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SI21096A1 - Carboxylic acid derivatives that inhibit the binding of integrins to,their receptors - Google Patents

Carboxylic acid derivatives that inhibit the binding of integrins to,their receptors Download PDF

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SI21096A1
SI21096A1 SI200100288A SI200100288A SI21096A1 SI 21096 A1 SI21096 A1 SI 21096A1 SI 200100288 A SI200100288 A SI 200100288A SI 200100288 A SI200100288 A SI 200100288A SI 21096 A1 SI21096 A1 SI 21096A1
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amino
alkyl
dihydro
carbonyl
methyl
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SI200100288A
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SI21096B (en
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Ronald J. Biediger
Qi Chen
George W. Holland
Jamal M. Kassir
Wen Li
Robert V. Market
Ian L. Scott
Chengde Wu
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Texas Biotechnology Corporation
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Priority claimed from US09/973,142 external-priority patent/US6972296B2/en
Application filed by Texas Biotechnology Corporation filed Critical Texas Biotechnology Corporation
Publication of SI21096A1 publication Critical patent/SI21096A1/en
Publication of SI21096B publication Critical patent/SI21096B/en

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Abstract

A method for the inhibition of the binding of alpha4beta1 integrin to its receptors, for example VCAM-1 (vascular cell adhesion molecule-1) and fibronectin; compounds that inhibit this binding; pharmaceutically active compositions comprising such compounds; and to the use of such compounds either as above, or in formulations for the control or prevention of diseases states in which alpha4beta1 is involved.

Description

TEXAS BIOTECHNOLOGY CORPORATIONTEXAS BIOTECHNOLOGY CORPORATION

Derivati karboksilne kisline, ki inhibirajo vezavo integrinov na njihove receptorjeCarboxylic acid derivatives that inhibit the binding of integrins to their receptors

Navzkrižna referenca na sorodne prijaveCross-reference to related applications

Ta prijava je delna nadaljevalna prijava US patentne prijave štev. 09/707,068, vloženeThis application is a partial continuation of US patent application no. 09 / 707,068, filed

6. novembra 2000, kije delna nadaljevalna prijava US patentne prijave št. 09/565,920, vložene 5. maja 2000, s prednostjo US provizorične patentne prijave št. 60/132,971, vložene 7. maja 1999.November 6, 2000, which is a partial continuation of US patent application no. No. 09 / 565,920, filed May 5, 2000, with priority U.S. provisional patent application no. 60 / 132,971, filed May 7, 1999.

Področje izumaFIELD OF THE INVENTION

Predloženi izum je usmerjen na splošno na inhibicijo vezave α4βι integrina na njegove receptorje, npr. VCAM-1 (vaskularna celična adhezijska molekula-1) in fibronektin. Izum se tudi nanaša na spojine, ki inhibirajo to vezavo; na farmacevtsko aktivne sestavke, ki obsegajo take spojine; in na uporabo takih spojin bodisi kot zgoraj ali v pripravkih za kontrolo ali preprečevanje bolezenskih stanj, v katere je vpleten α4βμThe present invention is directed generally to inhibiting the binding of α 4 βι integrin to its receptors, e.g. VCAM-1 (vascular cell adhesion molecule-1) and fibronectin. The invention also relates to compounds that inhibit this binding; to pharmaceutically active compositions comprising such compounds; and to the use of such compounds either as above or in preparations for the control or prevention of disease states involving α 4 βμ

Ozadje izumaBACKGROUND OF THE INVENTION

Kadar tkivo napadejo mikroorganizmi ali kadar je poškodovano, igrajo glavno vlogo pri vnetnem odzivu bele krvničke, imenovane tudi levkociti. Eden od najbolj pomembnih vidikov vnetnega odziva vključuje celični adhezijski dogodek. Običajno najdemo bele krvničke, ko krožijo skozi krvni pretok. Vendar, kadar je tkivo inficirano ali postane poškodovano, bele krvničke prepoznajo napadeno ali poškodovano tkivo, se vežejo na steno kapilare in migrirajo skozi kapilaro v prizadeto tkivo. Te dogodke mediira družina proteinov, ki jih imenujemo celične adhezijske molekule.When tissue is attacked by microorganisms or when it is damaged, they play a major role in the inflammatory response of white blood cells, also called leukocytes. One of the most important aspects of the inflammatory response involves a cell adhesion event. Usually white blood cells are found as they circulate through the bloodstream. However, when the tissue is infected or becomes damaged, the white blood cells recognize the affected or damaged tissue, bind to the capillary wall and migrate through the capillary to the affected tissue. These events are mediated by a family of proteins called cell adhesion molecules.

-2So trije glavni tipi belih krvničk: granulociti, monociti in limfociti. Integrin α4βι (imenovan tudi VLA-4 za zelo pozen antigen-4) je heterodimeren protein, eksprimiran na površini monocitov, limfocitov in dveh podrazredov granulocitov: eozinofllci in bazofilci. Ta protein igra ključno vlogo v celični adheziji zaradi svoje sposobnosti, da prepozna in veže VCAM-1 in fibronektin, proteine, ki so v povezavi z endotelnimi celicami, s katerimi je obložena notranja stena kapilar.-2 There are three main types of white blood cells: granulocytes, monocytes, and lymphocytes. Integrin α 4 βι (also called VLA-4 for very late antigen-4) is a heterodimeric protein expressed on the surface of monocytes, lymphocytes and two subclasses of granulocytes: eozinofllci and basophils. This protein plays a key role in cell adhesion because of its ability to recognize and bind VCAM-1 and fibronectin, proteins that bind to endothelial cells lining the inner wall of the capillaries.

Po infekciji ali poškodbi tkiva, ki obdaja kapilaro, endotelne celice eksprimirajo vrsto adhezijskih molekul, vključno VCAM-1, ki so kritične za vezavo belih krvničk, ki so potrebne za borbo proti infekciji. Pred vezavo na VCAM-1 ali fibronektin se bele krvničke v začetku vežejo na določene adhezijske molekule, da upočasnijo njihov tok, in dopustijo, da se celice kotalijo vzdolž aktiviranega endotelija. Monociti, limfociti, bazofilci in eozinofllci so potem sposobni, da se trdno vežejo na VCAM-1 ali fibronektin na steni krvne žile preko α4β] integrina. Obstaja dokaz, da so take interakcije tudi vključene v transmigracijo teh belih krvničk v poškodovano tkivo kot tudi v sam začetni kotalilni dogodek.Following infection or damage to the tissue surrounding the capillary, endothelial cells express a variety of adhesion molecules, including VCAM-1, that are critical for the binding of white blood cells that are required to fight infection. Prior to binding to VCAM-1 or fibronectin, white blood cells initially bind to specific adhesion molecules to slow their flow and allow the cells to roll along the activated endothelium. Monocytes, lymphocytes, basophils and eosinophils are then capable of binding firmly to VCAM-1 or fibronectin on the blood vessel wall via α 4 β] integrin. There is evidence that such interactions are also involved in the transmigration of these white blood cells into the damaged tissue as well as in the initial rolling event.

Čeprav migracija belih krvničk na mesto poškodbe pomaga pri obrambi pred infekcijo in uniči tuj material, lahko v mnogih primerih ta migracija postane nekontrolirana, z belimi krvničkami, ki navalijo na sceno, pri čemer povzročijo zelo razširjeno poškodbo tkiva. Zato so lahko spojine, ki so sposobne blokirati ta proces, koristne kot terapevtska sredstva. Tako bi bilo koristno, da razvijemo inhibitorje, ki bi preprečili vezavo belih krvničk na VCAM-1 in fibronektin.Although the migration of white blood cells to the site of injury helps to defend against infection and destroy foreign material, in many cases this migration can become uncontrolled, with white blood cells invading the scene, causing widespread tissue damage. Therefore, compounds capable of blocking this process may be useful as therapeutic agents. Thus, it would be useful to develop inhibitors that would prevent the binding of white blood cells to VCAM-1 and fibronectin.

Nekatere od bolezni, kijih lahko zdravimo z inhibicijo α4β! vezave, so, vendar niso na to omejene, ateroskleroza, revmatoidni artritis, astma, alergija, multipla skleroza, lupus, vnetna črevesna bolezen, zavrnitev presadka, kontaktna hipersenzibilnost in diabetes tipa I. Poleg tega, da ga najdemo na nekaterih belih krvničkah, najdemo α4βι tudi na različnih rakavih celicah, vključno kot so celice levkemije, melanoma, limfoma in sarkoma. Domnevalo seje, daje lahko celična adhezija, ki vključuje α4βι, vključena v metastaze določenih karcinomov. Inhibitorji α4βι vezave so lahko zato tudi koristni pri zdravljenju nekaterih oblik raka.Some of the diseases that can be treated by inhibiting α 4 β! attachments include, but are not limited to, atherosclerosis, rheumatoid arthritis, asthma, allergies, multiple sclerosis, lupus, inflammatory bowel disease, graft rejection, contact hypersensitivity and type I. Diabetes In addition to being found on some white blood cells, α 4 βι also on various cancer cells, including cells of leukemia, melanoma, lymphoma and sarcoma. The assumption of the session is that cell adhesion involving α 4 βι may be involved in the metastasis of certain cancers. Α 4 βι binding inhibitors may therefore also be useful in the treatment of some cancers.

Izolacija in čiščenje peptida, ki inhibira vezavo α4βι na protein, je opisana v US patentu 5,510,332. Peptidi, ki inhibirajo vezavo, so opisani v WO 95/15973, EP 0 341 915, EP 0 422 938 Al, US patentu 5,192,746 in WO 96/06108. Nove spojine, ki so koristne za inhibiranje in preprečevanje celične adhezije in s celično adhezijo mediiranih patologij, so opisane v WO 96/22966, WO 98/04247 in WO 98/04913.Isolation and purification of a peptide that inhibits α 4 βι binding to a protein is described in U.S. Patent 5,510,332. Binding inhibitory peptides are described in WO 95/15973, EP 0 341 915, EP 0 422 938 Al, US Patent 5,192,746 and WO 96/06108. Novel compounds useful for inhibiting and preventing cell adhesion and cell adhesion-mediated pathologies are described in WO 96/22966, WO 98/04247 and WO 98/04913.

Zato je predmet izuma, da zagotovimo nove spojine, ki so inhibitorji α4β! vezave, in farmacevtske sestavke, ki vključujejo take nove spojine.It is therefore an object of the invention to provide novel compounds that are α 4 β inhibitors! bindings, and pharmaceutical compositions incorporating such novel compounds.

Kratek povzetek izumaA brief summary of the invention

Predloženi izum je usmerjen na spojine s formulo IThe present invention is directed to compounds of formula I

Formula I kjer Y pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR1, C(R2)(R3), NR5, CH, O in S; q je celo število od 3 do 10;Formula I wherein Y at each occurrence is independently selected from the group consisting of C (O), N, CR 1 , C (R 2 ) (R 3 ), NR 5 , CH, O and S; q is an integer from 3 to 10;

A izberemo iz skupine, ki obstoji iz O, S, C(R16)(R17) in NR6;A is selected from the group consisting of O, S, C (R 16 ) (R 17 ) and NR 6 ;

E izberemo iz skupine, ki obstoji iz CH2, O, S in NR ;E is selected from the group consisting of CH 2 , O, S and NR;

J izberemo iz skupine, ki obstoji iz O, S in NR8;J is selected from the group consisting of O, S and NR 8 ;

T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število od 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b, where b is an integer from 0 to 3;

M izberemo iz skupine, ki obstoji iz C(R9)(R10) in (CH2)u, kjer je u celo število od 0 do 3;M is selected from the group consisting of C (R 9 ) (R 10 ) and (CH 2 ) u , where u is an integer from 0 to 3;

L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1;

X izberemo iz skupine, ki obstoji iz CO2B, PO3H2;X is selected from the group consisting of CO 2 B, PO 3 H 2 ;

SO3H, SO2NH2, SO2NHCOR12, OPO3H2, C(O)NHC(O)R13,SO 3 H, SO 2 NH 2 , SO 2 NHCOR 12 , OPO 3 H 2 , C (O) NHC (O) R 13 ,

C(O)NHSO2R14, hidroksila, tetrazolila in vodika;C (O) NHSO 2 R 14 , hydroxyl, tetrazolyl and hydrogen;

W izberemo iz skupine, ki obstoji iz C, CR15 in N; inW is selected from the group consisting of C, CR 15 and N; and

B, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 in R17 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so: vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)-C(O)(Cr C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)-NH(CrC3 alkilna), -NHC(O)NH(Cr C6alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)-NH-(Ci-C3)alkilna, C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 at each occurrence is independently selected from the group consisting of: hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C (O) (C 1 -C 3 alkyl), -NHC (O ) N (C r C 3 alkyl) C (O) -NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C-C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, -C (O) -NH- (C 1 -C 3 ) alkyl , C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, ar alkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group ;

kjer so B, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 in R17 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali ki odtegne elektrone; kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč;where B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; wherein when L is NR 11 , R 4 and R 11 together may form a ring;

in kjer, kadar je M C(R9)(R10), lahko R9 in R10 skupaj tvorita obroč;and where, when MC (R 9 ) (R 10 ), R 9 and R 10 together can form a ring;

in kjer, kadar je A NR6 in vsaj en Y CR1, lahko R1 in R6 skupaj tvorita obroč; ali na njihovo farmacevtsko sprejemljivo sol; pod pogojem, da kadar je A C(R16)(R17), E ni NR7.and wherein when A is NR 6 and at least one Y CR 1 , R 1 and R 6 together may form a ring; or a pharmaceutically acceptable salt thereof; provided that when AC (R 16 ) (R 17 ), E is not NR 7 .

Za formulo I imajo lahko sedaj prednostne spojine A kot NR6; E kot NR7; J kot O; M kot C(R9)(R10); q kot 4 ali 5; T kot (CH2)b, kjer je b 0; L kot (CH2)n, kjer je n 0; X kot CO2B; W kot C ali CR15; R4 kot aril, alkilaril, aralkil, heterociklil, alkilheterociklil ali heterociklilalkil; ter R6, R7, R9, R10 in R15 neodvisno kot vodik ali nižji alkil.For Formula I, compounds A may now be preferred as NR 6 ; E as NR 7 ; J as O; M as C (R 9 ) (R 10 ); q as 4 or 5; T as (CH 2 ) b, where b is 0; L as (CH 2 ) n , where n is 0; X as CO 2 B; W as C or CR 15 ; R 4 is aryl, alkylaryl, aralkyl, heterocyclyl, alkylheterocyclyl or heterocyclylalkyl; and R 6 , R 7 , R 9 , R 10 and R 15 independently as hydrogen or lower alkyl.

Natančneje lahko spojine v smislu predloženega izuma opišemo s formulo IIMore specifically, the compounds of the present invention can be described by Formula II

____ Formula II kjer Y pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR1, C(R2)(R3), NR5, CH, O in S;____ Formula II wherein Y at each occurrence is independently selected from the group consisting of C (O), N, CR 1 , C (R 2 ) (R 3 ), NR 5 , CH, O and S;

q je celo število od 3 do 7;q is an integer from 3 to 7;

T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b, where b is an integer from 0 to 3;

L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1; W izberemo iz skupine, ki obstoji iz C, CR15 in N; inL is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1; W is selected from the group consisting of C, CR 15 and N; and

B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 in R15 neodvisno izberemo iz skupine, v kateri so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(Cr C3 alkilna), -NHC(O)N(C,-C3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(Cr C6alkilna), -NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH(C1-C3 alkilna), C(O)N(CrC3 alkilna)2,B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 15 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, - N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (O) N (C, -C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (Ci-C 3) amino, -C (O) O- (Ci-C 3) alkyl, -C (O) NH (C 1 -C 3 alkyl), C (O) N (C r C 3 alkyl) 2,

-CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(C1-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, heteroaryl, diaryl, diaryl , aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl ) group;

kjer so B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 in R15 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone;wherein B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 15 are unsubstituted or substituted by at least one electron or electron withdrawing group ;

kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč;wherein when L is NR 11 , R 4 and R 11 together may form a ring;

in kjer R9 in R10 skupaj lahko tvorita obroč;and wherein R 9 and R 10 together may form a ring;

in kjer, kadar je vsaj en Y CR1, lahko R1 in R6 skupaj tvorita obroč;and where, when at least one Y is CR 1 , R 1 and R 6 may together form a ring;

ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof.

Za formulo II imajo lahko sedaj prednostno spojine q kot 4 ali 5; W kot C ali CR15; T kot (CH2)b, kjer je b 0; L kot (CH2)n, kjer je n 0; R4 kot aril, alkilaril, aralkil, heterociklil, alkilheterociklil ali heterociklilalkil; in R6, R7, R9, R10 in R15 kot neodvisno vodik ali nižji alkil.For Formula II, the compounds q may now be preferred as 4 or 5; W as C or CR 15 ; T as (CH 2 ) b, where b is 0; L as (CH 2 ) n , where n is 0; R 4 is aryl, alkylaryl, aralkyl, heterocyclyl, alkylheterocyclyl or heterocyclylalkyl; and R 6 , R 7 , R 9 , R 10 and R 15 are independently hydrogen or lower alkyl.

Natančneje lahko spojine v smislu predloženega izuma opišemo s formulo IIIMore specifically, the compounds of the present invention can be described by Formula III

Formula III kjer Y pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR1, C(R2)(R3), NR5, CH, O in S; q je celo število od 2 do 5;Formula III wherein Y at each occurrence is independently selected from the group consisting of C (O), N, CR 1 , C (R 2 ) (R 3 ), NR 5 , CH, O and S; q is an integer from 2 to 5;

T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b , where b is an integer from 0 to 3;

L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1;

R5, R6, R7, R11 in R18 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina; inR 5 , R 6 , R 7 , R 11 and R 18 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl , alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, aralkyl (O) NH (benzyl) group; and

B, R1, R2, R3, R4, R9 in R10 neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)-C(O)(CiC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(Cr C6alkilna), -NHSO2(Cj-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(Ci-C3 alkilna), -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;B, R 1 , R 2 , R 3 , R 4 , R 9 and R 10 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkyloxy, thioalkoxy, hydroxyalkyl , aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C ( O) (CIC 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, -C (O ) NH- (C 1 -C 3 alkyl), -C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide , cycloalkyl, cycloalkenyl, -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C r C 3 alkyl ), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group;

kjer so B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 in R18 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč; in kjer lahko R9 in R10 skupaj tvorita obroč;wherein B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 18 are unsubstituted or substituted by at least one electron or electron withdrawing group ; wherein when L is NR 11 , R 4 and R 11 together may form a ring; and wherein R 9 and R 10 together may form a ring;

in kjer, kadar je vsaj en Y CR1, lahko R1 in R6 skupaj tvorita obroč;and where, when at least one Y is CR 1 , R 1 and R 6 may together form a ring;

ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof.

Za formulo III imajo lahko sedaj prednostne spojine R18 kot vodik, alkil, aril, aralkil, cikloalkil, alkilheterociklil, heterociklilalkil ali heterociklil; T kot (CH2)b, kjer je b 0; L kot (CH2)n, kjer je n 0; Y kot CR1 in C(R2)(R3) in q kot 2 ali 3.For formula III, R 18 compounds may now be preferred as hydrogen, alkyl, aryl, aralkyl, cycloalkyl, alkylheterocyclyl, heterocyclylalkyl or heterocyclyl; T as (CH 2 ) b, where b is 0; L as (CH 2 ) n , where n is 0; Y as CR 1 and C (R 2 ) (R 3 ) and q as 2 or 3.

V formuli III je lahko del molekuleIn Formula III, it may be part of a molecule

in njene farmacevtsko sprejemljive soli, kjer R , R , R in R pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -OH,and pharmaceutically acceptable salts thereof, wherein, at each occurrence, R, R, R and R are independently selected from the group consisting of the following, such as halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkyloxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -OH,

-CO2H, -SH, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)-C(O)(Ci-C3 alkilna),-CO 2 H, -SH, -CN, -NO 2 , -NH 2 , alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C (O) (C 1 -C 3 alkyl),

-NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(C,-C6alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(CrC3 alkilna),NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C, -C 6 alkyl), -NHSO 2 (C-C 3 alkyl ), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, -C (O) NH- (C r C 3 alkyl),

C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;C (O) N (C 1 -C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C r C 3 alkyl), -SO 3 - (C-C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) groups;

R18 izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna)skupina;R 18 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkyloxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl , aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C (O) NH (benzyl) groups;

R izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)-C(O)(Ci-C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6 alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(CrC3)alkilna,R is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C (O) (C 1 -C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl , alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C r C 3 ) alkyl,

-C(O)NH-(CrC3 alkilna), -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2,-C (O) NH- (C r C 3 alkyl), -C (O) N (C r C 3 alkyl) 2, -CH = NOH, -PO 3 H 2,

-OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in-OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclylalkyl, alkylaryl, alkylaryl, alkylaryl; -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and

-C(O)NH(benzilna) skupina;-C (O) NH (benzyl) group;

c je celo število od 0 do 2;c is an integer from 0 to 2;

d je celo število od 0 do 3;d is an integer from 0 to 3;

e je celo število od 0 do 4; in je i celo število od 0 do 2.e is an integer from 0 to 4; and i is an integer from 0 to 2.

V eni izvedbi je R18 aralkil; R4 je aril; T je (CH2)b, kjer je b 0; L je (CH2)n, kjer je n 0; in so B, R6, R7, R9 in R10 vsakokrat neodvisno vodik.In one embodiment, R 18 is aralkyl; R 4 is aryl; T is (CH 2 ) b , where b is 0; L is (CH 2 ) n , where n is 0; and B, R 6 , R 7 , R 9 and R 10 are each independently hydrogen.

Natančneje lahko spojine v smislu predloženega izuma opišemo s formulo IVMore specifically, the compounds of the present invention can be described by Formula IV

-1010-1010

Formula IV kjer T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število od 0 do 3;Formula IV wherein T is selected from the group consisting of C (O) and (CH 2 ) b, wherein b is an integer from 0 to 3;

L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1;

g je celo število 0 do 7;g is an integer from 0 to 7;

B, R4, R9, R10 in R23 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna,B, R 4 , R 9 , R 10 and R 23 are independently selected at each occurrence from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl ,

-CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)-C(O)(Ci-C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(Ci-C6 alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(Cr -CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C (O) (Ci -C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (Ci-C 6 alkyl), -NHSO 2 ( C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, -C (O) NH - (C r

C3 alkilna), -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna,C 3 alkyl), -C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl , cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl,

-SO2-(CrC3 alkilna), -SO3-(C]-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; in-SO 2 - (C r C 3 alkyl), -SO 3 - (C] -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; and

R , R , R in R vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi,R, R, R and R are each independently selected from the group consisting of the following, such as alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkoxy,

-1111 karboksaldlehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina;-1111 carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl O) NH (benzyl) group;

kjer so B, R4, R6, R7, R9, R10, R11, R18 in R23 nesubstituirani ali substituirani vsaj z eno skupino, ki daje elektrone ali ki odtegne elektrone;wherein B, R 4 , R 6 , R 7 , R 9 , R 10 , R 11 , R 18 and R 23 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group;

kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč;wherein when L is NR 11 , R 4 and R 11 together may form a ring;

in kjer R9 in R10 skupaj lahko tvorita obroč;and wherein R 9 and R 10 together may form a ring;

ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof.

Sedaj prednostne spojine v smislu predloženega izuma lahko tudi opišemo s formulo VThe presently preferred compounds of the present invention can also be described by Formula V

____ Formula V kjer je h celo število od 0 do 5;____ Formula V where h is an integer from 0 to 5;

B, R9, R10, R24 in R23 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna,B, R 9 , R 10 , R 24 and R 23 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl,

-CF3, -CO2H, -SH, -CN, -no2,-CF 3 , -CO 2 H, -SH, -CN, -no 2 ,

-NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi,-NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy,

-N(CrC3 alkil)-C(O)(CrC3 alkilna),N (C r C 3 alkyl) -C (O) (C r C 3 alkyl),

-NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(Ci-C6 alkilna),NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (Ci-C 6 alkyl),

-1212-1212

-NHSO2(C!-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna,-NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl,

-C(O)NH-(CrC3 alkilna), -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2,-C (O) NH- (C r C 3 alkyl), -C (O) N (C r C 3 alkyl) 2, -CH = NOH, -PO 3 H 2,

-OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna,-OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclylalkyl, alkylaryl, alkylaryl, alkylaryl;

-SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) groups;

R pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)C(O)(CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(C,-C3alkilna),R at each occurrence is independently selected from the group consisting of the following, such as halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, - CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (Ci-C 3 alkyl) C (O) (C r C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C 1 -C 3 alkyl),

-NHC(O)NH(CrC6 alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), -N(CrC3 alkil)SO2(C,-C3 alkilna), N-(C1-C3alkil)SO2(arilna), -C alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(Cr C3)alkilna, -C(O)NH-(CrC3 alkilna), -C(O)N(CrC3 alkilna)2, -CH=NOH,NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C-C 3 alkyl), -NHSO 2 (aryl), -N (C r C 3 alkyl) SO 2 (C, -C 3 alkyl ), N- (C 1 -C 3 alkyl) SO 2 (aryl), -C alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, -C (O) NH- (C r C 3 alkyl), -C (O) N (C r C 3 alkyl) 2, -CH = NOH,

-PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna,-PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl alkylheterocyclyl, heterocyclylalkyl, sulfonyl,

-SO2-(C1-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group;

R6, R7 in R1S vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna,R 6 , R 7 and R 1S are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxaldehyde, carboxaldehyde , cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl,

-1313 heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina; in-1313 heterocyclylalkyl, carbamate, aryloxyalkyl group, hydrogen and -C (O) NH (benzyl) group; and

R26 izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, -CF3, alkoksikarbonilna, heterocikloilna, karboksi, -C(O)O-(CrC3 alkilna), -C(O)NH-(CrC3)alkilna, C(O)N(C,-C3 alkilna)2, -PO3H2, haloalkilna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, biarilna, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), sulfonamido, ariloksialkilna in -C(O)NH(benzilna) skupina;R 26 is selected from the group consisting of the following, such as hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, -CF3, alkoxycarbonyl, heterocikloilna, carboxy, -C (O) O- (C r C 3 alkyl) , -C (O) NH- (C r C 3 ) alkyl, C (O) N (C, -C 3 alkyl) 2 , -PO 3 H 2 , haloalkyl, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl , aroyl, biaryl, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C 1 -C 3 alkyl), sulfonamido, aryloxyalkyl and -C (O) NH (benzyl) group;

kjer so B, R6, R7, R9, R10, R18, R24, R25, R26 in R27 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali ki odtegne elektrone; kjer lahko R18 in R24 skupaj tvorita obroč;wherein B, R 6 , R 7 , R 9 , R 10 , R 18 , R 24 , R 25 , R 26 and R 27 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; wherein R 18 and R 24 may together form a ring;

R24 in R25 lahko skupaj tvorita obroč;R 24 and R 25 may together form a ring;

R25 in R26 lahko skupaj tvorita obroč;R 25 and R 26 may together form a ring;

in kjer R9 in R10 lahko skupaj tvorita obroč;and wherein R 9 and R 10 together may form a ring;

ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof.

Sedaj prednostne spojine s formulo V imajo B, R6, R7, R9, R10, R24, R25 in R26 vsakokrat neodvisno vodik in R kot substituiran ali nesubstituiran aralkil.Preferred compounds of formula V now have B, R 6 , R 7 , R 9 , R 10 , R 24 , R 25 and R 26 each independently of hydrogen and R as substituted or unsubstituted aralkyl.

Druge sedaj prednostne spojine v smislu predloženega izuma lahko opišemo s formulo VIOther now preferred compounds of the present invention can be described by Formula VI

Formula VI kjer Z pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR30, C(R31)(R32), NR33, CH, O in S;Formula VI wherein Z at each occurrence is independently selected from the group consisting of C (O), N, CR 30 , C (R 31 ) (R 32 ), NR 33 , CH, O and S;

-1414 z je celo število od 3 do 6;-1414 z is an integer from 3 to 6;

kje celo število od 0 do 5;where is an integer from 0 to 5;

T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število od 0 do 3;T is selected from the group consisting of C (O) and (CH2) b, where b is an integer from 0 to 3;

L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1; R , R , R , R in R vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1; R, R, R, R and R are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, heterocyclylalkyl, heterocyclylalkyl, heterocyclylalkyl, heterocyclylalkyl benzyl) group;

B, R4, R9, R10, R30, R31 in R32 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O) (CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3 alkilna), -NHC(O)NH(C,-C6 alkilna), -NHSO2(C,-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -CfOjO-fOrCajalkilna, -C(O)NH-(Cr C3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(C]-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; in R pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O) (Cr C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(C1-C3 alkilna), -NHC(O)NH(C,-C6 B, R 4 , R 9 , R 10 , R 30 , R 31 and R 32 are independently selected at each occurrence from the group consisting of the following, such as hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3, -CO 2 H, -SH, -CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C, -C 6 alkyl), -NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -CfOjO-fOrCajalkyl, -C (O) NH- (C r C 3 ) alkyl, -C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl a, -SO 2 - (C] -C 3 alkyl), -SO 3 - (C r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; and R at each occurrence is independently selected from the group consisting of the following, such as halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C 1 -C 3 alkyl), -NHC (O) NH (C, -C 6

-1515 alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH-(Ci-C3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; kjer so B, R4, R6, R7, R9, R10, R11, R18, R29, R30, R31, R32 in R33 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; kjer, kadar je L NR11, R4 in R11 skupaj lahko tvorita obroč;-1515 alkyl), -NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, -C (O) NH- (Ci-C 3) alkyl, -C (O) N (C r C 3 alkyl) 2, -CH = NOH, -PO 3 H 2, -OPO 3 H 2, haloalkyl, alkoxyalkoxy, karboksaldehidna, carboxamide, cycloalkyl, cycloalkenyl, -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) groups; wherein B, R 4 , R 6 , R 7 , R 9 , R 10 , R 11 , R 18 , R 29 , R 30 , R 31 , R 32 and R 33 are unsubstituted or substituted by at least one electron-giving group or pulls off electrons; wherein when L is NR 11 , R 4 and R 11 together may form a ring;

in kjer R9 in R10 skupaj lahko tvorita obroč;and wherein R 9 and R 10 together may form a ring;

ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof.

Nekatere spojine s formulami I-VI lahko pripravimo iz novih intermediatov s formulo VII in formulo VIII.Some compounds of formulas I-VI can be prepared from novel intermediates of formula VII and formula VIII.

R25 R 25

Formula VII kjer R24 in R25 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -SH, -OH,Formula VII wherein R 24 and R 25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -SH , -OH,

-CO2H, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(C,-C3 alkil)-C(O)(CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6alkilna), alkilamino,-CO 2 H, -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C, -C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC ( O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), alkylamino,

-NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkenilamino, di(Cr -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkenylamino, di (C r

-1616-1616

C3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(CrC3)alkilna,C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, -C (O) NH- (C r C 3 ) alkyl,

-C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), -SO3-(C!-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; in R18 in R24 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina;-C (O) N (C, -C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl , aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) groups; and R 18 and R 24 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyloxy, carboxaldehyde, carboxalkyl , cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, benzyloxyalkyl, aryloxyalkyl group ;

kjer so R18, R24, R25 in R34 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone;wherein R 18 , R 24 , R 25 and R 34 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group;

in kjer lahko R24 in R25 skupaj tvorita obroč; s pridržkom, da kadar R24 in R23 skupaj tvorita obroč, nastali obroč ni benzen. Sedaj prednostne spojine s formulo VII imajo R34 kot vodik; R18 kot aralkil; in R24 in R25 vsakokrat neodvisno kot vodik, nižji alkil ali nižji alkil, kjer R24 in R25 skupaj tvorita obroč.and wherein R 24 and R 25 may together form a ring; with the proviso that when R 24 and R 23 together form a ring, the resulting ring is not benzene. Now preferred compounds of formula VII have R 34 as hydrogen; R 18 as aralkyl; and R 24 and R 25 are each independently hydrogen, lower alkyl or lower alkyl, wherein R 24 and R 25 together form a ring.

Formula VIII prikazuje sedaj prednostne nove intermediateFormula VIII now shows preferred new intermediates

-1717 kjer R24 in R25 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -SH, -OH,-1717 wherein R 24 and R 25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3, -SH, -OH,

-CO2H, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6 alkilna),-CO 2 H, -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (O ) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl),

-NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(C]-C3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(CrC3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C] -C 3) amino, -C (O) O- (C r C 3 alkyl), - C (O) NH- (C r C 3 ) alkyl, -C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, karboksaldehidna, carboxamide, cycloalkyl, cycloalkenyl, -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C 3 alkyl), -SO 3 - (C r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group;

R34 izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina; inR 34 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkyloxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl , aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C (O) NH (benzyl) groups; and

R35 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(C,-C3 alkil)-C(O)(C,-C3 alkilna), -NHC(O)N(Ci-C3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6 alkilna),R 35 at each occurrence is independently selected from the group consisting of the following, such as halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH. -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C (O) (C 1 -C 3 alkyl), -NHC (O ) N (C 1 -C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl),

-NHSO2(C!-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)0-(CrC3)alkilna, -C(O)NH-(CrC3)alkilna, -C(O)N(C,-C3 alkilna)2, -CH-NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna,-NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, - C (O) NH- (C r C 3 ) alkyl, -C (O) N (C, -C 3 alkyl) 2 , -CH-NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy , carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl,

-1818 cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; kjer so R24, R25, R34 in R35 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; in je m celo število od 0 do 5. Sedaj prednostne spojine s formulo VIII imajo R34 kot vodik; m kot celo število od 1 do 3 in R35 v vsakem pojavljanju kot alkil, halogen, alkoksi, haloalkil, sulfonil, -OH ali -CN.-1818 -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C-C 3 alkyl), -SO 3 - (Ci-C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; wherein R 24 , R 25 , R 34 and R 35 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; and m is an integer from 0 to 5. Now preferred compounds of formula VIII have R 34 as hydrogen; m as an integer from 1 to 3 and R 35 in each occurrence as alkyl, halogen, alkoxy, haloalkyl, sulfonyl, -OH or -CN.

Sedaj prednostne spojine s formulo I so:Preferred compounds of formula I are now:

(3S)-3-[({[2-metil-4-(2-metilpropil)-6-okso-1 -(fenilmetil)-1,6-dihidro-5pirimidinil] amino} karbonil)amino]-3 -(4-metilfenil)propanoj ska kislina;(3S) -3 - [({[2-methyl-4- (2-methylpropyl) -6-oxo-1- (phenylmethyl) -1,6-dihydro-5-pyrimidinyl] amino} carbonyl) amino] -3 - ( 4-methylphenyl) propanoic acid;

(3 S)-3 -(1,3-benzodioksol-5-il)-3 -[({[2-okso-1 -(fenilmetil)-4-propil-1,2-dihidro-3 piridinil] amino }karbonil)amino]propanoj ska kislina;(3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[2-oxo-1- (phenylmethyl) -4-propyl-1,2-dihydro-3 pyridinyl] amino} carbonyl) amino] propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-4-etil-2-okso-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-ethyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid;

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-2-okso-4-propil-1,2-dihidro-3 piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-4-propyl-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3 - (4 -methylphenyl) propanoic acid;

(3 S )-3 - {[({1 -[(2-klorofenil)metil]-4-metil-2-okso-1,2-dihidro-3 piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3 - (4 -methylphenyl) propanoic acid;

(3 S) - 3 - {[({6-metil-2-okso-1 -(fenilmetil)-4- [(fenilmetil)oksi] -1,2-dihidro-3 piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ska kislina;(3 S) -3 - {[({6-methyl-2-oxo-1- (phenylmethyl) -4 - [(phenylmethyl) oxy] -1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} - 3- (4-methylphenyl) propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-2,4-dimetil-6-okso-l,6-dihidro-5pirimidinil} amino)karbonil]amino} -3 -(4-metilfenil)propanoj ska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2,4-dimethyl-6-oxo-1,6-dihydro-5-pyrimidinyl} amino) carbonyl] amino} -3 - (4 -methylphenyl) propanoic acid;

-1919 (3S)-3-{[({4-amino-l-[(2-klorofenil)metil]-6-metil-2-okso-l,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina;-1919 (3S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] -6-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} - 3- (4-methylphenyl) propanoic acid;

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-metil-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metiloksi)fenil]propanojska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4- methyloxy) phenyl] propanoic acid;

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-metil-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(3,4-dimetilfenil)propanojska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3. 4-dimethylphenyl) propanoic acid;

(3S)-3-{[({4-amino-l-[(2-klorofenil)metil]-2-okso-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-l,2-dihidro-3piridiml}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid;

(3S)-3-[( {[ 1 -[(2-klorofenil)metil]-4-( 1,4-oksazinan-4-il)-2-okso-1,2-dihidro-3 piridinil]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina;(3S) -3 - [({[1 - [(2-chlorophenyl) methyl] -4- (1,4-oxazinan-4-yl) -2-oxo-1,2-dihydro-3 pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid;

(3S)-3-[({[l-[(2-klorofenil)metil]- 2-okso-4-(propilamino)-l,2-dihidro-3piridinil]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina;(3S) -3 - [({[1 - [(2-chlorophenyl) methyl] -2-oxo-4- (propylamino) -1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] -3- (4 -methylphenyl) propanoic acid;

(3S)-3-{[({l-[(2-bromofenil)metil]-4-metil-2-okso-l,2-dihidro-3piridinil} amino)karbonilamino } -3 -(4-metilfenil)propanoj ska kislina;(3S) -3 - {[({1 - [(2-bromophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonylamino} -3- (4-methylphenyl) propane ska acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-[3-metil-4-metiloksi)fenil]propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- [3-methyl -4-methyloxy) phenyl] propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-2-okso-4-fenil-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-4-phenyl-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid;

-2020 (3S)-3-{ [({l-[(2-klorofenil)metil]-4-[(2-{[2-metiloksi)etil]oksi}etil)oksi]-2-okso1,2-dihidro-3 -piridinil} aminokarbonil] amino} -3 -(4-metilfenil)propanj ska kislina;-2020 (3S) -3- {[({1 - [(2-chlorophenyl) methyl] -4 - [(2 - {[2-methyloxy) ethyl] oxy} ethyl) oxy] -2-oxo 1,2- dihydro-3-pyridinyl} aminocarbonyl] amino} -3- (4-methylphenyl) propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-6-metil-2-okso-l,2-dihidro-3piridinil} amino)karbonil]amino} -3 - [4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-6-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - [4-methylphenyl) propanoic acid;

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-( 1,1 -dimetiletil)amino]-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-[4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- (1,1-dimethylethyl) amino] -2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- [4-methylphenyl) propanoic acid;

(3 S)-3 - {[({1 - [(2-klorofenil)metil] -4-hidroksi-2-okso-1,2-dihidro-3 piridinil} amino)karbonil]amino}-3-fenilpropanojska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3-phenylpropanoic acid ;

(3S)-3-{[({l-[(2-klorofenil)metil]-4-[4-metiltetrahidro-l(2H)-pirazinil]-2-okso-l,2dihidro-3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- [4-methyltetrahydro-1 (2H) -pyrazinyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid;

(3S)-3-{[({l -[(2-klorofenil)metil] -4-hidroksi-2-okso-1,2-dihidrb-3 piridinil} amino)karbonil] amino} -3-(4-metiloksi)fenil]propanoj ska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- (4- methyloxy) phenyl] propanoic acid;

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3 piridinil}amino)karbonil]amino}-3-(3,5-dimetilfeniljpropanojska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- (3 , 5-dimethylphenylpropanoic acid;

(3 S)-3- {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3 piridinil}amino)karbonil]amino}-3-(3-metilfenil)propanojska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- (3 -methylphenyl) propanoic acid;

(3S)-3 - {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-[3-(metiloksi)fenil]propanojska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- [3- ( methyloxy) phenyl] propanoic acid;

(3S)-3-[3,5-bis(metiloksi)fenil]-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-l,2dihidro-3-piridiml}amino)karbonil]amino}propanojska kislina;(3S) -3- [3,5-bis (methyloxy) phenyl] -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl) } amino) carbonyl] amino} propanoic acid;

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3 -2121 kinolinil}amino)karbonil]amino}-3-[4-metilfenil]propanojska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 -2121 quinolinyl} amino) carbonyl] amino} -3- [4-methylphenyl] propanoic acid;

(3 S)-3- {[({1 - [(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3 piridinil} amino)karbonil] amino } -3 - [3 ~(trifluorometil)fenil]propanoj ska kislina;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3 - [3 ~ (trifluoromethyl) phenyl] propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-4-({etil[etilamino)karbonil]amino}karbonil)amino]2-okso-1,2-dihidro-3 -piridinil} amino)karbonil] amino } -3 - [4-metiIfenil]propanoj ska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4 - ({ethyl [ethylamino) carbonyl] amino} carbonyl) amino] 2-oxo-1,2-dihydro-3-pyridinyl } amino) carbonyl] amino} -3- [4-methylphenyl] propanoic acid;

(3 S)-3 - {[({4-( 1 -azetanil)-1 - [(2-klorofenil)metil] -2-okso-1,2-dihidro-3 piridinil}amino)karbonil]amino} -3-(4-metilfenil)propanojska kislina;(3 S) -3 - {[({4- (1-azetanyl) -1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} - 3- (4-methylphenyl) propanoic acid;

(3 S)-3-[({ [ 1 -[(2-klorofenil)metil]-4-({2-[(2- {[2(metiloksi)etil]oksi}etil)oksi]etil}oksi)-2-okso-l,2-dihidro-3piridini 1]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina;(3 S) -3 - [({[1 - [(2-chlorophenyl) methyl] -4 - ({2 - [(2- {[2 (methyloxy) ethyl] oxy} ethyl) oxy] ethyl} oxy) -2-oxo-1,2-dihydro-3-pyridines 1] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid;

(3 S)-3 - {[({1 -[(2-fluorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3 piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3 S) -3 - {[({1 - [(2-fluorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- (4 -methylphenyl) propanoic acid;

(3S)-3-{[({l-[(2-kloro-6-fluorofenil)metil]-4-hidroksi-2-okso-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina;(3S) -3 - {[({1 - [(2-chloro-6-fluorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid;

(3S)-3-{[({l-[(2-klorofenil)metil]-5-metil-2-okso-l,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid;

(3S)-3-(l,3-benzodioksol-5-il)-3-((((2-okso-l-((4-trifluorometil)fenil)metil)-l,2dihidro-3-piridinil)amino)karbonil)amino)propanojska kislina, (3 S)-3-(((( 1 -((2-klorofenil)metil)-2-okso-1,2-dihidro-3 piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina,(3S) -3- (1,3-benzodioxol-5-yl) -3 - ((((2-oxo-1 - ((4-trifluoromethyl) phenyl) methyl) -1,2-dihydro-3-pyridinyl) amino ) carbonyl) amino) propanoic acid, (3 S) -3 - (((((1 - ((2-chlorophenyl) methyl) -2-oxo-1,2-dihydro-3 pyridinyl) amino) carbonyl) amino) - 3- (4-methylphenyl) propanoic acid,

-2222 (3S)-3-((((l-((2-fluorofenil)metil)-2-okso-l,2-dihidro-3piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina, (3 S)-3 -((((1 -((2-bromofenil)metil)-2-okso-1,2-dihidro-3 piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina, (3 S)-3 -((((1 -((2,4-diklorofenil)metil)-2-okso-1,2-dihidro-3 piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina, (3 S)-3 -((((1 -((2-kloro-6-fluorofenil)metil)-2-okso-1,2-dihidro-3 piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina, (3 S)-3-((((1 -((2-klorofenil)metil)-4-hidroksi-2-okso-1,2-dihidro-3piridinil)amino)karbonil)amino)-3-(4-trifluorometil)oksi)fenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-2-okso-1,2-dihidropiridin-3 i 1] amino } karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina,-2222 (3S) -3 - (((((1 - ((2-fluorophenyl) methyl) -2-oxo-1,2-dihydro-3-pyridinyl) amino) carbonyl) amino) -3- (4-methylphenyl) propanoic acid acid, (3 S) -3 - (((((1 - ((2-bromophenyl) methyl) -2-oxo-1,2-dihydro-3 pyridinyl) amino) carbonyl) amino) -3- (4-methylphenyl) ) propanoic acid, (3 S) -3 - (((((1 - ((2,4-dichlorophenyl) methyl) -2-oxo-1,2-dihydro-3 pyridinyl) amino) carbonyl) amino) -3- (4-methylphenyl) propanoic acid, (3 S) -3 - (((((1 - ((2-chloro-6-fluorophenyl) methyl) -2-oxo-1,2-dihydro-3 pyridinyl) amino) carbonyl ) amino) -3- (4-methylphenyl) propanoic acid, (3 S) -3 - ((((1 - ((2-chlorophenyl) methyl) -4-hydroxy-2-oxo-1,2-dihydro- 3pyridinyl) amino) carbonyl) amino) -3- (4-trifluoromethyl) oxy) phenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -2-oxo- 1,2-dihydropyridine-3 and 1] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid,

4- {[3 -[({[(1 S)-2-karboksi-1 -(4-metilfenil)etil] amino} karbonil)amino] -1-(2klorobenzil)2-okso-1,2-dihidropiridin-4-il] amino }benzoj ska kislina, (3 S)-3 - {[({1 -(2-klorobenzil)-4- [(2,2-dimetilpropanoil)amino] -2-okso-1,2dihidropiridin-3-il} amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3S)-3-[({[4-{ [terc.butilamino)karbonil] amino } -1 -(2-klorobenzil)-2-okso-1,2dihidropiridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 -[( {[ 1 -(2-cianobenzil)-4-hidroksi-2-okso-1,2dihidropiridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina,4- {[3 - [({[(1S) -2-carboxy-1- (4-methylphenyl) ethyl] amino} carbonyl) amino] -1- (2-chlorobenzyl) 2-oxo-1,2-dihydropyridine- 4-yl] amino} benzoic acid, (3 S) -3 - {[({1- (2-chlorobenzyl) -4 - [(2,2-dimethylpropanoyl) amino] -2-oxo-1,2-dihydropyridine- 3-yl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[4- {[tert-butylamino) carbonyl] amino} -1- (2-chlorobenzyl) ) -2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-cyanobenzyl) - 4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid,

-2323 (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 i 1] amino} karbonil)amino]-3 -(2,3 -dihidro-1,4-benzodioksin-6-il)propanoj ska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(7-metoksi-1,3-benzodioksol-5-il)propanojska kislina, (3 S )-3 - [({[ 1 ~(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksi-4-metoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3,4-dimetoksifenil)propanojska kislina, (3 S)-3 - [({[ 1 -(4-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il] amino}karbonil)amino]-3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi- 5 -metil-2-okso-1,2dihidropiridin-3 -il]amino } karbonil)amino]-3 -(4-metilfenil)propanoj ska kislina, (3 S)-3-[({[1 -(2,6-difluorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-l,2-dihidropiridin-3i 1] amino } karbonil)amino]-3 -(3,5 -dimetoksifenil)propanoj ska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina,-2323 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 and 1] amino} carbonyl) amino] -3 - (2 , 3-dihydro-1,4-benzodioxin-6-yl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2- dihydropyridin-3 yl] amino} carbonyl) amino] -3- (7-methoxy-1,3-benzodioxol-5-yl) propanoic acid, (3 S) -3 - [({[1 ~ (2-chlorobenzyl) -4-Hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxy-4-methoxyphenyl) propanoic acid, (3 S) -3 - [({[1 - (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3,4-dimethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (4-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2,6-difluorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl ) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine- 3i 1] amino} carbonyl) amino] -3- (3,5-dimethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1 , 2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid,

-2424 (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il] amino } karbonil)amino]-3 -(3 -etoksifenil)propanoj ska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3-metoksi-4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3,5-dimetoksi-4-metilfenil)propanojska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3,4-dimetilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-5 -etil-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 -[2-kloro-5-(triflurometil)benzil]-4-hidroksi-2-oks0-1,2-dihidropiridin-3 il}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3-metilfenil)propanojska kislina, (3 S)-3-[({ [ 1 -(2-kloro-6-metilbenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3i 1]amino } karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 -il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2,6-dimetoksibenzil)-4-hidroksi-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina,-2424 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3 - ethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3 - (3-methoxy-4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl ) amino] -3- (3,5-dimethoxy-4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2] -dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3,4-dimethylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -5-ethyl-4- hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[({1- [2-chloro- 5- (Trifluoromethyl) benzyl] -4-hydroxy-2-ox0-1,2-dihydropyridin-3 yl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [ ({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3-methylphenyl) propanoic and acid, (3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3i] amino} carbonyl ) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7- tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2,6-dimethoxybenzyl) -4 -hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid,

-2525 (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il] amino} karbonil)amino] -3 -(3 -propoksifenil)propanoj ska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-5-propil-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5,6-dimetil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-5 -propil-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3 S)-3 -(3 -butoksifenil)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]propanojska kislina, (3 S)-3 - {[({1 -(2-kloro-5-(metilsulfonil)benzil] -4-hidroksi-2-okso-1,2-dihidropiridin-3 il}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-[3-(2-metoksietoksi)fenil]propanojska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3,4-dipropoksifenil)propanojska kislina, (3S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il] amino} karbonil)amino] -3 - [3 -(difluorometoksi)fenil]propanoj ska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina,-2525 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3 - propoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3yl] amino} carbonyl) amino ] -3- (3-Ethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridine- 3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-5-propyl] 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid, (3 S) -3- (3-butoxyphenyl) -3 - [({[1 - ( 2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] propanoic acid, (3 S) -3 - {[({1- (2-chloro-5- (methylsulfonyl) benzyl] -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({ [1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- [3- (2-methoxyethoxy) phenyl ] propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- ( 3,4-dipropoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] - 3- [3- (difluoromethoxy) phenyl] propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine- 3yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid,

-2626 (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-metilbenzil)-4-hidroksi-5,6-dimetil-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-cianobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina,-2626 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridine3] -yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-cyanobenzyl) -4-hydroxy-2 -oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid,

- [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(2-naftil)propanojska kislina in (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5,6-dimetil-2-okso-l,2-dihidropiridin-3iljamino} karbonil)amino] -3 -(3,4-dietoksifenil)propanoj ska kislina, (3 S)-3-[({ [ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3S)-3-[({[l -(2-klorobenzil)-4-hidroksi- 5 -metil-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4-metoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metilbenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina,- [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (2-naphthyl) propanoic acid and (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridine-3-ylamino} carbonyl) amino] -3- (3,4-diethoxyphenyl ) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine- 3 yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo- 1,2-Dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4-methoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) prop opanoic acid,

-2727 (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3i 1] amino} karbonil)amino] -3 -(3 -izopropoksifenil)propanoj ska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il] amino } karbonil)amino] -3 -(3 -etoksifenil)propanoj ska kislina, (3 S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3il]amino } karbonil)amino] -3 -(1 -metil-1 H-indol-5 -il)propanoj ska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(2,3-dihidro-l-benzofuran-5-il)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il] amino } karbonil)amino] -3 -(3,5 -dietoksifenil)propanoj ska kislina, (3 S)-3 - [( {[5-kloro-1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il] amino} karbonil)amino] -3 -(3 -izopropoksifenil)propanoj ska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-propoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-fenilpropanojska kislina,-2727 (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino ] -3- (3-Isopropoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7 -tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6 -Ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (1-methyl-1H-indol-5-yl) propanoic acid , (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] - 3- (2,3-Dihydro-1-benzofuran-5-yl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo- 2,5,6,7-Tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3,5-diethoxyphenyl) propanoic acid, (3 S) -3 - [({ [5-chloro-1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid , (3 S) - 3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propane acetic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 -yl] amino} carbonyl) amino] -3- (3-propoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo] -2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3-phenylpropanoic acid,

-2828 (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il] amino} karbonil)amino] -3 -(1,3 -dietil-2-okso-2,3 -dihidro-1Hbenzimidazol-5-il)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il] amino} karbonil)amino] -3 -(3 -trifluorometoksi)fenil]propanoj ska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5,6-dimetil-2-okso-l,2dihidropiridin-3-il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3 S )-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 -il] amino} karbonil)amino] -3 -(1 -metil-1 H-indol-5 il)propanojska kislina, (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-5-ciklopropil-4-hidroksi-2-okso-1,2dihidropiridin-3-il]amino}karbonil)amino]-3-(3-izopropoksiferiil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-5-ciklopropil-4-hidroksi-2-okso-1,2dihidropiridin-3 -il] amino } karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina, (3S)-3-[({[l-(2-kloro-5-metoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-6-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(l-metil-lH-indol-6-il)propanojska kislina,-2828 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (1,3-diethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) propanoic acid, (3S) -3 - [({[1- (2-chloro- 6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-trifluoromethoxy) phenyl] propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3 -isopropoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 -yl] amino} carbonyl) amino] -3- (1-methyl-1H-indol-5 yl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5-Cyclopropyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3 S) -3 - [({[1 - (2-chloro-6-ethoxybenzyl) -5-cyclopropyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) nyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-5-methoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-6-methyl-2-oxo-1 , 2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy- 5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (1-methyl-1H-indol-6-yl) propanoic acid,

-2929 (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 - i 1] amino} karbonil)amino] -3 - [3 -(ciklopropiloksi)fenil] propanojska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-[3-(ciklopropilmetoksi)fenil]propanojska kislina, (3 S)-3-[({ [ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3 -il] amino } karbonil)amino] -3 - [3 -(ciklopropilmetoksi)fenil] propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 -il] amino} karbonil)amino]-3 -(3,5 -dimetilfenil)propanoj ska kislina, (3S)-3-[({[l-(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil]amino } -3 - {3 - [(difluorometil)oksi] fenil} propanojska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 - [(1,1,2,2-tetrafluoroetil)oksi] fenil}-propanojska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil]amino} -3-( 1 -etil-1 H-indol-5 -il)-propanojska kislina in (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il}amino)karbonil]amino}-3-[3-(dietilamino)fenil]propanojska kislina,-2929 (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 - and 1] amino} carbonyl) amino] -3- [3- (cyclopropyloxy) phenyl] propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 2,5,6,7-Tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- [3- (cyclopropylmethoxy) phenyl] propanoic acid, (3 S) -3 - [({ [1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3 - [3- (cyclopropylmethoxy) phenyl] propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta] [ b] pyridin-3-yl] amino} carbonyl) amino] -3- (3,5-dimethylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorophenyl) methyl] -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3 - {3 - [(difluoromethyl) oxy] phenyl} propanoic acid, ( 3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] py idin-3-yl} amino) carbonyl] amino} -3 - {3 - [(1,1,2,2-tetrafluoroethyl) oxy] phenyl} -propanoic acid, (3S) -3 - {[({l- [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- (1-ethyl -1H-indol-5-yl) -propanoic acid and (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7 -tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- [3- (diethylamino) phenyl] propanoic acid,

-3030 (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 - il] amino } karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3i 1] amino} karbonil)amino] -3 -(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3-[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(6-metoksi-2-naftil)propanojska kislina, (3S)-3-[({[l -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-metilfenil)piOpanojska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi- 5 -metil-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-[3-(dietilamino)fenil]propanojska kislina in (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il}amino)karbonil]amino}-3-(l-metil-lH-indol-5-il)propanojska kislina,-3030 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine) -3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5 -methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro- 6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3 S) -3- [ ({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3 -isopropoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (6-methoxy-2-naphthyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6] , 7-tetrahydro-1Hcyclo penta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3-methylphenyl) pyanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 5-methyl-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- [3- (diethylamino) phenyl] propanoic acid and (3S) -3 - {[({1 - [ (2-chloro-6-methylphenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- ( 1-methyl-1H-indol-5-yl) propanoic acid,

-3131 (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [(metilsulfonil)amino] fenil} propanoj ska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [(metilsulfonil)amino] fenil }propanoj ska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil] amino } -3 - {3 [metil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il} amino)karbonil] amino} -3 - {3 [metil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil]amino} -3 - {3 [etil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil]amino} -3 - {3 [etil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il} amino)karbonil] amino} -3 -(1 H-indol-5 -il)propanoj ska kislina, in farmacevtsko sprejemljive soli gornjih spojin.-3131 (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl } amino) carbonyl] amino} -3 - {3 [(methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] -4 -hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3 - {3 [(methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino ) carbonyl] amino} -3 - {3 [methyl (methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] -4-hydroxy -2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [methyl (methylsulfonyl) amino] phenyl} propanoic acid, (3S ) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl ] amino} -3 - {3 [ethyl (methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] -4-hydro oxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [ethyl (methylsulfonyl) amino] phenyl} propanoic acid, ( 3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3- yl} amino) carbonyl] amino} -3- (1H-indol-5-yl) propanoic acid, and the pharmaceutically acceptable salts of the above compounds.

Sedaj prednostne spojine s formulo VII so:Preferred compounds of formula VII are now:

-3232-3232

5-(2-klorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-benzil-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5-benzyl-6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-benzil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5-benzyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,5-dimetilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,5-dimethylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,4-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,4-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-(2-metoksibenzil)-3,5 -dihidro [ 1,3 ]oksazolo[4,5 -c]piridin-2,4-dion,- (2-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,5-difluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,5-difluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2-kloro-5-(metiltio)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2-chloro-5- (methylthio) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(4-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-5-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-5-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[3,5-bis(trifluorometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3,5-bis (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-3333-3333

5-(4-terc.butilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-tert-butylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(3 -klorobenzil)-3,5 -dihidro[ 1,3] oksazolo [4,5 -c]piridin-2,4-dion,5- (3-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(4-klorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[3-(trifluorometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-bromobenzil)-3,5-dihidro[l,3]oksazolo[4,5-cipiridin-2,4-dion,5- (2-bromobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-cypyridine-2,4-dione,

5-(3,4-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3,4-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(4-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[4-(triflurometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [4- (Trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(3-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(piridin-2-ilmetil)-3,5 -dihidro [ 1,3 ]oksazolo [4,5 -c]piridin-2,4-dion,5- (pyridin-2-ylmethyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,4-diflurobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,4-diflurobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,6-difluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-difluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[3-(trifluorometoksi)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (trifluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[4-(triflurometoksi)benzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [4- (trifluoromethoxy) benzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-3434-3434

5-[2-(triflurometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (Trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[3-(metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,3-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,3-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(3,5-dimetilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3,5-dimethylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-7-pentil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-pentyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,4-diklorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,4-dichlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-7-etil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-ethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

7-butil-5 -(2-klorobenzil)-3,5 -dihidro [1,3] oksazolo[4,5 -c]piridin-2,4-dion,7-butyl-5- (2-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2-kloro-5-(triflurometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2-chloro-5- (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-(2,6-diklorobenzil)-3,5 -dihidro[ 1,3] oksazolo[4,5 -c]piridin-2,4-dion,- (2,6-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro- 5-fluorobenzil)-3,5 -dihidro[ 1,3] oksazolo[4,5 -c]piridin-2,4-dion,5- (2-chloro-5-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-metilbenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-methylbenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(4-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b][l,3]oksazolo[5,4-d]piridin2,4(3H)-dion,5- (2-chlorobenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4-d] pyridine 2,4 (3H) -dione,

7-metil-5-[4-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-methyl-5- [4- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-3535-3535

5-(4-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenziI)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

4- [(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H)-il)metil]-N,Ndimetilbenzensulfonamid,4- [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H) -yl) methyl] -N, N-dimethylbenzenesulfonamide,

5- (mezitilmetil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (mesitylmethyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-3,5,6,7,8,9-heksahidro[l,3]oksazolo[4,5-c]kinolin-2,4-dion,5- (2-chlorobenzyl) -3,5,6,7,8,9-hexahydro [1,3] oxazolo [4,5-c] quinoline-2,4-dione,

5-(2-klorobenzil)-7-etil-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-ethyl-6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2-(metiltio)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (methylthio) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

2-[(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H)-il)metil]-N,Ndimetilbenzensulfonamid,2 - [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H) -yl) methyl] -N, N-dimethylbenzenesulfonamide,

5-(2,6-dimetoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dimethoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

- [2-(triflurometoksi)benzil]-3,5 -dihidro [1,3] oksazolo[4,5 -c]piridin-2,4-dion,- [2- (trifluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-(2-klorobenzil)-6,7-dimetil-3,5 -dihidro[ 1,3] oksazolo [4,5 -c]piridin-2,4-dion,- (2-chlorobenzyl) -6,7-dimethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2-kloro-5-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2-chloro-5- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-(4-kloro-2-metoksibenzil)-3,5 -dihidro [1,3] oksazolo [4,5 -c]piridin-2,4-dion,- (4-chloro-2-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-5,6,7,8,9,10-heksahidro-2H-ciklopenta[b][l,3]oksazolo[5,4d]piridin-2,4(3H)-dion,5- (2-chlorobenzyl) -5,6,7,8,9,10-hexahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4d] pyridine-2,4 (3H) -dione,

-3636-3636

5-[2-(difluorometoksi)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (difluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

7-metil-5-[(lR)-l-feniletil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-methyl-5 - [(1R) -1-phenylethyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(4-klorobenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chlorobenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,6-dimetilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dimethylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

3-kloro-2-[(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H)il)metil]benzonitril,3-chloro-2 - [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H) yl) methyl] benzonitrile,

5-(2-kloro-6-metilbenzil)-6,7-dimetil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-methylbenzyl) -6,7-dimethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

2-[(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H-il)metil]benzonitril,2 - [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H-yl) methyl] benzonitrile,

-(2-kloro-6-metoksibenzil)-7-metil-3,5 -dihidro [1,3] oksazolo[4,5 -c]piridin-2,4-dion,- (2-chloro-6-methoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[3-(metiltio)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (methylthio) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-7-ciklopropil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-cyclopropyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(3-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2,6-diklorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dichlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

7-metil-5-(4-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-methyl-5- (4-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(3,5-dimetoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3,5-dimethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

-3737-3737

5-(2,6-difluorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-difluorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[3-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-etoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-etoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-fluoro-6-metoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-fluoro-6-methoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-metoksibenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-methoxybenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(5-kloro-2-fluorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (5-chloro-2-fluorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-7-izopropil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-isopropyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(5-fluoro-2-metilbenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (5-fluoro-2-methylbenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

7-metil-5-[(lS)-l-feniletil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-methyl-5 - [(1S) -1-phenylethyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-5-izopropoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- (2-chloro-5-isopropoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(5-acetil-2-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (5-acetyl-2-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-d]piridazin-2,4-dion,5- (2-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-d] pyridazine-2,4-dione,

5-[2-fluoro-6-(trifluorometil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- [2-fluoro-6- (trifluoromethyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione,

-3838-3838

5-(2-kloro-6-metilbenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b][l,3]oksazolo[5,4d]piridin-2,4(3H)-dion,5- (2-chloro-6-methylbenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4d] pyridine-2,4 (3H) -dione,

5-(2-kloro-6-etoksibenzil)-7-etil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-ethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-propoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-propoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-izobutoksibenzil)-7-metil-3,5 -dihidrof 1,3] oksazolo[4,5 -c]piridin-2,4dion,5- (2-chloro-6-isobutoxybenzyl) -7-methyl-3,5-dihydro 1,3] oxazolo [4,5-c] pyridine-2,4 dione,

5-(2-kloro-6-etoksibenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b][l,3]oksazolo[5,4d]piridin-2,4(3H)-dion,5- (2-chloro-6-ethoxybenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4d] pyridine-2,4 (3H) -dione,

5-(2-kloro-6-izopropoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- (2-chloro-6-isopropoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-(2,2,2-trifluoroetoksi)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c]piridin-2,4-dion,5- (2-chloro-6- (2,2,2-trifluoroethoxy) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione,

5-(2-kloro-6-etoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-d]piridazin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-d] pyridazine-2,4-dione,

5-[2-kloro-6-(2-metoksietoksi)benzil]-5,6,7,8-tetrahidro-2Hciklopenta[b][l,3]oksazolo[5,4-d]piridin-2,4(3H)-dion,5- [2-chloro-6- (2-methoxyethoxy) benzyl] -5,6,7,8-tetrahydro-2Hcyclopenta [b] [1,3] oxazolo [5,4-d] pyridine-2,4 ( 3H) -dione,

5-(2-kloro-6-etoksibenzil)-6,7-dimetil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- (2-chloro-6-ethoxybenzyl) -6,7-dimethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-etoksibenzil)-7-etil-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- (2-chloro-6-ethoxybenzyl) -7-ethyl-6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4dione,

5-(2-klorobenzil)-7-etil-3,5-dihidro[l,3]oksazolo[4,5-d]piridazin-2,4-dion,5- (2-chlorobenzyl) -7-ethyl-3,5-dihydro [1,3] oxazolo [4,5-d] pyridazine-2,4-dione,

-3939-3939

5-(2-kloro-6-etoksibenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-etoksibenzil)-7-ciklopropil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- (2-chloro-6-ethoxybenzyl) -7-cyclopropyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-5-propoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-5-propoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-5-metoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-5-methoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-6-etoksibenzil)-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-(2-kloro-5-etoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-5-ethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2-kloro-5-(piperidin-l-ilsulfonil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c]piridin-2,4-dion,5- [2-chloro-5- (piperidin-1-ylsulfonyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione,

5-[2-kloro-5-(pirolidin-l-ilsulfonil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c]piridin-2,4-dion,5- [2-chloro-5- (pyrrolidin-1-ylsulfonyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione,

5-[2-kloro-6-(ciklopentilmetoksi)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c] piridin-2,4-dion,5- [2-chloro-6- (cyclopentylmethoxy) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione,

5-[2-(benziloksi)-6-klorobenzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- [2- (Benzyloxy) -6-chlorobenzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione,

5-[2,3-dikloro-6-etoksibenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b][l,3]oksazolo[5,4d] piridin-2,4(3H)-dion,5- [2,3-dichloro-6-ethoxybenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4d] pyridine-2,4 (3H) - dion,

5-[2-kloro-5-(trifluorometil)benzil[-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion in5- [2-chloro-5- (trifluoromethyl) benzyl [-7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione

-4040-4040

5-(2-kloro-5-fluorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion.5- (2-Chloro-5-fluorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione.

Mišljeni so tudi derivati, kot estri, karbamati, aminali, amidi, optični izomeri in predzdravila.Also intended are derivatives such as esters, carbamates, aminals, amides, optical isomers and prodrugs.

Predloženi izum se tudi nanaša na farmacevtske sestavke, ki obsegajo fiziološko sprejemljivo razredčilo in vsaj eno spojino v smislu predloženega izuma.The present invention also relates to pharmaceutical compositions comprising a physiologically acceptable diluent and at least one compound of the present invention.

Predloženi izum se nadalje nanaša na postopek za inhibiranje vezave α4βι integrina na VCAM-1, ki obsega izpostavljanje celice, ki eksprimira α4βι integrin, na celico, ki eksprimira VCAM-1, v prisotnosti učinkovite inhibitome količine spojine v smislu predloženega izuma. VCAM-1 je lahko na površini vaskularne endotelne celice, antigen prikazujoče celice ali drugega celičnega tipa. α4βι je lahko na beli krvnički, kot je monocit, limfocit, granulocit; korenska celica; ali katerakoli druga celica, ki naravno eksprimira α4βι·The present invention further relates to a method of inhibiting the binding of α 4 βι integrin to VCAM-1, comprising exposing a cell expressing α 4 βι integrin to a cell expressing VCAM-1 in the presence of an effective inhibitory amount of a compound of the present invention . VCAM-1 may be on the surface of a vascular endothelial cell, a display cell antigen, or other cell type. α 4 βι may be on white blood cells such as monocyte, lymphocyte, granulocyte; root cell; or any other cell that naturally expresses α 4 βι ·

Pri izumu gre tudi za postopek za zdravljenje bolezenskih stanj, ki jih mediira α4βι vezava, ki obsega dajanje učinkovite količine spojine v smislu predloženega izuma, bodisi same ali v pripravku, prizadetemu pacientu.The invention also relates to a method of treating disease states mediated by α 4 βι binding, comprising administering an effective amount of a compound of the present invention, either alone or in a composition to an affected patient.

Podroben opis izumaDETAILED DESCRIPTION OF THE INVENTION

Definicije izrazovDefinitions of terms

Izraz alkil, kot se tukaj uporablja sam ali v kombinaciji, se nanaša na Ci-C12 ravne ali razvejene, substituirane ali nesubstituirane nasičene verižne ostanke, izvedene iz nasičenih ogljikovodikov z odstranitvijo enega atoma vodika, razen če je pred izrazom alkil Cx-Cy oznaka. Reprezentativni primeri alkilnih skupin so med drugim metil, etil, n-propil, izo-propil, n-butil, sek.butil, izobutil in terc.butil.The term alkyl, as used herein alone or in combination, refers to Ci-C 12 straight or branched, substituted or unsubstituted saturated chain residues derived from saturated hydrocarbons by removal of one hydrogen atom, unless preceded by the term alkyl C x -C y mark. Representative examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, isobutyl and tert-butyl.

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Izraz alkenil, kot se tukaj uporablja, se sam ali v kombinaciji nanaša na nesubstituiran raven ali substituiran ali nesubstituiran razvejen alkenilni ostanek z 2 do 10 atomi ogljika. Primeri takih ostankov so, vendar nanje niso omejeni, etenil, E- in Zpentenil, decenil ipd.The term alkenyl as used herein refers, alone or in combination, to an unsubstituted level or a substituted or unsubstituted branched alkenyl radical having 2 to 10 carbon atoms. Examples of such residues include, but are not limited to, ethenyl, E- and pentenyl, decenyl, and the like.

Izraz alkinil, kot se tukaj uporablja, se sam ali v kombinaciji nanaša na substituiran ali nesubstituiran raven ali substituiran ali nesubstituiran razvejen alkinilni ostanek z 2 do 10 atomi ogljika. Primeri takih ostankov so, vendar nanje niso omejeni, etinil, propinil, propargil, butinil, heksinil, decinil ipd.The term alkynyl as used herein refers, alone or in combination, to a substituted or unsubstituted level or a substituted or unsubstituted branched alkynyl radical having 2 to 10 carbon atoms. Examples of such residues include, but are not limited to, ethynyl, propynyl, propargyl, butynyl, hexynyl, decinyl and the like.

Izraz nižji, ki modificira alkil, alkenil, alkinil ali alkoksi, se nanaša na Ci-C6 enoto za posamezno funkcionalnost. Npr. nižji alkil pomeni Ci-C6alkil.The term lower, modifying alkyl, alkenyl, alkynyl or alkoxy, it refers to a Ci-C 6 unit for a particular functionality. E.g. lower alkyl is a Ci-C 6 alkyl.

Izraz alifatski acil, kot se tukaj uporablja, se sam ali v kombinaciji nanaša na ostanke s formulo alkil-C(O)-, alkenil-C(O)- in alkinil-C(O)-, izvedene iz alkan-, alken- ali alkinkarboksilne kisline, kjer so izrazi alkil, alkenil in alkinil, kot je definirano zgoraj. Primeri takih alifatskih acilnih ostankov so, vendar niso nanje omejeni, med drugim acetil, propionil, butiril, valeril, 4-metilvaleril, akriloil, krotil, propiolil in metilpropiolil.The term aliphatic acyl as used herein refers, alone or in combination, to residues of the formula alkyl-C (O) -, alkenyl-C (O) -, and alkynyl-C (O) - derived from alkane-, alkene- or alkynecarboxylic acids, wherein the terms are alkyl, alkenyl and alkynyl as defined above. Examples of such aliphatic acyl residues are, but are not limited to, acetyl, propionyl, butyryl, valeryl, 4-methylvaleryl, acryloyl, crotyl, propiolyl and methylpropiolyl.

Izraz cikloalkil, kot se tukaj uporablja, se nanaša na alifatski obročni sistem s 3 do 10 atomi ogljika in 1 do 3 obroči, ki vključuje, vendar nanje ni omejen, med drugim ciklopropil, ciklopentil, cikloheksil, norbornil in adamantil. Cikloalkilne skupine so lahko nesubstituirane ali substituirane z enim, dvema ali tremi substituenti, neodvisno izbranimi izmed nižjega alkila, haloalkila, alkoksi, tioalkoksi, amino, alkilamino, dialkilamino, hidroksi, halo, merkapto, nitro, karboksaldehida, karboksi, alkoksikarbonila in karboksamida.The term cycloalkyl as used herein refers to an aliphatic ring system of 3 to 10 carbon atoms and 1 to 3 rings, including, but not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl and adamantyl. Cycloalkyl groups may be unsubstituted or substituted with one, two or three substituents independently selected from lower alkyl, haloalkyl, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino, hydroxy, halo, mercapto, nitro, carboxaldehyde, carboxyl, carboxyl, and carboxyl.

Cikloalkil vključuje cis ali trans oblike. Nadalje so lahko substituenti bodisi v endo bodisi v ekso legah pri premoščenih bicikličnih sistemih.Cycloalkyl includes cis or trans forms. Furthermore, they may be substituents either in endo or exo positions in bridged bicycle systems.

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Izraz cikloalkenil, kot se tukaj uporablja sam ali v kombinaciji, se nanaša na cikličen karbocikel s 4 do 8 atomi ogljika in eno ali več dvojnimi vezmi. Primeri takih cikloalkenilnih ostankov so, vendar niso omejeni nanje, ciklopentenil, cikloheksenil, ciklopentadienil ipd.The term cycloalkenyl, as used herein alone or in combination, refers to a cyclic carbocycle of 4 to 8 carbon atoms and one or more double bonds. Examples of such cycloalkenyl residues are, but are not limited to, cyclopentenyl, cyclohexenyl, cyclopentadienyl and the like.

Izraz cikloalkilalkil, kot se tukaj uporablja, se nanaša na cikloalkilno skupino, pripeto na nižji alkilni ostanek, ki vključuje, vendar ni omejen na cikloheksilmetil.The term cycloalkylalkyl as used herein refers to a cycloalkyl group attached to a lower alkyl moiety which includes, but is not limited to, cyclohexylmethyl.

Izraz halo ali halogen, kot se tukaj uporablja, se nanaša na I, Br, C1 ali F.The term halo or halogen as used herein refers to I, Br, C1 or F.

Izraz haloalkil, kot se tukaj uporablja, se nanaša na nižji alkilni ostanek, na katerega je pripet vsaj en halogenski substituent, med drugim npr. klorometil, fluoroetil, trifluorometil in pentafluoroetil.The term haloalkyl, as used herein, refers to a lower alkyl moiety to which at least one halogen substituent is attached, e.g. chloromethyl, fluoroethyl, trifluoromethyl and pentafluoroethyl.

Izraz alkoksi, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na alkil etrski ostanek, kjer je izraz alkil, kot je definiran zgoraj. Primeri primernih alkil etrskih ostankov so, vendar nanje niso omejeni, metoksi, etoksi, n-propoksi, izo-propoksi, nbutoksi, izo-butoksi, sek.butoksi, terc.butoksi ipd.The term alkoxy, as used herein, alone or in combination, refers to an alkyl ether residue wherein the term is alkyl as defined above. Examples of suitable alkyl ether residues are, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like.

Izraz alkoksialkil, kot se tukaj uporablja, se nanaša na Ry-O-Rz, kjer je Ry nižji alkil, kot je definiran zgoraj, in je Rz alkilen -((CH2)W-), kjer je w celo število od 1 do 6. Reprezentativni primeri so med drugim metoksimetil, metoksietil in etoksietil.The term alkoxyalkyl as used herein refers to R y -OR z , where R y is lower alkyl as defined above, and R z is alkylene - ((CH 2 ) W -), where w is an integer from 1 to 6. Representative examples include, but are not limited to, methoxymethyl, methoxyethyl and ethoxyethyl.

Izraz alkenoksi, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo alkenil-O, pod pogojem, da ostanek ni enolni eter, kjer je izraz alkenil, kot je definirano zgoraj. Primeri primernih alkenoksi ostankov vključujejo, vendar niso nanje omejeni, aliloksi, E- in Z- 3-metil-2-propenoksi ipd.The term alkenoxy, as used herein, alone or in combination, refers to a residue of the formula alkenyl-O, provided that the residue is not a single ether, wherein the term is alkenyl, as defined above. Examples of suitable alkenoxy residues include, but are not limited to, allyloxy, E- and Z-3-methyl-2-propenoxy and the like.

Izraz alkinoksi, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo alkinil-O, pod pogojem, da ostanek ni -inol eter. Primeri primernih alkinoksi ostankov vključujejo, vendar nanje niso omejeni, propargiloksi, 2-butiniloksi ipd.The term alkoxy as used herein, alone or in combination, refers to a residue of the formula alkynyl-O, provided that the residue is not -inol ether. Examples of suitable alkynoxy residues include, but are not limited to, propargyloxy, 2-butynyloxy and the like.

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Izraz karboksi, kot se tukaj uporablja, se nanaša na -C(O)O-.The term carboxy as used herein refers to -C (O) O-.

Izraz tioalkoksi se nanaša na tioetrski ostanek s formulo alkil-S-, kjer je alkil, kot je definirano zgoraj.The term thioalkoxy refers to a thioether moiety of the formula alkyl-S-, where alkyl is as defined above.

Izraz sulfonamido, kot se tukaj uporablja, se nanaša na -SO2NH2.The term sulfonamido as used herein refers to -SO 2 NH 2 .

Izraz karboksaldehid, kot se tukaj uporablja, se nanaša na -C(O)R, kjer je R vodik.The term carboxaldehyde as used herein refers to -C (O) R, where R is hydrogen.

Izrazi karboksamid ali amid, kot se tukaj uporablja, se nanaša na -C(O)NRaRb, kjer sta Ra in Rb vsak neodvisno vodik, alkil ali katerikoli drugi primerni substituent.The term carboxamide or amide as used herein refers to -C (O) NR a R b, wherein R a and R b are each independently hydrogen, alkyl or any other suitable substituent.

Izraz alkoksialkoksi, kot se tukaj uporablja, se nanaša na R^O-R^O-, kjer je Rc nižji alkil, kot je definiran zgoraj, in je R^ alkilen, kjer je alkilen -(CH2)n-, kjer je n' celo število od 1 do 6. Reprezentativni primeri alkoksialkoksi skupin vključujejo med drugim metoksimetoksi, etoksimetoksi, t-butoksimetoksi.The term alkoxyalkoxy, as used herein, refers to R ^ OR ^ O-, where R c is lower alkyl than defined above, and R ^ alkylene, wherein alkylene is - (CH 2 ) n -, where n 'an integer from 1 to 6. Representative examples of alkoxyalkoxy groups include, inter alia, methoxymethoxy, ethoxymethoxy, t-butoxymethoxy.

Izraz alkilamino, kot se tukaj uporablja, se nanaša na ReNH-, kjer je Re nižja alkilna skupina, npr. med drugim etilamino, butilamino.The term alkylamino, as used herein, refers to R e NH-, where R e is a lower alkyl group, e.g. inter alia ethylamino, butylamino.

Izraz alkenilamino, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo alkenil-NH- ali (alkenil)2N-, kjer je izraz alkenil, kot je definirano zgoraj, pod pogojem, da ostanek ni enamin. Primer takega alkenilamino ostanka je alilamino ostanek.The term alkenylamino, as used herein, alone or in combination, refers to a radical of the formula alkenyl-NH- or (alkenyl) 2 N-, wherein the term alkenyl is as defined above, provided that the residue is not enamine. An example of such an alkenylamino residue is the allylamino residue.

Izraz alkinilamino, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo alkinil-NH- ali (alkinil)2N-, kjer je izraz alkinil, kot je definirano zgoraj, pod pogojem, da ostanek ni amin. Primer takega alkinilamino ostanka je propargil amino ostanek.The term alkynylamino, as used herein, alone or in combination, refers to a residue of the formula alkynyl-NH- or (alkynyl) 2 N-, wherein the term is alkynyl as defined above, provided that the residue is not an amine. An example of such an alkynylamino residue is the propargyl amino residue.

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Izraz dialkilamino, kot se tukaj uporablja, se nanaša na RfRgN-, kjer Rf in Rg neodvisno izberemo izmed nižjega alkila, npr. med drugim dietilamino in metil propilamino.The term dialkylamino as used herein refers to RfR g N-, where Rf and R g are independently selected from lower alkyl, e.g. among others diethylamino and methyl propylamino.

Izraz alkoksikarbonil, kot se tukaj uporablja, se nanaša na alkoksilno skupino, kot je preje definirana, pripeto na starševski molekulski del preko karbonilne skupine. Primeri alkoksikarbonila vključujejo med drugim metoksikarbonil, etoksikarbonil in izopropoksikarbonil.The term alkoxycarbonyl, as used herein, refers to an alkoxyl group, as defined above, attached to the parent molecular moiety through a carbonyl group. Examples of alkoxycarbonyl include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

Izraz aril ali aromatski, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na substituirano ali nesubstituirano karbociklično aromatsko skupino z okoli 6 do 12 atomi ogljika, kot fenil, naftil, indenil, indanil, azulenil, fluorenil in antracenil; ali heterociklično aromatsko skupino z vsaj enim endocikličnim atomom N, O ali S, kot furil, tienil, piridil, pirolil, oksazolil, tiazolil, imidazolil, pirazolil, 2-pirazolinil, pirazolidinil, izoksazolil, izotiazolil, 1,2,3-oksadiazolil, 1,2,3-triazolil, 1,3,4tiadiazolil, piridazinil, pirimidinil, pirazinil, 1,3,5-triazinil, 1,3,5-tritianil, indolizinil, indolil, izoindolil, 3H-indolil, indolinil, benzo[b]furanil, 2,3-dihidrobenzofuranil, benzo[b]tiofenil, ΙΗ-indazolil, benzimidazolil, benztiazolil, purinil, 4H-kinolizinil, izokinolinil, cinolinil, ftalazinil, kinazolinil, kinoksalinil, 1,8-naftridinil, pteridinil, karbazolil, akridinil, fenazinil, fenotiazinil, fenoksiazinil, pirazolo[l,5-c]triazinil ipd. Aralkil in alkilaril uporabljata izraz alkil, kot je definirano zgoraj. Obroči so lahko večkratno substituirani.The term aryl or aromatic, as used herein, alone or in combination, refers to a substituted or unsubstituted carbocyclic aromatic group of about 6 to 12 carbon atoms such as phenyl, naphthyl, indenyl, indanyl, azulenyl, fluorenyl and anthracenyl; or a heterocyclic aromatic group with at least one endocyclic N, O or S atom such as furyl, thienyl, pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxazadyl, 1,2,3-oxazolyl, 1,2,3-oxazolyl 1,2,3-triazolyl, 1,3,4 thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-tritiyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo [ b] furanyl, 2,3-dihydrobenzofuranyl, benzo [b] thiophenyl, N-indazolyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, isoquinolinyl, quinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, 1,8-naphthyridinyl, 1,8 acridinyl, phenazinyl, phenothiazinyl, phenoxyazinyl, pyrazolo [1,5-c] triazinyl and the like. Aralkyl and alkylaryl use the term alkyl as defined above. The rings may be substituted several times.

Izraz aralkil, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na arilno substituiran alkilni ostanek, kjer sta izraza alkil in aril, kot je definirano zgoraj. Primeri primernih aralkilnih ostankov vključujejo, vendar nanje niso omejeni, fenilmetil, fenetil, fenilheksil, difenilmetil, piridilmetil, tetrazolil metil, furilmetil, imidazolil metil, indolilmetil, tienilpropil ipd.The term aralkyl, as used herein, alone or in combination, refers to an aryl-substituted alkyl moiety wherein the terms alkyl and aryl are as defined above. Examples of suitable aralkyl residues include, but are not limited to, phenylmethyl, phenethyl, phenylhexyl, diphenylmethyl, pyridylmethyl, tetrazolyl methyl, furylmethyl, imidazolyl methyl, indolylmethyl, thienylpropyl and the like.

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Izraz aralkenil, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na arilno substituiran alkenilni ostanek, kjer sta izraza aril in alkenil, kot je definirano zgoraj.The term aralkenyl, as used herein, alone or in combination, refers to an aryl-substituted alkenyl moiety wherein the terms are aryl and alkenyl, as defined above.

Izraz arilamino, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo aril-ΝΗ-, kjer je aril, kot je definirano zgoraj. Primeri arilamino ostankov so, vendar niso omejeni nanje, fenilamino(anilido), naftilamino, 2-, 3- in 4piridilamino ipd.The term arylamino, as used herein, alone or in combination, refers to a residue of the formula aryl-ΝΗ-, wherein aryl is as defined above. Examples of arylamino residues are, but are not limited to, phenylamino (anilido), naphthylamino, 2-, 3- and 4-pyridylamino and the like.

Izraz benzil kot se tukaj uporablja, se nanaša na C6H5-CH2-.The term benzyl as used herein refers to C 6 H 5 -CH 2 -.

Izraz biaril, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo aril-aril, kjer je izraz aril, kot je definirano zgoraj.The term biaryl, as used herein, alone or in combination, refers to a moiety of the formula aryl-aryl, wherein the term aryl is as defined above.

Izraz tioaril, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo aril-S-, kjer je izraz aril, kot je definirano zgoraj. Primer tioarilnega ostanka je tiofenilni ostanek.The term thioaryl, as used herein, alone or in combination, refers to a moiety of the formula aryl-S-, wherein the term is aryl as defined above. An example of a thioaryl residue is a thiophenyl residue.

Izraz aroil, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na ostanek s formulo aril-CO-, kjer je izraz aril, kot je definirano zgoraj. Primeri primernih aromatskih acilnih ostankov vključujejo, vendar niso omejeni nanje, benzoil, 4halobenzoil, 4-karboksibenzoil, naftoil, piridilkarbonil ipd.The term aroyl, as used herein, alone or in combination, refers to a residue of the formula aryl-CO-, wherein the term is aryl as defined above. Examples of suitable aromatic acyl residues include, but are not limited to, benzoyl, 4halobenzoyl, 4-carboxybenzoyl, naphthoyl, pyridylcarbonyl and the like.

Izraz heterociklil, kot se tukaj uporablja, sam ali v kombinaciji, se nanaša na nearomatski 3- do 10-členski obroč z vsaj enim endocikličnim atomom N, O ali S. Heterocikel je lahko po izbiri arilno kondenziran. Heterocikel je lahko tudi po izbiri substituiran z vsaj enim substituentom, ki ga neodvisno izberemo iz skupine, v kateri so med drugim vodik, halogen, hidroksil, amino, nitro, trifluorometil, trifluorometoksi, alkil, aralkil, alkenil, alkinil, aril, ciano, karboksi, karboalkoksi, karboksialkil, okso, arilsulfonil in aralkilaminokarbonil.The term heterocyclyl as used herein, alone or in combination, refers to a non-aromatic 3- to 10-membered ring with at least one endocyclic N, O or S. The heterocycle may optionally be aryl fused. The heterocycle may also be optionally substituted by at least one substituent independently selected from the group consisting of, inter alia, hydrogen, halogen, hydroxyl, amino, nitro, trifluoromethyl, trifluoromethoxy, alkyl, aralkyl, alkenyl, alkynyl, aryl, cyano, carboxy, carboalkoxy, carboxyalkyl, oxo, arylsulfonyl and aralkylaminocarbonyl.

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Izraz alkilheterociklil, kot se tukaj uporablja, se nanaša na alkilno skupino, kot je preje definirana, pripeto na starševski molekulski del preko heterociklilne skupine, ki vključuje, vendar ni omejena na 2-metil-5-tiazolil, 2-metil-l-pirolil in 5-etil-2-tienil.The term alkylheterocyclyl as used herein refers to an alkyl group as previously defined attached to the parent molecular moiety through a heterocyclyl group including, but not limited to, 2-methyl-5-thiazolyl, 2-methyl-1-pyrrolyl and 5-ethyl-2-thienyl.

Izraz heterociklilalkil, kot se tukaj uporablja, se nanaša na heterociklilno skupino, kot je preje definirana, pripeto na starševski molekulski del preko alkilne skupine, ki vključuje, vendar ni omejena na 2-tienilmetil, 2-piridinilmetil in 2-( 1 -piperidinil) etil.The term heterocyclylalkyl as used herein refers to a heterocyclyl group as previously defined attached to the parent molecular moiety through an alkyl group including, but not limited to, 2-thienylmethyl, 2-pyridinylmethyl and 2- (1-piperidinyl) ethyl.

Izraz heterocikloil, kot se tukaj uporablja, se nanaša na ostanke s formulo heterociklil-C(O)-, kjer je izraz heterociklil, kot je definirano zgoraj.The term heterocycloyl as used herein refers to residues of the formula heterocyclyl-C (O) - wherein the term is heterocyclyl as defined above.

Izraz aminal, kot se tukaj uporablja, se nanaša na hemi-acetal s strukturo RhCCNRiRjjfNRkRi)-, kjer so Rh, Rj, Rj, Rr in Ri vsak neodvisno vodik, alkil ali katerikoli drugi primeren substituent.The term aminal, as used herein, refers to a hemi-acetal having the structure RhCCNRiRjjNNkkR1) -, wherein R h , R 1, R 1, R 2 and R 1 are each independently hydrogen, alkyl or any other suitable substituent.

Izraz ester, kot se tukaj uporablja, se nanaša na -C(O)Rm, kjer je Rm vodik, alkil ali katerikoli drugi primeren substituent.The term ester as used herein refers to -C (O) R m , wherein R m is hydrogen, alkyl, or any other suitable substituent.

Izraz karbamat, kot se tukaj uporablja, se nanaša na spojine na osnovi karbaminske kisline NH2C(O)OH.The term carbamate as used herein refers to compounds based on carbamic acid NH 2 C (O) OH.

Izraz optični izomeri, kot se tukaj uporablja, se nanaša na spojine, ki se razlikujejo le v stereokemiji vsaj enega atoma, vključno na enantiomere, diastereomere in racemate.The term optical isomers, as used herein, refers to compounds that differ only in the stereochemistry of at least one atom, including enantiomers, diastereomers and racemates.

Uporaba gornjih izrazov je mišljena, da zajema substituirane in nesubstituirane dele. Substitucija je lahko z eno ali več skupinami, kot so alkoholi, etri, estri, amidi, sulfoni, sulfidi, hidroksil, nitro, ciano, karboksi, amini, heteroatomi, nižji alkil, nižji alkoksi, nižji alkoksikarbonil, alkoksialkoksi, aciloksi, halogeni, trifluorometoksi, trifluorometil, alkil, aralkil, alkenil, alkinil, aril, ciano, karboksi, karboalkoksi, karboksialkil, cikloalkil, cikloalkilalkil, heterociklil, alkilheterociklil, heterociklilalkil, okso, arilsulfonil in aralkilaminokarbonil ali katerikoli od substituentov prejšnjihThe use of the above terms is intended to encompass substituted and unsubstituted moieties. The substitution may be with one or more groups such as alcohols, ethers, esters, amides, sulfones, sulfides, hydroxyl, nitro, cyano, carboxy, amines, heteroatoms, lower alkyl, lower alkoxy, lower alkoxycarbonyl, alkoxyalkyloxy, acyloxy, halogens, trifluoromethoxy, trifluoromethyl, alkyl, aralkyl, alkenyl, alkynyl, aryl, cyano, carboxy, carboalkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, alkylheterocyclyl, heterocyclylalkylalkyl, aryl sulfonylcarbonyl and aryl sulfonylcarbonyl inary

-4747 odstavkov ali katerikoli od teh substituentov je bodisi pripet direktno ali s primernimi povezovalci. Povezovalci so tipično kratke verige z 1 do 3 atomi, ki vsebujejo katerokoli kombinacijo -C-, -C(O)-, -NH-, -S-, -S(O)-, -0-, -C(0)0- ali -S(O)O-.-4747 paragraphs or any of these substituents are either attached directly or with suitable linkers. The linkers are typically short chains with 1 to 3 atoms containing any combination of -C-, -C (O) -, -NH-, -S-, -S (O) -, -0-, -C (0) 0- or -S (O) O-.

Obroči so lahko večkratno substituirani.The rings may be substituted several times.

Izraza ki odtegne elektrone ali ki daje elektrone se nanašata na sposobnost substituenta, da odtegne ali daje elektrone glede na tisto vodika, če vodik zaseda isti položaj v molekuli. Strokovnjak dobro razume te izraze in se obravnavajo v Advanced Organic Chemistrv J. March. 1985, str. 16-18, ki je vključena tukaj kot referenca. Skupine, ki odtegnejo elektrone, so med drugim halo, nitro, karboksil, nižji alkenil, nižji alkinil, karboksaldehid, karboksiamido, aril, kvarterni amonij, trifluorometil, sulfonil in aril nižji alkanoil. Skupine, ki dajejo elektrone, vključujejo take skupine, kot hidroksi, nižji alkil, amino, nižji alkilamino, di(nižjialkil)amino, ariloksi, merkapto, nižji alkiltio, nižji alkilmerkapto in disulfid. Strokovnjak bo upošteval, da imajo lahko zgornji substituenti ob različnih kemičnih pogojih lastnosti dajanja elektronov ali odtegovanja elektronov. Nadalje predloženi izum predvideva katerokoli kombinacijo substituentov, izbrano izmed zgoraj navedenih skupin.The terms electron withdrawing or electron giving refer to the substituent's ability to withdraw or give electrons relative to that of hydrogen if the hydrogen occupies the same position in the molecule. These terms are well understood by one skilled in the art and are discussed in Advanced Organic Chemistry J. March. 1985, p. 16-18, which is incorporated herein by reference. The electron withdrawing groups include halo, nitro, carboxyl, lower alkenyl, lower alkynyl, carboxaldehyde, carboxyamido, aryl, quaternary ammonium, trifluoromethyl, sulfonyl and aryl lower alkanoyl. Electron donating groups include such groups as hydroxy, lower alkyl, amino, lower alkylamino, di (lower alkyl) amino, aryloxy, mercapto, lower alkylthio, lower alkylmercapto and disulfide. It will be appreciated by one of skill in the art that the above substituents may have electron-donating or electron-withdrawing properties under different chemical conditions. The present invention further provides for any combination of substituents selected from the above groups.

Najbolj prednostni substituenti, ki dajejo elektrone ali odtegnejo elektrone, so halo, nitro, alkanoil, karboksaldehid, arilalkanoil, ariloksi, karboksil, karboksamid, ciano, sulfonil, sulfoksid, heterociklil, gvanidin, kvatemami amonij, nižji alkenil, nižji alkinil, sulfonijeve soli, hidroksi, nižji alkoksi, nižji alkil, amino, nižji alkilamino, di(nižji alkiljamino, amin nižji alkil merkapto, merkaptoalkil, alkiltio, karboksi nižji alkil, arilalkoksi, alkanoilamino, alkanoil(nižji alkil)amino, nižji alkilsulfonilamino, arilsulfonilamino, alkilsulfonil(nižji alkiljamino, arilsulfonil(nižji alkil)amino, nižji alkilkarboksamid, di(nižji alkiljkarboksiamid, sulfonamid, nižji alkilsulfonamid, di(nižji alkil)sulfonamid, nižji alkilsulfonil, arilsulfonil in alkilditio.The most preferred electron-donating or electron-withdrawing substituents are halo, nitro, alkanoyl, carboxaldehyde, arylalkanoyl, aryloxy, carboxyl, carboxamide, cyano, sulfonyl, sulfoxide, heterocyclyl, guanidine, quaternary ammonium, lower alkynyl, lower alkenyl, ammonium, lower alkynyl, lower alkynyl hydroxy, lower alkoxy, lower alkyl, amino, lower alkylamino, di (lower alkylamino, amine lower alkyl mercapto, mercaptoalkyl, alkylthio, carboxy lower alkyl, arylalkoxy, alkanoylamino, alkanoyl (lower alkyl) amino, lower alkylsulfonylamino, aryl sulfonylamino, arylalkylsulfonylamino alkylamino, arylsulfonyl (lower alkyl) amino, lower alkylcarboxamide, di (lower alkylcarboxamide, sulfonamide, lower alkylsulfonamide, di (lower alkyl) sulfonamide, lower alkylsulfonyl, arylsulfonyl and alkyldithio.

Kot se tukaj uporablja, je izraz sestavek namenjen temu, da obsega produkt, ki zajema specificirane sestavine v specificiranih količinah, kot tudi katerikoli produkt,As used herein, the term composition is intended to encompass a product comprising specified ingredients in specified quantities as well as any product,

-4848 ki izhaja direktno ali indirektno iz kombinacije specificiranih sestavin v specificiranih količinah.-4848 derived directly or indirectly from a combination of specified ingredients in specified quantities.

Kot se tukaj uporablja, vključuje izraz sesalci ljudi in druge živali.As used herein, it includes the term mammals of humans and other animals.

Obroč, definiran z Y v formulah I, II in III, je lahko monocikličen heterocikel ali aromatski obroč ali je lahko bicikličen obroč.The ring defined by Y in formulas I, II and III may be a monocyclic heterocycle or an aromatic ring or it may be a bicyclic ring.

Črtkane črte, uporabljene v formulah I, II, III, IV in VI, nakazujejo, daje lahko vez tej lokaciji bodisi enojna ali dvojna. Vez med npr. atomoma Y in W je lahko enojna ali dvojna, Če je Y in/ali W substituent, kot N, C ali CH. Zato je lahko obroč, ki ga definira Y, v formulah bodisi nasičen ali nenasičen, glede na to, kateri W in/ali Y izberemo. V formulah IV in VI črtkana črta nakazuje, da dušik vsebujoč obroč po izbiri vsebuje dvojne vezi pri navedenih lokacijah.The dashed lines used in formulas I, II, III, IV, and VI indicate that the bond at this location can be either single or double. The connection between e.g. the atoms Y and W may be single or double, if Y and / or W is a substituent such as N, C or CH. Therefore, the ring defined by Y may be saturated or unsaturated in the formulas, depending on which W and / or Y we choose. In formulas IV and VI, the dashed line indicates that the nitrogen-containing ring optionally contains double bonds at the indicated locations.

V formulah določene R skupine potencialno substituirajo večkrat svoje pridružene obroče. R19, R20, R21, R23, R27, R28, R29 in R25 lahko vsak substituira svoje pridružene obroče več kot enkrat. Npr. za R19, kadar je c ničla, je pridružen obroč nesubstituiran z vodiki pri legah C-2 in C-4; in za R23, kadar je g ničla, so vodiki pri legah C-2 - C-5.In the formulas, certain R groups potentially substitute their associated rings several times. R 19 , R 20 , R 21 , R 23 , R 27 , R 28 , R 29 and R 25 may each substitute their associated rings more than once. E.g. for R 19 , when c is zero, the associated ring is unsubstituted by hydrogen at positions C-2 and C-4; and for R 23 , when g is zero, the hydrogen at positions C-2 is C-5.

Primerni substituenti za arilne, alkilne, cikloalkilne, heterociklilne skupine ali obroč, definiran z Y in W v zgoraj opisanih formulah, kadar so prisotni, vključujejo alkohole, amine, heteroatome ali kakršnokoli kombinacijo arilnih, alkoksi, alkoksialkoksi, alkilnih, cikloalkilnih ali heterociklilnih skupin, pripetih bodisi direktno ali preko primernih povezovalcev. Povezovalci so tipično kratke verige z 1 do 3 atomi, ki vsebujejo katerokoli kombinacijo C, C=O, CO2, O, N, S, S=O, SO2, kot so npr. med drugim etri, amidi, amini, sečnine, sulfamidi, sulfonamidi.Suitable substituents for aryl, alkyl, cycloalkyl, heterocyclyl groups, or the ring defined by Y and W in the formulas described above, when present, include alcohols, amines, heteroatoms or any combination of aryl, alkoxy, alkoxyalkoxy, alkyl, cycloalkyl or heterocyclyl groups, attached either directly or through suitable connectors. The linkers are typically short chains of 1 to 3 atoms containing any combination of C, C = O, CO 2 , O, N, S, S = O, SO 2 , such as e.g. among others ethers, amides, amines, ureas, sulfamides, sulfonamides.

123567* 8 ·123567 * 8 ·

Npr. R , R , R , R , R , R inR v gornjih formulah so lahko neodvisno, vendar niso omejeni nanje: vodik, alkil, fenil, tienilmetil, izobutil, n-butil, 2-tienilmetil, 1,3-tiazol2-il-metil, benzil, tienil, 3-piridinilmetil, 3-metil-l-benzotiofen-2-il, alil, 3-4949 metoksibenzil, propil, 2-etoksietil, ciklopropilmetil, benzilsulfanilmetil, benzilsulfonilmetil, fenilsulfanilmetil, fenetilsulfanilmetil, 3-fenilpropilsulfanilmetil,E.g. R, R, R, R, R, R and R in the above formulas may be independently but are not limited to: hydrogen, alkyl, phenyl, thienylmethyl, isobutyl, n-butyl, 2-thienylmethyl, 1,3-thiazol2-yl- methyl, benzyl, thienyl, 3-pyridinylmethyl, 3-methyl-1-benzothiophen-2-yl, allyl, 3-4949 methoxybenzyl, propyl, 2-ethoxyethyl, cyclopropylmethyl, benzylsulfanylmethyl, benzylsulfonylmethyl, phenylsulfanylmethyl, phenethylsulfanylmethyl, methyl

4-((2-toluidinokarbonil)amino)benzil, 2-piridiniletil, 2-(lH-indol-3-il)etil, 1Hbenzimidazol-2-il, 4-piperidinilmetil, 3-hidroksi-4-metoksibenzil, 4-hidroksifenetil, 4aminobenzil, fenilsulfonilmetil, 4-(acetilamino)fenil, 4-metoksifenil, 4-aminofenil, 4klorofenil, (4-(benzilsulfonil)amino)fenil), (4-(metilsulfonil)amino)fenil, 2aminofenil, 2-metilfenil, izopropil, 2-okso-l-pirolidinil, 3-(metilsulfanil)propil, (propilsulfanil)metil, oktilsulfanilmetil, 3-aminofenil, 4-((2toluidinokarbonil)amino)fenil, 2-((metilbenzil)amino)benzil, metilsulfaniletil, hidroksi, kloro, fluoro, bromo, ureido, amino, metansulfonilamino, acetilamino, etilsulfanilmetil, 2-klorobenzil, 2-bromobenzil, 2-fluorobenzil, 2-kloro-6-fluorobenzil,4 - ((2-toluidinocarbonyl) amino) benzyl, 2-pyridinylethyl, 2- (1H-indol-3-yl) ethyl, 1H-benzimidazol-2-yl, 4-piperidinylmethyl, 3-hydroxy-4-methoxybenzyl, 4-hydroxyphenethyl , 4aminobenzyl, phenylsulfonylmethyl, 4- (acetylamino) phenyl, 4-methoxyphenyl, 4-aminophenyl, 4-chlorophenyl, (4- (benzylsulfonyl) amino) phenyl), (4- (methylsulfonyl) amino) phenyl, 2aminophenyl, 2-methylphenyl, isopropyl , 2-oxo-1-pyrrolidinyl, 3- (methylsulfanyl) propyl, (propylsulfanyl) methyl, octylsulfanylmethyl, 3-aminophenyl, 4 - ((2toluidinocarbonyl) amino) phenyl, 2 - ((methylbenzyl) amino) benzyl, methylsulfanylethyl, hydroxy , chloro, fluoro, bromo, ureido, amino, methanesulfonylamino, acetylamino, ethylsulfanylmethyl, 2-chlorobenzyl, 2-bromobenzyl, 2-fluorobenzyl, 2-chloro-6-fluorobenzyl,

2-kloro-4-fluorobenzil, 2,4-diklorobenzil, 2-kloro-6-metoksibenzil, 2-cianobenzil, 2,6difluorobenzil, 2-kloro-5-(trifluorometil)benzil, 2-kloro-6-metilbenzil, 2,6dimetoksibenzil, 2-kloro-5-(metilsulfonil)benzil, 2-kloro-6-cianobenzil, 2-kloro-6etoksibenzil, 2-kloro-5-metoksibenzil, 2-kloro-5-fluorobenzil, 5-kloro-2-fluorobenzil, etil, propil, butil, pentil, ciklopropil, terc.butilamino, propilamino, 4-metil-lpiperazinil, 1-azetidinil, 4-morfolino, (4-karboksifenil)amino, pivaloilamino), ((terc.butilamino)karbonil)amino, trifluorometil, benziloksi, 2-(2-metoksietoksi)etoksi,2-chloro-4-fluorobenzyl, 2,4-dichlorobenzyl, 2-chloro-6-methoxybenzyl, 2-cyanobenzyl, 2,6difluorobenzyl, 2-chloro-5- (trifluoromethyl) benzyl, 2-chloro-6-methylbenzyl, 2 , 6-dimethoxybenzyl, 2-chloro-5- (methylsulfonyl) benzyl, 2-chloro-6-cyanobenzyl, 2-chloro-6ethoxybenzyl, 2-chloro-5-methoxybenzyl, 2-chloro-5-fluorobenzyl, 5-chloro-2- fluorobenzyl, ethyl, propyl, butyl, pentyl, cyclopropyl, tert-butylamino, propylamino, 4-methyl-piperazinyl, 1-azetidinyl, 4-morpholino, (4-carboxyphenyl) amino, pivaloylamino), (((tert-butylamino) carbonyl) amino, trifluoromethyl, benzyloxy, 2- (2-methoxyethoxy) ethoxy,

2-(2-(2-metoksietoksi)etoksi)etoksi in 2-(2-(2-(2-metoksietoksi)etoksi)etoksi)etoksi.2- (2- (2-methoxyethoxy) ethoxy) ethoxy and 2- (2- (2- (2- (2-methoxyethoxy) ethoxy) ethoxy) ethoxy).

R4 substituent za formule zgoraj je lahko, vendar ni omejen na l,3-benzodioksol-5-il, l-naftil, tienil, 4-izobutoksifenil, 2,6-dimetilfenil, aliloksifenil, 3-bromo-4metoksifenil, 4-butoksifenil, l-benzofuran-2-il, 2-tienilmetil, fenil, metilsulfanil, fenilsulfanil, fenetilsulfanil, 4-bromo-2-tienil, 3-metil-2-tienil, 4-metilfenil, 3,5bis(metiloksi)fenil, 4-(metiloksi)fenil, 4-fluorofenil, 3-(metiloksi)fenil, 3,4,5tris(metiloksi)fenil, 2,3-dihidro-l-benzofuran-5-il, 3-fluoro fenil, 4(trifluorometil)fenil, 4-fluoro-3-(trifluorometil)fenil, 4-(l,l-dimetiletil)fenil, 3,5dimetilfenil, 4-hidroksifenil, 3,4-dimetiIfenil, 3-metil-4-(metiloksi)fenil, 4-hidroksi-3metilfenil, 3-metilfenil, 2,3-dihidro-inden-5-il, 2-metilfenil, 2,6-bis(metiloksi)fenil,The R 4 substituent for the formulas above may be but is not limited to 1,3-benzodioxol-5-yl, 1-naphthyl, thienyl, 4-isobutoxyphenyl, 2,6-dimethylphenyl, allyloxyphenyl, 3-bromo-4methoxyphenyl, 4-butoxyphenyl , 1-benzofuran-2-yl, 2-thienylmethyl, phenyl, methylsulfanyl, phenylsulfanyl, phenethylsulfanyl, 4-bromo-2-thienyl, 3-methyl-2-thienyl, 4-methylphenyl, 3,5bis (methyloxy) phenyl, 4 - (methyloxy) phenyl, 4-fluorophenyl, 3- (methyloxy) phenyl, 3,4,5tris (methyloxy) phenyl, 2,3-dihydro-1-benzofuran-5-yl, 3-fluoro phenyl, 4 (trifluoromethyl) phenyl, 4-fluoro-3- (trifluoromethyl) phenyl, 4- (1,1-dimethylethyl) phenyl, 3,5-dimethylphenyl, 4-hydroxyphenyl, 3,4-dimethylphenyl, 3-methyl-4- (methyloxy) phenyl, 4 -hydroxy-3methylphenyl, 3-methylphenyl, 2,3-dihydro-inden-5-yl, 2-methylphenyl, 2,6-bis (methyloxy) phenyl,

2,6-dihidroksifenil, 4-kloro fenil, 3-kloro fenil, 3,4-diklorofenil, 4((trifluorometil)oksi)fenil, 4-etilfenil, 4-(etiloksi)fenil, metil, 2-propil, 4,5-dihidro-l,3-5050 oksazol-2-il, 3-(trifluorometil)fenil, 4-(trifluorometoksi)fenil, 2,3-dihidro-l,4benzodioksin-6-il, 7-metoksi-l,3-benzodioksol-5-il, 3-etoksi-4-metoksifenil, 3,4dimetoksifenil, 3,4-dietoksifenil, 3-etoksifenil, 3-metoksi-4-metilfenil, 3,5-dimetoksi4-metilfenil, 3-propoksifenil, 3-butoksifenil, 3-(2-metoksietoksi)fenil, 3,4dipropoksifenil, 3-(difluorometoksi)fenil, 2-naftil, 3-izopropoksifenil, 1-metil-1Hindol-5-il, 2,3-dihidro-l-benzofuran-5-il, l,3-dietil-2-okso-2,3-dihidro-lHbenzimidazol-5-il, 3-(trifluorometoksi)fenil, 1-metil-lH-indol-6-il, 3(ciklopropoksi)fenil, 3-(ciklopropilmetoksi)fenil, 3-(difluorometoksi)fenil, 3-(1,1,2,2tetrafluoroetoksi)fenil, l-etil-lH-indol-5-il, 3-(dietilamino)fenil, 6-metoksi-2-naftil, 3[(metilsulfonil)amino] fenil, 3 - [metil(metilsulfonil)amino] fenil, 3 [etil(metilsulfonil)amino]fenil, lH-indol-5-il, 3-fluoro-4-metoksifenil in 3(difluorometil)fenil.2,6-dihydroxyphenyl, 4-chloro phenyl, 3-chloro phenyl, 3,4-dichlorophenyl, 4 ((trifluoromethyl) oxy) phenyl, 4-ethylphenyl, 4- (ethyloxy) phenyl, methyl, 2-propyl, 4, 5-dihydro-1,3-5050 oxazol-2-yl, 3- (trifluoromethyl) phenyl, 4- (trifluoromethoxy) phenyl, 2,3-dihydro-1,4-benzodioxin-6-yl, 7-methoxy-1,3 -benzodioxol-5-yl, 3-ethoxy-4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3-ethoxyphenyl, 3-methoxy-4-methylphenyl, 3,5-dimethoxy4-methylphenyl, 3-propoxyphenyl, 3 -butoxyphenyl, 3- (2-methoxyethoxy) phenyl, 3,4dipropoxyphenyl, 3- (difluoromethoxy) phenyl, 2-naphthyl, 3-isopropoxyphenyl, 1-methyl-1Hindol-5-yl, 2,3-dihydro-1-benzofuran -5-yl, 1,3-diethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl, 3- (trifluoromethoxy) phenyl, 1-methyl-1H-indol-6-yl, 3 (cyclopropoxy) phenyl, 3- (cyclopropylmethoxy) phenyl, 3- (difluoromethoxy) phenyl, 3- (1,1,2,2tetrafluoroethoxy) phenyl, 1-ethyl-1H-indol-5-yl, 3- (diethylamino) phenyl, 6- methoxy-2-naphthyl, 3 [(methylsulfonyl) amino] phenyl, 3- [methyl (methylsulfonyl) amino] phenyl, 3 [ethyl (methylsulfonyl) amino] phenyl , 1H-indol-5-yl, 3-fluoro-4-methoxyphenyl and 3 (difluoromethyl) phenyl.

Dve neodvisni R1, R2, R3 ali R5 skupini skupaj sta lahko povezani, da tvorita obroč.The two independent R 1 , R 2 , R 3 or R 5 groups together may be joined together to form a ring.

R4 in R11 sta lahko povezana, da tvorita obroč, kot med drugim 1-pirolidino, 1piperidino, 4-metil-l-piperazino, 4-acetil-l-piperazino in 4-morfolino.R 4 and R 11 may be linked to form a ring, such as, for example, 1-pyrrolidino, 1-piperidino, 4-methyl-1-piperazino, 4-acetyl-1-piperazino and 4-morpholino.

R9 in R10 sta lahko povezana, da tvorita obroč, kot med drugim ciklopropil, ciklobutil, ciklopentil in cikloheksil.R 9 and R 10 may be linked to form a ring, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, among others.

OkrajšaveAbbreviations

Okrajšave, ki smo jih uporabili v shemah in primerih, ki sledijo, so: BOC za tbutiloksikarbonil; DMF za dimetilformamid; THF za tetrahidrofuran; DME za dimetoksietan; DMSO za dimetilsulfoksid; NMM za N-metilmorfolin; DIPEA za diizopropiletilamin; CDI za l,l'-karbonildiimidazol; TBS za TRIS-zapufrano fiziološko solno raztopino; Ms za metansulfonil, TMEDA za Ν,Ν,Ν',Ν'tetrametiletilendiamin, DCE za 1,2-dikloroetan, NCS za N-klorosukcinimid, NBS za N-bromosukcinimid, DPPA za difenilfosforilazid, DEAD za dietil azodikarboksilat, m-CPBA za 3-kloroperoksibenzojsko kislino, TFAA za trifluoroacetanhidrid, DCM zaThe abbreviations used in the schemes and examples that follow are: BOC for tbutyloxycarbonyl; DMF for dimethylformamide; THF for tetrahydrofuran; DME for dimethoxyethane; DMSO for dimethylsulfoxide; NMM for N-methylmorpholine; DIPEA for diisopropylethylamine; CDI for 1,1'-carbonyldiimidazole; TBS for TRIS-buffered saline; Ms for methanesulfonyl, TMEDA for Ν, Ν, Ν ', Ν'tetramethylethylenediamine, DCE for 1,2-dichloroethane, NCS for N-chlorosuccinimide, NBS for N-bromosuccinimide, DPPA for diphenylphosphorylazide, DEAD for diethyl azodicarboxylate, CPA 3-chloroperoxybenzoic acid, TFAA for trifluoroacetic anhydride, DCM for

-5151 diklorometan, LHMDS za litijev bis(trimetilsilil)amid in Cbz za benziloksikarbonil. Amino kisline so okrajšane, kot sledi: C za L-cistein; D- za L-aspartinovo kislino; E za L-glutaminsko kislino; G za glicin; H za L-histidin; I za L-izolevcin; L za L-levcin; N za L-asparagin; P za L-prolin; Q za L-glutamin; S za L-serin; T za L-treonin; V za L-valin in W za L-triptofan.-5151 dichloromethane, LHMDS for lithium bis (trimethylsilyl) amide and Cbz for benzyloxycarbonyl. The amino acids are abbreviated as follows: C for L-cysteine; D- for L-aspartic acid; E for L-glutamic acid; G for glycine; H for L-histidine; And for L-isoleucine; L for L-leucine; N for L-asparagine; P for L-proline; Q for L-glutamine; S for L-serine; T for L-threonine; V for L-valine and W for L-tryptophan.

Primeri postopkov, ki jih lahko uporabimo za sintetiziranje spojin z zgoraj opisanimi formulami, so prikazani v shemah, ki sledijo. Podroben opis reprezentativnih spojin v smislu predloženega izuma je naveden v spodnjih primerih.Examples of processes that can be used to synthesize compounds of the formulas described above are shown in the following schemes. A detailed description of representative compounds of the present invention is provided in the examples below.

-52- 52 Shema 1 spodaj prikazuje postopek, opisan v primeru 1.-52- 52 Scheme 1 below illustrates the procedure described in Example 1.

NO2 NO 2

H2, Pd/C MeOHH 2 , Pd / C MeOH

NH2 NH 2

NEt3, DCM trimetilacetil^L klorid || |NEt 3 , DCM trimethylacetyl ^ L chloride || |

Shema 1Scheme 1

-53- 53 2, je prikazana spodaj.-53- 53 2, is shown below.

Shema 2, ki prikazuje postopek primeraScheme 2 illustrating the case process

2n<ias.NH4CI MeOH, 70 °C2n <ias.NH 4 CI MeOH, 70 ° C

Shema 2Scheme 2

-5454 Shema-5454 Scheme

3, ki prikazuje postopek primera3 showing the process of the case

3, je prikazana spodaj.3, is shown below.

HNHN

OHOH

NO2 NO 2

OOh

NaH, DMFNaH, DMF

Cl OCl O

NO,NO,

OHOH

POCI3 70 °CPOCI3 70 ° C

Shema 3Scheme 3

-55- 55 irikazuje postopek primera 4, je prikazana spodaj.-55- 55 illustrates the procedure of Example 4 is shown below.

ceif

ClCl

Nq2 aceton,refluks o N q 2 acetone, reflux o

OHOH

K2CO3, MelK 2 CO 3 , Mel

Shema 4Scheme 4

Shema 5Scheme 5

Shema 6, ki prikazuje postopek primera 6, je prikazana spodaj.Scheme 6 illustrating the process of Example 6 is shown below.

Shema 6Scheme 6

-56- 56 --56- 56 -

a) n-BuLi, TMEDA, THFa) n-BuLi, TMEDA, THF

Shema 7, ki prikazuje postopek primera 7, je prikazana spodaj.Scheme 7 illustrating the process of Example 7 is shown below.

BrNr

NH 'N ONH 'N O

II

NN

b) Brz, THFb) Br z , THF

A 28A 28

Shema 7Scheme 7

Shema 8, ki prikazuje postopek primera 8, je prikazana spodaj.Scheme 8 illustrating the process of Example 8 is shown below.

Zn bas .VOdNH4Cl MeOH, 65 °CZn bass. HydroH 4 Cl MeOH, 65 ° C

ClCl

OHOH

NH,NH,

OOh

CDI, DMF 70 °CCDI, DMF 70 ° C

Shema 8Scheme 8

-57Shema 9, ki prikazuje postopek primera 9, je prikazana spodaj.-57 Scheme 9 illustrating the process of Example 9 is shown below.

Shema 9Scheme 9

-58- 58 Shema 10, ki prikazuje postopek primera 10, je prikazana spodaj.-58- 58 Scheme 10 illustrating the process of Example 10 is shown below.

MeOMeO

O O 37O O 37

NH uNH u

Me OMe 35Me OMe 35

36, MeOH, refluks36, MeOH, reflux

Shema 10Scheme 10

-59- 59 Shema 11, ki prikazuje postopek primera 11, je prikazana spodaj.-59- 59 Scheme 11 illustrating the process of Example 11 is shown below.

Shema 11Scheme 11

Shema 12, ki prikazuje postopek primera 12, je prikazana spodaj.Scheme 12 illustrating the process of Example 12 is shown below.

Shema 12Scheme 12

Shema 13, ki prikazuje postopek primera 13, je prikazana spodaj.Scheme 13 illustrating the process of Example 13 is shown below.

'ci'ci

Cl . OHCl. OH

NaH, DMF, 55 °CNaH, DMF, 55 ° C

Shema 13Scheme 13

-60- 60 Shema 14, ki prikazuje postopek primera 14, je prikazana spodaj60 A diagram 14 illustrating the process of Example 14 is shown below

ΚΟγ^ΟΕ. ΚΟγ ^ ΟΕ. cer cer f ί H Τ-ΥΎf ί H Τ-ΥΎ n-cho n -cho EDCI, DMF EDCI, DMF AcOH, EtOH AcOH, EtOH o o o o Cl o o Cl o o refluks reflux 51 51 52 52

NaOH, THF MeOH, H2ONaOH, THF MeOH, H 2 O

Shema 14Scheme 14

-61- 61-61- 61

NN

OOh

NH,NH,

Shema 15Scheme 15

Shema 16, ki prikazuje postopek primera 16, je prikazana spodaj.Scheme 16 illustrating the process of Example 16 is shown below.

CbzHNCbzHN

OH NHBocOH NHBoc

Cs2C03, Mel DMFCs 2 C0 3 , Mel DMF

CbzHNCbzHN

OMe NHBocOMe NHBoc

a) H,, Pd/C, MeOHa) H,, Pd / C, MeOH

b) 2- tiofenkarboksaldehid NaBH(OAc)3, ClCH2CH2Clb) 2- Thiophenecarboxaldehyde NaBH (OAc) 3 , ClCH 2 CH 2 Cl

COOEtCOOEt

a) CDI, CH2Cl2 H,Na) CDI, CH 2 Cl 2 H, N

Shema 16Scheme 16

-62- 62 Shema 17, ki prikazuje postopek primera 17, je prikazana spodaj.-62- 62 Scheme 17 illustrating the process of Example 17 is shown below.

oo

O NHBocAbout NHBoc

a) i-BuOCOCl, NMM, DME pjQa) i-BuOCOCl, NMM, DME pjQ

b) NaBH4, H2Ob) NaBH 4 , H 2 O

a) DMSO, (COCI)2 CH2Cl2 a) DMSO, (COCI) 2 CH 2 Cl 2

NHBocNHBoc

b) 69b) 69

c) NEtjc) NO

OHCOHC

NHBocNHBoc

Shema 17Scheme 17

-63- 63 Shema 18, ki prikazuje postopek primera-63- 63 Scheme 18 showing the case process

18, je prikazana spodaj.18, is shown below.

Shema 18Scheme 18

postopek primerathe case procedure

19, je prikazana spodaj.19, is shown below.

-64- 64 Shema 20, ki prikazuje postopek primera 20, je prikazana spodaj.-64- 64 Scheme 20 illustrating the process of Example 20 is shown below.

NO2 NO 2

OHOH

CP 0H CP 0H

PPh3, DEAD CH2C12 PPh 3 , DEAD CH 2 C1 2

OOh

103103

Shema 20Scheme 20

Shema 21, ki prikazuje postopek primera 21, je prikazana spodaj.Scheme 21 illustrating the process of Example 21 is shown below.

TFAA,TFAA,

TEATEA

DCMDCM

-65- 65 Shema 22, ki prikazuje postopek primera 22, je prikazana spodaj-65- 65 A diagram 22 illustrating the process of Example 22 is shown below

Shema 22Scheme 22

Shema 23, ki prikazuje postopek primera 23, je prikazana spodajScheme 23 illustrating the process of Example 23 is shown below

HH

a) n-BuLi, TMEDA, THFa) n-BuLi, TMEDA, THF

b) t-BuLib) t-BuLi

Shema 23Scheme 23

Shema 24, ki prikazuje postopek primera 24, je prikazana spodajScheme 24 illustrating the process of Example 24 is shown below

Shema 24Scheme 24

-66- 66 Shema 25, ki prikazuje postopek primera 25, je prikazana spodaj.-66- 66 Scheme 25 illustrating the process of Example 25 is shown below.

OMeOMe

a) NaH, TMEDA, THF, -20 °Ca) NaH, TMEDA, THF, -20 ° C

b) n-BuLi, -20 °Cb) n-BuLi, -20 ° C

c) HCOOMe, -20 °Cc) HCOOMe, -20 ° C

OH O OOH O O

OMeOMe

NH,NH,

ClCl

MeOH, ref luksMeOH, ref lux

114114

Cl oCl o

115115

NaNO2, HNOj, AcOH, H2O, RTNaNO 2 , HNOj, AcOH, H 2 O, RT

Cl O 0H a) Zn, Et3N HCI DMF, 55 °CCl O 0 H a) Zn, Et 3 N HCl DMF, 55 ° C

NO, 1 b) CDI, 80 °CNO, 1 b) CDI, 80 ° C

116116

NaOH, H2O,NaOH, H 2 O,

THF, MeOHTHF, MeOH

Cl O <Cl O <

119119

Shema 25Scheme 25

-67- 67 Shema 26, ki prikazuje postopek primera 26, je prikazana spodaj, a) KOH, DMSO,-67- 67 Scheme 26 illustrating the process of Example 26 is shown below, a) KOH, DMSO,

b) Zn, Et3NHCl,b) Zn, Et 3 NHCl,

O DMF, 80° C OO DMF, 80 ° C O

c) CDI, 80° Cc) CDI, 80 ° C

120120

Shema 26Scheme 26

Shema 27, ki prikazuje postopek primera 27, je prikazana spodaj.Scheme 27 illustrating the process of Example 27 is shown below.

OH no2 OH no 2

Shema 27Scheme 27

-68- 68 Shema 28, ki prikazuje postopek primera 28, je prikazana spodaj.-68- 68 Scheme 28 illustrating the process of Example 28 is shown below.

Shema 28Scheme 28

Shema 29, ki prikazuje postopek primera 29, je prikazana spodaj.Scheme 29 illustrating the process of Example 29 is shown below.

oo

126126

Shema 29Scheme 29

-69- 69 Shema 30, ki prikazuje postopek primera 30, je prikazana spodaj.-69- 69 Scheme 30 illustrating the procedure of Example 30 is shown below.

Shema 30Scheme 30

Shema 31, ki prikazuje postopek primera 31, je prikazana spodaj.Scheme 31 illustrating the process of Example 31 is shown below.

ci o 46ci o 46

a) NaH, THF, 0 °Ca) NaH, THF, 0 ° C

b) /-BuNCO,qgreti do s.t.b) / -BuNCO, qheat up to s.t.

Shema 31Scheme 31

ci o 130ci o 130

-70- 70-70- 70

Shema 32 t-BuOOCScheme 32 t-BuOOC

Ph^N L'Ph ^ N L '

Z,Z,

PhPh

BrNr

THF, -78 °C, ugreti do s.t.THF, -78 ° C, warmed to m.p.

132132

DME, refluksDME, reflux

H2, Pd/C EtOH, HOAcH 2 , Pd / C EtOH, HOAc

Shema 33Scheme 33

-71CN-71CN

NaOt-Bu, EtOH THF, RTNaOt-Bu, EtOH THF, RT

ClCl

OEtOEt

CNCN

ClCl

135135

OEtOEt

HOAc, Ac2O NaNO2 HOAc, Ac 2 O NaNO 2

OEtOEt

ClCl

139139

NN

NHNH

BH3, THF refluks.BH 3 , THF reflux.

NH,NH,

ClCl

136136

ClCl

EtEt

COOEt ClCOCH2COOMeCOOEt ClCOCH 2 COOMe

NaH, THF, 0 °C, ugreti do s.tNaH, THF, 0 ° C, warmed to s.t.

COOMeCOOMe

COOEt NaH, DMFCOOEt NaH, DMF

OC do 60°COC to 60 ° C

ClCl

141141

Shema 3^Scheme 3 ^

-72- 72 --72- 72 -

145145

a) NaH, DMF, 0°C do S.t.a) NaH, DMF, 0 ° C to S.t.

b) Eti, S.t.b) Eti, S.t.

•N ^0• N ^ 0

DMF, POČI 3 70 °CDMF, POI 3 70 ° C

OHCOHC

X>X>

147147

Shema 36Scheme 36

-7373-7373

Et ιEt ι

O >0O> 0

DMF, 55 °CDMF, 55 ° C

Cl o h2nCl oh 2 n

151151

NaOH, H20, THF, MeOHNaOH, H 2 O, THF, MeOH

Et iEt i

CO,EtCO, Et

OEtOEt

154154

Cl OCl O

Shema 37Scheme 37

NaOH, H20, THF, MeOHNaOH, H 2 O, THF, MeOH

Shema 38Scheme 38

-74- 74 --74- 74 -

a) Zn, Et3N HCl DMF, 55 °Ca) Zn, Et 3 N HCl DMF, 55 ° C

Cl o 160Cl o 160

b) CDI, 80 °Cb) CDI, 80 ° C

-7575-7575

Shema 41Scheme 41

H2, Pd/C, AcOH EtOH, 35 °CH 2 , Pd / C, AcOH EtOH, 35 ° C

-7676-7676

Spojine v smislu predloženega izuma lahko uporabimo v obliki farmacevtsko sprejemljivih soli, izvedenih iz anorganskih ali organskih kislin. Fraza farmacevtsko sprejemljiva sol pomeni tiste soli, ki so v obsegu zdrave medicinske presoje primerne za uporabo v stiku s tkivi ljudi in nižjih živali brez nepotrebne toksičnosti, iritacije, alergičnega odziva itd. in so sorazmerne z razumnim razmerjem korist/riziko. Farmacevtsko sprejemljive soli so dobro znane v stroki. Npr. S. M. Berge et al. opisuje farmacevtsko sprejemljive soli podrobno v F Pharmaceutical Sciences, 1977, 66: 1 et seq. Soli lahko pripravimo in situ med končno izolacijo in čiščenjem spojin v smislu izuma ali posebej z reakcijo proste bazne funkcije s primemo organsko kislino. Reprezentativne kislinske adicijske soli vključujejo, vendar niso omejene nanje, acetat, adipat, alginat, citrat, aspartat, benzoat, benzensulfonat, bisulfat, butirat, kamforat, kaffasulfonat, diklukonat, glicerofosfat, hemisulfat, heptanoat, heksanoat, fumarat, hidroklorid, hidrobromid, hidrojodid, 2-hidroksietansulfonat (izotionat), laktat, maleat, metansulfonat, nikotinat, 2-naftalensulfonat, oksalat, palmitoat, pektinat, persulfat, 3-fenilpropionat, pikrat, pivalat, propionat, sukcinat, tartrat, tiocianat, fosfat, glutamat, bikarbonat, p-toluensulfonat in undekanoat. Tudi bazične dušik vsebujoče skupine lahko kvatemiziramo s takimi sredstvi, kot so nižji alkil halidi, kot so metil, etil, propil in butil kloridi, bromidi in jodidi; dialkil sulfati, kot dimetil, dietil, dibutil in diamil sulfati; halidi z dolgo verigo, kot so decil, lavril, miristil in stearil kloridi, bromidi in jodidi; arilalkil halidi, kot benzil in fenetil bromidi in drugi. Pri tem dobimo v vodi ali v olju topne ali disperzibilne produkte. Primeri kislin, ki jih lahko uporabimo za tvorbo farmacevtsko sprejemljivih kislinskih adicijskih soli, so take anorganske kisline, kot so klorovodikova, bromovodikova, žveplova in fosforjeva kislina, in take organske kisline, kot so oksalna, maleinska, jantarna in citronska kislina.The compounds of the present invention can be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. The phrase pharmaceutically acceptable salt means those salts which, within the scope of sound medical judgment, are suitable for use in contact with the tissues of humans and animals, without unnecessary toxicity, irritation, allergic response, etc. and are proportionate to the reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. E.g. S. M. Berge et al. describes pharmaceutically acceptable salts in detail in F Pharmaceutical Sciences, 1977, 66: 1 et seq. The salts may be prepared in situ during the final isolation and purification of the compounds of the invention or, in particular, by the reaction of a free base function with organic acid added. Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, kaffasulfonate, dicluconate, glycerophosphate, hemisulfate, heptanoate, hexanorochydrohydrate, fumarate, hydrate, fumarate , 2-hydroxyethanesulfonate (isothionate), lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmitoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, phosphate p-toluenesulfonate and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as lower alkyl halides such as methyl, ethyl, propyl and butyl chlorides, bromides and iodides; dialkyl sulfates such as dimethyl, diethyl, dibutyl and diamyl sulfates; long-chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyl halides such as benzyl and phenethyl bromides and others. Soluble or dispersible products are obtained in water or in oil. Examples of acids that can be used to form pharmaceutically acceptable acid addition salts are inorganic acids such as hydrochloric, hydrobromic, sulfuric and phosphoric acids, and such organic acids as oxalic, maleic, succinic and citric acid.

Bazične adicijske soli lahko pripravimo in situ med končno izolacijo in čiščenjem spojin v smislu predloženega izuma s presnovo dela, ki vsebuje karboksilno kislino, s primemo bazo, kot hidroksidom, karbonatom ali bikarbonatom farmacevtsko sprejemljivega kovinskega kationa ali z amoniakom ali organskim primarnim,The base addition salts may be prepared in situ between the final isolation and purification of the compounds of the present invention by metabolizing a carboxylic acid moiety with a base such as hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or ammonia or organic primary,

-7777 sekundarnim ali terciarnim aminom. Farmacevtsko sprejemljive soli vključujejo, vendar niso omejene nanje, katione na osnovi alkalijskih ali zemeljskoalkalijskih kovin, kot so litijeve, natrijeve, kalijeve, kalcijeve, magnezijeve in aluminijeve soli ipd., in netoksične kvarteme amoniakove in aminske katione, ki vključujejo med drugim amonij, tetrametilamonij, tetraetilamonij, metilamonij, dimetilamonij, trimetilamonij, trietilamonij, dietilamonij in etilamonij. Drugi reprezentativni organski amini, koristni za tvorbo baznih adicijskih soli, vključujejo etilendiamin, etanolamin, dietanolamin, piperidin, piperazin ipd.-7777 secondary or tertiary amines. Pharmaceutically acceptable salts include, but are not limited to, cations based on alkali or alkaline earth metals such as lithium, sodium, potassium, calcium, magnesium and aluminum salts, etc., and non-toxic quartemic ammonia and amine cations, including but not limited to ammonium, tetramethylammonium , tetraethylammonium, methylammonium, dimethylammonium, trimethylammonium, triethylammonium, diethylammonium and ethylammonium. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine and the like.

Dozirne oblike za lokalno dajanje spojine v smislu predloženega izuma so praški, spreji, mazila in inhalacij ska sredstva. Aktivno spojino pomešamo ob sterilnih pogojih s farmacevtsko sprejemljivim nosilcem in kakršnimikoli potrebnimi konzervimimi sredstvi, pufri ali poganjalnimi sredstvi, ki se lahko zahtevajo. Očesni pripravki, očesna mazila, praški in raztopine so prav tako mišljeni, da so v obsegu predloženega izuma.Dosage forms for topical administration of a compound of the present invention are powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservatives, buffers or propellants that may be required. Eye preparations, eye ointments, powders and solutions are also intended to be within the scope of the present invention.

Dejanske dozirne nivoje aktivnih sestavin v farmacevtskih sestavkih v smislu predloženega izuma lahko variiramo tako, da dobimo količino aktivne spojine (spojin), ki je učinkovita, da dosežemo želen terapevtski odziv za posameznega pacienta, sestavke in način dajanja. Izbran dozirni nivo bo odvisen od aktivnosti posamezne spojine, načina dajanja, resnosti stanja, ki ga zdravimo, ter stanja in anamneze pacienta, ki ga zdravimo. Vendar je v okviru stroke, da začnemo z dozami spojine pri nivojih, ki so nižji od zahtevanih za doseganje želenega terapevtskega učinka, in da postopoma povečujemo doziranje, dokler ne dosežemo želenega učinka.The actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention can be varied to obtain an amount of active compound (s) that is effective to achieve the desired therapeutic response for the individual patient, compositions and route of administration. The dosage level selected will depend on the activity of each compound, the route of administration, the severity of the condition being treated, and the condition and history of the patient being treated. However, it is within the skill of the art to start doses of a compound at levels lower than required to achieve the desired therapeutic effect, and to gradually increase the dosage until the desired effect is achieved.

Kadar se uporablja v gornjih ali drugih zdravljenjih, lahko terapevtsko učinkovito količino ene od spojin v smislu predloženega izuma uporabimo v čisti obliki ali, kadar take oblike obstajajo, v obliki farmacevtsko sprejemljive soli, estra ali predzdravila. Po drugi strani lahko dajemo spojino kot farmacevtski sestavek, ki vsebuje zadevno spojino v kombinaciji z enim ali več farmacevtsko sprejemljivimi ekcipienti. Fraza terapevtsko učinkovita količina spojine v smislu izuma pomeni zadostno količinoWhen used in the above or other treatments, a therapeutically effective amount of one of the compounds of the present invention can be used in pure form or, when such forms exist, in the form of a pharmaceutically acceptable salt, ester or prodrug. Alternatively, the compound may be administered as a pharmaceutical composition containing the compound in combination with one or more pharmaceutically acceptable excipients. The phrase a therapeutically effective amount of a compound of the invention means a sufficient amount

-7878 spojine za zdravljenje motenj pri razumnem razmerju korist/riziko, primernem za katerokoli zdravljenje. Vendar se bo razumelo, da bo celotno dnevno uporabo spojin in sestavkov v smislu predloženega izuma določil lečeči zdravnik v obsegu zdrave medicinske presoje. Specifičen terapevtsko učinkovit dozni nivo za kateregakoli posameznega pacienta bo odvisen od številnih faktorjev, ki vključujejo motnjo, ki jo zdravimo, in resnost motnje; aktivnost uporabljene specifične spojine; uporabljen specifičen sestavek; starost, telesno težo, splošno zdravje, spol in prehrano pacienta; čas dajanja, način dajanja in hitrost izločanja uporabljene specifične spojine; trajanje zdravljenja; zdravila, uporabljena v kombinaciji ali naključno z uporabljeno specifično spojino; in podobne faktorje, znane v medicini. Npr. jev okviru stroke, da začnemo z dozami spojine pri nivojih, ki so nižji od zahtevanih za doseganje želenega terapevtskega učinka, in da postopoma povečujemo doziranje, dokler ne dosežemo želenega učinka.-7878 Compounds for the treatment of disorders at a reasonable benefit / risk ratio, suitable for any treatment. However, it will be understood that the full daily use of the compounds and compositions of the present invention will be determined by the treating physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any individual patient will depend on a number of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound used; the specific composition used; patient's age, weight, overall health, gender, and diet; the time of administration, the route of administration and the rate of elimination of the specific compound used; duration of treatment; drugs used in combination or accidentally with the specific compound used; and similar factors known in medicine. E.g. It is within the scope of the art to begin dosing the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved.

Celotna dnevna doza spojin v smislu predloženega izuma, dajana človeku ali nižji živali, je lahko v območju od okoli 0,0001 do okoli 1000 mg/kg/dan. Za namene oralnega dajanja so lahko bolj prednostne doze v območju od okoli 0,001 do okoli 5 mg/kg/dan. Če je želeno, lahko učinkovito dnevno dozo porazdelimo v večkratne doze za namene dajanja. Torej lahko sestavki za enkratno dozo vsebujejo take količine ali njihove alikvote za popolnitev dnevne doze.The total daily dose of the compounds of the present invention administered to a human or lower animal may range from about 0.0001 to about 1000 mg / kg / day. For oral administration, doses in the range of about 0.001 to about 5 mg / kg / day may be more preferred. If desired, the effective daily dose can be divided into multiple doses for administration purposes. Therefore, single dose compositions may contain such amounts or aliquots thereof to complete the daily dose.

Pri predloženem izumu gre tudi za farmacevtske sestavke, ki obsegajo spojine v smislu predloženega izuma, formulirane skupaj z enim ali več netoksičnimi farmacevtsko sprejemljivimi nosilci. Farmacevtske sestavke lahko specialno formuliramo za oralno dajanje v trdni ali tekoči obliki, za parenteralno injekcijo ali za rektalno dajanje.The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions can be formulated specifically for oral administration in solid or liquid form, for parenteral injection or for rectal administration.

Farmacevtske sestavke v smislu predloženega izuma lahko dajemo ljudem in drugim sesalcem oralno, rektalno, parenteralno, intracistemalno, intravaginalno, intraperitonealno, lokalno (kot s praški, mazili ali kapljicami), bukalno ali kot oralni ali nazalni sprej. Izraz parenteralno, kot se tukaj uporablja, se nanaša na načineThe pharmaceutical compositions of the present invention may be administered to humans and other mammals by oral, rectal, parenteral, intracystemal, intravaginal, intraperitoneal, topical (as with powders, ointments or drops), buccally or as an oral or nasal spray. The term parenteral, as used herein, refers to ways

-7979 dajanja, ki vključujejo intravensko, intramuskulamo, intraperitonealno, intrastemalno, subkutano in intraartikulamo injekcijo in infuzijo.-7979 administration involving intravenous, intramuscular, intraperitoneal, intrastemal, subcutaneous and intraarticular injection and infusion.

Pri drugem vidiku gre pri predloženem izumu za farmacevtski sestavek, ki obsega komponento v smislu predloženega izuma in fiziološko prenesljivo razredčilo. Predloženi izum vključuje eno ali več spojin, kot je opisano zgoraj, formuliranih v sestavke skupaj z enim ali več netoksičnimi, fiziološko prenesljivimi ali sprejemljivimi razredčili, nosilci, adjuvansi ali vehikli, ki jih tukaj skupaj imenujemo razredčila, med drugim za parenteralno injekcijo, za intranazalno dajanje, za oralno dajanje v trdni ali tekoči obliki, za rektalno ali lokalno dajanje.In another aspect, the present invention is a pharmaceutical composition comprising a component of the present invention and a physiologically acceptable diluent. The present invention includes one or more compounds as described above, formulated into compositions together with one or more non-toxic, physiologically acceptable or acceptable diluents, carriers, adjuvants or vehicles, collectively referred to herein as diluents, inter alia for parenteral injection, for intranasal administration, for oral administration in solid or liquid form, for rectal or topical administration.

Sestavke lahko tudi dajemo skozi kateter za lokalno dajanje pri tarčnem mestu, preko intrakoronamega stenta (cevna naprava, sestavljena iz fine žične mreže) ali preko biorazgradljivega polimera. Spojine so lahko tudi kompleksirane na ligande, kot protitelesa, za ciljano dajanje.The compositions can also be administered via a catheter for local administration at the target site, via an intracoronal stent (tube device consisting of a fine wire mesh) or via a biodegradable polymer. The compounds may also be complexed to ligands, such as antibodies, for targeted administration.

Sestavki, primerni za parenteralno injekcijo, lahko obsegajo fiziološko sprejemljive sterilne vodne ali nevodne raztopine, disperzije, suspenzije ali emulzije in sterilne praške za rekonstituiranje v sterilne injekcijske raztopine ali disperzije. Primeri primernih vodnih in nevodnih nosilcev, razredčil, topil ali vehiklov so voda, etanol, polioli (propilenglikol, polietilenglikol, glicerol ipd.), rastlinska olja (kot olivno olje), injekcijski organski estri, kot etil oleat, in njihove primerne zmesi.Compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and non-aqueous vehicles, diluents, solvents or solvents are water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol, etc.), vegetable oils (as olive oil), injectable organic esters such as ethyl oleate, and suitable mixtures thereof.

Ti sestavki lahko tudi vsebujejo adjuvanse, kot konzervima, omočilna, emulgirna in dispergima sredstva. Preprečevanje učinka mikroorganizmov lahko zagotovimo z različnimi protibakterijskimi in protiglivičnimi sredstvi, kot so npr. parabenz, klorobutanol, fenol, sorbinska kislina ipd. Lahko je tudi zaželeno, da vključimo izotonična sredstva, npr. sladkorje, natrijev klorid ipd. Podaljšano absorpcijo injekcijske farmacevtske oblike lahko dosežemo z uporabo sredstev, ki odložijo absorpcijo, npr. aluminijevega monostearata in želatine.These compositions may also contain adjuvants such as preservatives, wetting, emulsifying and dispersing agents. The prevention of the effect of microorganisms can be ensured by various antibacterial and antifungal agents, such as e.g. parabenz, chlorobutanol, phenol, sorbic acid and the like. It may also be desirable to include isotonic agents, e.g. sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be achieved by using absorption delaying agents, e.g. aluminum monostearate and gelatin.

-8080-8080

Suspenzije lahko poleg aktivnih spojin vsebujejo suspendirna sredstva, kot npr. etoksilirane izostearil alkohole, polioksietilen sorbitol in sorbitan estre, mikrokristalno celulozo, aluminijev metahidroksid, bentonit, agar-agar in tragant ali zmesi teh snovi ipd.In addition to the active compounds, the suspensions may contain suspending agents, such as e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth or mixtures thereof.

V nekaterih primerih je za podaljšanje učinka zdravila zaželeno, da upočasnimo absorpcijo zdravila iz subkutane ali intramuskulame injekcije. To lahko dosežemo z uporabo tekoče suspenzije kristalnega ali amorfnega materiala s slabo vodotopnostjo. Hitrost absorpcije zdravila je potem odvisna od njegove hitrosti raztapljanja, ki je lahko po drugi strani odvisna od velikosti kristalov in kristalne oblike. Po drugi strani dosežemo odloženo absorpcijo parenteralno dajane zdravilne oblike z raztapljanjem ali suspendiranjem zdravila v oljnem vehiklu.In some cases, to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends on its rate of dissolution, which in turn may depend on the size of the crystals and the crystal shape. On the other hand, delayed absorption of the parenterally administered dosage form is achieved by dissolving or suspending the drug in an oily vehicle.

Injekcijske depojske oblike izdelamo s tvorbo mikrozakapsulimih matric zdravila v biorazgradljivih polimerih, kot je polilaktid-poliglikolid. V odvisnosti od razmerja zdravila proti polimeru in od narave uporabljenega posameznega polimera lahko kontroliramo hitrost sproščanja zdravila. Primeri drugih biorazgradljivih polimerov so poli(ortoestri) in poli(anhidridi). Depojske injekcijske pripravke tudi pripravimo z zajetjem zdravila v liposome ali mikroemulzije, ki so kompatibilne s telesnimi tkivi.Injectable depot forms are produced by the formation of microcapsules of drug matrix in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer and the nature of the individual polymer used, the rate of drug release can be controlled. Examples of other biodegradable polymers are poly (orthoesters) and poly (anhydrides). Depot injection preparations are also prepared by incorporating the drug into liposomes or microemulsions that are compatible with body tissues.

Injekcijske pripravke lahko steriliziramo, npr. s filtracijo skozi filter, ki zadrži bakterije, ali z vdelavo sterilizimih sredstev v obliki sterilnih trdnih sestavkov, ki jih lahko raztopimo ali dispergiramo v sterilni vodi ali drugem sterilnem injekcijskem mediju tik pred uporabo.Injectable compositions can be sterilized, e.g. by filtration through a bacteria-retaining filter, or by embedding sterilizers in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium just before use.

Trdne dozirne oblike za oralno dajanje so kapsule, tablete, pilule, praški in granule. V takih trdnih dozirnih oblikah je lahko aktivna spojina pomešana z vsaj enim inertnim farmacevtsko sprejemljivim ekscipientom ali nosilcem, kot §o natrijev citrat ali dikalcijev fosfat, in/ali a) polnila ali razredčila, kot škrobi, laktoza, saharoza, glukoza, manitol in silicijeva kislina; b) veziva, kot karboksimetilceluloza, alginati, želatina, polivinilpirolidon, saharoza in gumi akacije; c) vlažilna sredstva, kot glicerol, d)Solid dosage forms for oral administration are capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound may be mixed with at least one inert pharmaceutically acceptable excipient or carrier such as § citrate or dicalcium phosphate, and / or a) fillers or diluents such as starches, lactose, sucrose, glucose, mannitol and silicon acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia gum; c) moisturizing agents such as glycerol d)

-8181 razpadna sredstva, kot agar-agar, kalcijev karbonat, krompirjev škrob ali škrob tapioke, alginska kislina, nekateri silikati in natrijev karbonat; e) sredstva, ki zavirajo raztapljanje, kot parafin; f) pospeševalci absorpcije, kot kvarteme amonijeve spojine; g) omočila, kot cetil alkohol in glicerol monostearat; h) absorbenti, kot kaolin in bentonitna glina, in i) maziva, kot so smukec, kalcijev stearat, magnezijev stearat, trdni polietilen glikoli, natrijev lavril sulfat in njihove zmesi. V primeru kapsul, tablet in pilul lahko dozirna oblika tudi obsega pufrska sredstva.-8181 decomposition agents such as agar-agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) dissolving agents such as paraffin; f) absorption enhancers, such as quartemons of ammonium compound; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay; and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.

Trdne sestavke podobnega tipa lahko tudi uporabimo kot polnila v mehkih in trdopolnjenih želatinskih kapsulah ob uporabi takih ekscipientov, kot je laktoza ali mlečni sladkor, kot tudi polietilenglikoli z visoko molekulsko maso ipd.Solid compositions of a similar type can also be used as fillers in soft and hard gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

Trdne dozirne oblike tablet, dražej, kapsul, pilul in granul lahko pripravimo s preslojitvami in skorjami, kot so enterične preslojitve in druge preslojitve, dobro znane v stroki farmacevtskega formuliranja. Po izbiri lahko vsebujejo motnila in so lahko tudi take sestave, da sproščajo aktivno sestavino (sestavine) le ali prednostno v določenem delu intestinalnega trakta, po izbiri na zadržan način.Solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared by coats and crusts, such as enteric coats and other coats well known in the art of pharmaceutical formulation. Optionally, they may contain disorders and may also be of such composition that they release the active ingredient (s) only or preferably in a particular part of the intestinal tract, optionally in a restrained manner.

Primeri obložnih sestavkov, kijih lahko uporabimo, so polimerne snovi in voski.Examples of coating compositions that can be used are polymeric substances and waxes.

Aktivne spojine so lahko tudi v mikro-zakapsulirani obliki, če je primemo, z enim ali več od zgoraj omenjenih ekscipientov.The active compounds may also be in micro-encapsulated form, if appropriate, with one or more of the excipients mentioned above.

Tekoče dozirne oblike za oralno dajanje so farmacevtsko sprejemljive emulzije, raztopine, suspenzije, sirupi in eliksirji. Poleg aktivnih spojin lahko tekoče dozirne oblike vsebujejo inertna razredčila, ki se običajno uporabljajo v stroki, kot je npr. voda ali druga topila, solubilizima sredstva in emulgatorji, kot etil alkohol, izopropil alkohol, etil karbonat, etil acetat, benzil alkohol, benzil benzoat, propilen glikol, 1,3butilen glikol, dimetil formamid, olja (zlasti olje bombaževega semena, arašidovo olje, koruzno olje, olje kalčkov, olivno olje, ricinovo olje in sezamovo olje), glicerol,Liquid dosage forms for oral administration are pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, liquid dosage forms may contain inert diluents commonly used in the art, such as e.g. water or other solvents, solubilizers and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3butylene glycol, dimethyl formamide, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol,

-8282 tetrahidrofurfuril alkohol, polietilen glikoli in estri sorbitana in maščobnih kislin ter njihove zmesi.-8282 Tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan and fatty acid esters and mixtures thereof.

Poleg inertnih razredčil lahko oralni sestavki vključujejo tudi adjuvanse, kot omočila, emulgima in suspendima sredstva, sladila, arome in sredstva za vonj.In addition to inert diluents, oral compositions may also include adjuvants such as wetting, emulsifying and suspending agents, sweeteners, flavors and odorants.

Sestavki za rektalno ali vaginalno dajanje so prednostno supozitoriji, ki jih lahko pripravimo z mešanjem spojin v smislu predloženega izuma s primernimi nedražečimi ekscipienti ali nosilci, kot je kakavovo maslo, polietilenglikol ali supozitorijski vosek, ki so trdni pri sobni temperaturi, vendar tekoči pri telesni temperaturi ter se zato stalijo v rektumu ali vaginalni votlini in sprostijo aktivno spojino.Rectal or vaginal administration compositions are preferably suppositories that can be prepared by mixing the compounds of the present invention with suitable non-irritant excipients or carriers, such as cocoa butter, polyethylene glycol or suppository wax, which are solid at room temperature but flowing at body temperature and therefore settle in the rectum or vaginal cavity and release the active compound.

Spojine v smislu predloženega izuma lahko tudi dajemo v obliki liposomov. Kot je znano v stroki, so liposomi na splošno izvedeni iz fosfolipidov ali drugih lipidnih snovi. Liposome tvorijo mono- ali multi-lamelami hidratizirani tekoči kristali, ki so dispergirani v vodnem mediju. Uporabimo lahko katerikoli- netoksičen, fiziološko sprejemljiv in metabolizabilen lipid, ki je sposoben tvoriti liposome. Predloženi sestavki v liposomski obliki lahko vsebujejo poleg spojine v smislu predloženega izuma stabilizatorje, konzervima sredstva, ekscipiente ipd. Prednostni lipidi so naravni in sintetski fosfolipidi in fosfatidil holini (lecitini), uporabljeni posebej ali skupaj.The compounds of the present invention may also be administered in the form of liposomes. As is well known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellae hydrated liquid crystals, which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposomal form may contain in addition to the compound of the present invention stabilizers, preservatives, excipients and the like. Preferred lipids are natural and synthetic phospholipids and phosphatidyl cholines (lecithins) used alone or in combination.

Postopki za tvorbo liposomov so znani v stroki. Glej npr. Prescott, Ed., Methods in Celi Biologv, Vol. XIV, Academic Press, New York, Ν.Υ. (1976), str. 33 et seq.Methods for forming liposomes are known in the art. See, e.g. Prescott, Ed., Methods in Whole Biology, Vol. XIV, Academic Press, New York, Ν.Υ. (1976), p. 33 et seq.

Izraz farmacevtsko sprejemljiva predzdravila, kot se tukaj uporablja, predstavlja tista predzdravila spojin v smislu predloženega izuma, ki so v obsegu zdrave medicinske presoje primerna za uporabo v kontaktu s tkivi ljudi in nižjih živali brez nepotrebne toksičnosti, iritacije, alergičnega odziva ipd., ki sovpadajo z razumnim razmerjem korist/riziko, in so učinkovita za njihovo nameravano uporabo, kot tudi amfoterne oblike, kjer je mogoče, spojin v smislu izuma. Predzdravila v smislu predloženega izuma se lahko hitro pretvorijo in vivo v starševsko spojino z gornjoThe term pharmaceutically acceptable prodrugs, as used herein, means those prodrugs of the compounds of the present invention that are, within the scope of sound medical judgment, suitable for use in contact with human and lower animal tissues without undue toxicity, irritation, allergic response, etc., coincidentally. with a reasonable benefit / risk ratio, and are effective for their intended use as well as amphoteric forms where possible of the compounds of the invention. The prodrugs of the present invention can be rapidly converted in vivo to the parent compound above

-8383 formulo, npr. s hidrolizo v krvi. Temeljita diskusija je v T. Higuchi in V. Stella, Prodrugs as Novel Deliverv Svstems, V. 14, A.C.S. Symposium Series, in v Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press (1987), vključena semkaj kot referenca.-8383 formula, e.g. by hydrolysis in the blood. A thorough discussion is in T. Higuchi and V. Stella, Prodrugs as Novel Deliverv Svstems, V. 14, A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers and Drug Design, American Pharmaceutical Association and Pergamon Press (1987), incorporated herein by reference.

Spojine v smislu predloženega izuma, ki se tvorijo z in vivo pretvorbo različne spojine, ki smo jo dali sesalcu, so namenjene, da so vključene v obseg predloženega izuma.The compounds of the present invention, which are formed by in vivo conversion of the various compounds administered to the mammal, are intended to be included within the scope of the present invention.

Spojine v smislu predloženega izuma lahko obstajajo kot stereoizomeri, kjer so prisotni asimetrični ali kiralni centri. Ti stereoizomeri so R ali S v odvisnosti od konfiguracije substituentov okoli kiralnega atoma ogljika. Predloženi izum zajema različne stereoizomere in njihove zmesi. Stereoizomeri so enantiomeri in diastereomeri ter zmesi enantiomerov ali diastereomerov. Posamezne stereoizomere spojin v smislu predloženega izuma lahko pripravimo sintetsko iz tržno dostopnih izhodnih snovi, ki vsebujejo asimetrične ali kiralne centre, ali s pripravo racemnih zmesi, čemur sledi ločenje, kije dobro znano strokovnjaku. Primeri teh metod ločenja so (1) pritrditev zmesi enantiomerov na kiralno pomožno snov, ločenje dobljene zmesi diastereomerov s prekristalizacijo ali kromatografijo in sproščanje optično čistega produkta iz pomožne snovi ali (2) direktno ločenje zmesi optičnih enantiomerov na kiralnih kromatografskih kolonah.The compounds of the present invention may exist as stereoisomers where asymmetric or chiral centers are present. These stereoisomers are R or S, depending on the configuration of the substituents around the chiral carbon atom. The present invention encompasses various stereoisomers and mixtures thereof. Stereoisomers are enantiomers and diastereomers and mixtures of enantiomers or diastereomers. The individual stereoisomers of the compounds of the present invention can be prepared synthetically from commercially available starting materials containing asymmetric or chiral centers, or by preparing racemic mixtures, followed by separation well known to one skilled in the art. Examples of these separation methods are (1) attaching a mixture of enantiomers to a chiral excipient, separating the resulting diastereomer mixture by recrystallization or chromatography, and releasing an optically pure product from the excipient, or (2) directly separating a mixture of optical enantiomers on chiral chromatographic columns.

Spojine v smislu izuma lahko obstajajo v nesolvatiranih kot tudi solvatiranih oblikah, vključno kot so hidratizirane oblike, kot hemi-hidrati. Na splošno so solvatirane oblike s farmacevtsko sprejemljivimi topili, kot so med drugim voda in etanol, ekvivalentne nesolvatiranim oblikam za namene izuma.The compounds of the invention may exist in unsolvated as well as solvated forms, including hydrated forms such as hemi-hydrates. Generally, solvated forms with pharmaceutically acceptable solvents, such as, for example, water and ethanol, are equivalent to unsolvated forms for the purposes of the invention.

Pri drugem vidiku predloženi izum zajema postopek inhibiranja vezave α4βι integrina na VCAM-1. Postopek v smislu predloženega izuma lahko uporabimo bodisi in vitro ali in vivo. V skladu s postopkom v smislu predloženega izuma celico, ki eksprimiraIn another aspect, the present invention provides a method of inhibiting the binding of α 4 βι integrin to VCAM-1. The process of the present invention can be used either in vitro or in vivo. In accordance with the method of the present invention, an expressing cell

-8484 α4βι integrin, izpostavimo celici, ki eksprimira VCAM-1, v prisotnosti učinkovite inhibitome količine spojine v smislu predloženega izuma.-8484 α 4 βι integrin is exposed to a cell expressing VCAM-1 in the presence of an effective inhibitory amount of a compound of the present invention.

Celica, ki eksprimira α4βι integrin, je lahko naravno nastopajoča bela krvnička, maščobna celica ali drug celični tip, ki naravno eksprimira α4βι na celični površini, ali celica, transfektirana z ekspresijskim vektorjem, ki vsebuje poli-nukleotid (npr. genomsko DNA ali cDNA), ki kodira α4βι integrin. V posebno prednostni izvedbi je α4βι integrin prisoten na površini bele krvničke, kot je monocit, limfocit ali granulocit (npr. eozinofilec ali bazofilec).A cell expressing α 4 βι integrin may be a naturally occurring white blood cell, fat cell, or other cell type that naturally expresses α 4 βι on the cell surface, or a cell transfected with an expression vector containing a polynucleotide (e.g., genomic DNA or cDNA) encoding α 4 βι integrin. In a particularly preferred embodiment, the α 4 βι integrin is present on the surface of the white blood cell, such as a monocyte, lymphocyte, or granulocyte (e.g., eosinophil or basophil).

Celica, ki eksprimira VCAM-1, je lahko naravno nastopajoča celica (npr. endotelna celica) ali celica, transfektirana z ekspresijskim vektorjem, ki vsebuje polinukleotid, ki kodira VCAM-1. Postopki za pripravo transfektiranih celic, ki eksprimirajo VCAM-1, so dobro znani v stroki.A cell expressing VCAM-1 may be a naturally occurring cell (e.g., an endothelial cell) or a cell transfected with an expression vector containing a polynucleotide encoding VCAM-1. Methods for the preparation of transfected cells expressing VCAM-1 are well known in the art.

Kjer VCAM-1 obstaja na površini celice, ekspresijo tega VCAM-1 prednostno inducirajo vnetni citokini, kot tumorski nekrozni faktor-α, interlevkin-4 in interlevkin1β.Where VCAM-1 exists on the cell surface, expression of this VCAM-1 is preferentially induced by inflammatory cytokines such as tumor necrosis factor-α, interleukin-4 and interleukin1β.

Kadar so celice, ki eksprimirajo α4βι integrin in VCAM-1, v živem organizmu, dajemo spojino v smislu predloženega izuma v učinkoviti količini živemu organizmu. Prednostno je spojina v farmacevtskem sestavku v smislu predloženega izuma. Postopek v smislu predloženega izuma je posebno uporaben pri zdravljenju bolezni, povezanih z nekontrolirano migracijo belih krvničk v poškodovano tkivo. Take bolezni so, vendar niso nanje omejene, astma, ateroskleroza, revmatoidni artritis, alergija, multipla skleroza, lupus, vnetna črevesna bolezen, zavrnitev presadka, kontaktna hipersenzibilnost, diabetes tipa I, levkemija in možganski karcinom. Dajanje prednostno izvedemo preko intravaskulamega, subkutanega, intranazalnega, transdermalnega ali oralnega dajanja.Where the cells expressing α 4 βι integrin and VCAM-1 are in a living organism, a compound of the present invention in an effective amount to the living organism. Preferably the compound is in the pharmaceutical composition of the present invention. The method of the present invention is particularly useful in the treatment of diseases associated with the uncontrolled migration of white blood cells into damaged tissue. Such diseases are, but are not limited to, asthma, atherosclerosis, rheumatoid arthritis, allergy, multiple sclerosis, lupus, inflammatory bowel disease, graft rejection, contact hypersensitivity, type I diabetes, leukemia and brain cancer. Administration is preferably via intravascular, subcutaneous, intranasal, transdermal or oral administration.

-8585-8585

Pri predloženem izumu gre tudi za postopek za selektivno inhibicijo vezave α4β[ integrina na protein, ki obsega izpostavljanje integrina proteinu v prisotnosti učinkovite inhibitome količine spojine v smislu predloženega izuma. Pri prednostni izvedbi α4βι integrin eksprimiramo na površini celice, ki je bodisi naravno nastopajoča ali je celica, transformirana za ekspresijo α4βι integrina. Protein, na katerega se veže α4βι integrin, lahko eksprimiramo bodisi na celični površini ali je lahko del ekstracelulamega matriksa. Zlasti prednostna proteina sta fibronektin ali invazin.In the present invention also provides a process for selectively inhibiting the binding of α 4 β [integrin to a protein comprising exposing the integrin to the protein in the presence of an effective inhibitory amount of a compound of the present invention. In a preferred embodiment, α 4 βι integrin is expressed on the surface of a cell that is either naturally occurring or is a cell transformed for α 4 βι integrin expression. The protein to which α 4 βι integrin binds can be expressed either on the cell surface or may be part of the extracellular matrix. Particularly preferred proteins are fibronectin or invasin.

Sposobnost spojin v smislu predloženega izuma za inhibiranje vezave je podrobno opisana v nadaljevanju v primerih. Ti primeri so predstavljeni za opisovanje prednostnih izvedb in uporabnosti izuma in niso mišljeni, da bi omejevali izum, razen če ni drugače navedeno v zahtevkih, ki so temu dodani.The ability of the compounds of the present invention to inhibit binding is described in detail below in the Examples. These examples are presented to describe preferred embodiments and utility of the invention and are not intended to limit the invention unless otherwise stated in the claims appended thereto.

Primer 1Example 1

Sinteza (3 S)-3-{ [({1 -[(2-klorofenil)metil]-4-etil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ske kisline (10)Synthesis of (3S) -3- {[({1 - [(2-chlorophenyl) methyl] -4-ethyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - (4 -methylphenyl) propionic acid (10)

Stopnja ena: Spojino 1 (20,8 g, 135 mmol) raztopimo v metanolu (270 ml) in dodamo paladij na oglju (10 % Pd na osnovi suhe mase, tip Degussa E101 NE/W, -50% vsebnosti vode, 5,75 g, 2,7 mmol Pd). Atmosfero nadomestimo z vodikom (preklapljanje med vakuumom in vodikom iz balona 5-krat), zmes mešamo preko noči, nato filtriramo. Filtrat koncentriramo v vakuumu in ostanek prevzamemo v zmesi heksanketil acetat 1:1 ter izperemo z zmesjo 4:1 vode in nasičenega NaHCO3, nasičenega NaHCO3 in slanice. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 2 (12,43 g, 74 %) kot belo trdno snov. Ta material uporabimo brez čiščenja.Step One: Dissolve compound 1 (20.8 g, 135 mmol) in methanol (270 ml) and add palladium on charcoal (10% Pd on a dry weight basis, Deguss type E101 NE / W, -50% water content, 5, 75 g, 2.7 mmol Pd). The atmosphere was replaced by hydrogen (switching between vacuum and hydrogen from the balloon 5 times), the mixture was stirred overnight, then filtered. The filtrate was concentrated in vacuo and the residue taken up in a 1: 1 mixture of hexanethyl acetate and washed with a mixture of 4: 1 water and saturated NaHCO 3 , saturated NaHCO 3 and brine. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure to give compound 2 (12.43 g, 74%) as a white solid. Use this material without cleaning.

Stopnja dve: Spojino 2 (2,64 g, 21,3 mmol) raztopimo v diklorometanu (50 ml) in ohladimo na 0 °C. Hladno raztopino zaporedoma obdelamo s trietilaminom (3,6 ml,Step two: Dissolve compound 2 (2.64 g, 21.3 mmol) in dichloromethane (50 ml) and cool to 0 ° C. The cold solution was successively treated with triethylamine (3.6 ml,

25,6 mmol) in trimetilacetil kloridom (2,90 ml, 23,4 mmol). Raztopino mešamo pri25.6 mmol) and trimethylacetyl chloride (2.90 ml, 23.4 mmol). The solution was stirred at

-8686 sobni temperaturi 6 ur, nato refluktiramo preko noči. Zmes porazdelimo med diklorometan in vodni NaOH (2N). Organski sloj izperemo s slanico, posušimo nad MgSO4, filtriramo in filtrat koncentriramo, da dobimo spojino 3 (3,33 g, 75%).-8686 room temperature for 6 hours, then refluxed overnight. The mixture was partitioned between dichloromethane and aqueous NaOH (2N). The organic layer was washed with brine, dried over MgSO 4 , filtered and the filtrate concentrated to give compound 3 (3.33 g, 75%).

Stopnja tri: Spojino 3 (0,50 g, 2,4 mmol) raztopimo v suhem THF, (9,6 ml) in TMEDA (1,1 ML, 7,2 mmol) pod atmosfero suhega dušika. Dobljeno raztopino ohladimo na med -20 in -10 °C in zaporedoma obdelamo z n-butillitijem (1,6 M v heksanih, 2,25 ml) in t-butillitijem (1,7 M v pentanu, 2,1 ml) po kapljicah preko brizge. Po 30 minutah pustimo, da pride temperatura kopeli na -5 do 0 “C, in obdelamo z etiljodidom preko brizge (0,77 ml, 9,6 mmol). Raztopino mešamo 2 uri pri 0 °C, nato pri sobni temperaturi preko noči. Zmes pogasimo z metanolom in koncentriramo do suhega. Ostanek čistimo s filtriranjem skozi silikagel, z eluiranjem s 3:1 heksani:etil acetatom in nato prekristaliziranjem iz heksanov, da dobimo spojino 4 (0,32 g, 56%).Step Three: Compound 3 (0.50 g, 2.4 mmol) was dissolved in dry THF, (9.6 mL) and TMEDA (1.1 ML, 7.2 mmol) under a dry nitrogen atmosphere. The resulting solution was cooled to between -20 and -10 ° C and sequentially treated with n-butyllithium (1.6 M in hexanes, 2.25 ml) and t-butyllithium (1.7 M in pentane, 2.1 ml). drops over the syringe. After 30 minutes, allow the bath temperature to reach -5 to 0 ° C and treat with ethyliodide via a syringe (0.77 ml, 9.6 mmol). The solution was stirred for 2 hours at 0 ° C, then at room temperature overnight. The mixture was quenched with methanol and concentrated to dryness. The residue was purified by filtration through silica gel, eluting with 3: 1 hexanes: ethyl acetate and then recrystallizing from hexanes to give compound 4 (0.32 g, 56%).

Stopnja štiri: Spojino 4 (0,32 g, 1,3 mmol) raztopimo v ledoctu-(4,5 ml) in obdelamo s kalijevim jodidom (0,65 g, 3,9 mmol). Dobljeno zmes segrevamo v oljni kopeli, regulirani pri 115 °C, 1 uro. Zmes ohladimo, razredčimo z vodo in naravnamo na pH 6 ob uporabi 2N NaOH in 2N HC1. Zmes ekstrahiramo s kloroformom (4-krat). Združene ekstrakte izperemo z vodnim natrijevim tiosulfatom, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 5 (0,25 g, 86 %) kot belo trdno snov. Ta material uporabimo brez nadaljnjega čiščenja.Step four: Dissolve compound 4 (0.32 g, 1.3 mmol) in ice-cold (4.5 ml) and treat with potassium iodide (0.65 g, 3.9 mmol). The resulting mixture was heated in an oil bath regulated at 115 ° C for 1 hour. The mixture was cooled, diluted with water and adjusted to pH 6 using 2N NaOH and 2N HCl. The mixture was extracted with chloroform (4 times). The combined extracts were washed with aqueous sodium thiosulphate, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give compound 5 (0.25 g, 86%) as a white solid. Use this material without further purification.

Stopnja pet: Spojino 5 (0,25 g, 1,1 mmol) raztopimo v THF (45 ml) in obdelamo po kapljicah z raztopino kalijevega bis(trimetilsilil)amida (0,5 M v toluenu, 2,7 ml) pri 0 °C. Dobljeno raztopino obdelamo z 2-klorobenzilbromidom (0,16 ml, 1,2 mmol) in raztopino pustimo ogreti na sobno temperaturo preko noči. Zmes porazdelimo med 2N HC1 in etil acetat. Organski sloj izperemo s slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s kromatografijo (SiO2, gradientna elucija 4:1, ki se preklopi na 2:1 heksani:etil acetat), da dobimo spojino 6 (0,16 g, 41 %).Step Five: Compound 5 (0.25 g, 1.1 mmol) was dissolved in THF (45 ml) and treated dropwise with a solution of potassium bis (trimethylsilyl) amide (0.5 M in toluene, 2.7 ml) at 0 ° C. The resulting solution was treated with 2-chlorobenzyl bromide (0.16 ml, 1.2 mmol) and the solution allowed to warm to room temperature overnight. The mixture was partitioned between 2N HCl and ethyl acetate. The organic layer was washed with brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography (SiO 2 , gradient elution 4: 1, which was switched to 2: 1 hexanes: ethyl acetate) to give compound 6 (0.16 g, 41%).

-8787-8787

Stopnja šest: Spojino 6 (0,16 g, 0,46 mmol) suspendiramo v 1:1 vodi koncentrirani HC1 (4,6 ml). Suspenzijo 4 ure spravljamo do refluksa, v tem času pa se spojina raztopi. Zmes ohladimo, razredčimo z vodo in ekstrahiramo z dietil etrom. Vodni sloj naravnamo bazično s prebitno raztopino nasičenega natrijevega bikarbonata in zmes ekstrahiramo z etil acetatom. Ekstrakte združimo, izperemo s slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 7 (0,081 g, 67 %).Step Six: Compound 6 (0.16 g, 0.46 mmol) was suspended in 1: 1 water concentrated HCl (4.6 mL). The suspension was refluxed for 4 hours, during which time the compound dissolved. The mixture was cooled, diluted with water and extracted with diethyl ether. The aqueous layer was made basic with an excess of saturated sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The extracts were combined, washed with brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give compound 7 (0.081 g, 67%).

Stopnja sedem: Spojino 7 (0,080 g, 0,30 mmol) raztopimo v 1,2-dikloroetanu (1,2 ml) in DIPEA (0,115 ml, 0,66 mmol) in ohladimo na 0 °C. Mrzlo raztopino hitro obdelamo z raztopino fosgena (1,93 M v toluenu, 0,170 ml, 0,33 mmol). Po 30 minutah hitro dodamo preko brizge raztopino spojine 8 (0,068 g, 0,33 mmol) v 1,2-dikloroetanu (0,5 ml). Dobljeno zmes segrevamo na 55 °C 1 uro. Zmes porazdelimo med diklorometan in 2N HC1. Organski sloj izperemo z nasičenim vodnim NaHCO3 in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo, da dobimo spojino 9 (0,110 g, 74 %).Step seven: Compound 7 (0.080 g, 0.30 mmol) was dissolved in 1,2-dichloroethane (1.2 ml) and DIPEA (0.115 ml, 0.66 mmol) and cooled to 0 ° C. The cold solution was quickly treated with a phosgene solution (1.93 M in toluene, 0.170 ml, 0.33 mmol). After 30 minutes, a solution of compound 8 (0.068 g, 0.33 mmol) in 1,2-dichloroethane (0.5 ml) was rapidly added via syringe. The resulting mixture was heated to 55 ° C for 1 hour. The mixture was partitioned between dichloromethane and 2N HCl. The organic layer was washed with saturated aqueous NaHCO 3 and brine, dried over MgSO 4 and filtered. The filtrate was concentrated to give compound 9 (0.110 g, 74%).

Stopnja osem: Spojino 9 (0,11 g, 0,22 mmol) raztopimo v 2:1 THF:H2O (0,88 ml) in obdelamo z raztopino 2N NaOH (0,33 ml). Metanol dodajamo po kapljicah, dokler ne dobimo homogene raztopine. Zmes mešamo 20 minut, razredčimo z vodo in izperemo z etil etrom. Vodni sloj nakisamo z 2N HC1 in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo s slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo, da dobimo (3S)-3-{[({l-[(2-klorofenil)metil]-4-etil-2-okso-l,2dihidro-3-piridinil} amino)karbonil]amino} -3-(4-metilfenil)propanojsko kislino (10, 0,095 g, 92 %).Step Eight: Compound 9 (0.11 g, 0.22 mmol) was dissolved in 2: 1 THF: H 2 O (0.88 ml) and treated with a solution of 2N NaOH (0.33 ml). Methanol was added dropwise until a homogeneous solution was obtained. The mixture was stirred for 20 minutes, diluted with water and washed with ethyl ether. The aqueous layer was acidified with 2N HCl and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over MgSO 4 and filtered. The filtrate was concentrated to give (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-ethyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3 - (4-methylphenyl) propanoic acid (10, 0.095 g, 92%).

Primer 2Example 2

Sinteza (3 S)-3- {[({6-metil-2-okso-1 -(fenilmetil)-4-[fenilmetil)oksi]-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojske kisline (15)Synthesis of (3S) -3- {[({6-methyl-2-oxo-1- (phenylmethyl) -4- [phenylmethyl) oxy] -1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - (4-methylphenyl) propanoic acid (15)

-8888-8888

Stopnja ena: K suspenziji spojine 11 (1,0 g, 5,9 mmol) in K2CO3 (2,40 g, 17,6 mmol) v acetonu (50 ml) dodamo benzilbromid (2,31 g, 13,5 mmol). Po refluktiranju preko noči reakcijsko zmes ohladimo in zmes porazdelimo med etil acetat in nasičen NaHCO3. Organski sloj izperemo z razredčeno HC1 in slanico, sušimo nad MgSO4, filtriramo in filtrat koncentriramo, da dobimo spojino 12 (1,60 g, 80 %).Step One: To a suspension of compound 11 (1.0 g, 5.9 mmol) and K 2 CO 3 (2.40 g, 17.6 mmol) in acetone (50 ml) was added benzyl bromide (2.31 g, 13. 5 mmol). After refluxing overnight, the reaction mixture was cooled and the mixture partitioned between ethyl acetate and saturated NaHCO 3 . The organic layer was washed with dilute HCl and brine, dried over MgSO 4 , filtered and the filtrate was concentrated to give compound 12 (1.60 g, 80%).

Stopnja dve: Spojino 12 (0,30 g, 0,86 mmol), cinkov prah (0,30 g, 4,6 mmol) in nasičeni vodni NH4C1 (0,30 ml) zamešamo v MeOH (18 ml). To zmes pustimo mešati 1 uro pri sobni temperaturi, preden dodamo dodatni cink (0,30 g, 4,6 mmol). Dobljeno heterogeno zmes refluktiramo preko noči. Po filtracijo vroče zmesi in koncentriranju filtrata pod zmanjšanim tlakom ostanek raztopimo v etil acetatu, izperemo z nasičenim vodnim NaHCO3 in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 13 (0,18 g, 66 %).Step two: Compound 12 (0.30 g, 0.86 mmol), zinc powder (0.30 g, 4.6 mmol) and saturated aqueous NH 4 Cl (0.30 mL) were mixed in MeOH (18 mL). This mixture was allowed to stir at room temperature for 1 hour before additional zinc (0.30 g, 4.6 mmol) was added. The resulting heterogeneous mixture was refluxed overnight. After filtration of the hot mixture and concentration of the filtrate under reduced pressure, the residue was dissolved in ethyl acetate, washed with saturated aqueous NaHCO 3 and brine. The organic layer was dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give compound 13 (0.18 g, 66%).

Stopnja tri: Spojino 13 (0,30 g, 0,94 mmol) in DIPEA (0,40 ml, 2,3 mmol) raztopimo v CH2C12 in zmes ohladimo na 0 °C. K raztopini po kapljicah dodamo fosgen (1,9 M v toluenu, 0,55 ml, 1,0 mmol). Reakcijsko zmes mešamo pri 0 °C 15 minut, preden dodamo spojino 8 (0,19 g, 0,94 mmol) v CH2C12 (2 ml). Dobljeno raztopino mešamo pri sobni temperaturi preko noči, nato zlijemo v etil acetat ter izperemo z nasičenim vodnim NaHCO3, 1 N HC1 in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s flash kromatografijo na silikagelu ob eluiranju z 1:1, ki narašča do 1:2, heksani:etil acetatom, da dobimo spojino 14 (0,33 g, 64 %).Step Three: Dissolve compound 13 (0.30 g, 0.94 mmol) and DIPEA (0.40 mL, 2.3 mmol) in CH 2 Cl 2 and cool the mixture to 0 ° C. Phosgene (1.9 M in toluene, 0.55 ml, 1.0 mmol) was added dropwise to the solution. The reaction mixture was stirred at 0 ° C for 15 minutes before adding compound 8 (0.19 g, 0.94 mmol) in CH 2 Cl 2 (2 ml). The resulting solution was stirred at room temperature overnight, then poured into ethyl acetate and washed with saturated aqueous NaHCO 3 , 1 N HCl and brine. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with 1: 1 increasing to 1: 2 hexanes: ethyl acetate to give compound 14 (0.33 g, 64%).

Stopnja štiri: Raztopino spojine 14 (0,33 g, 0,6 mmol) v THF (6 ml) obdelamo z 2N NaOH (2 ml). Dodajamo MeOH, dokler ne dobimo homogene raztopine. Reakcijsko zmes mešamo 30 minut pri sobni temperaturi in zlijemo v H2O (50 ml). Vodni sloj izperemo z dietil etrom (2-krat) in nato nakisamo z IN HC1. Vodni sloj ekstrahiramo z etil acetatom (2-krat). Združene etil acetatne ekstrakte speremo s slanico (2-krat), sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-{[({6-metil-2-okso-l-(fenilmetil)-4-[(fenilmetil)oksi]-l,2-dihidro-3-8989 piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino (15, 0,26 g, 90 %) kot umazano belo trdno snov. Tal.: 124-126 °C.Step four: A solution of compound 14 (0.33 g, 0.6 mmol) in THF (6 mL) was treated with 2N NaOH (2 mL). MeOH was added until a homogeneous solution was obtained. The reaction mixture was stirred for 30 minutes at room temperature and poured into H 2 O (50 ml). The aqueous layer was washed with diethyl ether (2 times) and then acidified with 1N HCl. The aqueous layer was extracted with ethyl acetate (2 times). The combined ethyl acetate extracts were washed with brine (2 times), dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - {[({6-methyl-2-oxo-1- (phenylmethyl) -4 - [(phenylmethyl) oxy] -1,2-dihydro-3-8989 pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid (15, 0.26 g, 90%) as a dirty white solid. Mp: 124-126 ° C.

Primer 3Example 3

Sinteza (3S)-3-{[({4-amino-l-[(2-klorofenil)metil]-6-metil-2-okso-l,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojske kisline (22)Synthesis of (3S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] -6-methyl-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3 - (4-methylphenyl) propanoic acid (22)

Stopnja ena: K raztopini spojine 11 (10,00 g, 58,8 mmol) v brezvodnem DMF (120 ml) dodamo pri 0 “C NaH (60 % disperzija v mineralnem olju, 5,40 g, 135 mmol). Zmes mešamo pri 0 °C 15 minut pred dodatkom 2-klorobenzilklorida (12,3 g, 76,4 mmol). Po mešanju pri 55 °C preko noči zmes zlijemo v led-vodo in 2-krat izperemo z Et2O. Vodni sloj nakisamo in s filtriranjem dobljene oborine dobimo spojino 16 (14,7 g, 85 %).Step One: To a solution of Compound 11 (10.00 g, 58.8 mmol) in anhydrous DMF (120 mL) was added at 0 “C NaH (60% dispersion in mineral oil, 5.40 g, 135 mmol). The mixture was stirred at 0 ° C for 15 minutes before the addition of 2-chlorobenzyl chloride (12.3 g, 76.4 mmol). After stirring at 55 ° C overnight, the mixture was poured into ice-water and washed twice with Et 2 O. The aqueous layer was acidified and filtration of the resulting precipitate yielded compound 16 (14.7 g, 85%).

Stopnja dve: V bučo, ki vsebuje spojino 16 (8,00 g, 28,6 mmol), zaprto z gumijevim prekatom in balonom, pri sobni temperaturi pod atmosfero suhega dušika dodamo preko brizge POCI3 (30,0 ml, 322 mmol). Dušikov vod odstranimo in reakcijsko zmes mešamo preko noči pri 70 °C, nato zlijemo preko ledu (300 ml) in mešamo 30 minut. Dobljeno zmes ekstrahiramo z diklorometanom (300 ml), organsko fazo sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 17 (7,3 g, 86 %) kot temno rjavo trdno snov.Step two: To a flask containing compound 16 (8.00 g, 28.6 mmol) sealed with a rubber compartment and a balloon was added at room temperature under a dry nitrogen atmosphere via a POCI3 syringe (30.0 mL, 322 mmol). The nitrogen water was removed and the reaction was stirred overnight at 70 ° C, then poured over ice (300 ml) and stirred for 30 minutes. The resulting mixture was extracted with dichloromethane (300 ml), the organic phase was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give compound 17 (7.3 g, 86%) as a dark brown solid.

Stopnja tri: V 250 ml bučo, opremljeno s hladilnikom in gumijevim prekatom, opremljenim z balonom, dodamo pri sobni temperaturi raztopino spojine 17 (2,1 g, 7,05 mmol), metanola (55 ml) in vodnega amonijevega hidroksida (28-30 %, 70,0 ml,Step Three: A solution of compound 17 (2.1 g, 7.05 mmol), methanol (55 ml) and aqueous ammonium hydroxide (28-) was added to a 250 ml flask equipped with a refrigerator and a balloon-equipped rubber compartment. 30%, 70.0 ml,

1,14 mol). Reakcijsko zmes segrevamo 60 ur na 65 °C, odprto le v balon. Zmes filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 18 (1,5 g, 76 %) kot rjavo trdno snov.1.14 mol). The reaction mixture was heated to 65 [deg.] C. for 60 hours, open only to the balloon. The mixture was filtered and the filtrate was concentrated under reduced pressure to give compound 18 (1.5 g, 76%) as a brown solid.

Stopnja štiri: K raztopini spojine 18 (0,3 g, 1,02 mmol) v metanolu (50 ml) pri sobni temperaturi zaporedoma dodamo nasičeni vodni amonijev klorid (2 ml) in cinkov prahStep four: To a solution of compound 18 (0.3 g, 1.02 mmol) in methanol (50 ml) at room temperature was added successively saturated aqueous ammonium chloride (2 ml) and zinc powder

-9090 (0,30 g, 4,6 mmol). Po mešanju 30 minut pri sobni temperaturi dodamo dodatni cink (0,30 g, 4,6 mmol) in reakcijsko zmes refluktiramo preko noči. Reakcijsko zmes vroče filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek porazdelimo med etil acetat in IN NaOH. Raztopino filtriramo in vodno fazo ekstrahiramo z etil acetatom. Združene organske faze sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 19 (0,21 g, 78 %) kot rjavo trdno snov.-9090 (0.30 g, 4.6 mmol). After stirring for 30 minutes at room temperature, additional zinc (0.30 g, 4.6 mmol) was added and the reaction was refluxed overnight. The reaction mixture was hot filtered and the filtrate was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and 1N NaOH. The solution was filtered and the aqueous phase extracted with ethyl acetate. The combined organic phases were dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to give compound 19 (0.21 g, 78%) as a brown solid.

Stopnja pet: Raztopino spojine 19 (0,10 g, 0,38 mmol), NMM (0,040 ml, 0,38 mmol) in spojine 20 (0,14 g, 0,38 mmol) v brezvodnem DMF (5 ml) segrevamo na 50 °C preko noči. Zmes ohladimo in razredčimo z etil acetatom (60 ml). Organski sloj izperemo z 0,5N NaOH (3 x 30 ml) in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s flash kromatografijo na silikagelu ob eluiranju z 9:1, ki naraste do 17:3 CHCl3:MeOH, da dobimo spojino 21 (0,120 g, 65 %) kot rumeno peno.Step Five: A solution of compound 19 (0.10 g, 0.38 mmol), NMM (0.040 mL, 0.38 mmol) and compound 20 (0.14 g, 0.38 mmol) in anhydrous DMF (5 mL) was heated. at 50 ° C overnight. The mixture was cooled and diluted with ethyl acetate (60 ml). The organic layer was washed with 0.5N NaOH (3 x 30 ml) and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue purified by flash chromatography on silica gel eluting with 9: 1 increasing to 17: 3 CHCl 3 : MeOH to give compound 21 (0.120 g, 65%) as a yellow foam.

Stopnja šest: Raztopino spojine 21 (0,120 g, 0,25 mmol) v THF (6 ml) obdelamo z 2N NaOH (2 ml). Dodajamo metanol, dokler ne dobimo homogene raztopine. Reakcijsko zmes mešamo 30 minut pri sobni temperaturi in zlijemo v H2O (50 ml). Vodni sloj izperemo z dietil etrom (2-krat) in nato nakisamo z IN HC1. Vodni sloj ekstrahiramo z etil acetatom (2-krat). Združene etil acetatne ekstrakte izperemo s slanico (2-krat), sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-{ [((4-amino-1 -[(2-klorofeniI)metil]-6-metil-2-okso-1,2-dihidro-3piridinil}amino)-karbonil]amino}-3-(4-metilfenil)propanojsko kislino (22, 0,100 g, 89 %) kot umazano belo trdno snov, tal.: 145-147 °C.Step Six: A solution of compound 21 (0.120 g, 0.25 mmol) in THF (6 mL) was treated with 2N NaOH (2 mL). Methanol is added until a homogeneous solution is obtained. The reaction mixture was stirred for 30 minutes at room temperature and poured into H 2 O (50 ml). The aqueous layer was washed with diethyl ether (2 times) and then acidified with 1N HCl. The aqueous layer was extracted with ethyl acetate (2 times). The combined ethyl acetate extracts were washed with brine (2 times), dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3- {[((4-amino-1 - [(2-chlorophenyl) methyl] -6-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) ) -carbonyl] amino} -3- (4-methylphenyl) propanoic acid (22, 0.100 g, 89%) as a dirty white solid, mp: 145-147 ° C.

Primer 4Example 4

Sinteza (3S)-3-[({[l-[(2-klorofenil)metil]-4-(metiloksi)-2-okso-l,2-dihidro3 -piridini 1] amino} karbonil)amino] -3 -(4-metilfeni l)propanoj ske kislineSynthesis of (3S) -3 - [({[1 - [(2-chlorophenyl) methyl] -4- (methyloxy) -2-oxo-1,2-dihydro3-pyridines 1] amino} carbonyl) amino] -3 - (4-methylphenyl) propanoic acid

-9191-9191

Stopnja ena: K raztopini spojine 23 (10,00 g, 64,0 mmol) v brezvodnem DMF (130 ml) pri 0 °C dodamo NaH (60 % disperzija v mineralnem olju, 5,90 g, 147 mmol). Zmes mešamo pri 0 °C 15 minut pred dodatkom 2-klorobenzilklorida (13,4 g, 83,3 mmol). Po mešanju pri 55 °C preko noči zmes zlijemo v ledeno vodo in izperemo z Et2O (2-krat). Vodni sloj nakisamo in s filtriranjem dobljene oborine dobimo spojino 24(13,5 g, 75%).Step One: To a solution of compound 23 (10.00 g, 64.0 mmol) in anhydrous DMF (130 ml) at 0 ° C was added NaH (60% dispersion in mineral oil, 5.90 g, 147 mmol). The mixture was stirred at 0 ° C for 15 minutes before the addition of 2-chlorobenzyl chloride (13.4 g, 83.3 mmol). After stirring at 55 ° C overnight, the mixture was poured into ice water and washed with Et 2 O (2 times). The aqueous layer was acidified and filtration of the precipitate obtained gave compound 24 (13.5 g, 75%).

Stopnja dve: Suspenzijo spojine 24 (1,0 g, 3,6 mmol), K2CO3 (0,85 g, 6,2 mmol) in Mel (1,18 g, 8,3 mmol) v acetonu (20 ml) refluktiramo preko noči. Reakcijsko zmes razredčimo z etil acetatom ter izperemo z nasičenim vodnim NaHCO3, IN HC1 in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 25 (0,74 g, 70 %).Step Two: Suspension of compound 24 (1.0 g, 3.6 mmol), K 2 CO 3 (0.85 g, 6.2 mmol) and Mel (1.18 g, 8.3 mmol) in acetone (20 ml) is refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous NaHCO 3 , 1N HCl and brine. The organic layer was dried over MgSO 4 , filtered and the filtrate was concentrated under reduced pressure to give compound 25 (0.74 g, 70%).

(3 S)-3 -[({[ 1 -[(2-klorofenil)metil]-4-(metiloksi)-2-okso-1,2-dihidro3-piridinil]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 25 po postopkih, opisanih v primeru 3. MS: izrač.: (M+H)+ = 469,93; ugot.: (M+H)+ = 470,01.(3 S) -3 - [({[1 - [(2-chlorophenyl) methyl] -4- (methyloxy) -2-oxo-1,2-dihydro3-pyridinyl] amino} carbonyl) amino] -3- ( 4-Methylphenyl) propanoic acid was prepared from compound 25 according to the procedures described in Example 3. MS: Calc .: (M + H) + = 469.93; found: (M + H) + = 470.01.

Primer 5Example 5

Sinteza (3S)-3-[{({l-[(2-klorofenil)metil]-4-fluoro-2-okso-l,2-dihidro3 -piridinil} amino)karbonil] amino} -3-(4-metilfenil)propanoj ske kislineSynthesis of (3S) -3 - [{({1 - [(2-chlorophenyl) methyl] -4-fluoro-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid

Stopnja ena: Spojino 3 (0,65 g, 3,1 mmol) raztopimo v suhem THF (12,4 ml) in TMEDA (0,90 ml, 6 mmol) pod atmosfero suhega dušika. Dobljeno raztopino ohladimo na med -15 in -10 °C ter po kapljicah preko brizge dodamo n-butillitij (1,6 M v heksanih, 7,75 ml, 12,4 mmol). Po 1,5 urah dodamo k hladni raztopini hitro preko brizge raztopino N-fluorobenzensulfonimida (1,07 g, 3,4 mmol) v THF (5 ml). Raztopino mešamo 1 uro pri 0 °C, nato pri sobni temperaturi 3 ure. Zmes pogasimo z vodo in ekstrahiramo s kloroformom (4-krat). Združene organske ekstrakte izperemo s slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanimStep One: Compound 3 (0.65 g, 3.1 mmol) was dissolved in dry THF (12.4 ml) and TMEDA (0.90 ml, 6 mmol) under a dry nitrogen atmosphere. The resulting solution was cooled to between -15 and -10 ° C and n-butyllithium (1.6 M in hexanes, 7.75 ml, 12.4 mmol) was added dropwise via syringe. After 1.5 hours, a solution of N-fluorobenzenesulfonamide (1.07 g, 3.4 mmol) in THF (5 ml) was added rapidly to the cold solution via a syringe. The solution was stirred for 1 hour at 0 ° C, then at room temperature for 3 hours. The mixture was quenched with water and extracted with chloroform (4 times). The combined organic extracts were washed with brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure

-9292 tlakom in ostanek čistimo s kromatografijo (SiO2, zamašilni gel, ob uporabi 4:1, ki preklopi na 3:1, heksanov:etil acetata), da dobimo spojino 26 (0,177 g, 25 %).The -9292 pressure and the residue were purified by chromatography (SiO 2 , stopper gel using 4: 1 switching to 3: 1, hexanes: ethyl acetate) to give compound 26 (0.177 g, 25%).

(3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-fluoro-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 26 po postopkih, opisanih v primeru 1. MS: izrač.: (M+H)+= 458,12; ugot.: (M+H)+ = 458,01.(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-fluoro-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid was prepared from compound 26 according to the procedures described in Example 1. MS: calc .: (M + H) + = 458.12; found: (M + H) + = 458.01.

Primer 6Example 6

Sinteza (3 S)-4-kloro-3 - {[({1 - [(2-klorofenil)metil]-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojske kislineSynthesis of (3S) -4-chloro-3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4 -methylphenyl) propanoic acid

Stopnja ena: Spojino 3 (0,65 g, 3,1 mmol) raztopimo v THF (21 ml) in TMEDA (1,20 ml, 7,75 mmol) in ohladimo na -15 °C. Raztopino obdelamo z n-butillitijem (1,6 M v heksanih, 4,8 ml, 7,8 mmol). Zmes vzdržujemo med -20 in -10 °C 1 uro, nato ohladimo na -78 °C. Trden N-klorosukcinimid (0,45 g, 3,4 mmol) dodamo, medtem ko je aparat pod pozitivnim tokom dušika. Reakcijsko zmes pustimo, da se postopoma ogreje do sobne temperature, nato mešamo preko noči. Zmes pogasimo z vodo in ekstrahiramo s kloroformom (4-krat). Organske sloje združimo, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek prekristaliziramo iz heksanov, da dobimo spojino 27 (0,25 g, 33 %).Step One: Compound 3 (0.65 g, 3.1 mmol) was dissolved in THF (21 ml) and TMEDA (1.20 ml, 7.75 mmol) and cooled to -15 ° C. The solution was treated with n-butyllithium (1.6 M in hexanes, 4.8 ml, 7.8 mmol). The mixture was maintained between -20 and -10 ° C for 1 hour, then cooled to -78 ° C. Solid N-chlorosuccinimide (0.45 g, 3.4 mmol) was added while the apparatus was under a positive stream of nitrogen. The reaction mixture was allowed to gradually warm to room temperature, then stirred overnight. The mixture was quenched with water and extracted with chloroform (4 times). The organic layers were combined, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was recrystallized from hexanes to give compound 27 (0.25 g, 33%).

(3S)-4-kloro-3-{ [({l-[(2-klorofenil)metil]-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 27 po postopkih, opisanih v primeru 1.(3S) -4-chloro-3- {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid is prepared from compound 27 according to the procedures described in Example 1.

Primer 7Example 7

Sinteza (3 S)-4-bromo-3 - {[( {1 - [(2-klorofenil)metil] -2-okso-1,2-dihidro3 -piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ske kislineSynthesis of (3S) -4-bromo-3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3 - (4 -methylphenyl) propanoic acid

-9393-9393

Stopnja ena: Spojino 3 (2,00 g, 9,6 mmol) raztopimo v suhem THF (32 ml) in TMEDA (2,20 ml, 14,4 mmol) pod atmosfero suhega dušika. Dobljeno raztopino ohladimo na med -20 in -10 °C in po kapljicah dodamo preko brizge n-butil litij (1,60 M v heksanih, 18,0 ml, 28,8 mmol). Po končanem dodajanju raztopino ohladimo na 78 °C in po kapljicah preko brizge dodamo brom (0,49 ml, 10,5 mmol). Raztopino pustimo počasi ogreti na sobno temperaturo preko noči, nato pogasimo z vodo in ekstrahiramo s kloroformom. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek prekristaliziramo iz heksanov, da dobimo spojino 28 (1,32 g, 48 %) kot rjavkasto belo trdno snov.Step One: Compound 3 (2.00 g, 9.6 mmol) was dissolved in dry THF (32 ml) and TMEDA (2.20 ml, 14.4 mmol) under a dry nitrogen atmosphere. The resulting solution was cooled to between -20 and -10 ° C and n-butyl lithium (1.60 M in hexanes, 18.0 ml, 28.8 mmol) was added dropwise via syringe. After complete addition, the solution was cooled to 78 ° C and bromine (0.49 ml, 10.5 mmol) was added dropwise via syringe. The solution was slowly warmed to room temperature overnight, then quenched with water and extracted with chloroform. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from hexanes to give compound 28 (1.32 g, 48%) as a brownish white solid.

(3 S)-4-bromo-3 - {[({1 - [(2-klorofenil)metil]-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 28 po postopkih, opisanih v primeru 1.(3 S) -4-Bromo-3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid is prepared from compound 28 according to the procedures described in Example 1.

Primer 8Example 8

Sinteza (3 S)-3- {[({1 - [(2-klorofenil)metil] -4-hidroksi-2-okso-1,2dihidro-3 -piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ske kisline (32)Synthesis of (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3 - (4 -methylphenyl) propionic acid (32)

Stopnja ena: K raztopini spojine 24 (1,5 g, 5,3 mmol) v metanolu (50 ml) pri sobni temperaturi zaporedoma dodamo nasičen amonijev klorid (1,5 ml) in cinkov prah (1,5 g, 23 mmol). Po mešanju 30 minut pri sobni temperaturi dodamo dodaten cinkov prah (1,5 g, 23 mmol) in reakcijsko zmes refluktiramo preko noči. Reakcijsko zmes filtriramo, ko je vroča, in filtrat koncentriramo pod zmanjšanim tlakom. Dobljenemu ostanku dodajamo HC1 (IN), dokler pH ni približno 4, in dobljeno oborino zberemo s filtriranjem, da dobimo spojino 29 (0,80 g, 57 %) kot rjavo trdno snov.Step One: To a solution of Compound 24 (1.5 g, 5.3 mmol) in methanol (50 ml) at room temperature was added successively saturated ammonium chloride (1.5 ml) and zinc powder (1.5 g, 23 mmol). . After stirring for 30 minutes at room temperature, additional zinc powder (1.5 g, 23 mmol) was added and the reaction was refluxed overnight. The reaction mixture was filtered when hot and the filtrate was concentrated under reduced pressure. HCl (IN) was added to the resulting residue until the pH was about 4, and the resulting precipitate was collected by filtration to give compound 29 (0.80 g, 57%) as a brown solid.

Stopnja dve: Raztopino spojine 29 (0,26 g, 1,0 mmol) in CDI (0,25 g, 1,6 mmol) v DMF (10 ml) segrevamo na 70 °C preko noči. Po ohlajenju na sobno temperaturo zmes razredčimo z etil acetatom ter izperemo z IN HC1 (3-krat) in slanico. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 30 (0,14 g, 50 %) kot rjavo trdno snov.Step Two: A solution of Compound 29 (0.26 g, 1.0 mmol) and CDI (0.25 g, 1.6 mmol) in DMF (10 ml) was heated to 70 ° C overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with 1N HCl (3 times) and brine. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give compound 30 (0.14 g, 50%) as a brown solid.

-9494-9494

Stopnja tri: Raztopino spojine 30 (0,1 g, 0,36 mmol) in spojine 8 (0,082 g, 0,40 mmol) v brezvodnem DMF (5 ml) segrevamo preko noči na 70 °C. Zmes ohladimo, razredčimo z etil acetatom in izperemo z IN HC1 (3-krat) in slanico. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s flash kromatografijo (SiO2), z eluiranjem z 9:1 CHCl3:MeOH, da dobimo spojino 31 (0,17 g, 97 %).Step Three: A solution of compound 30 (0.1 g, 0.36 mmol) and compound 8 (0.082 g, 0.40 mmol) in anhydrous DMF (5 ml) was heated overnight at 70 ° C. The mixture was cooled, diluted with ethyl acetate and washed with 1N HCl (3 times) and brine. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (SiO 2 ) eluting with 9: 1 CHCl 3 : MeOH to give compound 31 (0.17 g, 97%).

Stopnja štiri: Raztopino spojine 31 (0,170 g, 0,35 mmol) v THF (3 ml) obdelamo z 2N NaOH (1 ml). Dodajamo metanol, dokler ne dobimo homogene raztopine. Reakcijsko zmes mešamo 30 minut pri sobni temperaturi in zlijemo v H2O (50 ml). Vodni sloj izperemo z dietil etrom (2-krat) in nato nakisamo z IN HC1. Vodni sloj ekstrahiramo z etil acetatom (2-krat). Združene etil acetatne ekstrakte izperemo s slanico (2-krat), sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-l,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino (32, 0,150 g, 94 %) kot umazano belo trdno snov. Tal.: 113-115 °C.Step four: A solution of compound 31 (0.170 g, 0.35 mmol) in THF (3 mL) was treated with 2N NaOH (1 mL). Methanol is added until a homogeneous solution is obtained. The reaction mixture was stirred for 30 minutes at room temperature and poured into H 2 O (50 ml). The aqueous layer was washed with diethyl ether (2 times) and then acidified with 1N HCl. The aqueous layer was extracted with ethyl acetate (2 times). The combined ethyl acetate extracts were washed with brine (2 times), dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino } -3- (4-methylphenyl) propanoic acid (32, 0.150 g, 94%) as a dirty white solid. Melting point: 113-115 ° C.

Primer 9Example 9

Sinteza (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso-4-fenil-l,2-dihidro3 -piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ske kislineSynthesis of (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-4-phenyl-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid

Stopnja ena: Spojino 33 (pripravljeno iz spojine 28 po postopkih, opisanih v primeru 1, 0,20 g, 0,50 mmol) raztopimo v DMF (1,8 ml) in vodi (0,7 ml) ter obdelamo s K3PO4 (0,39 g, 1,86 mmol) in fenilboronsko kislino (0,113 g, 0,93 mmol). Dobljeno zmes deoksigeniramo (preklapljanje med vakuumom in dušikom 5-krat), nato dodamo tetrakis(trifenilfosfin)paladij(0) (8,7 mg, 0,050 mmol). Zmes deoksigeniramo kot prej in segrevamo preko noči pri 90 °C. Zmes ohladimo, razredčimo z vodo in ekstrahiramo z etil acetatom (2-krat). Združene ekstrakte izperemo s slanico, sušimo nad MgSO4 in filtriramo skozi silikagel ter koncentriramo pod zmanjšanim tlakom. Ostanek suspendiramo v 1:1 vodi koncentrirani HC1 (2 ml) in acetonitrilu (0,5 ml).Step One: Compound 33 (prepared from compound 28 according to the procedures described in Example 1, 0.20 g, 0.50 mmol) was dissolved in DMF (1.8 ml) and water (0.7 ml) and treated with K 3 PO 4 (0.39 g, 1.86 mmol) and phenylboronic acid (0.113 g, 0.93 mmol). The resulting mixture was deoxygenated (switching between vacuum and nitrogen 5 times), then tetrakis (triphenylphosphine) palladium (0) (8.7 mg, 0.050 mmol) was added. The mixture was deoxygenated as before and heated overnight at 90 ° C. The mixture was cooled, diluted with water and extracted with ethyl acetate (2 times). The combined extracts were washed with brine, dried over MgSO 4 and filtered through silica gel and concentrated under reduced pressure. The residue was suspended in 1: 1 water concentrated HCl (2 ml) and acetonitrile (0.5 ml).

-9595-9595

Suspenzijo spravljamo do refluksa 1 uro, nato ohladimo in porazdelimo med etil acetat in nasičen vodni NaHCO3. Etil acetatni sloj izperemo s slanico, sušimo nad MgSO4, filtriramo in koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s flash kromatografijo (SiO2, 3:1 heksani/etil acetat), da dobimo spojino 34 (0,115 g, 94 %). Ta material uporabimo brez čiščenja.The suspension was refluxed for 1 hour, then cooled and partitioned between ethyl acetate and saturated aqueous NaHCO 3 . The ethyl acetate layer was washed with brine, dried over MgSO 4 , filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO 2 , 3: 1 hexanes / ethyl acetate) to give compound 34 (0.115 g, 94%). Use this material without cleaning.

(3 S)-3 - {[( {1 - [(2-klorofenil)metil] -2-okso-4-fenil-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 34 po postopkih, opisanih v primeru 1. !H NMR (400 MHz, CD3OD): δ 2,25 (s, 3H), 2,50 (m, 2H), 4,89 (t, J = 5,9 Hz, IH), 5,34 (s, 2H), 6,40 (d, J = 7,0 Hz, IH), 7,0 (d, J - 8,0 Hz, 2H), 7,10 (d, J = 8,0 Hz, 2H), 7,18 (m, IH), 7,28 (m, 2H), 7,35 (m, 3H), 7,43 (m, IH), 7,49 (m, 3H).(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-4-phenyl-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid was prepared from compound 34 according to the procedures described in Example 1. ! H NMR (400 MHz, CD 3 OD): δ 2.25 (s, 3H), 2.50 (m, 2H), 4.89 (t, J = 5.9 Hz, 1H), 5.34 ( s, 2H), 6.40 (d, J = 7.0 Hz, 1H), 7.0 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 7.18 (m, 1H), 7.28 (m, 2H), 7.35 (m, 3H), 7.43 (m, 1H), 7.49 (m, 3H).

Primer 10Example 10

Sinteza (3 S)-3-[( {[2-metil]-4-(2-metilpropil)-6-okso-1 -(fenilmetil)-1,6dihidro-5-pirimidinil]amino}karbonil)amino]-3-(4-metilfenil)ptopanojske kisline (43)Synthesis of (3S) -3 - [({[2-methyl] -4- (2-methylpropyl) -6-oxo-1- (phenylmethyl) -1,6-dihydro-5-pyrimidinyl] amino} carbonyl) amino] - 3- (4-Methylphenyl) propanoic acid (43)

Stopnja ena: Spojino 35 (2,00 g, 18,2 mmol) raztopimo v 30 ml suhega metanola. Temu dodamo benzilamin (1,97 g, 18,2 mmol) in trietilamin (2,0 g, 20,0 mmol). Reakcijsko zmes mešamo 3 ure pri 50 °C in nato koncentriramo pod zmanjšanim tlakom. Ostanek porazdelimo med H2O in CH2C12. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 36 (2,3 g, 82 %).Step One: Dissolve compound 35 (2.00 g, 18.2 mmol) in 30 ml of dry methanol. To this were added benzylamine (1.97 g, 18.2 mmol) and triethylamine (2.0 g, 20.0 mmol). The reaction mixture was stirred for 3 hours at 50 ° C and then concentrated under reduced pressure. The residue is partitioned between H 2 O and CH 2 C1 2 . The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give compound 36 (2.3 g, 82%).

Stopnja dve: K raztopini spojine 37 (3,50 g, 26,5 mmol) v etanolu (10 ml) in piridinu (5 ml) dodamo izovaleraldehid (2,8 ml, 27 mmol) in piperidin (1 ml). Reakcijsko zmes segrevamo do refluksa 3 ure in koncentriramo pod zmanjšanim tlakom. Ostanek porazdelimo med 2N HC1 (15 ml) in etil acetat (30 ml). Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem z 2:1 heksani:etil acetatom, da dobimo spojino 38 (3,6 g, 67 %).Step Two: Isovaleraldehyde (2.8 ml, 27 mmol) and piperidine (1 ml) were added to a solution of compound 37 (3.50 g, 26.5 mmol) in ethanol (10 ml) and pyridine (5 ml). The reaction mixture was heated to reflux for 3 hours and concentrated under reduced pressure. The residue was partitioned between 2N HCl (15 ml) and ethyl acetate (30 ml). The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 2: 1 hexanes: ethyl acetate to give compound 38 (3.6 g, 67%).

-9696-9696

Stopnja tri: Raztopino spojine 38 (2,5 g, 12,48 mmol) in spojine 36 (2,52 g, 13,7 mmol) v suhem metanolu (25 ml) segrevamo do močnega refluksa 3 ure, ohladimo in koncentriramo pod zmanjšanim tlakom. Ostanek kromatografiramo na silikagelu z eluiranjem z 2:1 heksani:etil acetatom, da dobimo spojino 39 (2,75 g, 69 %).Step Three: A solution of Compound 38 (2.5 g, 12.48 mmol) and Compound 36 (2.52 g, 13.7 mmol) in dry methanol (25 ml) was heated to reflux for 3 hours, cooled and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 2: 1 hexanes: ethyl acetate to give compound 39 (2.75 g, 69%).

Stopnja štiri: K raztopini spojine 39 (2,5 g, 7,9 mmol) v CC14 (15 ml) dodamo NBS (1,4 g, 8,0 mmol), K2CO3 (11,0 g, 80,0 mmol) in benzoil peroksid (50 mg, 0,20 mmol). Reakcijsko zmes segrevamo do refluksa 1 uro, ohladimo na sobno temperaturo, razredčimo s H2O in ekstrahiramo s CH2C12. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek kromatografiramo na silikagelu z eluiranjem s 3:1 heksani:etil acetatom, da dobimo spojino 40 (0,62 g, 25 %).Step four: To a solution of compound 39 (2.5 g, 7.9 mmol) in CC1 4 (15 ml) was added NBS (1.4 g, 8.0 mmol), K2CO3 (11.0 g, 80.0 mmol) ) and benzoyl peroxide (50 mg, 0.20 mmol). The reaction mixture was heated to reflux for 1 hour, cooled to room temperature, diluted with H 2 O and extracted with CH 2 Cl 2 . The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 3: 1 hexanes: ethyl acetate to give compound 40 (0.62 g, 25%).

Stopnja pet: Spojino 40 (0,60 g, 1,9 mmol) obdelamo z 2N NaOH (5 ml) in THF (3 ml). Dobljeno zmes mešamo pri sobni temperaturi 2 uri, nakisamo z 2N HC1 in ekstrahiramo z etil acetatom. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 41 (560 mg, 98 %).Step Five: Compound 40 (0.60 g, 1.9 mmol) was treated with 2N NaOH (5 mL) and THF (3 mL). The resulting mixture was stirred at room temperature for 2 hours, acidified with 2N HCl and extracted with ethyl acetate. The organic layer was dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give compound 41 (560 mg, 98%).

Stopnja šest: K raztopini spojine 41 (0,56 g, 1,86 mmol) v suhem benzenu (10 ml) dodamo difenilfosforilazid (0,56 g, 2,0 mmol) in trietilamin (2,02 g, 2,0 mmol). Reakcijsko zmes segrevamo 1 uro na 90 °C, nato dodamo raztopino spojine 8 (0,39 g,Step Six: To a solution of compound 41 (0.56 g, 1.86 mmol) in dry benzene (10 ml) was added diphenylphosphorylazide (0.56 g, 2.0 mmol) and triethylamine (2.02 g, 2.0 mmol) ). The reaction mixture was heated to 90 ° C for 1 hour, then a solution of compound 8 (0.39 g,

1,9 mmol) v benzenu (2 ml). Reakcijsko zmes mešamo dodatno 1 uro pri 90 °C, ohladimo na sobno temperaturo, razredčimo z 10 % vodnim amonijevim kloridom in ekstrahiramo z etil acetatom. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek kromatografiramo na silikagelu z eluiranjem s 7:3 etil acetatom:heksanom, da dobimo spojino 42 (0,38 g, 40 %).1.9 mmol) in benzene (2 ml). The reaction mixture was stirred for an additional 1 hour at 90 ° C, cooled to room temperature, diluted with 10% aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 7: 3 ethyl acetate: hexane to give compound 42 (0.38 g, 40%).

Stopnja sedem: K raztopini spojine 42 (0,35 g, 0,7 mmol) v 1:1 zmesi THF:MeOH (8 ml) dodamo 2N NaOH (8 ml). Reakcijsko zmes mešamo pri sobni temperaturi 3 ure, nakisamo z 2N HC1 (10 ml) in ekstrahiramo z etil acetatom (20 ml). Organski slojStep seven: To a solution of compound 42 (0.35 g, 0.7 mmol) in a 1: 1 mixture of THF: MeOH (8 ml) was added 2N NaOH (8 ml). The reaction mixture was stirred at room temperature for 3 hours, acidified with 2N HCl (10 ml) and extracted with ethyl acetate (20 ml). Organic layer

-9797 sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3 S)-3 - [({[2-metil-4-(2-metilpropil)-6-okso-1 -(fenilmetil)-1,6-dihidro5-pirimidinil]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino (43, 250 mg, 75 %). MS: izrač.: (M+H)+= 477,25 m/z; ugot.: (M+H)+= 477,17 m/z.-9797 is dried over MgSO 4 , filtered and the filtrate is concentrated under reduced pressure to give (3 S) -3 - [({[2-methyl-4- (2-methylpropyl) -6-oxo-1- (phenylmethyl) - 1,6-dihydro5-pyrimidinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid (43, 250 mg, 75%). MS: calc .: (M + H) + = 477.25 m / z; found: (M + H) + = 477.17 m / z.

Primer 11Example 11

Sinteza (3 S )-3 -[({[2-metil-6-okso-1 -(fenilmetil)-1,6-dihidro5-pirimidinil]amino}karbonil)amino]-3-(4-metilfenil)propanojske kislineSynthesis of (3S) -3 - [({[2-methyl-6-oxo-1- (phenylmethyl) -1,6-dihydro5-pyrimidinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid

Stopnja ena: Raztopino spojine 36 (2,3 g, 15,5 mmol) in spojine 44 (3,36 g, 15,5 mmol) v absolutnem etanolu (35 ml) refluktiramo 3 ure in koncentriramo. Ostanek kromatografiramo na silikagelu z eluiranjem z 1:1 etil acetatom :heksanom, da dobimo spojino 45 (1,87 g, dobitek 55 %).Step One: A solution of compound 36 (2.3 g, 15.5 mmol) and compound 44 (3.36 g, 15.5 mmol) in absolute ethanol (35 ml) was refluxed for 3 hours and concentrated. The residue was chromatographed on silica gel eluting with 1: 1 ethyl acetate: hexane to give compound 45 (1.87 g, 55% yield).

(3 S)-3 - [( {[2-metil-6-okso-1 -(fenilmetil)-1,6-dihidro-5 pirimidinil]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 45 po postopkih, opisanih v primeru 10. fH NMR (400 MHz, CD3OD) δ 2,28 (s, 3H), 2,35 (s, 3H), 2,57 (m, 2H), 5,16 (m, IH), 5,30 (s, 2H), 7,13 (m, 4H), 7,30 (m, 5H), 8,50 (s, IH).(3S) -3 - [({[2-methyl-6-oxo-1- (phenylmethyl) -1,6-dihydro-5-pyrimidinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid was prepared from compound 45 according to the procedures described in Example 10. f H NMR (400 MHz, CD 3 OD) δ 2.28 (s, 3H), 2.35 (s, 3H), 2.57 (m, 2H) , 5.16 (m, 1H), 5.30 (s, 2H), 7.13 (m, 4H), 7.30 (m, 5H), 8.50 (s, 1H).

Primer 12Example 12

Sinteza (3 S)-3 - {[({[ 1 - [(2-klorofenil)metil-4- [({etil[(etilamino) karbonil]amino}karbonil)amino]-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojske kislineSynthesis of (3S) -3 - {[({[1 - [(2-chlorophenyl) methyl-4- [({ethyl [(ethylamino) carbonyl] amino} carbonyl) amino] -2-oxo-1,2- dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid

Stopnja ena: K raztopini spojine 46 (pripravljene po postopkih, opisanih v primeru 3, 0,50 g, 1,8 mmol) v THF (10 ml) pri 0 °C dodamo NaH (60 % disperzija v mineralnem olju, 0,23 g, 5,1 mmol). Zmes mešamo 10 minut pri 0 °C, nato dodamo etil izocianat (0,65 g, 9,15 mmol). Zmes mešamo pri sobni temperaturi preko vikenda, pogasimo z IN HC1 in ekstrahiramo z etil acetatom. Organski sloj sušimo nad MgSO4, filtriramoStep One: To a solution of compound 46 (prepared according to the procedures described in Example 3, 0.50 g, 1.8 mmol) in THF (10 ml) at 0 ° C was added NaH (60% dispersion in mineral oil, 0.23 g, 5.1 mmol). The mixture was stirred for 10 minutes at 0 ° C, then ethyl isocyanate (0.65 g, 9.15 mmol) was added. The mixture was stirred at room temperature over the weekend, quenched with 1N HCl and extracted with ethyl acetate. The organic layer was dried over MgSO 4 , filtered

-9898 in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 47 (0,60 g). Ta material uporabimo brez čiščenja.-9898 and the filtrate was concentrated under reduced pressure to give compound 47 (0.60 g). Use this material without cleaning.

(3 S)-3 - {[({1 -[(2-klorofenil)metil-4- [({etil [(etilamino) karbonil] amino }karbonil)amino]-2-okso-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 47 po postopkih, opisanih v primeru 3. Tal.: 128-130 °C.(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4- [({ethyl [(ethylamino) carbonyl] amino} carbonyl) amino] -2-oxo-1,2-dihydro- 3pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid is prepared from compound 47 according to the procedures described in Example 3. Mp: 128-130 ° C.

Primer 13Example 13

Sinteza (3S)-3-{ [({l-[(2-klorofenil)metil-4-hidroksi-2-okso-1,2dihidro-3-kinolinil}amino)karbonil]amino}-3-(4-metilfenil)propanojske kislineSynthesis of (3S) -3- {[({1 - [(2-chlorophenyl) methyl-4-hydroxy-2-oxo-1,2-dihydro-3-quinolinyl} amino) carbonyl] amino} -3- (4-methylphenyl) ) propanoic acid

Stopnja ena: K raztopini spojine 48 (2,00 g, 9,70 mmol) v brezvodnem DMF (25 ml) pri 0 °C dodamo NaH (60 % disperzija v mineralnem olju, 0,89 g, 22 mmol). Zmes mešamo pri 0 °C 15 minut pred dodatkom 2-klorobenzilklorida (2,03 g, 12,6 mmol). Po mešanju pri 55 °C preko noči zmes zlijemo v led-vodo in izperemo z Et2O (2-krat). Vodni sloj nakisamo in s filtriranjem dobljene oborine dobimo spojino 49 (3,45 g). Ta material uporabimo brez čiščenja.Step One: To a solution of compound 48 (2.00 g, 9.70 mmol) in anhydrous DMF (25 ml) at 0 ° C was added NaH (60% dispersion in mineral oil, 0.89 g, 22 mmol). The mixture was stirred at 0 ° C for 15 minutes before the addition of 2-chlorobenzyl chloride (2.03 g, 12.6 mmol). After stirring at 55 ° C overnight, the mixture was poured into ice-water and washed with Et 2 O (2 times). The aqueous layer was acidified and filtration of the precipitate obtained gave compound 49 (3.45 g). Use this material without cleaning.

(3 S)-3 - {[({1 - [(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro-3 kinolinil}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz spojine 49 po postopkih, opisanih v primeru 8. Tal.: 134-136 °C.(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 quinolinyl} amino) carbonyl] amino} -3- (4 -methylphenyl) propanoic acid was prepared from compound 49 according to the procedures described in Example 8. M.p .: 134-136 ° C.

Primer 14Example 14

Sinteza (3 S)-3 - {[({l-[(2-klorofenil)metil-5-metil-2-okso-1,2-dihidro3 -piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ske kisline (56)Synthesis of (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-5-methyl-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4- propionic acid methylphenyl) (56)

Stopnja ena: K suspenziji spojine 51 (1,67 g, 9,81 mmol) v DMF (33 ml) pri sobni temperaturi pod atmosfero suhega dušika zaporedoma dodamo 2-klorobenzilamin (1,30 ml, 10,8 mmol) in EDCI (2,35 g, 12,3 mmol). Dobljeno zmes močno mešamo 5 ur pri sobni temperaturi, razredčimo z etil acetatom ter izperemo z 2 N HC1, H2O (3-9999 krat), nasičenim vodnim NaHCO3 in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 52 (2,55 g, 100 %) kot bledo rumeno trdno snov.Step One: To a suspension of Compound 51 (1.67 g, 9.81 mmol) in DMF (33 mL) at room temperature under a dry nitrogen atmosphere was successively added 2-chlorobenzylamine (1.30 mL, 10.8 mmol) and EDCI ( 2.35 g, 12.3 mmol). The resulting mixture was stirred vigorously for 5 hours at room temperature, diluted with ethyl acetate and washed with 2 N HCl, H 2 O (3-9999 times), saturated aqueous NaHCO 3 and brine. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure to give compound 52 (2.55 g, 100%) as a pale yellow solid.

Stopnja dve: Raztopino spojine 52 (555 mg, 2,17 mmol) in 3-dimetilamino-2metilpropenala (738 mg, 6,5 mmol) v absolutnem metanolu (4,3 ml) in ledoctu (0,22 ml) segrevamo preko noči do refluksa. Dobljeno zmes ohladimo na sobno temperaturo, razredčimo z etil acetatom in izperemo z 2 N HC1 (2-krat), H2O in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s kromatografijo na silikagelu z eluiranjem s 7:3, ki narašča do 1:1, heksani:etil acetatom in končno 19:19:2 heksani:etil acetatom:metanolom, da dobimo spojino 53 (182 mg, 27 %) kot rumeno olje.Step Two: A solution of compound 52 (555 mg, 2.17 mmol) and 3-dimethylamino-2methylpropenal (738 mg, 6.5 mmol) in absolute methanol (4.3 ml) and glacial (0.22 ml) was heated overnight. to reflux. The resulting mixture was cooled to room temperature, diluted with ethyl acetate and washed with 2 N HCl (2 times), H 2 O and brine. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with 7: 3 increasing to 1: 1, hexanes: ethyl acetate and finally 19: 19: 2 hexanes: ethyl acetate: methanol to give compound 53 (182 mg, 27%) as yellow oil.

Stopnja tri: K raztopini spojine 53 (167 mg, 0,55 mmol) v THF (3 ml) dodamo 2 N NaOH (1 ml) in metanol (2 ml). Dobljeno zmes mešamo 15 minut, razredčimo s H2O in ekstrahiramo z etil etrom. Vodni sloj nakisamo z 2 N HC1 in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo s H2O in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 54 (139 mg, 91 %) kot belo trdno snov.Step Three: To a solution of compound 53 (167 mg, 0.55 mmol) in THF (3 ml) was added 2 N NaOH (1 ml) and methanol (2 ml). The resulting mixture was stirred for 15 minutes, diluted with H 2 O and extracted with ethyl ether. The aqueous layer was acidified with 2 N HCl and extracted with ethyl acetate. The ethyl acetate layer was washed with H 2 O and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give compound 54 (139 mg, 91%) as a white solid.

Stopnja štiri: Suspenziji spojine 54 (175 mg, 0,63 mmol) v THF (6,7 ml) in DIPEA (0,23 ml, 1,34 mmol) pri sobni temperaturi pod atmosfero suhega dušika dodamo preko brizge DPPA (0,29 ml, 1,34 mmol). Dobljeno zmes mešamo pri sobni temperaturi 15 minut, nato segrevamo do refluksa 3,5 ure. Zmes pustimo ohladiti na sobno temperaturo in dodamo raztopino spojine 8 (278 mg, 1,34 mmol) v THF (6,0 ml) preko kanile skupaj s THF (0,7 ml) splakovanjem. Dobljeno zmes mešamo pri sobni temperaturi preko noči, razredčimo z etil acetatom ter speremo z 2 N HC1 (2krat), nasičenim vodnim NaHCO3 in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem s 7:3, nato 3:2 in končno 1:1 heksani:etil acetatom, da dobimo spojino 55 (60 mg, 20 %) kot brezbarvno olje.Step four: Suspensions of compound 54 (175 mg, 0.63 mmol) in THF (6.7 mL) and DIPEA (0.23 mL, 1.34 mmol) at room temperature under a dry nitrogen atmosphere were added via a DPPA syringe (0, 29 ml, 1.34 mmol). The resulting mixture was stirred at room temperature for 15 minutes, then heated to reflux for 3.5 hours. The mixture was allowed to cool to room temperature and a solution of compound 8 (278 mg, 1.34 mmol) in THF (6.0 mL) was added via cannula along with THF (0.7 mL) flushing. The resulting mixture was stirred at room temperature overnight, diluted with ethyl acetate and washed with 2 N HCl (2 times), saturated aqueous NaHCO 3 and brine. The organic layer was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 7: 3, then 3: 2 and finally 1: 1 hexanes: ethyl acetate to give compound 55 (60 mg, 20%) as a colorless oil.

-100100-100100

Stopnja pet: K raztopini spojine 55 (60 mg, 0,12 mmol) v THF (3 ml) dodamo 0,192 N NaOH (0,65 ml, 0,12 mmol) in metanol (2 ml). Dobljeno zmes mešamo 24 ur pri sobni temperaturi, nato razredčimo s H2O. Organska topila odstranimo pod zmanjšanim tlakom in dobljeno vodno zmes ekstrahiramo z etil etrom. Vodno fazo liofiliziramo, da dobimo natrijevo sol (3S)-3-{[({l-[(2-klorofenil)metil-5-metil-2okso-l,2-dihidro-3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojske kisline (56, 56 mg, 95 %) kot umazano belo trdno snov. MS: izrač: za (C24H23C1N3O4)·: 452,14 m/z; ugot.: 451,99 m/z.Step Five: To a solution of compound 55 (60 mg, 0.12 mmol) in THF (3 mL) was added 0.192 N NaOH (0.65 mL, 0.12 mmol) and methanol (2 mL). The resulting mixture was stirred for 24 hours at room temperature, then diluted with H 2 O. The organic solvents were removed under reduced pressure and the resulting aqueous mixture was extracted with ethyl ether. The aqueous phase was lyophilized to give the (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-5-methyl-2oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino salt of carbonyl] amino} -3- (4-methylphenyl) propanoic acid (56, 56 mg, 95%) as a dirty white solid. MS: calc: for (C 24 H 23 ClN 3 O 4 ) ·: 452.14 m / z; Found: 451.99 m / z.

Primer 15Example 15

Sinteza (3 S)-3 -(1,3-benzodioksol-5-il)-3-[( {[2-okso-1 -(2-tienilmetil)-1,2dihidro-3-piridinil]amino}karboml)amino]propanojske kisline (62)Synthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[2-oxo-1- (2-thienylmethyl) -1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] propanoic acids (62)

Stopnja ena: K raztopini 2-tiofenmetanola (1,015 g, 8,89 mmol) v CH2C12 (17,8 ml), ohlajeni na 0 °C, pod atmosfero suhega dušika dodamo zaporedoma z brizgo trietilamin (2,98 ml, 21,4 mmol) in metansulfonil klorid (0,69 ml, 8,9 mmol). Dobljeno zmes mešamo 15 minut pri 0 °C, nato dodamo 2-hidroksi-3-nitropiridin (1,496 g, 10,7 mmol) in 4-dimetilaminopiridin (katalitsko). Zmes pustimo postopoma ogreti na sobno temperaturo in nato mešamo preko noči. Zmes razredčimo z etil acetatom ter izperemo z 2N HC1, H2O, nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4 in filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 58 (395 mg) kot rumeno voskasto trdno snov. Ta material uporabimo brez čiščenja.Step One: To a solution of 2-thiophenmethanol (1.015 g, 8.89 mmol) in CH 2 Cl 2 (17.8 ml) cooled to 0 ° C was added successively a triethylamine syringe (2.98 ml, under a dry nitrogen atmosphere). 21.4 mmol) and methanesulfonyl chloride (0.69 ml, 8.9 mmol). The resulting mixture was stirred for 15 minutes at 0 ° C, then 2-hydroxy-3-nitropyridine (1.496 g, 10.7 mmol) and 4-dimethylaminopyridine (catalytic) were added. The mixture was gradually warmed to room temperature and then stirred overnight. The mixture was diluted with ethyl acetate and washed with 2N HCl, H 2 O, saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give 58 (395 mg) as a yellow waxy solid. Use this material without cleaning.

Stopnja dve: K raztopini 58 (330 mg, 1,40 mmol) v ledoctu (6,6 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo železov prah (154 mg, 2,8 mmol, -325 mesh). Dobljeno raztopino segrevamo na 60 °C v oljni kopeli ob močnem mešanju 20 minut. Zmes ohladimo na sobno temperaturo, razredčimo z etil acetatom in filtriramo skozi celit. Filtrat izperemo s H2O, nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanimStep two: To a solution of 58 (330 mg, 1.40 mmol) in ice (6.6 mL) at room temperature under an atmosphere of dry nitrogen was added iron powder (154 mg, 2.8 mmol, -325 mesh). The resulting solution was heated to 60 ° C in an oil bath with vigorous stirring for 20 minutes. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered through celite. The filtrate was washed with H 2 O, saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure

-101101 tlakom. Ostanek filtriramo skozi silikagel z eluiranjem z 1:1 heksani.etil acetatom z naraščanjem do 1:3 heksani:etil acetatom, da dobimo 59 (188 mg, 12 % za dve stopnji) kot zelenkasto trdno snov.-101101 pressure. The residue was filtered through silica gel eluting with 1: 1 hexanes.ethyl acetate by increasing to 1: 3 hexanes: ethyl acetate to give 59 (188 mg, 12% by two steps) as a greenish solid.

Stopnja tri: K raztopini 59 (111 mg, 0,54 mmol) v CH2C12 (2,7 ml), ohlajeni na 0 °C pod atmosfero suhega dušika, dodamo zaporedoma z brizgo N,N-diizopropiletilamin (0,23 ml, 1,30 mmol) in fosgen (0,31 ml, 1,9M v toluenu, 0,59 mmol). Dobljeno zmes mešamo 15 minut pri 0 °C, nato dodamo raztopino β-amino estra 60 (167 mg, 0,70 mmol) v CH2C12 (2,7 ml) s kanilo skupaj s CH2C12 splakovanjem (1,0 ml). Dobljeno zmes pustimo ogreti na sobno temperaturo, mešamo 2 uri, razredčimo z etil acetatom ter izperemo z 2N HC1, H2O, nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4 in filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:1 heksani:etil acetatom, da dobimo 61 (231 mg, 91 %) kot vijoličasto peno.Step Three: Add N, N-diisopropylethylamine (0.23) to a solution of 59 (111 mg, 0.54 mmol) in CH 2 Cl 2 (2.7 ml) cooled to 0 ° C under a dry nitrogen atmosphere. ml, 1.30 mmol) and phosgene (0.31 ml, 1.9M in toluene, 0.59 mmol). The resulting mixture was stirred for 15 minutes at 0 ° C, then a solution of β-amino ester 60 (167 mg, 0.70 mmol) in CH 2 Cl 2 (2.7 ml) was added with cannula together with CH 2 Cl 2 flushing (1, 0 ml). The resulting mixture was allowed to warm to room temperature, stirred for 2 hours, diluted with ethyl acetate and washed with 2N HCl, H 2 O, saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1: 1 hexanes: ethyl acetate to give 61 (231 mg, 91%) as a purple foam.

Stopnja štiri: K raztopini estra 61 (227 mg, 0,48 mmol) v THF (6 ml) pri sobni temperaturi dodamo NaOH (2 ml, 2N v H2O, 4 mmol) in metanol (dovolj, da dobimo bistro raztopino, približno 2 ml). Dobljeno zmes mešamo 15 minut, nato razredčimo z vodo in ekstrahiramo z etrom. Vodno fazo nakisamo s HC1 (2N) in ekstrahiramo z etil acetatom. Organsko fazo izperemo s slanico, sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 62 (191 mg, 90 %) kot belo trdno snov. ’H NMR (400 MHz, CD3SOCD3) β 2,63 (d, j = 7,3 Hz, 2H), 4,99 (dt, J = 8,4,Step four: To a solution of ester 61 (227 mg, 0.48 mmol) in THF (6 ml) at room temperature was added NaOH (2 ml, 2N in H 2 O, 4 mmol) and methanol (enough to give a clear solution. about 2 ml). The resulting mixture was stirred for 15 minutes, then diluted with water and extracted with ether. The aqueous phase was acidified with HCl (2N) and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give 62 (191 mg, 90%) as a white solid. 1 H NMR (400 MHz, CD 3 SOCD 3 ) β 2.63 (d, j = 7.3 Hz, 2H), 4.99 (dt, J = 8.4,

7,3 Hz, IH), 5,30 (s, 2H), 5,98 (m, 2H), 6,21(dd, J = 7,5, 7,0 Hz, IH), 6,78 (dd, J =7.3 Hz, 1H), 5.30 (s, 2H), 5.98 (m, 2H), 6.21 (dd, J = 7.5, 7.0 Hz, 1H), 6.78 ( dd, J =

8.1, 1,6 Hz, IH), 6,85 (d, J = 8,1 Hz, IH), 6,88 (d, J = 1,6 Hz, IH), 6,97 (dd, J = 5,1,8.1, 1.6 Hz, 1H), 6.85 (d, J = 8.1 Hz, 1H), 6.88 (d, J = 1.6 Hz, 1H), 6.97 (dd, J = 5.1,

3,5 Hz, IH), 7,17 (dd, J = 3,5, 1,1 Hz, IH), 7,35 (dd, J = 7,0, 1,8 Hz, IH), 7,44 (dd, J =3.5 Hz, 1H), 7.17 (dd, J = 3.5, 1.1 Hz, 1H), 7.35 (dd, J = 7.0, 1.8 Hz, 1H), 7, 44 (dd, J =

5.1, 1,1 Hz, IH), 7,67 (d, J = 8,4 Hz, IH), 7,94 (dd, J = 7,5, 1,8 Hz, IH), 8,40 (s, IH).5.1, 1.1 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.94 (dd, J = 7.5, 1.8 Hz, 1H), 8.40 ( s, 1H).

Primer 16Example 16

Sinteza (3S)-3-(l,3-benzodioksol-5-il)-3-[({[(3S)-2-okso-l-(2tienilmetil)heksahidro-3-piridinil]amino}karbonil)amino]propanojske kisline (68)Synthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[(3S) -2-oxo-1- (2-thienylmethyl) hexahydro-3-pyridinyl] amino} carbonyl) amino] propanoic acids (68)

-102102-102102

Stopnja ena: K raztopini N-a-terc.butoksikarbonil-N-8-benziloksikarbonil-L-ornitina 63 (1,00 g, 2,73 mmol) in cezijevega karbonata (1,33 g, 4,1 mmol) v DMF (10 ml) pri sobni temperaturi dodamo z brizgo pod atmosfero suhega dušika jodometan (0,22 ml,Step One: To a solution of Na-tert-butoxycarbonyl-N-8-benzyloxycarbonyl-L-ornithine 63 (1.00 g, 2.73 mmol) and cesium carbonate (1.33 g, 4.1 mmol) in DMF (10 ml) at room temperature, iodomethane (0.22 ml,

3,3 mmol). Dobljeno zmes mešamo pri sobni temperaturi 18 ur, nato razredčimo z etil acetatom in izperemo s H2O, 10 % Na2S2O5, nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo ester 64 (1,21 g) kot bledo rumeno olje. Ta material vsebuje DMF, vendar ga uporabimo brez čiščenja.3.3 mmol). The resulting mixture was stirred at room temperature for 18 hours, then diluted with ethyl acetate and washed with H 2 O, 10% Na 2 S 2 O 5 , saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give ester 64 (1.21 g) as a pale yellow oil. This material contains DMF, but it is used without cleaning.

Stopnja dve: K raztopini 64 (0,86 g surovega materiala, pripravljenega v prejšnjem postopku, 1,94 mmol teor.) v metanolu (10 ml) pri 0 °C pod atmosfero suhega dušika dodamo paladij na oglju (300 mg, 10 % Pd, tip Degussa El01 NE/W, moker, 50 mas.% vode). Atmosfero dušika nadomestimo z vodikom (zamenjati 5-krat med vakuumom in vodikom, ki ga dobavlja balon) in zmes mešamo pri 0 °C 30 minut, nato filtriramo direktno v bučo, ki vsebuje 2-tiofenkarboksaldehid (177 mg, 1,58 mmol). Zmes koncentriramo (vodna kopel pri sobni temperaturi) in Ostanek prevzamemo v dikloroetanu (6 ml). K tej raztopini dodamo natrijev triacetoksiborohidrid (479 mg,Step two: To a solution of 64 (0.86 g of crude material prepared in the previous process, 1.94 mmol. Theorem) in methanol (10 ml) at 0 ° C under a dry nitrogen atmosphere was added palladium on charcoal (300 mg, 10% Pd, type Degussa El01 NE / W, wet, 50% by weight of water). The nitrogen atmosphere was replaced with hydrogen (replaced 5 times between vacuum and hydrogen supplied by the balloon) and the mixture stirred at 0 ° C for 30 minutes, then filtered directly into a flask containing 2-thiophenecarboxaldehyde (177 mg, 1.58 mmol) . The mixture was concentrated (water bath at room temperature) and the residue was taken up in dichloroethane (6 ml). To this solution was added sodium triacetoxyborohydride (479 mg,

2,26 mmol) in zmes mešamo 2 uri, razredčimo z etil acetatom ter izperemo z nasičenim NaHCO3 (2-krat) in slanico. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek filtriramo skozi silikagel z eluiranjem 7:3 heksani:etil acetatom, da dobimo laktam 65 (75 mg, 12 % za dve stopnji) kot brezbarvno olje.2.26 mmol) and the mixture was stirred for 2 hours, diluted with ethyl acetate and washed with saturated NaHCO 3 (2 times) and brine. The organic phase was dried over MgSO 4 , filtered and the filtrate was concentrated under reduced pressure. The residue was filtered through silica gel eluting with 7: 3 hexanes: ethyl acetate to give lactam 65 (75 mg, 12% over two steps) as a colorless oil.

Stopnja tri: V bučo, ki vsebuje 65 (89 mg, 0,29 mmol), zaprto z gumijevim prekatom, dodamo z brizgo pri sobni temperaturi pod atmosfero suhega dušika HC1 (7,2 ml, 4,0M v dioksanu, 28,8 mmol). Dušikovo iglo odstranimo in zmes v zaprti buči mešamo preko noči. Zmes razredčimo s CH2C12 in izperemo z nasičenim NaHCO3. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo amin 66 (60 mg, 100 %) kot svetlo rumeno olje. Ta material uporabimo brez čiščenja.Step Three: Add 65 g (65 mg, 0.29 mmol) flask closed with a rubber compartment to a flask at room temperature under an atmosphere of dry HC1 nitrogen (7.2 ml, 4.0M in dioxane, 28.8 mmol). The nitrogen needle was removed and the mixture was stirred overnight in a closed flask. The mixture was diluted with CH 2 C1 2 and washed with saturated NaHCO 3 . The organic phase was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure to give amine 66 (60 mg, 100%) as a pale yellow oil. Use this material without cleaning.

-103103-103103

Stopnja štiri: K raztopini β-amino estra 60 (75 mg, 0,32 mmol) v CH2C12 (0,6 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo karbonildiimidazol (51 mg, 0,32 mmol). Dobljeno zmes mešamo 5 minut pri sobni temperaturi in dodamo raztopino amina 66 (60 mg, 0,29 mmol) v CH2C12 (0,6 ml) s kanilo skupaj s CH2C12 (0,2 ml) splakovanjem. Dobljeno zmes mešamo pri sobni temperaturi 3 dni, nato razredčimo z etil acetatom in izperemo z 2N HC1 (2-krat), H2O, nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek filtriramo skozi silikagel z eluiranjem z 1:1 heksani:etil acetatom z naraščanjem do 2:3 heksanketil acetatom, da dobimo sečnino 67 (110 mg, 80 %).Step four: To a solution of β-amino ester 60 (75 mg, 0.32 mmol) in CH 2 Cl 2 (0.6 ml) at room temperature under an atmosphere of dry nitrogen was added carbonyldiimidazole (51 mg, 0.32 mmol). The resulting mixture was stirred for 5 minutes at room temperature and a solution of amine 66 (60 mg, 0.29 mmol) in CH 2 Cl 2 (0.6 ml) was cannulated with CH 2 Cl 2 (0.2 ml) rinsing. The resulting mixture was stirred at room temperature for 3 days, then diluted with ethyl acetate and washed with 2N HCl (2 times), H 2 O, saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 , filtered and the filtrate was concentrated under reduced pressure. The residue was filtered through silica gel eluting with 1: 1 hexanes: ethyl acetate with increasing to 2: 3 hexanecethyl acetate to give urea 67 (110 mg, 80%).

Stopnja pet: K raztopini sečnine 67 (108 mg, 0,23 mmol) v THF (3 ml) pri sobni temperaturi dodamo NaOH (1 ml, 2N v H2O, 2 mmol) in metanol (dovolj, da dobimo bistro raztopino, približno 2 ml). Dobljeno zmes mešamo 15 minut, nato razredčimo z vodo in ekstrahiramo z etrom. Vodno fazo nakisamo s HC1 (2N) in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo s slanico, sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 68 (92 mg, 90 %) kot belo peno. ‘H NMR (400 MHz, CD3SOCD3) δ 1,45 (m, IH), 1,76 (m, 2H), 2,62 (m, 2H), 3,25 (m prekrivajoč H2O, 2H), 4,01 (m, IH), 4,59 (d, J = 15,0 Hz, IH), 4,68 (d, J = 15,0 Hz, IH), 4,96 (m, IH), 5,97 (s, 2H), 6,24 (d, J = 6,6 Hz, IH), 6,71 (d, J = 8,4 Hz, IH), 6,75 (dd, J = 8,1, 1,5 Hz, IH), 6,82 (d, J = 8,1 Hz, IH), 6,85 (d, J = 1,5 Hz, IH), 6,97 (dd, J = 5,1, 3,3 Hz, IH), 7,03 (dd, J = 3,3, 1,5 Hz, IH), 7,42 (dd, J = 5,1, 1,5 Hz, IH), 12,06 (br, s, IH).Step Five: To a solution of urea 67 (108 mg, 0.23 mmol) in THF (3 ml) at room temperature was added NaOH (1 ml, 2N in H 2 O, 2 mmol) and methanol (enough to give a clear solution. about 2 ml). The resulting mixture was stirred for 15 minutes, then diluted with water and extracted with ether. The aqