 3.48; Ν, 8 · 07 · Measured values: C, 54 · 27; Η, 3.64; Ν, 7.84 Example 418 5- {5- | Y2SV2-Amine-based mouth-injector-3-yl) -propionate-l-ratio -3-yl} -3- (1-epiyl-1H-pyrrole-3-ylmethylene VI, 3-dihydro-indole-2-one The desired compound is via 5-bromo-3 -(2,5-dimethyl-small phenyl-l-pyrrole-3-ylmethylene) -1,3-dihydro-indole-2-one (L. Sim et al., J. Med. Chem ., 1998, 41, 2588), instead of 6-bromo-phthalimide of Example 32, made of trifluoroacetate. MS (APCI) m / z 580 (M + l) +; 1 H NMR (500 MHz, CD3 OD) 6 ppm 200301122

(321) 1·98 (s，3H) 2·01 (s，3H) 2·18 (s，3H) 2.28 (s，3H) 3·32 (m，4H)，4·02 (m，2H) 4·32 (dd，J=10.45, 5.46 Hz，1H) 4·37 (dd，J=10.61，5·93 Hz，1H) 4.49 (m，2H) 6·68 (m，1H) 7.01 (m，3H) 7.10 (m，3H) 7.25 (m，6H) 7.36 (t，J=8.73 Hz，2H) 7.47 (m，3H) 7.57 (m， 8H) 7.84 (d5 J=2.18 Hz, 2H) 7.93 (s, 2H) 8.13 (s, 1H) 8.32 (s, 1H) 8.38 (s, 2H) 8.60 (s, 1H) 8.73 (s，1H);對 C37H33N502之分析計算值：C，54.38 ; Η，3·79 ; N，7·24·實測值：C，54.45 ; H，3·92 ; N，6·97· 實例419 5-{5-f(2SV2-胺基-3-ΠΗ-吲哚-3-基V丙氣基1-吡啶-3-基丨各吡啶-3-基亞甲基-1,3-二氫-吲哚-2-酮所要之化合物係經由以5-溴基-3-吡啶-3-基亞甲基-1，3-二氫-啕哚-2-酮（L· Sun 等人，J· Med· Chem·，1998, 41，2588)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI)m/z 488 (M+l)+ ; 1 H NMR (500 MHz, CD3 OD) δ ppm 3.32 (m, 4H), 4.03 (m, 2H), 4.26 (dd, J=10.45, 5.46 Hz, 1H), 4.36 (dd, J=10.45, 5.77 Hz, 1H), 4.40 (dd5 J=10.29, 3.12 Hz, 1H), 4.49 (dd, J=10.29, 3.12 Hz, 1H), 7.01 (m, 1H), 7.05 (m5 3H), 7.08 (d, JN8.11 Hz, 1H)，7·12 (t5 J=7.64 Hz，2H)，7.23 (s，1H)，7·25 (s，1H), 7·38 (d，J=8.11 Hz， 1H)，7.57 (m，1H)，7·59 (m，1H)，7.61 (s，1H)，7.64 (dd，J=8.11，1.87 Hz，1H)，7.66 (m， 1H)，771 (m，1H)，7.78 (s，1H)，7.93 (s，1H)，7.99 (m，J=8.27, 5·77 Hz，3H)，8.09 (d， J=1.56 Hz, 1H), 8.34 (d, J=8.11 Hz, 2H), 8.41 (m, 2H), 8.56 (d, J=4.68 Hz, 1H), 8.67 (s，1H)，8.77 (d，J=5.30 Hz，1H)，9.01 (s，1H)，9.11 (d，J=8.11 Hz，1H)，9.69 (s，1H); 對 C30H25N5O2之分析計算值：C，49.22 ; Η，3·17 ; Ν，7·65·實測值 :C，49.23 ; Η，3·15; N，7.38. 實例420 5-{5-f(2S)-2-胺基-3-(111-口弓 1 口呆-3-基）-丙乳基 V口比咬-3-基}-3-(lH-口比啥-3- -329- 200301122(321) 1.98 (s, 3H) 2.01 (s, 3H) 2.18 (s, 3H) 2.28 (s, 3H) 3.32 (m, 4H), 4.02 (m, 2H) 4.32 (dd, J = 10.45, 5.46 Hz, 1H) 4.37 (dd, J = 10.61, 5.93 Hz, 1H) 4.49 (m, 2H) 6.68 (m, 1H) 7.01 (m, 3H) 7.10 (m, 3H) 7.25 (m, 6H) 7.36 (t, J = 8.73 Hz, 2H) 7.47 (m, 3H) 7.57 (m, 8H) 7.84 (d5 J = 2.18 Hz, 2H) 7.93 (s , 2H) 8.13 (s, 1H) 8.32 (s, 1H) 8.38 (s, 2H) 8.60 (s, 1H) 8.73 (s, 1H); Analytical calculated value for C37H33N502: C, 54.38; Η, 3.79 N, 7 · 24 · Measured values: C, 54.45; H, 3 · 92; N, 6 · 97 · Example 419 5- {5-f (2SV2-amino-3-ΠΗ-indole-3-yl V-propanyl 1-pyridin-3-yl. Each pyridin-3-ylmethylene-1,3-dihydro-indole-2-one is obtained via 5-bromo-3-pyridine- 3-ylmethylene-1,3-dihydro-pyridin-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing the 6-bromo group in Example 32 Phthalimidine, made from trifluoroacetate. MS (APCI) m / z 488 (M + l) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 3.32 (m, 4H), 4.03 (m, 2H), 4.26 (dd, J = 10.45, 5.46 Hz, 1H), 4.36 (dd, J = 10.45, 5.77 Hz, 1H), 4.40 (dd5 J = 10.29, 3.12 Hz, 1H), 4.49 (dd, J = 10.29, 3.12 Hz, 1H), 7.01 (m, 1H), 7.05 (m5 3H), 7.08 (d, JN8.11 Hz, 1H), 7.12 (t5 J = 7.64 Hz, 2H), 7.23 (s, 1H), 7.25 (s, 1H), 7.38 (d, J = 8.11 Hz, 1H), 7.57 (m, 1H), 7.59 (m, 1H), 7.61 (s, 1H), 7.64 (dd, J = 8.11, 1.87 Hz, 1H), 7.66 (m, 1H), 771 (m, 1H), 7.78 (s, 1H), 7.93 (s, 1H), 7.99 (m, J = 8.27, 5.77 Hz, 3H), 8.09 (d, J = 1.56 Hz, 1H), 8.34 ( d, J = 8.11 Hz, 2H), 8.41 (m, 2H), 8.56 (d, J = 4.68 Hz, 1H), 8.67 (s, 1H), 8.77 (d, J = 5.30 Hz, 1H), 9.01 ( s, 1H), 9.11 (d, J = 8.11 Hz, 1H), 9.69 (s, 1H); Analytical calculated value for C30H25N5O2: C, 49.22; Η, 3.17; Ν, 7.65 · Measured value: C, 49.23; Rhenium, 3.15; N, 7.38. Example 420 5- {5-f (2S) -2-Amino-3- (111-portal 1-portal-3-yl) -propionate V mouth than bite-3-yl} -3- (lH- mouth than what-3- -329- 200301122

(322) 基亞甲基VU-二氫哚-2-酮所要之化合物係經由以5-溴基-3-(1Η-吡咯-3-基亞甲基）-1，3-二氫 “5丨哚-2-酮（L· Sun 等人，J. Med. Chem·，1998, 41，2588)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 476 (M+l)+; 1 H NMR (500 MHz，CD3 OD) (5 ppm 3.32 (m，4H)，4.04 (m，2H)，(322) Methylene methylene VU-dihydrodol-2-one The desired compound is via 5-bromo-3- (1'-pyrrole-3-ylmethylene) -1,3-dihydro "5 Indole-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6-bromophthalimide in Example 32, made with trifluoroacetate MS (APCI) m / z 476 (M + l) +; 1 H NMR (500 MHz, CD3 OD) (5 ppm 3.32 (m, 4H), 4.04 (m, 2H),

4·32 (dd，J=10.45, 5.77 Hz，1H)，4.38 (dd，JN10.61，5·93 Hz，1H)，4·46 (dd，J=10.45， 3.28 Hz, 1H), 4.50 (dd, J-10.29, 3.12 Hz, 1H), 6.77 (dd, J=2.81, 1.56 Hz, 1H), 6.85 (dd，J=2.65, 2.03 Hz，1H)，6.91 (m，1H)，7.04 (m，5H)，7.13 (m，2H)，7.24 (s，1H)， 7.26 (s，1H)，7·39 (t，J=7·49 Hz，2H)，7.43 (s，1H)，7.48 (m，2H)，7.60 (m，J=8.73， 8.73 Hz，2H)，7.80 (s，1H)，7.84 (s，1H)，7.90 (m，2H)，8·09 (s，1H)，8·16 (s，1H)，8·28 (d，J=1.56Hz，lH)，8.39(s，2H)，8.59(s，lH)，8/70(s，lH);對 C29H25N502 之分析計算值·· C，51.42 ; Η，3·45 ; Ν，8·57·實測值：C，51.73 ; Η，3·41 ;Ν，8·58· 實例421 5-{5-「(2S)-2-胺基-3-(1Η-蜊哚-3-基V丙氧基1-吡啶-3-基卜3-(四氫-亞成喃-4-基）-1,3-二氫-沔丨口朵-2-酮4.32 (dd, J = 10.45, 5.77 Hz, 1H), 4.38 (dd, JN10.61, 5.93 Hz, 1H), 4.46 (dd, J = 10.45, 3.28 Hz, 1H), 4.50 ( dd, J-10.29, 3.12 Hz, 1H), 6.77 (dd, J = 2.81, 1.56 Hz, 1H), 6.85 (dd, J = 2.65, 2.03 Hz, 1H), 6.91 (m, 1H), 7.04 (m , 5H), 7.13 (m, 2H), 7.24 (s, 1H), 7.26 (s, 1H), 7.39 (t, J = 7.49 Hz, 2H), 7.43 (s, 1H), 7.48 ( m, 2H), 7.60 (m, J = 8.73, 8.73 Hz, 2H), 7.80 (s, 1H), 7.84 (s, 1H), 7.90 (m, 2H), 8.09 (s, 1H), 8 · 16 (s, 1H), 8.28 (d, J = 1.56Hz, lH), 8.39 (s, 2H), 8.59 (s, lH), 8/70 (s, lH); Analysis and calculation of C29H25N502 Value · C, 51.42; Η, 3.45; Ν, 8.57 · Measured value: C, 51.73; Η, 3.41; Ν, 8.58 · Example 421 5- {5-「(2S)- 2-Amino-3- (1H-Cindol-3-yl V Propoxy 1-Pyridin-3-yl Bu 3- (tetrahydro-arylene-4-yl) -1,3-dihydro-沔丨 Kuduo-2-one

所要之化合物係經由以5-溴基-3-(四氫-亞哌喃-4-基）-1，3-二氫 -口弓 1 哚-2-酮（L. Sun 等人，J· Med. Chem” 1998, 41，2588)，取代實例 32 中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 481 (M+l)+ ； 1 H NMR (400 MHz, DMSO-d6) δ ppm 3.02 (t5 J=5.52 Hz? 2H)3 3.19 (m，2H) 3.44 (t，J=5.52 Hz，2H)，3.80 (m，5H)，4.18 (dd，J=10.74, 5.83 Hz，1H)，4.34 (m，1H)，7.00 (m，1H)，7.10 (t，J=7.06 Hz，1H)，7·29 (d，J=2.15 Hz，1H)，7.38 (d，J= 7.98 Hz，1H)，7.49 (dd，J=8.13, 1.69 Hz，1H)，7.62 (m，2H)，7.85 (s，1H)，8.23 (s，2H)， 8.24 (s，1H)，8·32 (d，J=2.76 Hz，1H)，8·55 (d，J=1.53 Hz，1H)，10.67 (s，1H)，11.03 (d， -330- 200301122The desired compound is via 5-bromo-3- (tetrahydro-piperazin-4-yl) -1,3-dihydro-orbino-1 indol-2-one (L. Sun et al., J. Med. Chem "1998, 41, 2588), replacing 6-bromophthalimide in Example 32 and made from trifluoroacetate. MS (APCI) m / z 481 (M + l) + ; 1 H NMR (400 MHz, DMSO-d6) δ ppm 3.02 (t5 J = 5.52 Hz? 2H) 3 3.19 (m, 2H) 3.44 (t, J = 5.52 Hz, 2H), 3.80 (m, 5H), 4.18 (dd, J = 10.74, 5.83 Hz, 1H), 4.34 (m, 1H), 7.00 (m, 1H), 7.10 (t, J = 7.06 Hz, 1H), 7.29 (d, J = 2.15 Hz , 1H), 7.38 (d, J = 7.98 Hz, 1H), 7.49 (dd, J = 8.13, 1.69 Hz, 1H), 7.62 (m, 2H), 7.85 (s, 1H), 8.23 (s, 2H) , 8.24 (s, 1H), 8.32 (d, J = 2.76 Hz, 1H), 8.55 (d, J = 1.53 Hz, 1H), 10.67 (s, 1H), 11.03 (d, -330- 200301122

(323) J=1.84Hz，1H);對 C29H28N403之分析計算值：c，55.38 ; Η，4·21 ; Ν，7·78·實測值：C，55.29; Η，4·12; Ν，7·70· 實例422(323) J = 1.84Hz, 1H); Analysis and calculation of C29H28N403: c, 55.38; Η, 4.21. · 70 · Example 422

5454(2SV2-胺基-3-(1Η-吲哚-3-基丙氣基1-吡啶-3-基丨-3-(4-乙基-3,5-二甲基-1H-吡咯-2-基亞甲基）-1,3-二氫哚-2-酮所要之化合物係經由以5-澳基-3-(4-乙基-3,5-二甲基-lH-p比嘻-2-基亞甲基）-1，3-二氫-41 嗓-2-酮（L· Sun 等人，J. Med· Chem·，1998, 41， 2588)，取代實例32中之6-溴基鄰苯二曱醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 530 (M-l)+ ; 1H NMR (500 MHz，CD3 OD) 5 ppm 1.10 (t，J=7.52 Hz，3H)，2·31 (s，3H)，2·34 (s，3H)，2.49 (q，J=7.57 Hz，2H)，3.32 (m， 2H)，4·03 (m，1H)，4.36 (dd，J=10.59, 5.68 Hz，1H)，4.49 (m，1H)，7.05 (m，2H)，7.13 (t，J=7.06 Hz，1H)，7.25 (s，1H)，7·41 (m，2H)，7.61 (d，J=7.67 Hz，1H)，7·66 (s，1H)， 7·93 (d，J=1.53 Hz，1H)，8.07 (m，1H)，8.37 (s，1H)，8.72 (s，1H);對 C3 3 H3 3 N5 02 之分析計算值：C，54.94 ; H，4·29 ; N，8·34·實測值：C，55.03 ; H，4.09 ;Ν，8·20·5454 (2SV2-amino-3- (1'-indol-3-ylpropanyl 1-pyridin-3-yl) -3- (4-ethyl-3,5-dimethyl-1H-pyrrole- The desired compound is 2-ylmethylene) -1,3-dihydrodol-2-one via a 5-Alkyl-3- (4-ethyl-3,5-dimethyl-lH-p ratio Hex-2-ylmethylene) -1,3-dihydro-41 aceto-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6 of Example 32 -Bromodiphthalimide, made from trifluoroacetate. MS (APCI) m / z 530 (Ml) +; 1H NMR (500 MHz, CD3 OD) 5 ppm 1.10 (t, J = 7.52 Hz, 3H), 2.31 (s, 3H), 2.34 (s, 3H), 2.49 (q, J = 7.57 Hz, 2H), 3.32 (m, 2H), 4.03 (m, 1H) , 4.36 (dd, J = 10.59, 5.68 Hz, 1H), 4.49 (m, 1H), 7.05 (m, 2H), 7.13 (t, J = 7.06 Hz, 1H), 7.25 (s, 1H), 7 · 41 (m, 2H), 7.61 (d, J = 7.67 Hz, 1H), 7.66 (s, 1H), 7.93 (d, J = 1.53 Hz, 1H), 8.07 (m, 1H), 8.37 (s, 1H), 8.72 (s, 1H); Analytical calculated values for C3 3 H3 3 N5 02: C, 54.94; H, 4 · 29; N, 8.34. Found: C, 55.03; H, 4.09; Ν, 8.20 ·

(A-485149)會例 423(A-485149) Meeting 423

胺基-3-(111-31嗓-3·基V丙氧某I-?比咱>3-基卜3-環丙基亞甲基-1,3-二氫卜朵-2-產同所要之化合物係經由以5-溴基-3-環丙基亞甲基-1，3-二氫， -331 - (324)Amino-3- (111-31-Hydroxy-3 · V-propoxyl I-? Bizan> 3-kistriol 3-cyclopropylmethylene-1,3-dihydrobutor-2- The same compound is obtained via 5-bromo-3-cyclopropylmethylene-1,3-dihydro, -331-(324)

哚-2-酮（L· Sun 等人，J· Med· Chem·，1998, 41，2588)，取代實例 32 中之 6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 451 (M+l)+ ； 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.79 (m5 J=4.305 2.45 Hz, 2H), 0.93 (m，3H)，1.19 (m，5H)，2.52 (m，4H)，3.84 (s，2H)，4.19 (m，2H)，4.35 (m，2H)， 6.33 (d, J=11.66 Hz, 1H), 6.59 (d, J=11.05 Hz, 1H), 6.92 (d, J=7.98 Hz, 1H), 7.00 (m3 1H), 7.10 (t5 J=7.06 Hz, 2H), 7.29 (d, J=2.15 Hz, 2H)? 7.38 (d, J=8.29 Hz, 2H), 7.51 (m，2H)，7.62 (d，J=7.67 Hz，2H)，7·69 (m, J=5.06, 3.22 Hz，2H)，7.86 (d，J=1.84 Hz， 1H)，8.03 (d，JN1.53 Hz，1H)，8.23 (bi: s，3H)，8·24 (br s，3H)，8.32 (d，J=2.76 Hz，1H)， 8.33 (d，J=2.76 Hz，1H)，8.57 (d，J=1 ·53 Hz，1H)，8.60 (d，J=l.84 Hz，1H)，10.54 (s， 1H)，10.58 (s，1H)，11.03 (d，J=1.84Hz，2H);對 C28H26N402 之分析計算值：C，55.48 ; Η，4·05; Ν，7·99·實測值：C，55.63 ; Η，3·98; Ν，7·90· 實例424 5-{5-f(2S)-2-胺-3-(1Η-口弓I 口呆-3-基）-丙乳基V口比咬-3-基}-3-四乱ρ比洛- 2-基亞甲基-1，3-二氫-吲哚-2-酮所要之化合物係經由以5-溴基-3-四氫吡咯-2-基亞甲基-1，3-二氫』弓丨哚-2-酮（L· Sun等人，J. Med· Chem· 1998, 41，2588)，取代實例 32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 480 (M+l)+; 1 H NMR (400 MHz，CD3 OD) 5 ppm 1.53 (m，1H)，1·60 (m，1H)， 1.70 (m，1H)，2.01 (m，1H)，2·20 (m，2H)，2.49 (m，1H)，3.44 (m，2H)，4.01 (m，1H)， 4·32 (dd，J=10.43, 5·83 Hz，1H)，4.46 (m，1H)，7.05 (m，3H)，7.13 (t，J=7.67 Hz，1H)， 7.24 (s，1H)，7·38 (d，J=8.29 Hz，1H)，7.61 (m，2H)，7.92 (m，2H)，8·36 (s，1H)，8.59 (s，lH);對 C29H29N502之分析計算值：C，52.24; Η，4·03; Ν，8·83· 實測值：C，52.32 ; Η，4·24 ; N，8.63. 實例425 -332 - (325)Indol-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6-bromophthalimide in Example 32, made from trifluoroacetate . MS (APCI) m / z 451 (M + l) +; 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.79 (m5 J = 4.305 2.45 Hz, 2H), 0.93 (m, 3H), 1.19 (m , 5H), 2.52 (m, 4H), 3.84 (s, 2H), 4.19 (m, 2H), 4.35 (m, 2H), 6.33 (d, J = 11.66 Hz, 1H), 6.59 (d, J = 11.05 Hz, 1H), 6.92 (d, J = 7.98 Hz, 1H), 7.00 (m3 1H), 7.10 (t5 J = 7.06 Hz, 2H), 7.29 (d, J = 2.15 Hz, 2H)? 7.38 (d , J = 8.29 Hz, 2H), 7.51 (m, 2H), 7.62 (d, J = 7.67 Hz, 2H), 7.69 (m, J = 5.06, 3.22 Hz, 2H), 7.86 (d, J = 1.84 Hz, 1H), 8.03 (d, JN 1.53 Hz, 1H), 8.23 (bi: s, 3H), 8.24 (br s, 3H), 8.32 (d, J = 2.76 Hz, 1H), 8.33 (d, J = 2.76 Hz, 1H), 8.57 (d, J = 1.53 Hz, 1H), 8.60 (d, J = 1.84 Hz, 1H), 10.54 (s, 1H), 10.58 (s, 1H), 11.03 (d, J = 1.84Hz, 2H); Analysis and calculation of C28H26N402: C, 55.48; Η, 4.05; Ν, 7.99. Measured value: C, 55.63; Η, 3.98 Ν, 7 · 90 · Example 424 5- {5-f (2S) -2-Amine-3- (1'-oral arch I Oral-3-yl) -propiolactyl V Oral-3-yl } -3-tetrahydropyrrol-2-ylmethylene-1,3-dihydro-indole-2-one With 5-bromo-3-tetrahydropyrrole-2-ylmethylene-1,3-dihydro′indol-2-one (L. Sun et al., J. Med. Chem. 1998, 41, 2588), instead of 6-bromophthalimide in Example 32, made from trifluoroacetate. MS (APCI) m / z 480 (M + l) +; 1 H NMR (400 MHz, CD3 OD) 5 ppm 1.53 (m, 1H), 1.60 (m, 1H), 1.70 (m, 1H), 2.01 (m, 1H), 2.20 (m, 2H), 2.49 (m, 1H), 3.44 (m, 2H), 4.01 (m, 1H), 4.32 (dd, J = 10.43, 5.83 Hz, 1H), 4.46 (m, 1H), 7.05 (m, 3H), 7.13 (t, J = 7.67 Hz, 1H), 7.24 (s, 1H), 7.38 (d, J = 8.29 Hz, 1H ), 7.61 (m, 2H), 7.92 (m, 2H), 8.36 (s, 1H), 8.59 (s, lH); Analytical calculated value for C29H29N502: C, 52.24; Η, 4.03; Ν , 8.83 · Found: C, 52.32; Η, 4 · 24; N, 8.63. Example 425 -332-(325)

5-(5-{5-f(2S)-2-胺基-3-(1Η-㈣嗓-3-基）-丙氧基l-ρ比咬-3-基丨-2-氧基，酮基-1,2-二氫-亞啕哚-3-基甲基）-呋喃-2-羧酸所要之化合物係經由以5-(5-溴基-2-氧基，S同基-1,2-二氫-亞啕哚-3-基甲基）-呋喃-2-羧酸（L· Sun 等人，J. Med. Chem·，1998, 41，2588) ，取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 521 (M+l)+; 1 H NMR (400 MHz，DMSO-d6) (5 ppm 3.16 (d，J=6.75 Hz，2H)，3.86 (m，1H)，4·21 (dd，J=10.74, 6.44 Hz，1H)，4.41 (m，1H)， 6.97 (t, J=6.90 Hz, 1H), 7.03 (d, J=7.98 Hz, 1H), 7.08 (t, J=7.06 Hz, 1H), 7.29 (d, J= 2.46 Hz，1H)，7.37 (d，J=8.29 Hz，1H)，7.40 (d，J=3.99 Hz，1H)，7.44 (m，1H)，7.47 (s， 1H), 7.62 (m, 2H), 7.71 (τη, 1H), 8.17 (br s, 2H), 8.33 (d, J=2.45 Hz, 1H)3 8.71 (d5 J= 1.84 Hz，1H)，8.98 (d，J=1.84 Hz，1H)，10.84 (s，1H)，11.01 (d，J=2.15 Hz，1H):對 C30H24N4O5 之分析計算值：C，51.75 ; H，3·28 ; N，6.86.實測值： C，51.69 ; H，3.16; Ν，6·71· 實例426 5-{5-『(2S)-2-胺基-3-(lHWl哚-3-基V丙氣基1-吡啶-3-基丨-3-苯亞甲基- 1，3_二1 _口弓卜朵-2-酮所要之化合物係經由以3-苯亞甲基-5_溴基-1，3-二氫，哚-2-酮（L· Sun 等人，J. Med· Chem·，1998, 41，2588)，取代實例 32 中之 6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS (APCI) m/z 485 (M-l)+ ； 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m, 2H), 4.01 (m9 1H), 4.23 (dd3 J=10.61，5.62 Hz，1H)，4.37 (m，1H)，7.03 (m，2H)，7.13 (t，J=7.64 Hz，1H)，7.22 (s， 1H)，7.34 (t，JM7.49 Hz，1H)，7·39 (d，J=8.42 Hz，1H)，7·44 (m，2H)，7.53 (dd，J=8.27, 1.72 Hz，1H)，7.58 (d，J=8.11 Hz，1H)，7·62 (s，1H)，7.69 (d，J=7.80 Hz，1H)，7.78 (d， J=1.87 Hz, 1H), 7.83 (s, 1H), 8.00 (d, J=1.56 Hz, 1H), 831 (m, J=6.40, 2.96 Hz, 1H), 20030Π22 (326) 8.37(S，1H);對 C3 1H26N402之分析計算值：c，55.53 ; H，3.68; N，7.16. 實測值：C，55·74 ; H，3.50 ; N，7.05. 實例427 5-{5-[(2S}：?:胺.碁-M1H-吲哚各基丙氣某1-吡啶各某丨哚_2 3_ 二酮3-月亏所要之化合物係經由以5-溴基-1H-啕哚-2,3-二酮3-肪（L· Sun等人，J· Med· Chem·，1998, 41，2588)，取代實例32中之6-溴基鄰苯二甲醯亞胺，以三氟醋酸鹽製成。MS(ESI)m/z428 (M+l)+ ; 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m5 2H), 4.00 (m, 1H), 4.29 (dd, J=10.45, 5.77 Hz，1H)，4.44 (dd，J=10.61，3.12 Hz，1H)，7.05 (m，2H)，7.13 (t，JK7.17 Hz，1H)， 7.24 (s, 1H), 7.38 (d, J=8.11 Hz, 1H), 7.60 (d, J=8.11 Hz, 1H), 7.65 (dd, J=8.27, 2.03 Hz, 1H), 7.78 (m, 1H), 8.32 (d, J=1.87 Hz, 1H), 8.34 (s, 1H), 8.52 (s, 1H)；對 C24H21N503之分析計算值：c，51.30; H，3.54; N，10.68.實測值：C, 50.99； H, 3.33； N, 10.47. 下列化合物係經由以適當三丁基錫烷基試劑取代實例364 中之（1，1，1-三丁基錫烷基）苯，且以實例362A取代實例364中之80E而製成。實例428 (lSV2-(5-苯并R)1嘧吩-2-基-6-呋喃-2-基-吡啶-3-基氣基哚- 3-基甲基V乙胺 MS (APCI) m/z 465 (M-l)4* ； 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m, 2H), 3.99 (m，1H)，4.27 (dd，J=10.61，5·62 Hz，1H)，4.41 (m，1H)，6.47 (dd，J=3.43, 1.87 Hz，1H)，6·66 (d，J=3.43 Hz，1H)，7.01 (t，J=7.02 Hz，1H)，7.10 (t，J=8.11 Hz，1H)， 7.23 (s，1H)，7.35 (d，J=8.11 Hz，1H)，7.39 (d，J=1.25 Hz，1H)，7.56 (d，J=2.81 Hz， -334- (327) 1H)，7·58 (d，J=7.80 Hz，1H)，7.72 (s，1H)，8.31 (d，J=6.24 Hz，1H)，8.50 (d，J=2.81 1^，1玢，8.61(〇1，：[=6.241125111)，9.51(3，111);對(：271122>^023之分析計算值：C，52.57; H，3.40; N，7.81·實測值·· C，52.35 ; Η，3·20; Ν，7·73· 實例429 (lS)-2-(5-苯并塞吩-2-基-6-乙烯基-吡啶-3-基氧基V1-(1H-㈣哚-3- 某甲基V乙胺 MS (APCI) m/z 427 (M+lf ； 1 H NMR (400 MHz, DMSO-d6) δ ppm 3.15 (m, 2H)5 3·85 (m，1H)，4.17 (dd, J=10.76, 6.08 Hz，1H)，4.33 (dd，J=10.76, 2·96 Hz，1H), 5.44 (m，1H)，6.30 (dd，J=16.85, 2·18 Hz，1H)，6·93 (dd，J=16.69, 10.76 Hz，1H)，7.00 (t， J=7.33 Hz，1H)，7.08 (t，J=7.49 Hz，1H)，7.29 (d，J=2.18 Hz，1H)，7.36 (d，J=8.11 Hz， 1H)，7·51 (d，J=2.81 Hz，·1Η)，7.60 (d，J=8.11 Hz，1H)，7.77 (s，1H)，8.18 (d，J=5.93 Hz，1H)，8.25 (m，2H)，8.51 (d，J=2.81 Hz，1H)，8.67 (d，J=5.93 Hz，1H)，9·56 (s，1H)， ll.〇2(s，1H);對 C25H22N4OS之分析計算值：C，48·44; Η，3·28; Ν，7·29· 實測值·· C，48.38 ; H，3,32 ; N，7·02. 實例430 (!S)-2-(5-^ jrf 『b]口塞吩-2-基-6-p塞吩塵2-基-口比 < -3-基 & 基口朵- 3-基甲基V乙胺 MS (APCI) m/z 481 (M-l)+ ； 1 H NMR (500 MHz5 DMSO-d6) 5 ppm 3.15 (m, 2H), 3.85 (m，1H)，4.18 (dd，J=10.76, 6.08 Hz，1H)，4.34 (dd，J=10.61，3.12 Hz，1H)，6.71 (dd，J=3.59, 1·09 Hz，1H)，6·90 (dd，J=4.99, 3.74 Hz，1H)，7.00 (t，J=7.02 Hz，1H)， 7.08 (t, J=7.18 Hz, 1H), 7.29 (d, J=2.18 Hz, 1H), 7.36 (d, J=7.80 Hz, 1H), 7.55 (dd5 J-5.15, 1.09 Hz, 1H), 7.57 (d5 J=2.81 Hz, 1H)? 7.60 (d, J=7.80 Hz, 1H), 7.78 (s5 1H), 8·13 (d，J=5.93 Hz，1H)，8·23 (br s，2H)，8.50 (d，J=2.81 Hz，1H)，8.64 (d，J=5.93 Hz， lH)，9.50(s，lH)，lL02(d，J=1.56Hz，lUC27H22N4OS2i*；^t# 200301122 (328) 值：C，48.83 ; Η，3·12; Ν，6·99·實測值：C，48.74; Η，3·07; N，6.88. 實例431 (lS)-2-(5-苯并「b>塞吩-2-基-6-4咬-2-基比淀-3-基氧基丨嗓- 3-基甲基乙胺 MS (APCI) m/z 484 (M+l)+ ； 1 H NMR (500 MHz, DMSO-d6) 5 ppm 3.15 (m, 2H)35- (5- {5-f (2S) -2-amino-3- (1Η-㈣Hor-3-yl) -propoxyl-p-r--3-yl 丨 -2-oxy, Keto-1,2-dihydro-amidino-3-ylmethyl) -furan-2-carboxylic acid The desired compound is via 5- (5-bromo-2-oxy, S isopropyl- 1,2-Dihydro-arsonyl-3-ylmethyl) -furan-2-carboxylic acid (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing Example 32 6-Bromophthalimide, made from trifluoroacetate. MS (APCI) m / z 521 (M + l) +; 1 H NMR (400 MHz, DMSO-d6) (5 ppm 3.16 (d, J = 6.75 Hz, 2H), 3.86 (m, 1H), 4. · 21 (dd, J = 10.74, 6.44 Hz, 1H), 4.41 (m, 1H), 6.97 (t, J = 6.90 Hz, 1H), 7.03 (d, J = 7.98 Hz, 1H), 7.08 (t, J = 7.06 Hz, 1H), 7.29 (d, J = 2.46 Hz, 1H), 7.37 (d, J = 8.29 Hz, 1H), 7.40 (d, J = 3.99 Hz, 1H), 7.44 (m, 1H), 7.47 (s, 1H), 7.62 (m, 2H), 7.71 (τη, 1H), 8.17 (br s, 2H), 8.33 (d, J = 2.45 Hz, 1H) 3 8.71 (d5 J = 1.84 Hz, 1H ), 8.98 (d, J = 1.84 Hz, 1H), 10.84 (s, 1H), 11.01 (d, J = 2.15 Hz, 1H): Analysis and calculation of C30H24N4O5: C, 51.75; H, 3.28; N, 6.86. Found: C, 51.69; H, 3.16; N, 6.71. Example 426 5- {5-"(2S) -2-amino-3- (lHWl indol-3-yl V propane) 1-pyridin-3-yl 丨 -3-benzylidene-1,3_di-1_orbendol-2-one The desired compound is via 3-benzylidene-5_bromo- 1,3-dihydro, indol-2-one (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6-bromophthalimide in Example 32, Made of trifluoroacetate. MS (APCI) m / z 485 ( Ml) +; 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m, 2H), 4.01 (m9 1H), 4.23 (dd3 J = 10.61, 5.62 Hz, 1H), 4.37 (m, 1H), 7.03 (m, 2H), 7.13 (t, J = 7.64 Hz, 1H), 7.22 (s, 1H), 7.34 (t, JM7.49 Hz, 1H), 7.39 (d, J = 8.42 Hz, 1H) , 7.44 (m, 2H), 7.53 (dd, J = 8.27, 1.72 Hz, 1H), 7.58 (d, J = 8.11 Hz, 1H), 7.62 (s, 1H), 7.69 (d, J = 7.80 Hz, 1H), 7.78 (d, J = 1.87 Hz, 1H), 7.83 (s, 1H), 8.00 (d, J = 1.56 Hz, 1H), 831 (m, J = 6.40, 2.96 Hz, 1H ), 20030Π22 (326) 8.37 (S, 1H); Analysis and calculation of C3 1H26N402: c, 55.53; H, 3.68; N, 7.16. Found: C, 55.74; H, 3.50; N, 7.05. Example 427 5- {5-[(2S}:?: Amine. 碁 -M1H-indolyl propane gas 1-pyridine each indole_2 3_ dione 3-month depletion The required compound is -Bromo-1H-pyridin-2,3-dione 3-fat (L. Sun et al., J. Med. Chem., 1998, 41, 2588), replacing 6-bromo-o-benzene in Example 32 Dimethyimine, made from trifluoroacetate. MS (ESI) m / z428 (M + l) +; 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m5 2H), 4.00 (m, 1H), 4.29 (dd, J = 10.45, 5.77 Hz, 1H), 4.44 (dd, J = 10.61, 3.12 Hz, 1H), 7.05 (m, 2H), 7.13 (t, JK7.17 Hz, 1H), 7.24 (s, 1H), 7.38 (d, J = 8.11 Hz, 1H), 7.60 (d, J = 8.11 Hz, 1H), 7.65 (dd, J = 8.27, 2.03 Hz, 1H), 7.78 (m, 1H), 8.32 (d, J = 1.87 Hz, 1H), 8.34 (s, 1H), 8.52 (s, 1H); Analytical calculated values for C24H21N503: c, 51.30; H, 3.54; N, 10.68. Found: C, 50.99; H, 3.33; N, 10.47. The following compounds It was prepared by replacing (1,1,1-tributyltinalkyl) benzene in Example 364 with an appropriate tributyltin alkyl reagent and substituting 80E in Example 364 with Example 362A. Example 428 (1SV2- (5-BenzoR) 1pyrimin-2-yl-6-furan-2-yl-pyridin-3-ylcarbamoyl-3-ylmethyl Vethylamine MS (APCI) m / z 465 (Ml) 4 *; 1 H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m, 2H), 3.99 (m, 1H), 4.27 (dd, J = 10.61, 5.62 Hz, 1H) , 4.41 (m, 1H), 6.47 (dd, J = 3.43, 1.87 Hz, 1H), 6.66 (d, J = 3.43 Hz, 1H), 7.01 (t, J = 7.02 Hz, 1H), 7.10 ( t, J = 8.11 Hz, 1H), 7.23 (s, 1H), 7.35 (d, J = 8.11 Hz, 1H), 7.39 (d, J = 1.25 Hz, 1H), 7.56 (d, J = 2.81 Hz, -334- (327) 1H), 7.58 (d, J = 7.80 Hz, 1H), 7.72 (s, 1H), 8.31 (d, J = 6.24 Hz, 1H), 8.50 (d, J = 2.81 1 ^, 1 玢, 8.61 (〇1 ,: [= 6.241125111), 9.51 (3,111); Analytical calculated value for (: 271122 > ^ 023: C, 52.57; H, 3.40; N, 7.81 · Measured value · C, 52.35; Hf, 3.20; N, 7.73. Example 429 (1S) -2- (5-Benzethen-2-yl-6-vinyl-pyridin-3-yloxy V1 -(1H-pyridin-3-methyl Vethylamine MS (APCI) m / z 427 (M + lf; 1 H NMR (400 MHz, DMSO-d6) δ ppm 3.15 (m, 2H) 5 3 · 85 (m, 1H), 4.17 (dd, J = 10.76, 6.08 Hz, 1H), 4.33 (dd, J = 10.76 , 2.96 Hz, 1H), 5.44 (m, 1H), 6.30 (dd, J = 16.85, 2.18 Hz, 1H), 6.93 (dd, J = 16.69, 10.76 Hz, 1H), 7.00 ( t, J = 7.33 Hz, 1H), 7.08 (t, J = 7.49 Hz, 1H), 7.29 (d, J = 2.18 Hz, 1H), 7.36 (d, J = 8.11 Hz, 1H), 7.51 ( d, J = 2.81 Hz, · 1Η), 7.60 (d, J = 8.11 Hz, 1H), 7.77 (s, 1H), 8.18 (d, J = 5.93 Hz, 1H), 8.25 (m, 2H), 8.51 (d, J = 2.81 Hz, 1H), 8.67 (d, J = 5.93 Hz, 1H), 9.56 (s, 1H), ll.〇2 (s, 1H); Analytical calculation for C25H22N4OS: C , 48 · 44; Η, 3.28; N, 7.29 · Measured value ·· C, 48.38; H, 3, 32; N, 7.02. Example 430 (! S) -2- (5- ^ jrf "b" Orthophen-2-yl-6-p orthophenone 2-yl-ortho ratio < -3-yl & kidol-3-ylmethyl V ethylamine MS (APCI) m / z 481 (Ml) +; 1 H NMR (500 MHz5 DMSO-d6) 5 ppm 3.15 (m, 2H), 3.85 (m, 1H), 4.18 (dd, J = 10.76, 6.08 Hz, 1H), 4.34 (dd , J = 10.61, 3.12 Hz, 1H), 6.71 (dd, J = 3.59, 1.09 Hz, 1H), 6.90 (dd, J = 4.99, 3.74 Hz, 1H), 7.00 (t, J = 7.02 Hz, 1H), 7.08 (t, J = 7.18 Hz, 1H), 7.29 (d, J = 2.18 Hz, 1H), 7.36 (d, J = 7.80 Hz, 1H), 7.55 (dd5 J-5.15, 1.09 Hz, 1H), 7.57 (d5 J = 2.81 Hz, 1H)? 7.60 (d, J = 7.80 Hz, 1H), 7.78 (s5 1H), 8. 13 (d, J = 5.93 Hz, 1H), 8.23 (br s, 2H), 8.50 (d, J = 2.81 Hz, 1H), 8.64 (d, J = 5.93 Hz, lH), 9.50 (s, lH), lL02 (d, J = 1.56Hz, lUC27H22N4OS2i *; ^ t # 200301122 (328) Value: C, 48.83; Η, 3.12; Ν, 6.99. Found: C, 48.74; Η, 3 · 07; N, 6.88. Example 431 (1S) -2- (5-Benzo "b > Sphenphen-2-yl-6-4b-2-ylpyridine-3-yloxy 丨 3-3 -Methylmethylethylamine MS (APCI) m / z 484 (M + l) +; 1 H NMR (500 MHz, DMSO-d6) 5 ppm 3.15 (m, 2H) 3

3·84 (m，J=14.12 Hz，1H)，4.22 (dd，J=10.89, 5·98 Hz，1H)，4.38 (dd，J=10.74, 3.07 Hz, 1H), 6.98 (t, J=7.06 Hz, 1H)? 7.07 (t, J=7.52 Hz, 1H)? 7.29 (d, J=2.15 Hz, 1H), 7·35 (d，J=7.98 Hz，1H)，7.60 (d，J=7.98 Hz，1H)，7.63 (d，J=2.76 Hz，2H)，7.73 (s， 1H)，7.77 (d，J=3.38 Hz，1H)，8.16 (d，J=5.83 Hz, 1H)，8.29 (br s，2H)，8.56 (d，J= 2.76 Hz，1H)，8·63 (d，】=5·83 Hz，1H)，9.52 (s，1H)，11.02 (d，J=1 ·84 Hz，1H);對 C26H21N5OS之分析計算值：C，46.55; Η，2·93; Ν，8·48·實測值： C, 46.87 ； Η, 2.97 ； Ν, 8.46. 實例432 (18)-2-(5-笨并『1}1魂吩-2-基-6-0比1?井-2-基-^1比症-3-基乳基）-1-(11~1-1??1嗓-基曱基）·乙胺3.84 (m, J = 14.12 Hz, 1H), 4.22 (dd, J = 10.89, 5.98 Hz, 1H), 4.38 (dd, J = 10.74, 3.07 Hz, 1H), 6.98 (t, J = 7.06 Hz, 1H)? 7.07 (t, J = 7.52 Hz, 1H)? 7.29 (d, J = 2.15 Hz, 1H), 7.35 (d, J = 7.98 Hz, 1H), 7.60 (d, J = 7.98 Hz, 1H), 7.63 (d, J = 2.76 Hz, 2H), 7.73 (s, 1H), 7.77 (d, J = 3.38 Hz, 1H), 8.16 (d, J = 5.83 Hz, 1H), 8.29 (br s, 2H), 8.56 (d, J = 2.76 Hz, 1H), 8.63 (d,) = 5.83 Hz, 1H), 9.52 (s, 1H), 11.02 (d, J = 1 · (84 Hz, 1H); Analytical calculated values for C26H21N5OS: C, 46.55; Η, 2.93; Ν, 8.48. Measured values: C, 46.87; Η, 2.97; Ν, 8.46. Example 432 (18)- 2- (5-Bun and "1} 1 Soulphen-2-yl-6-0 to 1? Well-2-yl- ^ 1 ratio Zheng-3-yl milk group) -1- (11 ~ 1-1 ?? 1 vocal-methyl sulfonyl) · Ethylamine

MS (APCI) m/z 479 (M-l)+ ; 1H NMR (500 MHz，CD3 OD) 5 ppm 3·32 (m，2Η)， 4.02 (m, 1H), 4.33 (dd, J=10.61? 5.62 Hz, 1H), 4.47 (dd, J=10.61, 3.12 Hz, 1H), 7.02 (t, J=7.02 Hz, 1H)? 7.10 (t, J=7.18 Hz, 1H), 7.25 (s, 1H), 7.36 (d, J=8.11 Hz, 1H), 7.60 (d，J=7.80 Hz，1H)，7.63 (s，1H)，7.67 (d，J=2.50 Hz，1H)，8.25 (d，J=5.93 Hz， 1H)，8·32 (s，1H)，8.52 (d，J=1.87 Hz，1H)，8.58 (d，J=6.24 Hz，1H)，8.63 (d，J=2.18 Hz，1H)，9.09 (s，1H)，9.46 (s，1H). 實例433 {5-『(2S)-2-胺基-3-(1!1-口弓j噪-3-基）-丙乳基V3-苯并「b]口塞吩-2-基-p比淀- 2-基}_苯基-胺 -336- 200301122MS (APCI) m / z 479 (Ml) +; 1H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m, 2Η), 4.02 (m, 1H), 4.33 (dd, J = 10.61? 5.62 Hz , 1H), 4.47 (dd, J = 10.61, 3.12 Hz, 1H), 7.02 (t, J = 7.02 Hz, 1H)? 7.10 (t, J = 7.18 Hz, 1H), 7.25 (s, 1H), 7.36 (d, J = 8.11 Hz, 1H), 7.60 (d, J = 7.80 Hz, 1H), 7.63 (s, 1H), 7.67 (d, J = 2.50 Hz, 1H), 8.25 (d, J = 5.93 Hz , 1H), 8.32 (s, 1H), 8.52 (d, J = 1.87 Hz, 1H), 8.58 (d, J = 6.24 Hz, 1H), 8.63 (d, J = 2.18 Hz, 1H), 9.09 (s, 1H), 9.46 (s, 1H). Example 433 {5-『(2S) -2-Amino-3- (1! 1-portal jno-3-yl) -propanolactyl V3- Benzo [b] orphen-2-enyl-p-pyridine-2-yl} -phenyl-amine-336- 200301122

(329) 標題化合物係經由以實例362A·取代實例318中之實例381A 而製成。MS (APCI) m/z 492 (M+l)+ ; 1 H NMR (500 MHz，DMSO-d6) 5 ppm 3.16 (m, 2H), 3.83 (m, J=2.50 Hz, 1H), 4.13 (dd, J=10.61, 5.93 Hz5 1H)5 4.29 (dd, J= 10.45, 2.96 Hz, 1H), 6.86 (t, J=7.18 Hz, 1H)? 7.01 (t5 J=7.49 Hz, 1H)5 7.09 (t, J=7.33 Hz, 1H), 7.20 (t, J=7.80 Hz, 2H), 7.25 (m, 2H), 7.30 (d, J=2.18 Hz, 1H), 7.38 (d, J= 8·11 Hz，1H)，7.62 (d5 J=7.80 Hz，1H)，7.72 (d，JN3.12 Hz，1H)，8.11 (s，1H)，8.16 (d， J=3.12 Hz? 1H), 8.20 (d, J=6.24 Hz, 1H), 8.25 (br s, 2H), 8.38 (s, 1H), 8.64 (d, J= 6.24Hz，lH)，9.55(s，lH)，11.03(d，J=1.56Hz，lH);對 C29H25N50S之分析計算值：C，48.90 ; H，3·26; N，7.96·實測值：C，48.88 ; H，3.13; N，7.90· 實例434 {5-f(2S)-2-胺基-3-(lHWl哚-3-基V丙氧基1-3-笨并塞吩-2-基-吡啶- 2-^. }-这比 € -胺標題化合物係經由以3-胺基吡啶取代實例433中之苯胺而製成。MS (APCI) m/z 491 (M-l)+; 1H NMR (500 MHz，CD3 OD) 5 ppm 3·32 (m, 2H), 3.97 (m, 1H), 4.24 (dd, J=10.29, 5.93 Hz, 1H), 4.37 (dd, J=10.45, 3.28 Hz, 1H), 7·03 (t，J=7.18 Hz，1H)，7·11 (t，J=7.18 Hz，1H)，7.24 (s，1H)，7.37 (d，J=8.42 Hz，1H)， 7.59 (d，J=8.11 Hz，1H)，7.68 (d, J=3· 12 Hz，1H)，7.87 (dd，J=8.74, 5·62 Hz，1H), 8.05 (s, 1H), 8.24 (d, J=3.12 Hz, 1H), 8.30 (d, J=5.30 Hz, 1H), 8.32 (d, J=6.24 Hz, 1H)，8.42 (dd，J=8.73, 1·56 Hz，1H)，8.63 (d，J=6.24 Hz，1H)，9.15 (d，J=2.18 Hz，1H)， 9·53 (s，1H);對 C28H24N6OS之分析計算值：C，48.93; Η，3·26; N，10.07· 實測值：C，48.82 ; H，3·35 ; N，9.92. 實例435 6-{5-f(2S)-2-胺基嗓-3-基）-丙乳基V口比淀-3-基}-3H-苯并口号嗤-2-酉同 -337 - 200301 (330)(329) The title compound was prepared by replacing Example 381A in Example 318 with Example 362A. MS (APCI) m / z 492 (M + l) +; 1 H NMR (500 MHz, DMSO-d6) 5 ppm 3.16 (m, 2H), 3.83 (m, J = 2.50 Hz, 1H), 4.13 (dd , J = 10.61, 5.93 Hz5 1H) 5 4.29 (dd, J = 10.45, 2.96 Hz, 1H), 6.86 (t, J = 7.18 Hz, 1H)? 7.01 (t5 J = 7.49 Hz, 1H) 5 7.09 (t , J = 7.33 Hz, 1H), 7.20 (t, J = 7.80 Hz, 2H), 7.25 (m, 2H), 7.30 (d, J = 2.18 Hz, 1H), 7.38 (d, J = 8.11 Hz , 1H), 7.62 (d5 J = 7.80 Hz, 1H), 7.72 (d, JN3.12 Hz, 1H), 8.11 (s, 1H), 8.16 (d, J = 3.12 Hz? 1H), 8.20 (d, J = 6.24 Hz, 1H), 8.25 (br s, 2H), 8.38 (s, 1H), 8.64 (d, J = 6.24Hz, lH), 9.55 (s, lH), 11.03 (d, J = 1.56Hz , LH); Analysis and calculation of C29H25N50S: C, 48.90; H, 3.26; N, 7.96. Found: C, 48.88; H, 3.13; N, 7.90. Example 434 {5-f (2S)- 2-amino-3- (lHWl indol-3-yl V propoxy 1-3-benzethen-2-yl-pyridine- 2- ^. -Aminopyridine was prepared by substituting aniline in Example 433. MS (APCI) m / z 491 (Ml) +; 1H NMR (500 MHz, CD3 OD) 5 ppm 3.32 (m, 2H), 3.97 (m , 1H), 4.24 (dd, J = 10.29, 5.93 Hz, 1H), 4.37 (dd, J = 10.45, 3. 28 Hz, 1H), 7.03 (t, J = 7.18 Hz, 1H), 7.01 (t, J = 7.18 Hz, 1H), 7.24 (s, 1H), 7.37 (d, J = 8.42 Hz, 1H), 7.59 (d, J = 8.11 Hz, 1H), 7.68 (d, J = 3 · 12 Hz, 1H), 7.87 (dd, J = 8.74, 5.62 Hz, 1H), 8.05 (s, 1H ), 8.24 (d, J = 3.12 Hz, 1H), 8.30 (d, J = 5.30 Hz, 1H), 8.32 (d, J = 6.24 Hz, 1H), 8.42 (dd, J = 8.73, 1.556 Hz , 1H), 8.63 (d, J = 6.24 Hz, 1H), 9.15 (d, J = 2.18 Hz, 1H), 9.53 (s, 1H); Analysis and calculation of C28H24N6OS: C, 48.93; Η, 3.26; N, 10.07. Found: C, 48.82; H, 3.35; N, 9.92. Example 435 6- {5-f (2S) -2-amino group-3-yl) -propionate milk Base V-Hydro-3-yl} -3H-benzo slogan 嗤 -2- 酉同 -337-200301 (330)

所要之化合物係經由以6-溴基-3H-苯并呤峻-2-酮（C· Flouzat等人，J. Med. Chem.，1993, 36, 497)，取代實例32中之6-溴基鄰苯二曱醯亞胺而製成。MS(APCI)m/z401(M+l)+ ; iHNMRpOOMH^DMSO-ds) (5 ppm 3.16 (d5 J=9.67 Hz, 2H), 3.85 (m, 1H), 4.18 (dd, J=10.61, 5.93 Hz, 1H), 4.34 (dd, J=10.76, 2.96 Hz, 1H), 7.01 (t, J=7.49 Hz, 1H)5 7.10 (t5 J=7.49 Hz, 1H), 7.20 (d, J=8.11 Hz, 1H), 7.29 (d, J=2.18 Hz, 1H), 7.38 (d, J=8.11 Hz, 1H), 7.50 (dd5 J=8.11，1.56 Hz，1H)，7.62 (d，J=7.80 Hz，1H)，7·65 (s，1H)，7.70 (s，1H)，8·18 (s，2H)， 8·33 (d，J=2.81 Hz，1H)，8·55 (d，J=1.56 Hz，1H)，11.02 (s，1H)，11.81 (s，1H);對 C23H2〇N403之分析計算值：C，5〇·53 ; H，3·44 ; Ν，8·60·實測值： C, 50.71 ； H, 3.46 ； N, 8.42. 實例436 1-苯并咪唑小基甲基-2-『5-(3-甲某-1H-W唑-5-基V吡啶-3·其fi年1- 乙胺The desired compound was replaced by 6-bromo-3H-benzoxan-2-one (C. Flouzat et al., J. Med. Chem., 1993, 36, 497) in Example 32 Phthalimide. MS (APCI) m / z401 (M + l) +; iHNMRpOOMH ^ DMSO-ds) (5 ppm 3.16 (d5 J = 9.67 Hz, 2H), 3.85 (m, 1H), 4.18 (dd, J = 10.61, 5.93 Hz, 1H), 4.34 (dd, J = 10.76, 2.96 Hz, 1H), 7.01 (t, J = 7.49 Hz, 1H) 5 7.10 (t5 J = 7.49 Hz, 1H), 7.20 (d, J = 8.11 Hz , 1H), 7.29 (d, J = 2.18 Hz, 1H), 7.38 (d, J = 8.11 Hz, 1H), 7.50 (dd5 J = 8.11, 1.56 Hz, 1H), 7.62 (d, J = 7.80 Hz, 1H), 7.65 (s, 1H), 7.70 (s, 1H), 8.18 (s, 2H), 8.33 (d, J = 2.81 Hz, 1H), 8.55 (d, J = 1.56 Hz, 1H), 11.02 (s, 1H), 11.81 (s, 1H); Analytical calculated value for C23H2ON403: C, 50 · 53; H, 3.44; Ν, 8.60 · Measured value : C, 50.71; H, 3.46; N, 8.42. Example 436 1-benzimidazole small methyl-2--2-5- (3-methyl-1H-Wazole-5-yl Vpyridine-3. fi year 1-Ethylamine

實例436A } >臭基-5-環氣乙燒某甲氣基-f7比峻於5-溴-晚啶各醇（0·50克，2·87毫莫耳）、環氧乙烷基呷醇（〇·38 愛升5.74愛莫耳）及二表膦（ι·5〇克，5.74毫莫耳）在無水thf (20毫升）中之溶液内，添加偶氮二羧酸二·第三-丁酯（dba〇) (1.32克，5.74毫莫耳），並將反應混合物於室溫下攪拌i8小時，及濃縮。使殘留物於矽膠上藉急驟式管柱層析純化，以10% -35%醋酸乙酯/己烷溶離，提供所要之產物⑺·仙克，73% ) 〇Example 436A} > Sulfuryl-5-ring gas was used to burn a methylamino group-f7 more than 5-bromo-late pyridine alcohol (0.50 g, 2.87 mmol), ethylene oxide group To a solution of methyl alcohol (0.38 liters 5.74 emoles) and di-epiphosphine (50 grams, 5.74 millimoles) in anhydrous thf (20 ml), azodicarboxylic acid Tri-butyl ester (dba0) (1.32 g, 5.74 mmol), and the reaction mixture was stirred at room temperature for 8 hours, and concentrated. The residue was purified on a silica gel by flash column chromatography, and was dissolved with 10% -35% ethyl acetate / hexane to provide the desired product (⑺ · 仙克, 73%).

f 例 436B 臭·吡啶-3-基氧基）-而 -338 - 200301122f Example 436B (Pyridin-3-yloxy) -and -338-200301122

(331) 使實例436A (500毫克，2.17毫莫耳）與1H-苯并咪唑（28毫克，2·39亳莫耳）於2-丙醇（1〇毫升）中之溶液，在&下回流2小時。使反應混合物冷卻，以醋酸乙酯（5〇亳升）稀釋，龙以鹽水洗滌（2 X 25毫升）。使殘留物濃縮，並於矽膠上藉急騾式管柱層析純化，以1〇〇%醋酸乙酯至5%甲醇/醋酸乙酯溶離，提供所要之產物（1.08毫莫耳，50% )。(331) A solution of Example 436A (500 mg, 2.17 mmol) and 1H-benzimidazole (28 mg, 2.39 mmol) in 2-propanol (10 ml) was used under & Reflux for 2 hours. The reaction mixture was allowed to cool, diluted with ethyl acetate (50 mL), and the dragon was washed with brine (2 X 25 mL). The residue was concentrated and purified by flash column chromatography on silica gel and dissolved with 100% ethyl acetate to 5% methanol / ethyl acetate to provide the desired product (1.08 mmol, 50%) .

實例436CExample 436C

苯并咪峻小基-2-#基-丙氧基V?比咱：-3-某1各甲甚-Hi也小羧酸第三-丁酯產物係經由以實例436B取代實例203B中之實例202A而製成。Benzimidazole small group-2- # yl-propoxy V? Bizan: -3-some 1 each methyl even-Hi also small carboxylic acid third-butyl ester product is replaced by Example 436B in Example 203B Example 202A was prepared.

實例436D 1-苯_并咪唑-1-基甲基-245-(3-甲基-1H-吲唑-5-甚Wh啶！基氣基卜乙胺所要之化合物係經由以實例436C取代實例27C中之實例 27B ’ 以三氟醋酸鹽製成。MS(APCI)m/z400(M+l)+ ; iHNMR (400 MHz，CD3 OD) (5 ppm 2.53 (m，3H)，4.31 (dd，>13.81，4·91 Hz，2H)，4.42 (m， J=7.98, 3·38 Hz，1H)，4·54 (m，2H)，7.56 (m，3H)，7.67 (dd，J=8.75, 1·07 Hz，1H)， 7.78 (dd，J=5.83, 3.38 Hz，1H)，7.94 (dd，J=6.14, 3.07 Hz，1H)，8.05 (s，1H)，8.12 (s， 1H)，8.35 (s，1H)，8.64 (s，1H)，9.36 (s，1H). 實例437 245-(3-甲基丨也-5-基）比淀-3-基氧基1-1-嗎福g林-4·基甲基-乙胺Example 436D 1-Benzenimidazol-1-ylmethyl-245- (3-methyl-1H-indazole-5-even Whidine! The desired compound was substituted by Example 436C Example 27B in 27C is made from trifluoroacetate. MS (APCI) m / z400 (M + 1) +; iHNMR (400 MHz, CD3 OD) (5 ppm 2.53 (m, 3H), 4.31 (dd, > 13.81, 4.91 Hz, 2H), 4.42 (m, J = 7.98, 3.38 Hz, 1H), 4.54 (m, 2H), 7.56 (m, 3H), 7.67 (dd, J = 8.75, 1.07 Hz, 1H), 7.78 (dd, J = 5.83, 3.38 Hz, 1H), 7.94 (dd, J = 6.14, 3.07 Hz, 1H), 8.05 (s, 1H), 8.12 (s, 1H ), 8.35 (s, 1H), 8.64 (s, 1H), 9.36 (s, 1H). Example 437 245- (3-methyl 丨 also-5-yl) than lake 3--3-yloxy 1-1 -Morphoglin-4 · ylmethyl-ethylamine

實例437A H5-溴-峨症-3-基氧基V3-噁福琳冰某-而-9』, 所要之化合物係經由以嗎福琳取代實例437B中之1H-苯并 -339- 200301122 (332) 咪唑而製成。Example 437A H5-Bromo-Ezine-3-yloxy V3-oxalin-Bing-and-9 ", the desired compound was replaced with 1H-benzo-339-200301122 in Example 437B by morpholin 332) Made from imidazole.

實例437R 胺甲基酸第『2-(5-溴-吹咬-3_基氣基）小嗎福p林冰基甲莘三-丁於實例437Α(250亳克，〇·79毫莫耳）、異吲哚_丨，3•二酮（121毫克，0.82毫莫耳）及三苯膦（240亳克，〇 92毫莫耳）在無水thf(i〇毫升）中之溶液内，添加DIAD(0.16毫升，0.83亳莫耳），並於室溫下攪拌45分鐘.然後，使濃縮之殘留物藉急騾式管柱層析純化’以60%醋酸乙酯/己烷溶離，而得所要之中間物，使其溶於無水乙醇（10毫升）中。添加胼單水合物（4〇微升），並使反應混合物回流3小時。使混濁溶液冷卻，濃縮及溶於DMF (10毫升）中。添加二碳酸二·第三·丁酯（271毫克 1.25毫莫耳）與二乙胺（〇18毫升’ 1.25毫莫耳），並將透明浴液於室溫下攪拌15小時。將透明溶液以醋酸乙酯（25毫升）稀釋，並以鹽水（25毫升）及水（25毫升）洗滌。使濃縮之殘留物藉急驟式管柱層析進一步純化，以15%醋酸乙酯/己烷洛離’而传所要之產物。 _Example 437R Aminomethyl acid No. 2- (5-Bromo-bite-3_ylamino) morpholine p-Linbenylformamidine tri-butyrate in Example 437A (250 g, 0.79 mmol), Isoindole_, a solution of 3 • dione (121 mg, 0.82 mmol) and triphenylphosphine (240 g, 0.092 mmol) in anhydrous thf (10 mL) was added with DIAD ( 0.16 ml, 0.83 moles), and stirred at room temperature for 45 minutes. Then, the concentrated residue was purified by flash column chromatography 'and dissolved in 60% ethyl acetate / hexane to obtain the desired The intermediate was dissolved in absolute ethanol (10 ml). Rhenium monohydrate (40 microliters) was added and the reaction mixture was refluxed for 3 hours. The turbid solution was cooled, concentrated and dissolved in DMF (10 ml). Di-tert-butyl dicarbonate (271 mg 1.25 mmol) and diethylamine (0 18 ml '1.25 mmol) were added, and the clear bath was stirred at room temperature for 15 hours. The clear solution was diluted with ethyl acetate (25 ml) and washed with brine (25 ml) and water (25 ml). The concentrated residue was further purified by flash column chromatography, and the desired product was passed on as 15% ethyl acetate / hexane. _

實例437C 步—士 ·丁乳羧基胺基-3-嗎福淋-4-基·基）^比淀各基1各甲基4唑小藉酸第三-丁 j 產物係經由以實例437B取代實例2〇犯中之實例2〇2A而製成。Example 437C Step—Butyl carboxymethylamino-3-morpholin-4-yl group. ^ Compared with each group 1 and each methyl 4 azole small borrow acid third-butyric acid The product was substituted by Example 437B Example 20 was made from Example 202A.

實例437D 甲基-5_基）-吡啶；基氧i 遇^啉冰基曱基-乙胺所要之化合物係經由以實例437C取代實例27C中之實例 -340- 200301122 (333) 27B，以三氟醋酸鹽製成。MS(APCI)m/z369 (M+l)+ ; iHNMR^OO MHz，CD3 OD) 5 ppm 2.62 (s，3H)，2·73 (dd，J=11.51，4·76 Hz，2H)，2.86 (m，2H)， 2.98 (m，2H)，3.79 (t，J=4.45 Hz，4H)，4.04 (m，J=8.59, 3·38 Hz，1H)，4.47 (dd，J= 10.43, 5.52 Hz，1H)，4.59 (m，1H)，7.64 (d，J=8.59 Hz，1H)，7.76 (dd，J=8.90, 1.23 Hz，1H)，8.15 (s，1H)，8.24 (s，1H)，8.48 (s，1H)，8.78 (s，1H);對 C2 〇 H2 5 N5 02 之分析計算值：C，44.01 ; H，3·98 ; N，9.87·實測值：C，43.92 ; H，3.92 ;Ν，9·73·Example 437D Methyl-5-yl) -pyridine; oxo group i. The desired compound was substituted by Example 437C, Example 340-200301122 (333) 27B, and Made from fluoroacetate. MS (APCI) m / z369 (M + 1) +; iHNMR ^ OO MHz, CD3 OD) 5 ppm 2.62 (s, 3H), 2.73 (dd, J = 11.51, 4.76 Hz, 2H), 2.86 (m, 2H), 2.98 (m, 2H), 3.79 (t, J = 4.45 Hz, 4H), 4.04 (m, J = 8.59, 3.38 Hz, 1H), 4.47 (dd, J = 10.43, 5.52 Hz, 1H), 4.59 (m, 1H), 7.64 (d, J = 8.59 Hz, 1H), 7.76 (dd, J = 8.90, 1.23 Hz, 1H), 8.15 (s, 1H), 8.24 (s, 1H ), 8.48 (s, 1H), 8.78 (s, 1H); Analytical calculated values for C2 0H2 5 N5 02: C, 44.01; H, 3.98; N, 9.87. Found: C, 43.92; H , 3.92; N, 9.73 ·

實例438 5-「5-((2S)-2-胺基-3-笨基-丙乳基）-口比淀-3-基二氮-?弓1 口呆-2-酮所要之產物係經由以Boc-苯基丙胺醇取代實例36中之Boc-色胺酸而製成。MS(APCI)m/z360(M+l)+ ; iHNMRpOOMH^CDsOD) δ ppm 3.15 (d，J=7.49 Ηζ，2Η)，3.61 (s，2Η)，3.95 (m，1Η)，4.26 (dd，J=10.61，5·62 Hz，1H)，4.40 (dd，J=10.61，3·12 Hz，1H)，7.04 (d，J=8.11 Hz，IH)，7.33 (m，5H)， 7.58 (d，J=8.11 Hz，1H)，7.62 (s，1H)，7.96 (s，1H)，8.38 (d，J=2.50 Hz，1H)，8.60 (s， 1H);對 C22H21N302之分析計算值：C，51.39; Η，3·78; Ν，6·76·實測值：C，51.48 ; Η，3.63 ; Ν，6·75.Example 438 5- (5-((2S) -2-Amino-3-benzyl-propionyl) -Kyobido-3-yldiazine-? Gong 1 keto-2-one Prepared by replacing Boc-tryptophan acid in Example 36 with Boc-phenylpropanol. MS (APCI) m / z360 (M + l) +; iHNMRpOOMH ^ CDsOD) δ ppm 3.15 (d, J = 7.49 Ηζ , 2Η), 3.61 (s, 2Η), 3.95 (m, 1Η), 4.26 (dd, J = 10.61, 5.62 Hz, 1H), 4.40 (dd, J = 10.61, 3.12 Hz, 1H), 7.04 (d, J = 8.11 Hz, IH), 7.33 (m, 5H), 7.58 (d, J = 8.11 Hz, 1H), 7.62 (s, 1H), 7.96 (s, 1H), 8.38 (d, J = 2.50 Hz, 1H), 8.60 (s, 1H); Analysis and calculation of C22H21N302: C, 51.39; Η, 3.78; Ν, 6.76. Measured value: C, 51.48; Η, 3.63; 6.75.

實例439 5-『5-((2S)-2-胺基-3-苯基-丙氧基）-ρ比咬-3-基嘻-2-基亞甲基）-1,3㈣二复-沔|嗓_2·酉同所要之產物係經由以Boc-苯基丙胺醇取代實例39中之Boc-色胺酸而製成。MS (APCI) m/z 437 (M+l)+ ; 1 H NMR (500 MHz，CD3 OD) δ ppm 3.17 (d, J=7.80 Hz, 2H), 3.97 (m, 1H), 4.28 (dd, J=10.61, 5.62 Hz, 1H), 4.43 (dd, J=10.45, 2.96 Hz, 1H), 6.38 (m, 1H), 6.85 (d, J=3.74 Hz? 1H).7.06 (d? J=8.11 Hz, 1H), 7.25 (s, 1H\ 7.34 (m, 5H), 7.51 (dd, J=8.11, 1.87 Hz, 1H), 7.73 (s5 1H)5 7.94 (s, -341 - (334) 1H)，8·03 (s，1H)，8·38 (d，J=1.87 Hz，1H)，8·67 (s，1H)，13.32 (s，1H); 對 C27H24N402之分析計算值：C，53.27 ; H，3.70 ; Ν，7·76·實測值：C, 53.46 ； H, 3.69 ； N, 7.77. 實例440 5-「5-((2S)-2-胺基-3-笨基-丙氧基V吡啶各基1-3-哇喃-2-基亞甲基- 1,3-二氮-17¾] 口来-2-嗣所要之產物係經由以Boc-苯基丙胺醇取代實例412中之 Boc-色胺酸而製成。MS(APCI)m/z438 (M+l)+ ; 1 H NMR (500 MHz， CD3 OD) δ ppm 3.85 (m, 4H), 4.75 (m, 2H), 4.93 (m, 2H), 5.10 (dd, J=10.61, 3.12Example 439 5-"(5-((2S) -2-Amino-3-phenyl-propoxy) -ρ ratio of 3--3-methylhex-2-ylmethylene) -1,3 '沔 | 嗓 _2 · 酉 The same product was prepared by replacing Boc-tryptophan in Example 39 with Boc-phenylpropanol. MS (APCI) m / z 437 (M + l) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 3.17 (d, J = 7.80 Hz, 2H), 3.97 (m, 1H), 4.28 (dd, J = 10.61, 5.62 Hz, 1H), 4.43 (dd, J = 10.45, 2.96 Hz, 1H), 6.38 (m, 1H), 6.85 (d, J = 3.74 Hz? 1H). 7.06 (d? J = 8.11 Hz, 1H), 7.25 (s, 1H \ 7.34 (m, 5H), 7.51 (dd, J = 8.11, 1.87 Hz, 1H), 7.73 (s5 1H) 5 7.94 (s, -341-(334) 1H) , 8.03 (s, 1H), 8.38 (d, J = 1.87 Hz, 1H), 8.67 (s, 1H), 13.32 (s, 1H); Analysis and calculation of C27H24N402: C, 53.27 H, 3.70; N, 7.76. Found: C, 53.46; H, 3.69; N, 7.77. Example 440 5- "5-((2S) -2-amino-3-benzyl-propoxyl V-pyridine, each group 1-3-oxan-2-ylmethylene-1,3-diazine-17¾] The desired product is obtained by substituting Boc-phenylpropylamine in Example 412 And Boc-tryptophan acid. MS (APCI) m / z438 (M + 1) +; 1 H NMR (500 MHz, CD3 OD) δ ppm 3.85 (m, 4H), 4.75 (m, 2H), 4.93 (m, 2H), 5.10 (dd, J = 10.61, 3.12

Hz, 2H), 7.64 (dd, J=3.43, 1.56 Hz, 1H), 7.77 (d, J=8.11 Hz, 1H)? 7.82 (d, J=8.11 Hz, 1H), 8.08 (m, 2H)5 8.14 (m3 8H)3 8.22 (s, 1H), 8.39 (d, J=1.87 Hz, 1H), 8.42 (dd, J= 8.11, 1.87 Hz, 1H), 8.45 (s, 1H), 8.53 (s, 1H), 8.68 (s, 1H), 8.80 (d, J=1.56 Hz, 1H), 8.90 (d, J=1.87 Hz, 1H), 9.00 (d, J=1.56 Hz, 1H), 9.07 (s? 2H), 9.11 (d5 J=3.43 Hz, 1H)? 9.16 (br s, 2H), 9.44 (d, J=1.56 Hz, 1H), 11.54 (s, 1H), 11.57 (s, 1H)；對 C27H23N303之分析計算值：c，55.36 ; Η，3·74 ; N，6.21.實測值 :C，55.09 ; H，3·74 ; N，6.07. 實例441 (ISH-苯并咪咬小基甲基_2·「5-(3-甲基_1H•㈣唑_5_某吡咗·3·某举基1-乙胺實例441Α (2R)-1-苯并咪吨小某-3-芊氣基-丙-2-醇_ 將2-(3-苯基-丙基）-環氧乙烷（3 0克，18·27毫莫耳）與苯并咪唑（2.37克，20.1毫莫耳）於無水2-丙醇（50毫升）中之溶液，以氮滌氣，並回流2·5小時。使反應混合物冷卻，濃縮，並於 20030Π22 (335) 矽膠上藉急騾式管柱層析純化[•於2 : 1醋酸乙醋/己燒中之0(1分鐘）-15% (16分鐘）甲醇]，提供所要之產物（472克，91 %)。Hz, 2H), 7.64 (dd, J = 3.43, 1.56 Hz, 1H), 7.77 (d, J = 8.11 Hz, 1H)? 7.82 (d, J = 8.11 Hz, 1H), 8.08 (m, 2H) 5 8.14 (m3 8H) 3 8.22 (s, 1H), 8.39 (d, J = 1.87 Hz, 1H), 8.42 (dd, J = 8.11, 1.87 Hz, 1H), 8.45 (s, 1H), 8.53 (s, 1H), 8.68 (s, 1H), 8.80 (d, J = 1.56 Hz, 1H), 8.90 (d, J = 1.87 Hz, 1H), 9.00 (d, J = 1.56 Hz, 1H), 9.07 (s? 2H), 9.11 (d5 J = 3.43 Hz, 1H)? 9.16 (br s, 2H), 9.44 (d, J = 1.56 Hz, 1H), 11.54 (s, 1H), 11.57 (s, 1H); For C27H23N303 Analytical calculated values: c, 55.36; pyrene, 3.74; N, 6.21. Found: C, 55.09; H, 3.74; N, 6.07. 2. "5- (3-methyl_1H • oxazole_5_some pyridoxine · 3 · some given group 1-ethylamine Example 441A (2R) -1-benzimidone small certain -3- tritium gas -Propan-2-ol_-2- (3-phenyl-propyl) -ethylene oxide (30 g, 18.27 mmol) and benzimidazole (2.37 g, 20.1 mmol) The solution in anhydrous 2-propanol (50 ml) was purged with nitrogen and refluxed for 2.5 hours. The reaction mixture was cooled, concentrated, and purified by flash column chromatography on a silica gel of 3030Π22 (335). [• 2: 01 ethyl acetate acetate / hexyl Burning of (1 min) -15% (16 min) methanol], to provide the desired product (472 g, 91%).

實例441B (2S)-l-(2-疊氮...羞-3-芊氣某-丙某笨并味岫在〇°C下，於實例441Α(1·0克，3.54毫莫耳）與三苯膦（1抑克，5.31毫莫耳）在無水THF (30毫升）中之溶液内，添加疊氮化一苯基鱗醯（1·14毫升’ 5,31耄莫耳），接著添加DEAD(836微升）。將反應混合物於〇°C下攪拌30分鐘，及於室溫下15小時。然後’使濃縮之殘留物於矽膠上藉急驟式管柱層析純化，以60% -80%醋酸乙酯/己烷溶離，提供所要之產物。Example 441B (2S) -l- (2-Azide ... Sha-3-Houqi-Bing-Mou Ben and miso at 0 ° C in Example 441A (1.0 g, 3.54 mmol) To a solution of triphenylphosphine (1 g, 5.31 mmol) in anhydrous THF (30 ml), add monophenylazine azide (1.14 ml '5,31 mmol), then DEAD (836 μl) was added. The reaction mixture was stirred at 0 ° C. for 30 minutes and at room temperature for 15 hours. The concentrated residue was then purified by flash column chromatography on silica gel at 60% -80% ethyl acetate / hexane dissociates to provide the desired product.

實例441C (2-苯并咪也-1-基-1-主一氧基甲基-乙基胺甲基醢第三-丁酯在氮氣下，於實例441B (〜1克，〜3.54毫莫耳）在乙醇（25毫升）中之溶液内，添加10% Pd/C (230毫克）。將此懸浮液以氫蘇氣，並於氫（氣瓶）下攪拌1小時。將固體物質濾出，並使濾液濃縮。使殘留泡沫物溶於無水DMF (20毫升）中。然後 ’於室溫下添加三乙胺（1.08毫升，7.78毫莫耳）與二碳酸二-第三-丁酯（0.85克，3.89毫莫耳），並將溶液在氮氣下攪拌2 小時。添加EtOAc (200毫升），並將混合物以鹽水（2〇〇毫升）及水（100毫升）洗滌。使有機相濃縮，並使殘留物藉急驟式層析[於己淀中之60-80% (5分鐘）EtOAc]純化，獲得所要之產物。Example 441C (2-Benzimido-1-yl-1-main monooxymethyl-ethylaminemethylphosphonium tertiary-butyl ester under nitrogen, in Example 441B (~ 1 g, ~ 3.54 mmol) Ear) In a solution of ethanol (25 ml), 10% Pd / C (230 mg) was added. This suspension was subjected to hydrogen aeration and stirred under hydrogen (cylinder) for 1 hour. The solid matter was filtered off And the filtrate was concentrated. The residual foam was dissolved in anhydrous DMF (20 ml). Then triethylamine (1.08 ml, 7.78 mmol) and di-tertiary-butyl dicarbonate (at room temperature) were added 0.85 g, 3.89 mmol) and the solution was stirred under nitrogen for 2 hours. EtOAc (200 mL) was added and the mixture was washed with brine (200 mL) and water (100 mL). The organic phase was concentrated, The residue was purified by flash chromatography [60-80% (5 minutes) EtOAc in hexanes] to obtain the desired product.

實例441D (1SM2-苯并咪唑小基-1-羥甲基乙基胺曱某酸第三_丁醋_ -343 - 200301122Example 441D (1SM2-benzimidazolyl-1-hydroxymethylethylamine sulfonic acid tertiary butyl acetate--343-200301122

(336) 在氮氣下，於此實例（0·78克）在甲醇（20毫升）中之溶液内 ’添加10% Pd-C (450亳克）。將此反應混合物以氫滌氣，並、氧及86 C下攪:拌3.5天（氣瓶）。使滤液濃縮，並藉急驟式層析（於2 : 1 EtOAc /己烷中之（M5% CH3〇H)分離殘留油，而得所要之產物（199.7毫克，33% )。(336) To a solution of this example (0.78 g) in methanol (20 ml) under nitrogen was added 10% Pd-C (450 g). The reaction mixture was purged with hydrogen and stirred under oxygen and 86 C: stirred for 3.5 days (cylinder). The filtrate was concentrated and the residual oil was separated by flash chromatography (2: 1 EtOAc / hexane (M5% CH3OH)) to give the desired product (199.7 mg, 33%).

實例441E 唑-1-基甲ϋ(5·溴-吡啶各基氧基卩乙某肛腙甲甚酸第三-丁酯於溪…比咬-3-醇（1〇2毫克，〇·%毫莫耳）、實例441D(154毫克’ 〇·53毫莫耳）及三苯膦（2〇8毫克，〇 793毫莫耳）在無水THF (20毫升）中之溶液内，添加DEAD (125微升，〇 79毫莫耳），並將反應混合物於室溫下攪拌2小時，及濃縮。使殘留物於碎膠上藉急驟式管柱層析（於2 : 1 Et〇Ac /己烷中之〇-15%修 CH3〇H)純化，而得所要之產物（1〇〇毫克，43% )。Example 441E azole-1-ylformamidine (5.-bromo-pyridinyloxymethyl), an anthranilic acid, tertiary-butyl ester of Yuxi ... than bitol-3-ol (102 mg, 0.% MM), Example 441D (154 mg '0.53 mol) and triphenylphosphine (208 mg, 0793 mol) in anhydrous THF (20 ml) was added DEAD (125 Μl, 〇79 mmol), and the reaction mixture was stirred at room temperature for 2 hours, and concentrated. The residue was subjected to flash column chromatography on a gel (at 2: 1 EtAc / hexane). (0-15% of CH3OH) was purified to obtain the desired product (100 mg, 43%).

實例441F 峻-l-基第三-丁氣·某脖甚氫某V吡啶-3-基 II-甲基ϋ -1-致酸第三-丁酯產物係經由以實例447Ε取代實例2〇3Β中之實例2〇2八而製成。Example 441F Jun-l-yl tertiary-butane · Hydroxy-V-pyridin-3-yl II-methylfluorene-1-acid tertiary-butyl ester The product was replaced by Example 447E Example 203B Example 202 was prepared.

實例441G 4小基甲基-2-「5-(3-甲某-1H-W岫4签V毗啶-3-基氧 •344- (337) 某1-乙胺所要之化合物係經由以實例441F取代實例27C中之實例 27B，以三氟醋酸鹽製成。1 H NMR (300 MHz，CD3 0D) 5 ppm 2·63 (m， 3H)，4·53 (m，2H)，4.65 (m，1H)，5.09 (d，J=6.78 Hz，2H)，7.66 (m，2H)，7.74 (d，J= 1.70 Hz，1H)，7.77 (d，J=1.70 Hz，1H)，7·90 (m，1H)，8.02 (m，1H)，8.12 (m，1H)， 8.15 (d，J=2.37 Hz，1H)，8.46 (d，J=2.71 Hz，1H)，8.77 (d，J=1.70 Hz，1H)，9.40 (s，1H) :對 C23H22N60 之分析計算值：C，42.16 ; Η，2·93 ; Ν，9·22·實測值：C，42·08 ; H，3·24 ; N，9·13. 實例442 3-{3-「(2S)-2-胺基啕哚-3-基V丙氧基1-5-異喹啉-6-基-吡啶-4- 基}-丙婦月青實例442Α 3-乳基-5-(4-甲氣基-宇氧基比咬於3-氯基-5-羥基吡啶（2.0克，17.0毫莫耳）、4-曱氧基苯甲醇（2.85克，25.5毫莫耳）及三苯膦（6.68克，25.5毫莫耳）在無水 THF (100毫升）中之溶液内，逐滴添加DEAD (4.44克，25.5毫莫耳）。將所形成之溶液於室溫下攪拌3小時。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（NaaSO4)，過濾及在真空下濃縮。於矽膠上純化，使用20%醋酸乙酯/己烷，提供標題化合物（19克，53% )。 MS (DCI/NH3) m/e 250 (M+l)+.Example 441G 4-Smallylmethyl-2- "5- (3-methyl-1H-W 岫 4 sign V-pyridin-3-yloxy • 344- (337) The desired compound of 1-ethylamine is via Example 441F replaced Example 27B in Example 27C with trifluoroacetate. 1 H NMR (300 MHz, CD3 0D) 5 ppm 2.63 (m, 3H), 4.53 (m, 2H), 4.65 ( m, 1H), 5.09 (d, J = 6.78 Hz, 2H), 7.66 (m, 2H), 7.74 (d, J = 1.70 Hz, 1H), 7.77 (d, J = 1.70 Hz, 1H), 7 · 90 (m, 1H), 8.02 (m, 1H), 8.12 (m, 1H), 8.15 (d, J = 2.37 Hz, 1H), 8.46 (d, J = 2.71 Hz, 1H), 8.77 (d, J = 1.70 Hz, 1H), 9.40 (s, 1H): Analytical calculated value for C23H22N60: C, 42.16; Η, 2.93; N, 9.22. Measured value: C, 42 · 08; H, 3 · 24; N, 9.13. Example 442 3- {3-`` (2S) -2-Aminopyridin-3-yl Vpropoxyl 5--isoquinolin-6-yl-pyridine-4- Example} -Promethazine 442A 3-lactyl-5- (4-methylamino-uroxy) ratio of 3-chloro-5-hydroxypyridine (2.0 g, 17.0 mmol), 4- A solution of methoxybenzyl alcohol (2.85 g, 25.5 mmol) and triphenylphosphine (6.68 g, 25.5 mmol) in anhydrous THF (100 ml), DEAD (4.44 g, 25.5 mmol) was added dropwise. The resulting solution was stirred at room temperature for 3 hours. The reaction solution was separated between ethyl acetate and water. The organic layer was washed (brine), Dry (NaaSO4), filter, and concentrate under vacuum. Purify on silica gel using 20% ethyl acetate / hexane to provide the title compound (19 g, 53%). MS (DCI / NH3) m / e 250 ( M + l) +.

實例442B 3·氯基「5:(4-甲氧基-苄氣某吡啶-4-羧甲醛將DIPA (1.73克，17.16毫莫耳）於THF (1〇〇毫升）中之溶液，在 200301122Example 442B 3. Chloroyl 5: (4-methoxy-benzylpyridine-4-carboxaldehyde) A solution of DIPA (1.73 g, 17.16 mmol) in THF (100 ml), 200301122

(338) 0°C下，以n-BuLi (6·86毫升，17.16毫莫耳）逐滴處理，於〇°c下授拌30分鐘。在-78°C下，於反應物中，逐滴添加THF (10毫升）中之實例442A (3.56克，14.3毫莫耳）。將所形成之溶液於_ 78°C下攪拌1小時。以甲酸甲酯（2.0毫升）使混合物淬滅。使反應溶液於醋酸乙g旨與水之間作分液處理。將有機層洗牙条 (鹽水）’脫水乾燥（Na〗SO4) ’過濾、及在真空下濃縮。於碎膠上純化，使用20%醋酸乙酯/己烷，提供標題化合物（2·2克，56% ) 〇 MS (DCI/NH3) m/e 278 (M+l)+ ·(338) n-BuLi (6.68 ml, 17.16 mmol) was treated dropwise at 0 ° C, and the mixture was incubated at 0 ° C for 30 minutes. At -78 ° C, Example 442A (3.56 g, 14.3 mmol) in THF (10 mL) was added dropwise to the reaction. The resulting solution was stirred at -78 ° C for 1 hour. The mixture was quenched with methyl formate (2.0 ml). The reaction solution was subjected to liquid separation between ethyl acetate and water. The organic layer toothpick (brine) 'was dried (Na? SO4)' filtered and concentrated under vacuum. Purified on crushed gel using 20% ethyl acetate / hexane to provide the title compound (2.2 g, 56%). MS (DCI / NH3) m / e 278 (M + l) + ·

實例442C 氯基甲氧基-爷氧基X咬冰基·μ丙締月杳將甲基氰基騰酸二乙醋（212當克’ 1·2毫莫耳）於THF (4毫升）中之溶液，在0°C下，以LiHMDS(1.2毫升，L2毫莫耳）逐滴處理，在0 C下攪:拌3〇分鐘，以THF (1毫升）中之實例442B (277 毫克’ 1毫莫耳）處理。將所形成之溶液攪拌1小時。以水使混合物淬滅。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥讲％s〇4)，過滤及在真 2下濃縮。於矽膠上純化，使用20%醋酸乙酯/己烷，提供標題化合物（210 毫克，7〇% )。MS (DCI/NH3)m/e 301 (Μ+1)+·Example 442C Chloromethoxy-Ethoxy X X-Iceyl · μAcrylidine Dimethylacetonate (212 ng '1.2 mmol) in THF (4 ml) The solution was treated dropwise with LiHMDS (1.2 ml, L2 mmol) at 0 ° C, stirred at 0 C: stirred for 30 minutes, in THF (1 ml) Example 442B (277 mg ' Millimoles). The resulting solution was stirred for 1 hour. The mixture was quenched with water. The reaction solution was subjected to liquid separation between ethyl acetate and water. The organic layer was washed (brine), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification on silica gel using 20% ethyl acetate / hexane provided the title compound (210 mg, 70%). MS (DCI / NH3) m / e 301 (Μ + 1) + ·

實例442D 基-5-羥基-I啶士基)-丙烯腈於實例442C (L02克，3.4毫莫耳）在二氯曱烷（1〇亳升）中之洛液内’添加THA (1毫升）。將所形成之溶液攪拌兩小時。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（N^SO4)，過濾及在真空下濃縮。於矽 -346- (339)Example 442D-Hydroxy-5-hydroxy-I-pyridinyl) -acrylonitrile was added THA (1 mL) to the solution of Example 442C (L02 g, 3.4 mmol) in dichloromethane (10 liters) ). The resulting solution was stirred for two hours. The reaction solution was separated between ethyl acetate and water. The organic layer was washed (brine), dried (N ^ SO4), filtered and concentrated under vacuum. Yu Si -346- (339)

膠上純化，使用40%醋酸乙酯/己烷，提供標題化合物（600 毫克，98%)。MS(DCI/NH3)m/el81(M+l)+·Purified on gel using 40% ethyl acetate / hexanes to provide the title compound (600 mg, 98%). MS (DCI / NH3) m / el81 (M + l) + ·

實例442E QSV「2-「5-氯基-4-(2-氰基-乙烯基）-吡啶-3-甚氣基H-(1H-吲哚甲基)-乙基1-胺甲基酸第三-丁酯於實例442D (430毫克，2·39毫莫耳）、Ν·α-(第三·丁氧羰基）心色胺酸（762毫克，2.6毫莫耳）及三苯膦（138克，5 26毫莫耳）在無水THF (40毫升）中之溶液内，添加DBAD (88〇毫克，3 82 毫莫耳）°將所形成之溶液於室溫下攪拌3小時。使反應溶液於醋酸乙醋與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（NhSCXO，過濾及在真空下濃縮。於矽膠上純化，使用20%醋酸乙酯/己烷，提供標題化合物（34〇克，32 % )。MS (DCI/NH3) m/e 453 (M+l)+ ·Example 442E QSV "2-" 5-Chloro-4- (2-cyano-vinyl) -pyridine-3-verytyl H- (1H-indolemethyl) -ethyl 1-aminomethyl acid Tertiary-butyl ester in Example 442D (430 mg, 2.39 mmol), N · α- (tertiary butoxycarbonyl) cardiotryptophan (762 mg, 2.6 mmol) and triphenylphosphine ( 138 g, 5 26 mmol) In a solution in anhydrous THF (40 ml), DBAD (88 mg, 3 82 mmol) was added and the resulting solution was stirred at room temperature for 3 hours. The reaction was allowed to react The solution was separated between ethyl acetate and water. The organic layer was washed (brine), dried (NhSCXO, filtered, and concentrated under vacuum. Purified on silica gel using 20% ethyl acetate / hexane, provided The title compound (340 g, 32%). MS (DCI / NH3) m / e 453 (M + 1) + ·

CNCN

實例442g 基-乙烯基V5-I 4毗人竿_ ~基氣基 1-H1H-吲在N2下，於實例442£(330毫克，0.73蒼曰 •0笔旲耳）、6-(i，i，i-三甲基錫烷基）-異喹啉（276毫克，0.95亳莫：A ，，毛吴斗）、參（二苯亞甲基丙 -347- 200301 (340) 酉同）-一免（66.8毫克’ 0.073毫莫耳）及2-二環己基膦基-2，-二甲胺基-1，Γ-聯苯（57.3 ^:克，0.146毫莫耳）在無水DMF (1〇毫升）中之落液内’添加三乙胺。將所形成之溶液於1〇〇。〇下攪拌3小時。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（Na2 S04)，過濾及在真空下濃縮。於珍膠上純化，使用60%醋酸乙酯/己烷，提供標題化合物（61 毫克，17%)。MS(DCI/NH3)m/e546(M+l)+·Example 442g of phenyl-vinyl V5-I 4 is hexafluoro- 1-H1H-indene under N2, as in Example 442 £ (330 mg, 0.73 Cang • 0 pens), 6- (i, i, i-trimethylstannyl) -isoquinoline (276 mg, 0.95 mol: A, Mao Wudou), ginseng (diphenylmethylene propyl-347- 200301 (340) same)- One free (66.8 mg '0.073 mmol) and 2-dicyclohexylphosphino-2, -dimethylamino-1, Γ-biphenyl (57.3 g: 0.146 mmol) in anhydrous DMF (1 0mL) Triethylamine was added to the solution. The resulting solution was dissolved in 100%. Stir for 3 hours. The reaction solution was separated between ethyl acetate and water. The organic layer was washed (brine), dried (Na2SO4), filtered and concentrated under vacuum. Purified on gelatine using 60% ethyl acetate / hexane to provide the title compound (61 mg, 17%). MS (DCI / NH3) m / e546 (M + l) + ·

ίJ¾L^^ hiM(2S)-2-胺基-3-(1Η-4丨嗓-3-基V丙氣某1-5-異4淋_6·基-ρ比咬-4- 基丨-丙烯月青 MS (DCI/NH3) m/e 446 (M+l)+ ; 1 h NMR (300 MHz, D6 -DMSO) δ 1L06 (s ； 1H), 9.68 (s ； 1H), 8.68 (d ； 1H ； J=6.0 Hz), 8.58 (s ； 1H), 8.44 (d ； 1H ； J=8.4 Hz)，8.40(s; 1H)，8.23 (d; 1H; J=6.0Hz)，8.20 (s; 3H)，7.80 (d; 1H; J=8.4Hz)， 7.60 (d； 1H； J=8.4HzX7.44(d； 1H； J=17.1 Hz), 7.40 (d； 1H； J=8.4 Hz), 7.30 (s ; 1H)，7.11 (t ; 1H ; J=8.4 Hz)，7.01 (t ; 1H ； J=8.4 Hz), 6.24 (d ； 1H ； J= 17.1 Hz)，4·48 (m ; 1H)，4·31 (m ; 1H)，3.97 (m ; 1H)，3.17 (m ; 2H)ίJ¾L ^^ hiM (2S) -2-Amino-3- (1Η-4 丨 Hydr-3-yl V-propane, a 1-5--Iso-4 lyl-6-yl-ρ ratio bite-4-yl 丨- Acrylic Moongreen MS (DCI / NH3) m / e 446 (M + 1) +; 1 h NMR (300 MHz, D6 -DMSO) δ 1L06 (s; 1H), 9.68 (s; 1H), 8.68 (d; 1H; J = 6.0 Hz), 8.58 (s; 1H), 8.44 (d; 1H; J = 8.4 Hz), 8.40 (s; 1H), 8.23 (d; 1H; J = 6.0Hz), 8.20 (s; 3H), 7.80 (d; 1H; J = 8.4Hz), 7.60 (d; 1H; J = 8.4HzX7.44 (d; 1H; J = 17.1 Hz), 7.40 (d; 1H; J = 8.4 Hz), 7.30 (s; 1H), 7.11 (t; 1H; J = 8.4 Hz), 7.01 (t; 1H; J = 8.4 Hz), 6.24 (d; 1H; J = 17.1 Hz), 4.48 (m; 1H ), 4.31 (m; 1H), 3.97 (m; 1H), 3.17 (m; 2H)

實例443 V乙胺所要之產物係經由以碘化甲烷取代實例442中之醋酸乙酯，省略實例442C之步驟而製成。MS(DCI/NH3)m/e409(M+l)+ ; 1 H NMR (300 MHz，D6-DMSO) δ 11.06 (s ; 1H)，9.72 (s ; 1H)，8.68 (d : 1H ; J=6.0 Hz)，8.47 (d; 1H; J=8.4Hz)，8.37(s; lH)，8.32(s; 1H)，8.22 (m; 4H)，7.91 (d ： 1H； J=8.4Hz),7.61 (d ； 1H ； J=8.4 Hz), 7.40 (d ； 1H ; J=8.4 Hz)，7·30 -348- 200301122 (341) (s , 1H)，7·12 (t , 1H，J=8.4 Hz), 7·02 (t ; 1H ; J=8.4 Hz)，4.37 (m ; 1H) 4 22 (m ; 1H)3 3.89 (m ； 1H)，3·20 (m ; 2H)，2.29 (s ; 3H)· 實例444 5-{5-『(2S)-2-胺基嗓-3-基）-丙氧基i-p比淀各基卜Example 443 V ethylamine The desired product was prepared by replacing the ethyl acetate in Example 442 with methyl iodide and omitting the steps of Example 442C. MS (DCI / NH3) m / e409 (M + l) +; 1 H NMR (300 MHz, D6-DMSO) δ 11.06 (s; 1H), 9.72 (s; 1H), 8.68 (d: 1H; J = 6.0 Hz), 8.47 (d; 1H; J = 8.4Hz), 8.37 (s; lH), 8.32 (s; 1H), 8.22 (m; 4H), 7.91 (d: 1H; J = 8.4Hz), 7.61 (d; 1H; J = 8.4 Hz), 7.40 (d; 1H; J = 8.4 Hz), 7.30 -348- 200301122 (341) (s, 1H), 7.12 (t, 1H, J = 8.4 Hz), 7.02 (t; 1H; J = 8.4 Hz), 4.37 (m; 1H) 4 22 (m; 1H) 3 3.89 (m; 1H), 3.20 (m; 2H), 2.29 (s 3H) · Example 444 5- {5-『(2S) -2-Amino group-3-yl) -propoxy ip

二氫-吲哚-2-酮實例444A 3_甲基-1,3-二氤-吲嗓-2-酮將氧化巧哚（665毫克，5·0毫莫耳）於THF (10毫升）中之溶液，在_78。。’以n-BuLi(4·4毫升，11·〇毫莫耳）逐滴處理，於_78。。籲下擴;拌30分鐘。在-78°C下，於反應物中逐滴添加甲基破（2 毫升）。使所形成之溶液溫熱至室溫❹以水使混合物泮滅。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（Na2S〇4)，過濾及在真空下濃縮。於矽膠上純化，使用30%醋酸乙酯/己烷，提供標題化合物（63〇毫克，86%)。MS(DCI/NH3)m/el48(M+l)+· ±_MJ44^ 臭基-3-甲基-1,3-二乳丨噪-2-酉同在-10°C下，於實例444B (625毫克，4·25毫莫耳）在乙腈（1〇毫升）中之溶液内，添加NBS (757毫克，4.25毫莫耳）。將混合物於-10 C下擾拌1小時，及於0°C下2小時。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（Na2S〇4)，過濾及在真空下濃縮。於矽膠上純化，使用30%醋酸乙酯/己烷，提供標題化合物（640毫克，66% ) 。MS (DCI/NH3) m/e 227 (M+l)+· -349- (342)Example of dihydro-indole-2-one 444A 3-methyl-1,3-difluorene-indone-2-one Oxidoredoline (665 mg, 5.0 mmol) in THF (10 ml) The solution in _78. . ′ Was treated dropwise with n-BuLi (4.4 ml, 11.0 mmol) at -78. . Call for downward expansion; mix for 30 minutes. Methylsulfuric acid (2 ml) was added dropwise to the reaction at -78 ° C. The resulting solution was allowed to warm to room temperature and the mixture was quenched with water. The reaction solution was separated between ethyl acetate and water. The organic layer was washed (brine), dried (Na2SO4), filtered and concentrated under vacuum. Purification on silica gel using 30% ethyl acetate / hexane provided the title compound (63 mg, 86%). MS (DCI / NH3) m / el48 (M + l) + · ± _MJ44 ^ Sulfuryl-3-methyl-1,3-dilactate Noise-2- 酉 Same at -10 ° C, in Example 444B (625 mg, 4.25 mmol) in acetonitrile (10 ml) was added NBS (757 mg, 4.25 mmol). The mixture was stirred for 1 hour at -10 ° C and 2 hours at 0 ° C. The reaction solution was subjected to liquid separation between ethyl acetate and water. The organic layer was washed (brine), dried (Na2SO4), filtered and concentrated under vacuum. Purification on silica gel using 30% ethyl acetate / hexane provided the title compound (640 mg, 66%). MS (DCI / NH3) m / e 227 (M + l) + · -349- (342)

實例444C 5-{5彳(2SV2-胺基-3-(1Η-钊哚-3-基V丙氣基1-吡啶-3-基13-曱基-1,3- 二氫-啕哚-2-酮所要之產物係經由以實例44B取代實例32中之6-溴基鄰苯二曱醯亞胺而製成。iHNMRpOOMHiDfDMSO) 5 11.04(s ; 1H)， 10.49 (s ; 1H)，8·53 (s ; 1H)，8·30 (s ; 1H)，8.16 (s ; 2H)，7.64 (s ; 1H), 7.62 (d ； 1H； J=7.5 Hz), 7.53 (d； 1H； J=7.5 Hz), 7.38 (d； 1H； J=8.7 Hz), 7.30 (s； 1H)37.10 (t ； 1H ； J=8.7 Hz), 7.01 (t ； 1H ； J=8.7 Hz), 6.93 (d ； 1H ； J=8.7 Hz), 4.33 (m; 1H)，4.14 (m; 1H)，3.84 (m; 1H)，3.49 (q; 1H; J=7.5)，3.14 (m; 2H)，1.39 (d ； 3H ； J=7.5 Hz) ； MS (DCI/NH3) m/e 413 (M+l)+. 實例445 5-{5-f(2S)-2-胺基-3-ΠΗ-Κ1哚各基V丙氧基1-吡啶！基二甲某-Example 444C 5- {5fluoren (2SV2-amino-3- (1fluoren-zolin-3-yl V-propanyl 1-pyridin-3-yl 13-fluorenyl-1,3-dihydro-fluorindol- The desired product of 2-ketone was prepared by replacing Example 6B with 6-bromo-phthalimide of Example 32. iHNMRpOOMHiDfDMSO) 5 11.04 (s; 1H), 10.49 (s; 1H), 8 · 53 (s; 1H), 8.30 (s; 1H), 8.16 (s; 2H), 7.64 (s; 1H), 7.62 (d; 1H; J = 7.5 Hz), 7.53 (d; 1H; J = 7.5 Hz), 7.38 (d; 1H; J = 8.7 Hz), 7.30 (s; 1H) 37.10 (t; 1H; J = 8.7 Hz), 7.01 (t; 1H; J = 8.7 Hz), 6.93 (d; 1H; J = 8.7 Hz), 4.33 (m; 1H), 4.14 (m; 1H), 3.84 (m; 1H), 3.49 (q; 1H; J = 7.5), 3.14 (m; 2H), 1.39 (d ; 3H; J = 7.5 Hz); MS (DCI / NH3) m / e 413 (M + 1) +. Example 445 5- {5-f (2S) -2-amino-3-ΠΗ-K1 indole each V propoxy 1-pyridine!

1,3-二氫-吲哚-2-酮實例445A 3,3-二曱基-1,3-二氫-吲哚_2_酮將實例444A (500毫克，3.4毫莫耳）於THF (10毫升）中之溶液，在-78°C下，以n-BuLi (2.7毫升，6.8毫莫耳）逐滴處理，於-78 °C下攪拌30分鐘。在-78°C下，於反應物中逐滴添加甲基碘（2 毫升）。使所形成之溶液溫熱至室溫。以水使混合物淬滅。使反應溶液於醋酸乙酯與水之間作分液處理。將有機層洗滌（鹽水），脫水乾燥（Na〗SO4)，過濾及在真空下濃縮。於矽膠上純化，使用30%醋酸乙酯/己烷，提供標題化合物（41〇毫克，75%)。MS(DCI/NH3)m/el62(M+)+.1,3-Dihydro-indole-2-one Example 445A 3,3-Difluorenyl-1,3-dihydro-indole_2_one Example 444A (500 mg, 3.4 mmol) in THF The solution in (10 ml) was treated dropwise with n-BuLi (2.7 ml, 6.8 mmol) at -78 ° C, and stirred at -78 ° C for 30 minutes. Methyl iodide (2 ml) was added dropwise to the reaction at -78 ° C. The resulting solution was allowed to warm to room temperature. The mixture was quenched with water. The reaction solution was separated between ethyl acetate and water. The organic layer was washed (brine), dried (NaSO4), filtered, and concentrated under vacuum. Purification on silica gel using 30% ethyl acetate / hexanes provided the title compound (41 mg, 75%). MS (DCI / NH3) m / el62 (M +) +.

實例445B 20030Π22 (343) 5-{5-[(28)-2-胺基-3-(111-吲哚-3-基）-丙氫基1-吡啶-3-基}-3,3-二甲基-1，3_二氫-口弓1 口果·2-酮Example 445B 20030Π22 (343) 5- {5-[(28) -2-Amino-3- (111-indol-3-yl) -propanyl 1-pyridin-3-yl} -3,3- Dimethyl-1,3_dihydro-oral arch 1 Oral fruit · 2-one

標題化合物係經由以實例445Α取代實例444中之實例444Α 而製成。111圓11(3001^1^，06-01^0)(5 11.〇3(5;111)，10.49(8;1印，8.56 (s ; 1Η)，8.31 (s ; 1Η)，8.18 (s ; 2Η)，7·70 (s ; 1Η), 7.64 (s ； 1H)，7.61 (d ; 1H ； J=7.5Hz)，7.57(d; 1H; J=7.5Hz)，7.38 (d; 1H; J=8.7Hz)，7.27 (s; 1Η)，7·10 (t ； 1H ； J=8.7 Hz), 7.01 (t ； 1H ； J=8.7 Hz), 6.96 (d ； 1H ; J=8.7 Hz)，4.33 (m; 1H)，4.17 (m; 1H)，3.84 (m; 1H)，3.17 (m; 2H)，1.31 (s; 6H); MS (DCI/NH3) m/e 427 (M+l)+. 實例446 5-{5J(2S)-2-胺基-3-ΠΗ-Θ1哚-3-基V丙氳基l·吡啶各基M，3,3-三甲基 -1,3-二复弓1嗓-2-酉同實例446Α 1,3,3-三甲基-1.3-二 f. 哚-2-酮標題化合物係經由以實例445Α取代實例II2中之實例1〇2Α 而製成。MS (DCI/NH3 ) m/e 176 (M+l)+ ·The title compound was prepared by replacing Example 444A in Example 444 with Example 445A. 111 circle 11 (3001 ^ 1 ^, 06-01 ^ 0) (5 11.〇3 (5; 111), 10.49 (8; 1 India), 8.56 (s; 1Η), 8.31 (s; 1Η), 8.18 ( s; 2Η), 7.70 (s; 1Η), 7.64 (s; 1H), 7.61 (d; 1H; J = 7.5Hz), 7.57 (d; 1H; J = 7.5Hz), 7.38 (d; 1H ; J = 8.7Hz), 7.27 (s; 1Η), 7.10 (t; 1H; J = 8.7 Hz), 7.01 (t; 1H; J = 8.7 Hz), 6.96 (d; 1H; J = 8.7 Hz ), 4.33 (m; 1H), 4.17 (m; 1H), 3.84 (m; 1H), 3.17 (m; 2H), 1.31 (s; 6H); MS (DCI / NH3) m / e 427 (M + l) +. Example 446 5- {5J (2S) -2-Amino-3-ΠΗ-Θ1 indol-3-yl V propionyl l · pyridine each group M, 3,3-trimethyl-1, 3-Diplex bow 1 acyl-2-fluorene is the same as in Example 446A 1,3,3-trimethyl-1.3-di-f. The indole-2-one title compound was obtained by replacing Example 102 in Example II2 with Example 445A. And made. MS (DCI / NH3) m / e 176 (M + l) + ·

實例446Β 5-{5-「(28)-2-胺基-3-(111^1哚-3-基）-丙氫基1-吡啶各基丨-1,3,3-三甲基 -1，3-二氫丨嗓-2-酮標題化合物係經由以實例446Α取代實例444中之實例444Α 而製成。1«[丽11(300乂1^，06-01^0)(5 11.〇3(3:111)，8.60(5;111)，8.32 (s ; 1Η)，8.20 (s ; 2Η)，7.78 (s ; 1Η)，7.67 (d ; 1H ； J=7.5 Hz), 7.62 (d ； 1H ； j=7.5 Hz)，7.39 (d ; 1H ; J=8.7 Hz)，7·29 (s ; 1H)，7.14 (d ; 1H ; J=8.7 Hz)，7.10 (t; 1H; J=8.7Hz)，7.01 (t; 1H; J=8.7Hz)，4.35 (m; 1H)，4.28 (m ; 1H)，3.83 -351 - 200301122 (344) (m; 1H)，3.19 (s; 3H)，3·17 (m; 2H)，1.33 (s; 6H); MS (DCI/NH3) m/e 441 (M+l)+ · 實例447 5-{5-f(2S)-2-胺基-3-(111-4丨嗓-3-基）-丙氣基1_?比淀-3-基丨-3-乙基-1，3- 二氮·口弓1 口朵-2-酉同標題化合物係經由以碘化乙烷取代實例444中之碘甲烷而製成。！11腦尺（300]^112,〇6-〇]^3〇) 5 11.04 (s; 1H)，10.51 (s: 1Η)，8·53 (s； lH),8.30(s； lH),8.16(s； 2H), 7.64 (s ； 1H), 7.62 (d ； 1H ； J=7.5 Hz), 7.53 (d ; 1H ； J=7.5 Hz), 7.38 (d ； 1H ； J=8.7 Hz), 7.28 (s ； lH)，7.10(t; 1H ； J= 8.7 Hz), 7.01 (t ； 1H； J=8.7 Hz), 6.93 (d ； 1H ； J=8.7 Hz), 4.33 (m ； 1H)34.16 (m； lH),3.84(m； 1H), 3.49 (t ； 1H ； J=7.5), 3.14 (m ； 2H), 1.85(m； 2H), 1.09 (d ； 3H ； J=7.5 Hz) ； MS (DCI/NH3) m/e 427 (M+l)+. 實例448 ^{5-『(2S)-2-胺基吲哚-3-基V丙氧基1-吡啶-3-基丨-3-芊基-1，3- 二氫-吲哚-2-酮標題化合物係經由以氯化芊取代實例444中之碘甲烷而製成。1 H NMR (300 MHz，D6-DMSO) δ 11.04 (s ; 1H)，10.48 (s ; 1H)，8.38 (s ; 1H)，8.27 (s ; 1H), 8.15(s； 2H), 7.62 (d ； 1H ； J=7.5 Hz), 7.44 (d ； 1H ； J=7.5Hz),7.40(s； lH),7.39(d； 1H； J=8.7 Hz), 7.29 (s ； 1Η), 7.17(χη； 5H), 7.10 (t ； 1H ； J=8.7 Hz), 7.01 (t ； 1H ； J=8.7 Hz), 6.82 (d ； 1H ； J=8.7 Hz), 430 (m ; 1H)，4.12 (m ; 1H)，3.86 (m ; 1H)，3.40 (m ; 1H)，3.17 (m ; 2H)，3·01 (m，1H) ; MS (DCI/NH3) m/e 489 (M+l)+ · 熟請此藝者將明白的是，本發明並不限於前述說明例，且其可在未偏離其基本特質下，以其他特定形式具體表現。因此’想要的是’將此等實例於各方面視為說明性而非 •352- 200301122 (345) 限制性，可參考隨文，因此，來自於申請有改變，均意欲被包所附之申請專利範圍，而非前文實例專利範圍等效性之意義與範圍内之所含於其中。Example 446B 5- {5-"(28) -2-Amino-3- (111 ^ 1indol-3-yl) -propanyl 1-pyridinyl-1--1,3,3-trimethyl- The title compound was prepared by replacing Example 444A in Example 444 with Example 446A. 1 «[Li 11 (300 丽 1 ^, 06-01 ^ 0) (5 11 〇3 (3: 111), 8.60 (5; 111), 8.32 (s; 1Η), 8.20 (s; 2Η), 7.78 (s; 1Η), 7.67 (d; 1H; J = 7.5 Hz), 7.62 (d; 1H; j = 7.5 Hz), 7.39 (d; 1H; J = 8.7 Hz), 7.29 (s; 1H), 7.14 (d; 1H; J = 8.7 Hz), 7.10 (t; 1H; J = 8.7Hz), 7.01 (t; 1H; J = 8.7Hz), 4.35 (m; 1H), 4.28 (m; 1H), 3.83 -351-200301122 (344) (m; 1H), 3.19 (s; 3H), 3.17 (m; 2H), 1.33 (s; 6H); MS (DCI / NH3) m / e 441 (M + l) + · Example 447 5- {5-f (2S) -2- Amino-3- (111-4 丨 Hex-3-yl) -propanyl 1-? Biyodo-3-yl 丨 -3-ethyl-1,3-diazine · 1酉 The same title compound was prepared by replacing iodomethane in Example 444 with ethane iodide. 11 Brain ruler (300) ^ 112, 〇6-〇] ^ 3〇) 5 11.04 (s; 1H), 10.51 (s: 1Η), 8.53 (s; lH), 8.30 (s; lH), 8.16 (s; 2H), 7.64 (s; 1H), 7.62 (d ; 1H; J = 7.5 Hz), 7.53 (d; 1H; J = 7.5 Hz), 7.38 (d; 1H; J = 8.7 Hz), 7.28 (s; lH), 7.10 (t; 1H; J = 8.7 Hz ), 7.01 (t; 1H; J = 8.7 Hz), 6.93 (d; 1H; J = 8.7 Hz), 4.33 (m; 1H) 34.16 (m; lH), 3.84 (m; 1H), 3.49 (t; 1H; J = 7.5), 3.14 (m; 2H), 1.85 (m; 2H), 1.09 (d; 3H; J = 7.5 Hz); MS (DCI / NH3) m / e 427 (M + l) +. Example 448 (5-((2S) -2-aminoindol-3-yl) Vpropoxy1-pyridin-3-yl) -3-fluorenyl-1,3-dihydro-indole-2 -The ketone title compound was prepared by replacing the methyl iodide in Example 444 with hafnium chloride. 1 H NMR (300 MHz, D6-DMSO) δ 11.04 (s; 1H), 10.48 (s; 1H), 8.38 (s; 1H), 8.27 (s; 1H), 8.15 (s; 2H), 7.62 (d ; 1H; J = 7.5 Hz), 7.44 (d; 1H; J = 7.5Hz), 7.40 (s; lH), 7.39 (d; 1H; J = 8.7 Hz), 7.29 (s; 1Η), 7.17 (χη 5H), 7.10 (t; 1H; J = 8.7 Hz), 7.01 (t; 1H; J = 8.7 Hz), 6.82 (d; 1H; J = 8.7 Hz), 430 (m; 1H), 4.12 (m 1H), 3.86 (m; 1H), 3.40 (m; 1H), 3.17 (m; 2H), 3.01 (m, 1H); MS (DCI / NH3) m / e 489 (M + l) + · Those skilled in the art will appreciate that the present invention is not limited to the aforementioned illustrative examples, and it can be embodied in other specific forms without departing from its basic characteristics. Therefore, 'what I want' is to treat these examples in all respects as illustrative rather than • 352- 200301122 (345) Restrictive, refer to the accompanying text. Therefore, changes from the application are intended to be included in the package. The scope of the patent application, but not the meaning and scope of the equivalence of the foregoing example patent scope, is included therein.

-353 --353-

Claims

20030112 Class: Patent application Fanyuan L A compound of formula (I)

R4 or a therapeutically acceptable salt thereof; wherein fluorenyl X is selected from the group consisting of C (R8) and n; where R8 is selected from the group consisting of hydrazone, amine, carboxyl, cyano, fluorenyl, hydroxy, and fluorenyl ; X 'is selected from the group consisting of C and N; γ is selected from the group consisting of C and N; Qi and 、 are selected from the group including C (R9) and N; wherein R9 is selected from the group including L3 (R3) (r6); Z is selected from the group consisting of C and N; provided that X, X, Y, Y, and 0, 1 or 2 of Z are L1; is selected from the group consisting of a bond, -0, -NR5-, Hydrazone, decyl radical c (0)-, -S-, -s (o)-, -s (0) 2-, -s (o) 2n (r5)-, -n (r5) s (o) 2- ,, c (Rl2, -C (R12) 2N (R5)-, -N (R5) C (〇)-, and -C (0) N (R5)-; each dragon is drawn as its left end connected To R1, and its right end is connected to the aromatic ring ... L2 is selected from the group consisting of a bond, _〇 ·, -C (R12) 2_, each, seven (Han 5) -N (R5) C (0)- And -C (0) N (R5) "· L3 is selected from the group consisting of a bond, an alkylene group and an alkylene group, wherein the alkylene group and the alkylene group are optionally substituted with one or two substituents, The group is independently selected from the group consisting of alkoxy, amino, cyano and several groups;

200301122 R1 is selected from the group consisting of Fang, Iwanan, heteroaryl and heterocyclic ring; R2 and R4 are independent of the existence of A. ^ A exists, or is selected from the group consisting of hydrogen, alkynyl, amine, aryl, Xi | Yebubutyl alkyl A — 1 I Vanyl alkynyl, cyano, cyanofluorenyl, function I '"IH #i alkyl and nitro; or R2 and L1' and their wastes Linking < carbon atoms together to form a ring, selected from the group consisting of aryl, heteroaryl and conical rings; or R and L, and their connected groups to form a ring together with carbon atoms, selected from the group consisting of aryl, Heteroaryl and heterocyclic ring; provided that when L3 is alkylene, r, l2 and the carbon atom to which they are connected 3- form a ring selected from the group consisting of aryl, heteroaryl and heterocyclic ring; R3 Is absent, or is selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamino, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl, heteroaryl Alkoxy, heteroaryloxy and heterocyclic ring; R6 is selected from the group consisting of hydrogen, aryl, arylalkoxy, aralkylamino, aralkylthio, aryloxy, arylthio, ring Alkyl, heteroaryl, heteroaryl Fluorenyloxy, heteroaryloxy and heterocyclic ring; the condition is that when L1 and L2 are bonded, at least one of R3 and R6 is different, and R5 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, Alkylsulfonyl, arylalkynyl, arylsulfonyl and heteroarylsulfonyl; R7 is absent, or is selected from the group consisting of hydrogen, alkyl, cyanoalkenyl and _12_l3 (r3) ( r6); or R7 forms a ring together with L1 'and the carbon atom to which they are attached, selected from the group consisting of aryl, heteroaryl, and heterocyclic ring; and 20031122

Each R12 is selected from the group consisting of hydrogen, fluorenyl, alkyl, alkynyl, amine, aryl, cyano, dentyl, heteroaryl, heterocyclic, and nitro. 2. — compounds of formula (II)

Or a therapeutically acceptable salt thereof, wherein L1 is selected from the group consisting of a bond, -α, · N (Κ5, alkenyl, alkynyl, -N (R5) C (0)-, and -C (0) N (R5)-; L2 is selected from the group consisting of a bond, · α, _n (r5) c (0>) and C (0) N (R5)-; L3 is selected from the group consisting of a bond, alkylene And alkylene, wherein alkylene and alkylene are optionally substituted by one or two substituents, and the substituents are independently selected from the group consisting of amine, cyano, and warp; R1 is selected from the group consisting of aryl, heteroaryl And heterocyclic ring; amine hetero or RW is selected from the group consisting of gas, alkenyl, block 1 group, group, group, cyano, ... group, halo group, hydroxy group and heteroaryl group; wherein aryl group is selected from Including furyl "" radicals, thiazolyl and thienyl; together to form a ring, selected from the group consisting of a ring or a group, selected from the group R2 and L1, and the carbon to which they are attached including dihydrogen Base, tonyl and phenyl; R4 and L2, and the carbon atoms to which they are attached include dihydropyrrolyl, benzyl, pyrimidine 200301122

It is substituted by a keto group; the condition is that when L3 is an alkylene group, R4 forms a ring together with L2 and the # atom to which they are connected, and is selected from the group consisting of dihydropyrrolyl, phenyl, rhodime and pyrrolyl Where the ring may be substituted by a keto group as appropriate; R is absent 'or selected from the group consisting of hydrogen, aryl, arylamino, aralkylthio, aryloxy, arylthio, cycloalkyl, heteroaryl R6 is independently selected from the group consisting of hydrogen, aryl, arylalkoxy, arylfluorenylthio, aryloxy, arylthio, ring Alkyl, heteroaryl and heteroarylalkoxy, heteroaryloxy and heterocyclic ring; provided that when L1 and L2 are bonded, at least one of R3 and R6 is not hydrogen; R is selected from Including hydrogen, 'superior group, number group, pit group continuation group, arylcarbonyl group, arylsulfonyl group and heteroarylsulfonyl group; and X is selected from the group consisting of C (R8) and ^^; where R8 The system is selected from the group consisting of hydrogen, amine, carboxyl, cyano, and self. 3 · —Compounds of formula (III)

Or a therapeutically acceptable salt thereof L is selected from the group consisting of -N (R5) C (〇); and

200301 L2 is selected from the group consisting of a bond, -0-, _n (R5)-, -N (R5) C (0)-, and a C (0) N (R5)-; where L is a subunit The secondary group is substituted with one or two substituents independently selected from the group consisting of amine and hydroxyl; R1 is selected from the group consisting of aryl, heteroaryl and heterocyclic ring; R2 and R4 are independently selected from the group consisting of hydrogen and halogen; R3 and R6 are independently selected from the group consisting of hydrogen, aryl, arylalkoxy and heteroaryl; provided that when L1 and L2 are bonded, at least one of R3 and R6 is not hydrogen; and R5 is selected Includes hydrogen and alkyl. 4. The compound according to item 1 of the scope of patent application, wherein Li is a fluorenyl group. 5. The compound according to item 4 of the scope of patent application, wherein γι is c (R9), wherein R9 is -L2-L3 (R3) (R6), and wherein L2 is -0-. 6. The compound according to item 5 of the scope of patent application, which is selected from the group consisting of N, N-dimethyl-N- [2-({5-[(E) -2-pyridin-4-ylethenyl] p-pyridinyl} oxy) ethyl] amine; (1S) -2_ (1H-indol-3-yl) -1-[({5-[(Ε) -2-pyridin-4-ylethyl Fluorenyl] p-pyridin-3-yl} oxy) fluorenyl] ethylamine; (1R) -2_ (1H-indol-3-yl) -1-[({5-[(Ε) -2- Pyridin-4-ylvinylpyridin-3-yl} oxy) methyl] ethylamine; 1- (1Η-ΘΙΙ-3-yl > · 3-({5-[(Ε) -2 ^ Biyodo-4-ylethenyl] tr biyodo-3-yl} oxy) propan-2-ol; (lS) -2- (l-benzop-phenphen-3-yl) -1- [ ({5-[(E) -2-ρ than bityl acetoacetamidite · 3-yl} oxy) methyl] ethylamine;

(1S) -2,2-diphenyl small [({5-[(E) -2-pyridin-4-ylethynyl-3-methyl} oxy) methyl] ethylamine; (1S ) -l- {4-[(2,6 < Chloroyl) oxy] zekib 2_ (d (E) _2_pyridine · 4 · ylacetamidinyl-3-yl} oxy) ethyl Amine; (1S) -2- (fluorenyloxy) -l-[({5-[(E) -2-pyridin-4-ylvinyl] pyridine; yl} oxy) methyl] ethylamine; Ν , N-dimethyl-N-[(1S, 2S) -1-methyl-2-phenyl-2-({5-[(E) -2-pyridin-4-ylethenyl)> ratio Pyridyl groups} oxy) ethyl] amines; (1S) -2- (2-naphthyl) small [({5-[(E) -2-pyridinylvinyl] pyridin-3-yl} oxy (Methyl) ethylamine; (1S) -2-({2-chloro-5-[(E) -2-pyridin-4-ylvinyl] ρ is smaller than pyridyl)} (1Η -Indole-3-ylmethyl) ethylamine; (1S) -2-({6-chloroyl-5-[(E) -2-pyridinylethenylethyl], pyridin-3-yl} (Oxy) small (1'-indol-3-ylmethyl) ethylamine; (1S) -2_ (1H-indolyl) -i-[({5-[(z) · 2 · pyridinyl Vinyl] ρpyridine groups} oxy) fluorenyl] ethylamine; and N-[(2Ε) -3- (4-bromophenyl) propan-2-methyl] -N- [2-({ 5-[(E) -2-pyridin-4-ylvinyl; Cridineyl} oxy) ethyl] amine. The compound according to item 4 of the scope of patent application, wherein γ is c (R9), wherein R9 is -L2-L3 (R3) (R6), and wherein L2 is selected from the group consisting of a bond ... N (R5)-, -N (R5) C (0)-and -C (0) N (R5)-. The compound according to item 7 of the scope of patent application, which is selected from the group consisting of N-[(2S) -2-amino-3 ((1H-indol-3-yl) propyl] -N- {5-[(E ) -2-pyridin-4-ylvinylMidin-3-yl} amine;

(2S) -2-aminobenzylphenyl-N- {5-[(E) -24pyridin-4-ylvinyl >pyridin-3-ylbubutamine; N- (aminomethyl ) -5-[(E) -2-pyridin-4-ylvinyl] in amidoamine; and (1R > -Ethyl ethynyl wind lake base} -1- (fluorene-indol-3-ylmethyl) propylamine. The compound according to item 1 of the patent application scope, wherein L1 is a bond. According to the patent application scope, ninth The compound of item, wherein γ is C (R9), wherein R9 is -L2 -L3 (R3) (R6), and wherein l2 is _〇_. According to the compound of claim 10 of the scope of application, it is selected from 4- (5-{[(2 points of 2-amino groups (1H, 1H) propyl] oxy] pyridine; group) benzonitrile; (1S) -2- (lH-W indole groups ) -1-{[((5-isopyridinyl-6-ylpyridine; yl) oxemenyl) ethylamine; (lR) -2- (lH, indolyl) small {[(5-quinolineyl Pyridine; yl) oxy] methyl) ethylamine; (1S > 2 | Chloro-5-isocentric lindenyl < < shityl) oxy] ^ tadecylfluorenyl) ethylamine; (1S) -2-[(2-chlorojisoquinolinepyridylpyridine; yl) oxy] + (1oxole! Ylpyridyl) ethylamine; yl] oxy} pyridine Each group)] fluorenyl-oxy] pyridin-3-yl) iso 5- (5-{[((2S) -2-amino group each (1H, indolyl) propyl isoamidine-1,3 (2H) -diketone; 5- (5-{[(2S) -2-amino group (1H-indole group) propandol-1-one; fluorene- (1fluorene-indol-3-yl group) Fluorenyl) ethyl (lS) -2-[(5-tholin-6-yl-r-pyridin-3-yl) oxy200301122

Amine; (lS) -2 _ {[5- (lH "? Lazol-5-yl V than pyridinyl] oxydolylmethyl) ethylamine; 5- (5-{[((2S) -2- Amino-3- (lH-p-acyl-3-yl) propyl] oxy} p ratio lake 3-yl) 3 dihydro-2Η-indole-2-one; (lS) -2- { [5- (2,1,3-Benzobenzo-5-yl) ρ is smaller than Zid-3-yl] oxy} (ex.indol-3-ylmethyl) ethylamine; (1S ) -2- (lH-indole-3-yl) small {[((5-thieno [2,3-c] pyridin-2-ylpyridyl) oxy] methyl} ethylamine; (3Z) -5- (5-{[((2S) -2-amino-3- (lHW 丨 indol-3-yl) propyl] oxy} P) than 唉 -3 · yl) -3- (1Η-pyrrole- 2-ylmethylene) -1,3-dihydro-2H-indole-2-one; and 6- (5-{[((2R) · 2 · amino-3 · (1Η-indole) ) Propyl] oxy} eridinyl 3. benzothiazole-2 (3Η) -one. 12. The compound according to item 9 of the scope of patent application, wherein γ is c (r9), and R9 is -L2- L3 (R3) (R6), and wherein l2 is selected from the group consisting of a bond, N (R5) C (0)-, and -N (R5)-. 13. According to the 12th compound of the patent application scope, It is selected from the group consisting of (2S) -2-amino-3- (lH-W-l-3-yl) -N- [5 · (1,6-Lyn-2-ylwind lake-3-yl] c Hydrazine; N-[(2S) -2-amino groups (1H-W Indole groups) propyl] [5_ (1,6_pyridinyl) eridin-3-yl] amine; (1R) -1- (1H ′? 丨 -3-ylmethyl) -3- (5-Isoquinine-6-yl-p-pyridin-3-yl) propylamine; 2- (1H-indol-3-yl) -2- (5-isojunlin-6-yl-p-pyridine- 3-yl) ethylamine; and 2- (1H-pyridin-3-yl) -3- (5-isoquinolin-6-ylpyridin-3-yl) propanamine.

200301 14. The compound according to item 9 of the scope of patent application, wherein γ is c (R9), where R9 is -L2-L3 (R3) (R6), and wherein L2 is formed together with R4 and the atom to which they are connected. Heterocyclic ring. 15. The compound according to item 14 of the scope of patent application, which is (3Z) -3-[(2S) -2-amino-3- (1Η-indol-3-yl) propylene] -5 Iso-π-quelin-6-yl-1,3-yifeng-211-external 1: Paro [2,3-b] p is the same as 唉 -2-g. This is the compound according to item 1 of the scope of patent application, wherein L! Is selected from the group consisting of alkynyl, -N (R5) C (0)-, -N (R5)-, and -0-. 17. The compound according to item 16 of the application, which is selected from the group consisting of (lS) -2- (lH-indol-3-yl) -1-({[5- (pyridin-4-ylethynyl) Pyridine groups] oxy} methyl) ethylamine; 5-{[((2S) -2-amino-3- (1Η · indole-3 · yl) propyl] oxy] N_pyridine-4- Nicotinamide; N4- (3-{[((2S) -2-amino-3- (1Η-indol-3-yl) propyl] oxy} phenyl) p-pyrimidine-2.4-di Amines; N-[(2S) -2-amino groups (1Η-pyridin-3-yl) propyl] isoisoquinolin-5-ylpyridine · 3.5-diamine; and N-[(2S)- 2-Amino-3- (1H-indolyl) propylisoquinolinyloxy) pyridyl] amine. 18. The compound according to item 1 of the scope of patent application, wherein L1 and R2 together with the atoms to which they are attached form an aryl ring. 19. The compound according to item 18 of the scope of patent application, which is (lS) -2- (lH "indol-3-yl) -1-{[(6-pyridin-4-ylfluorinyl | yl) oxy Yl] fluorenyl) Ethylamine. -9-

20. The compound according to item 1 of the scope of patent application, which is selected from the group consisting of butoxy-5- [2- (4-pyridyl) ethenyl], pyridine; 3-methoxy-5 -[2- (4-pyridyl) ethenyl], pyridine; S; [2-amino each phenyl-propoxy> 5- [2- (4 · pyridyl) vinyl] pyridine Acid salt; 3- [2- (1Η-3-indolyl) _ethoxy ... pyridyl) vinylpyridine hydrochloride; 3- [2- (1Η-3earnoyl) · propoxy ] 士 [2- (4-pyridyl) vinylpyridine; S-3-Oamino-3- (4-methoxyphenyl) _propoxy] -5- [2- (4-pyridine ) Ethynylpyridinium hydrochloride; 3- (hexahydropyridin-4-yl) -5- [2- (4-pyridyl) vinyl] ridine; R-3- {2-amine 5- (2- (4-pyridyl) vinylpiperidine hydrochloride; 3- (1-methyl-imidazole-4-methoxy) -5-1 > (4 -Pyridyl) vinylpyridine; S-3- {2-amino-3- [3-hydroxyphenyl] -propoxyb 5- [2-part pyridyl) vinyl] pyridine trifluoroacetate; S-3- {2-Amino-3- [3-cyanophenyl] -propoxy} ± [2 propidyl) vinyl] pyridine hydrochloride; 3- [1- (4-cyano Benzyl) -imidazole + methoxy] -5-1 > pyridine Group) vinyl] pyridine; S-3- [2-amino-3- (1-methyl-1H-3-indolyl) · propoxy; μ5- [2- (4-pyridyl) ethyl Alkylide hydrochloride; S-3- [2-dimethylamino-3 · (1Η each indolylpropoxypyridyl) vinyl: Kidine hydrochloride; -10-

S-3- [2-Amino-3- (1-phenyl) -propoxy] -5- [2- (4-pyridyl) ethylfluorenyl] pyridine hydrochloride; 3- (2-amine Ethoxy) -5- [2- (4-p than alkyl) vinyl] p ratio bite hydrochloride; 3- (3-aminopropyloxy) -5- [2- (4-p Pyridyl) vinyl specific bite hydrochloride; S-3- (2-amino3-methylbutoxy > 5- [2- (4-pyridyl) vinyl] pyridine hydrochloride; Ml -Methyl-3-hexahydropyridyloxy) -5- [2- (4-pyridyl) ethenyl] P-pyridine trifluoroacetate; 3- (2-chlorofluorenyl) -5- [ 2- (4-p ratio yttrium) ethenyl] p ratio yettrifluoroacetate; 3- (N-fluorenyl-N-methylaminoethoxy) -5-〇 (4-p ratio ) Acetyl] p-trifluoroacetate; 3- (6- (N, N-dimethylamino) hexyloxy) -5- [2- (4-pyridyl) acetamidinyl Fluoroacetate; 3- (2-thiophenoxy-ethoxy) -5- [2- (4-pyridyl) ethenyl] pyridine trifluoroacetate; 3- (1-fluorenyl-3 -Tetrahydrop-biharyloxy) -5- [2- (4-p bipyridyl) ethenyl] P-trifluoroacetate; 3-[(1-methyl-2-hexahydropyridine ) Methoxy] -5- [2- (4-pyridyl) ethenyl] pyridine trifluoroacetate; 3- (1-pyridyl-ethyl Group) -5- [2- (4-pyridyl) vinyl] pyridine trifluoroacetate; 4- {5-[(2S) -2-aminoaminomethyl-3-yl) -propoxy]- Only than bite-3-yl JN-meryl-benzidine trifluoroacetate; 4- {5-[(2S) -2-amino-3- (1Η-ρ-induction-3-yl) -propyl Oxy] -p than yodo-3-yl} -benzyl

200301122 脒 Trifluoroacetate; 3-[(2S) -2-amino-3- (1Η-3-βbodoyl) -propoxy] -6- (3-τ? Bitoyl) -port Quinidine 4; 3-[(2S) -2-amino-3- (1Η-3-indolyl) -propoxy] -6- (3 ^ quinolinyl) -pyridinoline; 3-[(: 2S) -2-amino-3- (1Η-3- 啕 amino) -propoxy] -5 · 〇 (2-amino-4-p than pyridyl) vinylpyridine trifluoroacetate; 5-[(2S) -2- (Amino group) -propoxy] -3- [2- (2-Amino-4-P than phenyl) ethenyl] -2-chloro4pyridine Trifluoroacetate; (1S) -1- (1H-41H-3-ylfluorenyl) -2- (5-fan-2-yl-p-pylide-3-yloxy) -ethylamine; ( lS) -l- (lH-indole-3-ylmethyl) -2- (5-isoquinolin-5-yl4pyridyloxy) · ethylamine; 6- {5-[(2S) -2-amino-3- (1H-indol-3-yl) -propoxy] bitan-3-yl} -2H-isoquinolin-1-one; (1S) -2- [5- (3-Chloro-isopropylquinol-6-ylpyridin-3-yloxy] 丨 -3-ylmethyl) -ethylamine; (1S) -2-([3,4f] bipyridine- 5-yloxy) -i- (iH-W indol-3-ylmethyl) -ethylamine trifluoroacetic acid; (1S) -1- (1H-indol-3-ylfluorenyl) -2- [ 5- (2-p specific bite-2-yl-ethenyl) -p specific bite · 3 ·· oxyl] -ethylamine; (1S) -1- (1H-H | base -2- (5-p ratio-3-ylethenyl-P ratio bite-3 * yloxy) -ethylamine trifluoroacetate; (1S) -2- [5- (2-fluoro-pyridine -4-ylethynyl) _pyridin-3-yloxy] -1- (ιη-indole-3-ylfluorenyl) -ethylamine trifluoroacetate; (lS) -4- {5- [2 -Amino group) -propoxy] -ρ than bit-3-ylethoxy} -pyridin-2-ol trifluoroacetate; -12- (lS) -2- [6-chloro- 5- (1-chloro-isoquinolin-6-yl) -pyridin-3-yloxy] + (1H, indol-3-ylfluorenyl) -ethylamine trifluoroacetate; bis- [3- (4- > Phenylphenyl) -allyl]-{2- [5- (2-pyridin-4-yl-ethylfluorenyl)-? Pyridyl-3-yloxy] -ethyl} -amine Hydrochloride; N4- [3- (2-amino-ethoxy) -phenyl] -π dense lake-2,4-diamine hydrochloride; trans- [4- (2- {5- [(2S) -2-amino-3- (1Η-indolejyl) _propylamino] _, specific bite_3 group} -vinyl) -pyrimidin-2-yl] -aminomethyl ethyl ester Trifluoroacetate; 1-amino-6- {5-[(2S) -2-amino-3- (lH-pyridin-3-yl) _propoxy ppyridin · 3_yl}- Isoquinoline trifluoroacetate; 6- {5-[(2S) -2-amino-3- (1Η-indio-3-yl) -propoxy] j. Trifluoroacetate; (2S) -2-amino-3- (1fluorene-indole -3-yl) -N- [5- (2-pyridin-4-yl-ethenyl than fluoren-3-yl] •• propanolamine, (2S) -2-amino groups (fluoren-1- Group) -N- | > (24pyridinyl-vinyl "pyridinyl groups] propylamine hydrochloride; (2S) -2-amino-3-phenyl-N- [5- (2 -Pyridin-4-yl-vinyl > pyridine groups > propanilamine hydrochloride; S-2-amino-3- (imidin-4-yl) -N- [5- (24pyridine [Ethylidene] · pyridyl] -propionamine hydrochloride; (lR) -2- (lH ′? L-3-yl) small {[(5-isoquinoline-6-yl Pyridyl) oxy] methyl} ethylamine; (1S) -5- {5- [2 · amino-3- (lH-W each group) -propoxypyridine each group 1Η · ^ | Oxazolyl amines; (lS) -6- {5- [2-Amino-3- (1Η-tendo-3-yl) -propoxyρ-pyridinyl m

200301122 azole-3-ylamine; 2-amino-N-[(1S) -1- (1H-pyridin-3-ylfluorenyl) -2- (5-isoquinoline-6-ylpyridine- 3-yloxy) -ethyl] -acetamidamine; (2S) -2-amino-N-[(1S) -1- (1H-indol-3-ylmethyl) -2_ (5- Iso-4 phyllyl groups 4 pyridin-3-yloxy) -ethyl] -propanamide; 2-diamidino-N-[(1SH- (1H-indol-3-ylmethyl) -2 -(5-isoquinoline radicals-exo-3-yloxy) -ethyl] -acetamidamine; (IS) 1 (1H? Wood-3-ylmethyl) -2- [5 -(3-methyl-IH-p archa-5-yl) -koubito-3 · yloxy] -ethylamine; (1S) -1- (1H-deca-3-ylmethyl > 2- {5- [3- (1Η-ρ 比咯 _2_yl) _m, azole: yl] -lipidyl-3-yloxy} -ethylamine; (IS) 1 (1H? j Xy-3-ylmethyl) -2- [5- (3-phenyl-lH-pin-5-yl) bito-3_yloxy] -ethylamine; (lS) -2- [5 -(3-Cyclopropyl-1H-indazol-5-yl)-, which is smaller than the pyridyloxy] (1H ′? 1indol-3-ylmethyl) -ethylamine; (1S) -2- [5- (3-Ethyl-1H, oxazolyl)-, pyridinyloxyΗ- (1Η_indolylmethyl) -ethylamine; (1S) -H1HW1 indol-3-ylmethyl ) -2- {5- [3_ (1-methyl_1Η_imidazolyl ind-5-yl) -r Ethylamine; (1S) -H1HWI indolyl fluorenyl) _2- [5- (3-4azole_2_ylazole · 5-yl) is called hydrazine-3-yloxy] -ethylamine; ( lS) -2- {5- [3- (lH-imidazol-2-yl) Kazol-5-yl] -pyridyloxy (1H-indol-3-ylmethyl) -ethylamine; ( lS) -l- (lH-indole-3-ylmethyl) -2- [5- (3-sidephen-2-yl-1H vermazolyl) _t-14-14 200301122 ertan: bite Each oxy] -ethylamine; (lS) -l- (lH-indol-3-ylmethyl) -2- [5- (3-morpholin-4-yl] Η · 嗤) · Pyridin-3-yloxy] -ethylamine; (lS) -2- [5- (l, 3-dimethyl-1H-indo-5-yl) -pyridine; yloxy > Η1Η 』? 1 indol-3-ylmethyl) -ethylamine; (1S) -1- (1H-fluorenyl 1-methyl-3-ylmethyl) -2- [3- (3-fluorenyl-1fluorene-called 1 Jun-5-yl ^ phenoxy] -ethylamine; (lS) -l- (im-n-3-ylmethyl) -2- {5- [3- (4-methyl-hexahydro p ratio p well + yl)] η · indazol-5-yl] -pyridin-3-yloxybethylamine; (lS)-(5- {5- [2-Amino_3_ (lH-p? 丨(Three-3-yl) -propoxy] · ρ ratio bite | Kibbu 1Η 』Archidazol-3-yl) -dimethyl-amine; (1S)-(4- (5- (2-amino -3- (lH-p? 丨 -3-yl) -propoxy) -ρ than bis-3-yl) -benzyl) _phenyl-amine, (lS) -(4- (5- (2-Amino-3- (1Η-β | hex-3-yl) -propoxy) -p-ratio-3-yl) · phenyl) _ methanol; (lS) -2- (5- (4-fluorophenyl) -p is smaller than yodo-3-yllactyl) (1Η-ρ5 | mouth-3-ylmethyl) · ethylamine; (lS) -4- (5 -(2-amino-3- (1Η-fluoren-3-yl) -propoxy) -pyridin-3-yl) -benzoic acid; (1S) -2- (3-bromo-5-iso Quinoline-6-yl-phenoxyoxy > 1- (1fluoren-indol-3-ylfluorenyl) -ethylamine; NΦ (3- (5 · (2-amino-3--3- (1fluorene- Allyl groups) -propoxy) -pyridin-3-yl) -benzyl >pyrimidine-2,4-diamine; (lS) -3- (2-amino-3- (1Η-ρ? 1-Hydroxy-3-yl) -propanoyl) -5-isoρ-Quulin-6-yl-aniline; 8 & 9 ^ 3ΗΕΗΒΒ £ ΗΒΙβΡΒΒ3! &Amp; ίβΒ & Lin-6-yl-p than Yodo-3-yl)-: rc nitrogen p-ratio 1: 7 Well-l-Cause brother di-Ding @ zhi, 6- (5-Hexahydropyrine-1-yl- Pyridin-3-yl) -isoquinoline; ((2S) -2-amino-5- (5- (2-amino-3- (1Η-pyridinyl) -propoxy) -pyridine each ) -Phenyl- (3-chlorophenyl-methanone; (1S) -N6- (3- (5- (2-amino each (1H-indol-3-yl) -propoxy)- Pyridin-3-yl) -phenyl) -9H-purine-2,6-diamine; (3- (5-((2S) -2-amino group * 3- (1Η-ρ? 丨 Three-3 -Yl) -propoxy) -p than yodo-3-yl) -phenyl) _ ρ bis-2-yl-amine; (3- (5-((2S) -2-amino-3- (1'-Indol-3-yl) -propoxy) -pyridin-3-yl) -phenyl) -ρ-sechon-2-yl-amine, N- (3- (5-((2S)- 2-amino-3- (1'-indol-3-yl) -propoxy) -pyridin-3-yl) -phenyl) -acetamidamine; 6- (5- (4- (1Η-fluorene) Indole-3-ylmethyl) -hexahydropyrine-1-yl) -pyridin-3-yl) -isoquinone; 3-((2S) -2-amino-3- (1Η-pyridine) -3-yl) -propoxy) -5-isoquinoline-6-yl-benzoic acid; 4- (5-((2S) -2-amino-3- (1H-pyridin-3-yl ) -Propoxy) -pyridin-3-yl) -aniline; N- (4- (5-((2S) -2-amino-3- (1H-pyridin-3-yl) -propoxy ) -Pyridine-3- ) -Phenyl) -Ethylamine, N6- (4- (5-((2S) -2-amino-3- (lH-Win-3-yl) -propoxy) -pyridine) -Phenyl) -9H-purine-2,6-diamine; N4- (4- (5-((2S) -2-amino-3- (1Η-4ΐindol-3-yl) -propoxy ) -Pyridin-3-yl) -phenyl) -u Miyodo · 2,4-diamine, (4- (5-((2S) -2-amino-3- (1H-indol-3- ) -Propoxy) -pyridin-3-yl) -phenyl)-200301

0 dense lake-2-yl-amine; 3-((2S) -2-amino-3- (1fluorene-indol-3-yl) -propoxy) -5-isoquinolin-6-yl- Benzonitrile; 5f-fluorenyl-5-isoquinolin-6-yl_ (3,3 ') bipyridine; (7- (5-((2S) -2-amino-3- (1Η- Each of the indole groups) -propoxy) -pyridin-3-yl) -pyrido (2,3- (1) 0 bis-4-yl) -epi-amine,

(7- (5-((2S) -2-amino-3- (1H-pyridin-3-yl) -propoxy) -pyridin-3-yl) -pyrido (2,3-d) p-Mid-4-yl) -ethyl-amine, (7- (5-((2S) -2-amino-3- (1H-pyridin-3-yl) -propoxy) -pyridine- 3-yl) -pyrido (2,3-d). Peptidyl-4-yl) -fluorenyl-amine, (lS) -l- (lH-indol-3-ylfluorenyl) -2- ( 6-Isoquinone-6-yl-pycn-2-yloxy) -ethylamine; (1S) -2- (5-isoquinolin-6-yl-pyridin-3-yloxy) >1-phenyl-ethylamine; (1S) -l- (lH-indole-3-ylfluorenyl) -2- (6- (3-methyl-1H-oxazol-5-yl) -pyracine -2-yloxy) -ethylamine,

(1S) cyclohexylfluorenyl-2- (5-isoquinoline-6-ylpyridin-3-yloxy) -ethylamine; (1S) -1-fluorenyl-2- (5- (3 -Methyl-1H-indazol-5-yl) -pyridin-3-yloxy) -ethylamine; (lS) -2- (5- (3-methyl-1H-oxazol-5-yl) · Pyridin-3-yloxy) -1-phenyl-ethylamine; (1S) -2- (5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy ) Small phenyl-ethylamine; 4-((2S) -2-amino-3- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) propane ) -Benzonitrile; (1S) -2- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) berber-2-ylmethyl-ethyl Amine, 4-((2S) -2-amino-3- (5-isoquinolin-6-yl-pyridin-3-yloxy-propyl) -benz-17-

Nitrile; (1S) -2- (5-isofluorolin-6-yl-pyridin-3-yloxy) -1-fluoren-2-ylmethyl) -ethylamine; (1S) -1-fluorenyl 2- (5-isoquinoline-6-yl 4 than pyridin-3-yloxy) -ethylamine; (lS) -1- (4-fluoro-fluorenyl) -2- (5- (3- Fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy >ethylamine; (lS) -1- (4-gas-fluorenyl) -2- (5-isojunlin-6 -Kidobyo-3-yllactyl) -ethylamine, 2-((2S) -2-amino-3- (5- (3-methyl-1H-indazol-5-yl) -pyridine- 3-yloxy) -propyl) -benzonitrile; 2-((2S) -2-amino-3- (5-isojunin-6-yl) -p-pyridine-3-yllactyl ) -Propyl) -aspartitrile; (1S) -2-5- (3-methyl-1H41azole-5-yl) -pyridin-3-yloxy) -1-pyridin-4-ylmethyl -Ethylamine; (lS) -2- (5-Isophosphon-6-yl-pyridin-3-yloxy) small pyridin-4-ylmethyl-ethylamine; (lS) -l- (4- Fluorenyl-fluorenyl) -2- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) -ethylamine, (lS) -2- (5-iso Quinolin-6-yl-pyridin-3-yloxy) -1- (4-methyl-benzyl) -ethylamine; (1S) -2- (5- (3-fluorenyl-1H-oxazole -5-yl) -pyridin-3-yloxy) quinolin-3-ylmethyl-ethylamine; (1S) -2- (5-isoquinolin-6-yl-pyridin-3-yloxy base) Quinolin-3-ylfluorenyl-ethylamine; (1R) -1-fluorenyl-2- (5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy) -Ethylamine; (1R) -1-amidino-2- (5-isofluorin-6-yl-pyridin-3-yloxy) -ethylamine; 4-((2S) -2-amino- 3- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) -propyl)-(1S) -l- (4-fluorenyloxy-fluorene ) -2- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) -ethylamine; (1S) -1- (3-methyl-fluorenyl ) -2- (5- (3-methyl-1H-oxazol-5-yl) -pyridine-3-yloxy) -ethylamine, (lS) -l- (2-methyl-fluorenyl) -2- (5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy) -ethylamine, (1S) -2- (5- (3-methyl-1H -Indazol-5-yl) -pyridin-3-yloxy) -1- (4-nitro-fluorenyl) -ethylamine; (1S) small (4-methoxy-fluorenyl) -2- (5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy) -ethylamine; (1S) -1-biphenyl-4-ylmethyl-2- (5 -(3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy) -ethylamine; (lS) -2- (5- (3-fluorenyl-1H-oxazole-5 -Yl) -pyridin-3-yloxy) berber-1-ylmethyl-ethylamine; (lS) -1- (3-chloro-fluorenyl) -2- (5- (3-methyl- 1H-indazol-5-yl) -pyridine Pyridin-3-yloxy) -ethylamine; 3-((2S) -2-amino-3- (5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yl (Oxy) -propyl) -benzonitrile; (lS) -l- (3,4-difluoro-fluorenyl) -2- (5- (3-fluorenyl-1H-oxazol-5-yl) -Pyridyloxy) -ethylamine; (1S) -l- (3,4-dimethoxy-fluorenyl) -2- (5- (3-fluorenyl-1H-indazol-5-yl ) -Pyridin-3-yloxy) -ethylamine; (1S) -1- (3-fluoro-fluorenyl) -2- (5- (3-methyl-1H-indazol-5-yl)- Pyridine-3-yloxy 200301122

) -Ethylamine, (1S) -2- (5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy) -1- (3-trifluoromethyl-methyl (Yl) -ethylamine; (lS) -l- (4-ethoxyfluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy ] -Ethylamine; (1S) -l- (4-third-butyl · fluorenyl) -2- (5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yl (Oxy) -ethylamine;

(lS) -l- (4-methoxy-3-methyl-fluorenyl) -2- (5- (3-methyl-1H-oxazol-5-yl) -pyridine-3-yloxy -Ethylamine, 2-((2S) -2-amino-3- (5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yloxy) -propyl ) -4-fluorenyl-pan, (1S) -1-methyl-2- [5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -ethylamine (±) -1- (1Η-benzimidazol-2-ylmethyl) -2- (5-isoquinolin-6-yl-pyridin-3-yloxy) -ethylamine; (±) small (1H-indazol-3-ylmethyl) -2- (5-isopyridin-6-yl-supridin-3-yloxy) -ethylamine;

(1S) -l- (2-fluoro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxyethylamine, (1S) small (2-chloro-fluorenyl) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine, (1S) -2- [5 -(3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] small pyrimiphen-2-ylfluorenyl-ethylamine; (1R) small (1H-4 indol-3- Methyl) -2- [5- (3-methyl-1H-Wazole-5-yl) -pyridin-3-yloxy] -ethylamine; -20- 1- (4-chloro-fluorenyl ) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S) -2- [5- (3-methyl- 1H-indazol-5-yl) -pyridin-3-yloxy] small (4-pyrrole-1-yl-fyl) -ethylamine; (1S) -l- (4-methyl-fluorenylsulfide Methyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S) -2- [5- (3- Methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -1- (2-trifluorofluorenyl-fyl) -ethylamine; (1R) -1-fluorenyl-3- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -propylamine; (IR) -1-fluorenyl-4- [5- (3-methyl- lH-indazol-5-yl) -pyridine · 3-yloxy] -butylamine; (lS) -1- [5- (3-methyl-1Η-indazol-5-yl) -pyridine-3 -Alkyloxymethyl] each phenyl- propane ; (LS) -2- (5-isojunlin-6-ylpyridine-3-yloxy) -1- (1-methyl-1Η-ρ? | Pdor-3 · ylmethyl)- Ethylamine trifluoroacetate; (IS)-[1- (1H-Indol-3-ylmethyl) -2- (5-isoquinolin-6-yl-pyridin-3-yloxy) -ethyl Yl] -difluorenyl-amine, (1S) small benzo [b] thien-3-ylfluorenyl-2- [5- (3-methyl-1H-earmazol-5-yl) -pyridine- 3-yloxy] -ethylamine, (1S) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] small thiophen-3-ylfluorene -Ethylamine; (1S) -1-benzyloxyfluorenyl-2- (5-isoquinolin-6-yl4pyridinyloxy) -ethylamine; (1S) berberyloxymethyl- 2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine, (1S) -2- (5-isoquinolin-6-yl- Pyridine-3-yloxy) -1- (fluoren-2-yloxymethyl)-

200301122 Ethylamine; (lS) -2- (5-isoquinolin-6-yl-pyridin-3-yloxy) small (pyridin-3-yloxyfluorenyl) -ethylamine, (lS) -2 -(5-isojunlin-6-yl than bit-3-yloxy ^ yl) -1- (plin-7-yloxymethyl) -ethylamine, (2S) -4- [2- Amino-3- (5-isopentaline-6-yl-p than bita-3-yloxy) -propoxytyl] -benzonitrile; (2S) -Nf- (5- (3- Methyl-1H-indazol-5-yl) -pyridin-3-yl) -3-phenyl-propane-1,2-diamine; (2S) -N- (2-amino-3-phenyl) -Propyl) -N- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yl] -methanesulfonamide; (2S) -N- (2-amino- 3-phenyl-propyl) -N-〇 (3-methyl-1H-indazol-5-yl) -pyridin-3-yl] -aspartate amine, (2S) -N- (2-amine Phenyl-3-phenyl-propyl) -N- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yl] -benzylamine, (2S) -N- (2-amino-3-phenyl-propyl) -N- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yl] -ethylamine, (2S) -3- [2-Amino-3- (1fluoren-indol-3-yl) -propylene] -5-isoquinolin-6-yl-1,3-dihydro-oxolin-2-one ; (1S) -2- (5-isoquinolin-6-yl-pyridyloxy) small (1-methyl-1H-indol-3-ylmethyl) -ethylamine; (1S)- l- (lH- Indol-3-ylfluorenyl) -2- [5- (1fluorene-pyrrolo [2,3-b] pyridin-5-yl) -p-ratio-3-yloxy1yl] -ethylamine, (1S ) -2- {5- [2- (2-fluoro-pyridin-4-yl) -vinyl] -pyridin-3-yloxy} -1- (1Η--22-pyridin-3-ylmethyl ) -Ethylamine; (1S) Small (1H-pyridin-3-ylmethyl) -2- {5- [2- (2-methoxy ^ pyridinyl 4-ylethenyl) -Yloxy} -ethylamine; (lS) -l- (lH-pyridin-3-ylmethyl) -2- {5- [2- (2-phenoxybipyridine · 4 | 丞 ethyl association) [] -Pyridin-3-yloxy} -ethylamine; (lS) -2- {5- [2- (2-fluorenylthio-pyridin-4-yl) -ethenyl] -eryl Oxo} -1- (1Η-β1no-3-ylmethyl) -ethylamine; [4- (2- {5-[(2S) -2-amino-3- (1Η-indole each Group) · propoxybibiline_3 • bibylethenyl) -p-pyrazol-2-yl] apropyl-amine; [4- (2- {5-[(2S) -2-amine 3- (1Η-indolyl) propoxy > pyridin_3yl} ethenyl) · ^ bis-2-yl] -fluorenyl-amine, [4- (2- {5- [ (2S) -2-amino-3- (1H-indol-3-yl) -propoxy] · phyllyl) vinyl) -pyridin-2-yl] -ethyl-amine; [4 -(2- (5-[(2S) -2-amino-3- (1Η-indol-3-yl) -propoxy] • pyridyl} vinyl) -pyridin-2-yl] -Methyl-amine; (lS) -l- (lH-pyridyl methyl) -2- {5- [2- (2-pyridyl + yl, eryl · 'yl) vinyl] -pyridine -3-yloxy} -ethylamine; (± > 2- [5_ (3-methyl-1HW1 also-5-yl) -pyridinyloxy] + (2-methylxanthenyl-3 -Methyl) -Ethylamine; 7- {5-[(2S) -2-Amino-3- (1'-indolyl) -propoxy >2-ylamine; 2-phenyl-2- (3-pyridin-4-yl-1fluorenyl-pyrazolo [3,4seven > pyridinoyl) · ethylamine · each 2- 2-yl- ( 3-p specific disease ice-l-H-p ratio and [3,4-b] p ratio bite winteryl) · Yu · 2- 荇 -2-yl-2- (3-pyridin-4-yl- 1H-pyrazolo [3,4Hepta] pyridine-fluorenyl> Ethylamine -23-

(3-isoquinolin-6-yl-1H-pyrazolo [3,4-b] pyridin-6-yl) -phenyl-ethazolene; 2- (3-isoquinolin-6-yl- 1H-pyrazolo [3,4-b] pyridin-6-yl) -2-phenyl-ethylamine; (1S) berberyl-2- (3-pyridin-4-yl-1H-pyrazolo [3,4 hepta] pyridin-5-yloxy) -ethylamine; 2-fluorenyl each [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -Propylamine; (lS) -l- (lH-indole-3-ylmethyl) -2- (2-pyridin-4-yl- [1,7] pyridin-5-yloxy) -ethylamine (IR) -1- (1H-indol-3-ylfluorenyl) -2- (2-pyridin-4-yl- [1,7] pyridin-5-yloxy) -ethylamine, ( lS) -l- (lH-indole-3-ylmethyl) -2- (5-isoquinolin-6-yl-eridin-3-ylthio) -ethylamine; (IS) -1- (1H-indole-3-ylmethyl) -2- [5- (3-methyl-1H-indazol-5-yl > pyridin-3-ylthio) -ethylamine, (1S)- l- (4-bromo-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridyloxy] -ethylamine; (lS) -l- (lH -沔丨 indol-3-ylmethyl) -2- [5- (2-methyl-quinazolin-7-yl >> pyridin-3-yloxy] -ethylamine; (lS) -l- (lH-W indol-3-ylmethyl) -2- [5- (1Η-fluorin-5-yl) -pyridin-3-yloxy] -ethylamine, (lS) -l- (lH- Indole-3-ylmethyl) _2- {5- [4- ( 1'-tetrazol-5-yl) -phenyl] -pyridin-3-yloxy} -ethylamine; (lS) -1- (lH-indol-3-ylfluorenyl) -2- (5- Isoquinoline; yl-pyrimidin-4-yloxy) -ethylamine; '(1S) berberyl-2- [3- (3-methyl-1H-Wazole-5-yl) -phenoxy ] -Ethylamine; -24-

(IS) benzyl-2- [6- (3-fluorenyl-1H-indazol-5-yl) -pyridin-2-yloxy] -ethylamine; (1S) -2- [5- ( 3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] small (4-pyrimin-3-yl-fluorenyl) -ethylamine, (lS) -l- (4- Iodo-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine, [4-((2S) -2- Amino-3-benzyl-propoxy) -2- (3-methyl-1Η-ρ? | Jun-5-yl) -phenyl] -methanol; (lS) -2- [5- (lH -Private di-5-yl) bito-3-yloxy] -1- (1Η * Ή | carb-3-ylmethyl) -ethylamine; (lS) -2- [5- (lH -Benzotriazol-5-yl) -pyridin-3-yloxy] berenyl-ethylamine; (1S) -1-fluorenyl-2- [5- (3-morpholinolin-4-yl -1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine, (1S) -1-fluorenyl-2- {5- [3- (4-methyl-hexahydropyridine) -1-yl) -1Η4 | azole-5-yl] -pyridin-3-yloxy "yl} -ethylamine, (1S)-{5- [5- (2-amino-3-phenyl- (Propoxy) -pyridine groups; 1-1H-indazol-3-yl} -dimethyl-amine; (1S)-{5- [5- (2-amino-3-privyl-propionate) ) -P than -3--3-yl] -1H-P? 丨 -3-yl} · (2-methoxy-ethyl) -amine, {5- [5-((2S) -2- Amino-3-phenyl-propoxy) -pyridin-3-yl] -1HWl -3-yl}-(2-morpholin plin-4-yl-ethyl) -amine, 5- [5-((2S) -2-amino-3-phenyl-propoxy) -pyridine -3-yl] -1H-indazol-3-ylamine; N- {5- [5-((2S) -2-amino-3-phenyl-propoxy) -pyridin-3-yl; I-1H-oxazol-3-yl} -2,2,2-digas-ethylamine, (2S) -2-amino-N- [5- (3-methyl-1H-indazole- 5-yl) -pyridin-3-yl] -3-phenyl-propane

Fluorenamine; (1S) -2- [5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -1- (1H-fluorin-3-ylfluorenyl ) -Ethylamine; (1S) -1-fluorenyl-2- [5- (3-fluorenyl-1Η * Ή | Jun-5-yl) bito-3-yllactyl] -ethylamine, (1S ) -2- [5- (3-fluorenyl-1Η · fluorene-5-yl) than lake-3-yloxy] -1-fluorenyl-ethylamine, (6- {5-[(2S ) -2-Amino group (3-Hydroxy-3-yl) -propoxy] pyridin-3-yl} -co-17- 4-yl) -phenyl-amine, (1S) -2- [5- ( lH-indazol-6-yl) -pyridin-3-yloxy] -1- (lH-indol-3-ylmethyl) -ethylamine; 5- {5-[(2S) -2-amine 3- (1Η-indol-3-yl) -propoxy] -pyridin-3-yl} -2,3-dihydro-isoxolin-1-one; 6- {5-[(2S ) -2-Amino-3- (1Η-pyridin-3-yl) -propoxy] -pyridin-3-yl} -1Η-cockatoline-4- 酉, (lS) -l- ( lH-indole-3-ylmethyl) -2- [5- (4-phenyl-fluorin-6-yl) -pyridin-3-yloxy] -ethylamine; (6- {5- [ (2S) -2-amino-3- (1'-indolyl) -propoxy] -pyridin-3-ylpyridin-4-yl) -fluorenyl-amine I (6- {5- [(2S) -2-amino-3- (1H-pyridin-3-yl) -propoxy] -pyridinyl} -cockolin-4-yl) -methyl-amine; 6- {5 -[(2S) -2-amino-3- (1Η-indolyl) -propoxy ] -Pyridin-3-ylbocklin-4-ylamine, [(3S) -3- (5-isoquinolin-6-yl-pyridin-3-yloxymethyl) -1, 2, 3 , 4-tetrahydrocarba-9-yl] -methyl Sf ·, 3- (5-isoquinolin-6-yl-pyridin-3-yloxymethyl) -2,3,4,9 -Tetrahydro-111- / 3-carb-26-

200301 Koulin; 5- {5-[(2S) -2-amino-3- (1Η-indol-3-yl) -propoxy] -pyridin-3-yl} -1Η-indazole-3 -Carboxylic acid; 5- [5-((2S) -2-second-butoxyalkylamino-3-¾yl-propoxy) pyridin-3-yl] each methyl-indazole-1 -Tert-butyl carboxylic acid; 5- [5-((2S) -aziridin-2-ylmethoxy) -pyridin-3-yl] -3-methyl-1H-oxazole; (1S ) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridylyloxy] small (3-trifluoromethoxy-methylene) -ethylamine; (1S)- l- (3,5-dichloro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] * ethylamine, (lS) -l- (2,3-dichloro-fluorenyl) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S ) Small biphenyl-3-ylmethyl-2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (〇1- (3 -Chloro-4-fluoro-fluorenyl) -2- [5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yllactyl] • ethylamine, (lS) -1 -(4-chloro-3-fluoro-fluorenyl) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S ) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridylyloxy] small (4-trifluoromethoxy-methylene) -ethylamine; (1S)- l- (2-fluoro Methyl-4-trifluoromethyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -methylpyridin-3-yloxy ^ yl] -ethylamine, ( lS) -l- (3-fluoroyl-5-trifluoromethylyl) -2- [5- (3-methyl-1H-indazol-5-yl) -methylpyridin-3-yloxy " Propyl] -ethylamine, -27-

200301122 (lS) -l- (2-Methoxy-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine ; (3-{(2S) -2-Amino-3- [5- (3-methyl-1Η-ρ? 1a-5-yl) pyrazol-3-yloxy ^ yl] -propyl} -Phenyl) -dimethyl-amine; (1S) small (4-chloro-2-methyl-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -Pyridin-3-yloxy] -ethylamine, (lS) -1- (3-iodo-fluorenyl) -2- [5- (3-methyl-1H-Wazole-5-yl) -pyridine -3-yloxy] -ethylamine; (lS)-(lS) -l- (3-fluoroyl-4-methyl-fluorenyl) -2- [5- (3-methyl-1H-ind Azol-5-yl) -orbital-3-yloxy ^ yl] -ethylamine, (lS) -1- (3-fluoroyl-4-methoxy-fluorenyl) -2- [5- ( 3-methyl-1H-oxazol-5-yl) -pyridine-3-yloxy] -ethylamine, (1S) -2- [6-chloroyl-5- (3-fluorenyl-1H- Indazol-5-yl) -pyridyloxy] small (3,4-dichloro) -ethylamine, (lS) -l- (2-fluoro-6-trifluorofluorenyl-fluorenyl) -2- [5- (3-Methyl-1H-indazol-5-yl) -p-pyrene-3-yloxy] -ethylamine, (lS) -l- (4-fluoroyl-3- Trifluoromethyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -exo-bite-3-yloxyj-yl] -ethylamine, (1S) small furan 2-ylmethyl-2- [5- (3-methyl-1H-oxazol-5-yl -Pyridyloxy] -ethylamine; (1S) small benzofuran-2-ylmethyl-2- [5- (3-methyl-1H-earmazol-5-yl) -pyridine-3- Oxy] -ethylamine; (1S) small (3-fluoro-4-trifluoromethyl-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl)- Outer bite-3-yloxyi-yl] -ethylamine, -28-

200301122 (lS) -l- (4-chloro-3-methyl-fluorenyl) -2- [5- (3-methyl-1H-Wazole-5-yl) -pyridin-3-yloxy ] -Ethylamine; (1S) -1-P-furan-3-ylmethyl-2- [5- (3-fluorenyl-1Η-ρ5 丨 Jun-5-yl) -p ratio lake-3-yl Oxy] -ethylamine; (lS) -l- (2-fluoro-5-methyl-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridine -3-yloxy] -ethylamine; (lS) -l- (3-muryl-5-air-fluorenyl) -2_ [5- (3-methyl-lΗ-Θΐ 唆 -5-yl) -ρ is smaller than -3 -yloxy] -ethylamine; (1S) -2- [5- (3-methyl-1fluorenyl-oxazol-5-yl) -pyridin-3-yloxy] is smaller than (3 , 4,5-trifluoro-fluorenyl) -ethylamine; (1S) -l- (4-fluoro-3-methyl-fluorenyl) -2- [5- (3-methyl-1fluoren-indole Azol-5-yl) -pyridin-3-yloxy] -ethylamine; (lS) -1- (2,4-dichloro-fluorenyl) -2- [5- (3-methyl-1H- Indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (lS) -1- (4-arsenyl-3-difluoromethyl-fluorenyl) -2- [5- (3 * Methyl · 1ΗΉ | 嗤 -5-yl) _ ρ Biyodo-3-yloxy] -ethylamine, (1S) -2- [5- (3-methyl-1Η-indazol-5-yl ) -Pyridin-3-yloxy] small (2-trifluoromethoxy-methyl) -ethylamine; (lS) -l- (2,5-dioxo-fluorenyl) -2- [ 5- (3-methyl-1H-indazol-5-yl) -pyridine-3 -Methoxy] -ethylamine, (1S) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -1- (4-methylsulfide -L-yl) -ethylamine; (lS) -l- (2-cyclohexyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridine-3- Alkyloxy] •• Ethylamine, -29- 200301122

(lS) -l- (2,5-dichloro-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridyloxy] -ethylamine; ( lS) -l- (2,5-dimethyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine ; (LS) -l- (2,3-dimethyl-methylidene) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy]- Ethylamine

(lS) -l- (3,4-dichloro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridyloxy] -ethylamine; ( lS) -l- (2,4-dimethyl-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -ethylamine ; (LS) -l- (3-Gas-4-digasmethyl-fluorenyl) -2- [5- (3-methyl-1Η-ρ? 1 also 5-yl) _ Oral specific bite -3-yloxyi-yl] -ethylamine, (lS) -l- (3,5-dimethyl-fluorenyl) · 2- [5- (3-methyl-1H-indazol-5-yl ) -Pyridine-3-yloxy] -ethylamine; (1S) small biphenyl-2-ylmethyl-2- [5- (3-methyl-1fluoren-oxazol-5-yl) -pyridine- 3-yloxy] • ethylamine,

(lS) -l- (3,4-dimethyl-fluorenyl) -2- [5- (3-methyl-1fluorene-indazol-5-yl) -pyridin-3-yloxy] -ethyl Amine; (lS) -l- (2,3-difluoro-fluorenyl) -2-〇 (3-methyl-1fluorenyl-oxazole-5-yl) -pyridin-3-yloxy] -ethyl Amine; (lS) -l- (2,5-difluoro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy]- Ethylamine; (lS) -l- (2,6-dichloro-fluorenyl) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] -Ethylamine; -30- 200301122

(lS) -l- (2,4-Dimuryl-fluorenyl) -2- [5 · (3-methyl-1Η · Ή 丨 -5-yl) -p-ratio-3-yloxy] -Ethylamine; (lS) -l- (2,6-dimethyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy []]-Ethylamine; (lS) -l- (2,3-dihydro-benzo [1,4] dioxolane-6-ylmethyl) -2 · [5- (3-fluorenyl -1Η-indazol-5-yl) -pyridin-3-yloxy] -ethylamine;

(lS) -l- (3,5-Digas-fluorenyl) -2- [5- (3-methyl-1Η-ρ? 丨 -5-yl) bito-3-yloxy]- Ethylamine; (1S) S (2,6-difluoro-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -ethyl Amine; (1S) small benzo [1,3] dioxo-5-ylfluorenyl-2- [5- (3-fluorenyl-1H-indazol-5-yl)-. Specific sulfan-3-yloxy ^ yl] -ethylamine, (lS) -1- (4-fluoroyl-3-methyl-fluorenyl) -2- [5- (3-methyl-1H-indazole -5-yl) -pyridin-3-yloxy] -ethylamine; (1S) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy ] Small (2,4,6-trimethyl-methyl) -ethylamine »

(lS) -l- (2,4-dimethoxy-fluorenyl) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy]- Ethylamine; (1S) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] small (4-trifluoromethyl_fluorenyl) -ethyl Amine, (lS) -l- (5-fluoro-2-methyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy Yl] -ethylamine; (lS) -l- (3,5-bis-trifluorofluorenyl-benzyl) -2- [5- (3-fluorenyl-1HWIazole-5-yl) -pyridine- 3-yloxy] -ethylamine, -31-

200301 (lS) -l- (4-fluoro-2-methyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yllactyl ] -Ethylamine; (lS) -l- (5-Gas-2-methoxy-fluorenyl) -2- [5- (3-methyl-lH-ijjun-5-yl) specific bite- 3-yloxy 1-yl] -ethylamine, (1S) -2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -1- (2- Methyl-fluoren-1-ylmethyl) -ethylamine; (lS) -l- (2,2-difluoro-benzo [1,3] dioxolene-4-ylmethyl) -2 -[5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (lS) -1- (4-fluoro-fluoren-1-ylfluorenyl ) -2-〇 (3-methyl-1HWazol-5-yl) -pyridin-3-yloxy] • ethylamine, (1S) -2- [5- (3-methyl-1H-ind Azol-5-yl) -pyridin-3-yloxy] -1- (2,2,3,3-tetrafluoro-2,3-dihydro-benzo [1,4] dioxolene -6-ylmethyl) -ethylamine; (1S) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridyloxy] small (4-methyl ·: !:-1-ylmethyl) -ethylamine; (1S) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -l- ( 2,4,6-trifluoro-methylidene) -ethylamine; (lS) -2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-yloxy] small (2,3,4-trifluoro-fluorenyl) -ethylamine; (lS) -l- (4- 2-fluoro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S) -l- ( 4-bromo-3-fluoro-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S)- l- (2-bromo-4,6-difluoro-fluorenyl) -2- [5- (3-fluorenyl-1H "epazol-5-yl) -pyridine-3-yloxy]- Ethylamine, -32- 200301122

(1S) -l- (4-bromo-3-methyl-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -Ethylamine; (lS)-> odor-fluorenyl) -2- [5- (3-fluorenyl-1H-methylamino-5-yl) -p-pyridine-3-yloxy]- Ethylamine; (lS) -l- (3-methoxy-fluorenyl) -2-〇 (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -ethylamine ; (LS) -l- (3-bromo-fluorenyl) -2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy

Ethylamine, (lS) -l- (2-methoxy-fluoren-1-ylmethyl) -2- [5- (3-methyl-1HW 丨 azole-5-yl) -pyridyloxy ] -Ethylamine; (lR) -1- (4-chloro-benzyl) -2- [5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yloxy]- Ethylamine; (1R) -1-benzo [1,3] dioxolene-5-ylmethyl-2- [5- (3-fluorenyl-1H-indazol-5-yl)-^ 7bito-3-yloxy ^ yl] -ethylamine, (lR) -1- (3-fluoroyl-4-fluorenyl-fluorenyl) -2- [5- (3-methyl-1H-worm Azol-5-yl) -pyridin-3-yllactyl] -ethylamine,

(1S) -1-fluorenyl-2- [6-chloroyl-5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -ethylamine; (1S) -l- (4-bromo-fluorenyl) -2- [6-chloroyl-5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -ethylamine; (lS) -l- (4-chloro-fluorenyl) -2- [6-chloroyl-5- (3-fluorenyl-1H-earmazol-5-yl) -pyridin-3-yloxy]- Ethylamine; (1S) -2- [6-chloroyl-5- (3-methyl-1H-oxazol-5-yl) -pyridine-3-yloxy] small cyclohexylmethyl-ethylamine; -33-

200301122 (lS) -2- [6-chloroyl-5- (3-fluorenyl-lH-oxazol-5-yl) -pyridin-3-yloxy] -l- (2,6-dimethyl -Hanyl) -Ethylamine; (1S) -l- [6-Chloro-5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxyfluorenyl] -2 -Phenyl-propylamine; (1S) -l- [6-chloro-5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxymethyl] -2,2 -Diphenyl-ethylamine; (1S) -l- [5- (3-methyl-lΗ-oxazol-5-yl) -pyridin-3-yloxymethyl] -2-phenyl-propylamine (LS) -l- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxyfluorenyl] -2,2-diphenyl-ethylamine, (lS ) -3-methyl-l- [5- (3-fluorenyl-1H-4Iazole-5-yl) -pyridin-3-yloxyfluorenyl] -butylamine; (1S) -2- [6 -Chloro-5- (3-methyl-1H-earmazol-5-yl) -pyridin-3-yloxy] -1- (lH-indol-3-ylmethyl) -ethylamine; ( lS) -2- (6-chloro-5-p-cepheno [2,3-c] pyridin-2-yl-pyridin-3-yloxy) small (1H-called Methyl) -ethylamine; 5-[(2S) -2-amino-3- (1H-pyridin-3-yl) -propoxy] -3-isoquinolin-6-yl-pyridine-2 -Carbonitrile; (lS) -l- (lH-indol-3-ylmethyl) -2- [5- (3-phenyl-isoquinolin-6-yl) -pyridin-3-yloxy ] -Ethylamine; (lS) -2- [5- (3-ethyl -Isoquinolin-6-yl) -pyridin-3-yloxy] pyridin-3-ylfluorenyl) -ethylamine; (1S) small (1H-indol-3-ylmethyl) -2 -[5- (3-Syridin-4-yl-isoquinolin-6-yl) -pyridine-3-yloxy] -ethylamine, -34-

(1S) -2- [5- (3-furan-2-yl-isoquinolin-6-yl) -pyridin-3-yloxy] -1- (1H-indol-3-ylmethyl) -Ethylamine, (lS) -l- (lH-indol-3-ylfluorenyl) -2- [5- (3-phenylethynyl-isoquinolin-6-yl) -pyridin-3-yl Oxy] -ethylamine; (lS) -l- (lH-indol-3-ylmethyl) -2- [5- (3-prop-1-ynyl-isoquinolin-6-yl)- Pyridin-3-yloxy] -ethylamine, (1SH- (1H "? Indol-3-ylmethyl) -2- [5- (3-vinyl-isoquinolin-6-yl)- Pyridin-3-yloxy] -ethylamine, (1S) -6- {5- [2-amino-3- (1fluoren-l-indol-3-yl) -propoxy] -pyridin-3-yl } -Isopyrin-3-carbonitrile; (1S) -1- (1H-Morphyl-3-ylmethyl) -2- (5-Isoquinone-6-yl-6-ethyl Alkenyl ratio_ 3-yloxy) -ethylamine; (lS) -2- (6-Ethyl-5-isoisoquinone-6-ylpyridine-3-yloxyjyl) -1 -(1Η-ρ5 丨 Hydroxy-3-ylmethyl) -ethylamine; (lS) -2- (6-furan-2-yl-5-isoquinolin-6-yl-pyridin-3-yloxy > 1- (1H-indol-3-ylmethyl) -ethylamine, (1S) -1- (1H-fluorin-3-ylmethyl) -2- (5-isoquinoline-6- 6-phenylethynyl-pyridyl-3-yloxy) -ethylamine, 6- {5-[(2S) -2-amino-3- (1fluorene-indol-3-yl) -Propoxy] -pyridine -3-yl} -Isoquinol-5-ylamine, (lS) -l- (lH-leptal 1-l-methyl-3-ylfluorenyl) -2- [5- (8-fluorenyl- Isoquinone-6-yl) -pyridin-3-yloxy] -ethylamine; (lS) -2- [5- (4-chloro-pyrimido [2,3-c] pyridine-2- ) -Pyridin-3-yloxy] -l- (lH-indol-3-ylmethyl) -ethylamine; 200301122

(1S) -1- (1H-indole-3-ylmethyl) -2- [5- (4-phenyl ... cepheno [2,3pyridyl])-pyridin-3-yloxy []]-Ethylamine; (1SH- (1HW1 indol-3-ylmethyl tablet [5- (4-phenoxy ^ sedeno [2,3 bucket ratio < 2-yl) -pyridin-3-yl Oxy] -ethylamine; (lS) -l- (lH-indol-3-ylmethyl) -2- [5- (4-ethylfluorenylbenzopheno [2,3 bucket ratio < 2- ) -Pyridin-3-yloxy] -ethylamine; (1S) -2- [5- (4-ethyl-π-sepheno [2,3-c > pyridyl) -p-pyridyl Oxo] ^ (1'-indol-3-ylmethyl) -ethylamine; (1S)-(2- {5- [2-amino-3- (1'-oral-3-yl)- Propoxy] -ρ than bityl}}, [[2,3-c] pyridin-4-yl) -phenyl-amine; 5- {5-[(2S) -2-amino-3- (1'-Indol-3-yl) -propoxy] -pyridine_3-yl} · 33 monofluoro-1,3-diazine-acid-2-yl; 6- {5-[(2S)- 2-amino_3 · (1Η ^? 1 indol-3-yl) -propoxy] -pyridine; oxazo [4,5-b] pyridin-2-one; Nl- (5-isoquine Phenyl-6-ylpyridinyl) _ethane-1,2-diamine; hydrazine-2-sulfonic acid (2-amino-ethyl) (5-isoquinolinyl 4-pyridyl! Yl) _Enzyme ·

Tea minor acid (2-Amino-Ethyl) (5_isoamyl-6-yl · eridine; yl) amine Ethyl > (5-isoquinoline · 6-yl · amidin-3-yl) -fluorenamine; quinoline-5-sulfonic acid (2-amino-ethyl) dissociation, quinoline tolidine Each group) · Amidinobiphenyl-4-sulfonic acid (2-Amino-ethylΗ5-Isoquinoline radical 4pyridin_3 · yl >amidamine; 1-Amidino-1Η-imidazolium Acid (2-Amino-Ethyl) > (5-Isoquinolinedongyl · pyrimidin 3-yl) -fluorenamine;

200301122 3-amino-2- [5- (3-methylol-5-yl) than lake-3-yloxy] -propan-l-fresh, 2- [5- (3-fluorenyl-1H -Pyrim-5-yl) -pyridin-3-yloxy] -3-phenoxy-propylamine; 2- [5- (3-methyl-1H-oxazol-5-yl) -pyridine-3 -Yloxy] each (fluoren-2-yloxy) -propylamine; 3- (biphenyl-4-yloxy) -2- [5- (3-methyl-1H-indazol-5-yl ) -Pyridin-3-yloxy] -propylamine, 2- [5- (3-methyl-1H-indazol-5-yl) -pyridin-3-yloxy] -3- (fluorin-7 -Yloxy) -propylamine, 2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -3- (pyridin-4-yloxy)- Propylamine, 2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] each (fluorenyloxy) -propylamine, 3-{(2S) -2 -Amino-3- [5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -propyl} -1fluorene-indole-5-ol; (1S) -; U (5-Methoxy-1H-indol-3-ylmethyl) -2- [5- (3-methyl-1H-indazol-5-yl) -p Lactyl] -ethylamine, (lS) -l- (5-ethoxy-1H-indol-3-ylmethyl) -2- [5- (3-fluorenyl-1H-indazole-5- (Yl) is smaller than Yodo-3-yloxy "yl] -ethylamine, (1S) (5-butoxy-1H-indol-3-ylmethyl) -2- [5- (3-methyl- 1H-ind Azol-5-yl) -p-ratio-3-yloxy] -ethylamine, (lS) -1- (5-isopropoxy-1H-Win-3-ylmethyl) -2- [ 5- (3-methyl-1H-anthazol-5-yl) -pyridin-3-yloxy J-ethylamine; 3- (1H-indol-3-yl) -2- [5- (3 -Methenyl-1H-oxazol-5-yl: Ml: tetra-3-yloxy] -propan-1-ol; -37-

200301122 3- (1Η-θ 丨 Horan-3-yl) -2- [5- (3-fluorenyl-1H- 啕 Jun-5-yl) -orbital-3-yloxy] -propylamine, naphthalene 2-sulfonic acid (2-amino-ethyl)-[5- (3-fluorenyl-1H-indazol-5-yl) -pyridin-3-ylphosphonium amine; biphenyl glacial sulfonic acid (2 -Amino-ethyl)-[5- (3-fluorenyl-1H-oxazol-5-yl) -pyridin-3-yl] -acid amine, 5- {5-[(2S) -2-amine 3- (1Η- < indol-3-yl) -propoxy] -pyridin-3-yl} _3-isopropylidene-1,3-difluoro- 丨 -2--2-, 5- {5-[(2S) -2-amino-3- (1Η-indol-3-yl) -propoxy] -pyridin-3-yl} -3- (1Η-imidazol-2-ylmethylene ) -L, 3-dihydro-carbodol-2-one; 5- {5- [2-Amino-3- (1Η-ρ? 1 acyl-3, yl) -propoxy] -π ratio Yodo-3-yl} -3-p ratio-2 methylidene-1,3-diazepine-p5 | Homo-2-isopropyl, 5- {5-[(2S) -2-amino -3- (1Η-Indol-3-yl) -propoxy] -pyridin-3-yl} -3-furan-2-ylmethylene-1,3-diwind , 5- {5-[(2S) -2-amino-3- (1H-indol-3-yl) -propoxy] -pyridin-3-ylb 3- (5-methyl-anhydro -2-ylmethylene) -1,3-difluoro-p? | Homo-2-fluorene, 5- {5-[(2S) -2-amino-3- (1fluorene-indole-3- ) -Propoxy] -pyridin-3-yl} -3- (4,5- Dimethyl-furan-2-ylmethylene) -1,3-dihydro · oxindole-2-one; 5- {5-[(2S) -2-amino-3- (1Η-indole -3-yl) -propoxy] -pyridin-3-ylb 3-thien-2-ylmethylene-1,3-dihydrodol-2-one; 5- {5-[(2S)- 2-Amino-3- (1Η-clamin-3-yl) -propoxy] -pyridin-3-yl} -3- (1-methyl-1H-pyrrole-2-ylmethylene)- 1,3-dihydro-indole-2-one; 5- {5-[(2S) -2-amino-3- (1fluorene-indole-3-yl) -propoxy] -pyridine-3 -Yl} -3- (1Η-pyridinylidenesulfenylidene) -1,3-dihydroindole-2-one; -38- 5- {5-[(2S) -2-amino-3- (liiM 丨 indol-3-yl) -propoxy] -pyridin-3-yl} -3- (l-phenyl-1H- ^ p each-3-ylmethylene) -1,3-dichloro -Van-2- 嗣, 5- {5-[(2S) -2-amino-3- (1Η · Ή 丨 .Duo-3-yl) -propoxy] specific bit-3-yl} ^- 3-mouth than yodo-3-ylmethylene-1,3-three-wind 17-Same as 5- {5-[(2S) -2-amino-3- (1Η · Ήΐ Ήΐ- 3-based)-Propoxy! Base] bito-3-yl} -3- (1Η_ koubihiz-3-ylmethylene) -1,3-two-wind-throan-2- 嗣, 5- {5-[(2S) -2 -Amino-3- (1'-methyl? | Indol-3-yl) -propoxy] -pyridin-3-yl} -3- (tetrahydro-piperazin-4-yl) -1,3- Dihydro-oxolin-2-one; 5- {5-[(2S) -2-amino-3- (1H-indol-3-yl) -propoxy] -pyridin-3-yl}- 3- (4-ethyl-3,5-dimethyl-1H-pyrrole-2-ylfluorenylene) -1,3-dihydroindole-2-one; 5- {5-[(2S)- 2-amino-3- (1Η-pyridin-3-yl) -propoxy] -pyridin-3-yl} -3-cyclopropylmethylene-1,3-dihydro-P? I 2- 嗣, 5- {5-[(2S) -2-amino-3- (1Η-indolyl) -propoxy] -pyridin-3-yl} -3-tetrazolium -2-Methylene methylene-1,3-difluoro-p? | Homo-2-isopropyl, 5- (5- {5-[(2S) -2-amino-3- (1H-pyridine) -3-yl) -propoxy] -pyridin-3-yl} -2-keto-1,2-difonyl-sulfin-3-ylmethyl) -anan-2-reduced, 5- {5-[(2S) -2-amino-3- (1Η-indol-3-yl) -propoxy] -pyridin-3-yl} each benzylidene-1,3-dihydro- Oxindol-2-one; 5- {5-[(2S) -2-amino-3- (1Η-indol-3-yl) -propoxy] -pyridin-3-yl} -1Η-indion Indole-2,3-dione-3-monthly deficit; (lS) -2- (5-benzo [b] fluoren-2- -6-furan-2-yl-pyridin-3-yloxy) -1- (1Η-fluoren-3-ylmethyl) -ethylamine, (lS) -2- (5-benzo [b] Thien-2-yl-6-ethenyl-pyridin-3-yloxy) -1- (1fluoren-indol-3-ylmethyl) -ethylamine; 200301

(1S) -2- (5-benzo [b] thiophen-2-yl, each 4 phen-2-yl-pyridin-3-yloxy) + (1 indole · 3-ylmethyl) -ethyl Amine; (1S) -2- (5-benzo [b] thiophen-2-yl each pyrazol-2-yl-pyridinyloxy) small (1Η_indol-3-ylmethyl) -ethylamine ; (1S) -2- (5-Benzo [b] p-phenphen-2-yl-64--2-yl-p-pyridine-3-yloxyindol-3-ylmethyl) -ethyl Amine; {5-[(2S) -2-amino-3- (1fluoren-zolin-3-yl) -propoxy] -3-benzophenanthrene 1yl-p-pyridine-2-yl } -Phenyl-amine; {5-[(2S) -2-amino-3- (1H-pyridin-3-yl) -propoxy] -3-benzopyren-2-yl · Waijiyodo-2_ylpyridine-3-yl-amine; 6- {5-[(2S) -2-amino-3- (1H-indol-3-yl) -propoxy] -pyridine 3H • benzoxazol-2-one; 1-benzimidazole small group methyl-2- [5- (3-fluorenyl-1H-indazol-5-yl) -pyridyl lactyl] -Ethylamine; 2- [5- (3-methyl-1H-oxazol-5-yl) -pyridin-3-yloxy] -1-morpholine-4-ylmethyl-ethylamine, 5 -[5-((2S) -2-amino-3-phenyl-propoxy) -pyridin-3-yl] -1,3 · dihydro-indole-2-one; 5- [5- ((2S) -2-amino-3-phenyl-propoxy) -pyridin-3-yl] -3- (1fluorene-pyrrole-2-ylmethylene)- 1,3-diazine-4 | hex-2-fluorene; 5- [5-((2S) -2-amino-3-phenyl-propoxy) -pyridin-3-yl] -3-furan 2-ylidenesulfinyl-1,3-dihydro-Hj indol-2-one; (1S) -1-benzimidazol-1-ylmethyl-2- [5- (3-methyl-1H -Indazol-5-yl > pyridine · 3-yloxy] -ethylamine; • 40- 200301122

3- {H (2S) -2-Amino-3_ (iHH3-yl) -dioxyisoquinoline, each of which is 4-Hyd-4-yl} '• Bingfuchai; (1SH- (m, Hou-3 -Aminomethyl) -2- (5-Isoquinoline · 6-aminopyridyl-4-pyridine · 3 · yloxy) -Ethylamine; nodamine) -2 · Amino groups (1Η-deca [3 · (Propyl) _propoxy] "bite_3 · kibbmethyl-1,3-dichloro-l--2-yl; 5- {5-[(2S) -2-amino-3- (1Η-indole -3-yl) -propylmethyl-1,3-dihydro-indole-2-one; 5- {5-[(2S) -2-amino-3- (1fluorene-indole-3-yl ) · Glyceryl-1,3-dihydroindol-2-one;

Oxyl · pyridine; group} -3,3-dioxyl · pyridin-3-yl}-丨, 3,3-oxy} ^ each group} each ethoxyl · pyridin-3- Each group η 5- {5-[(2S) -2-amino-3- (1Η- 沔丨 -3--3-yl) · endo-1,3-dihydro-2--2-one; and 5- {5-[(2S) -2-Amino-3- (1Η-4 丨 Noise · 3_yl-1,3-—Wind-ρ? | Mouth fruit-2- 嗣. , A from L. The compound of the first item in the range of π, or a therapeutically acceptable salt thereof, and the agent. Use a scientifically acceptable load 22 · — a type that is deemed to be in need of treatment and scoop "... The method of the kinase, and the method of administering the disease to the patient, have been compounded according to the scope of the patent application or a therapeutically acceptable salt thereof according to the scope of the patent application. -41 · 200301122 For: — — — (2), a brief description of the representative symbols of the elements in this representative map: 柒, if there is a chemical formula in this case: please reveal the chemical formula that best shows the characteristics of the invention: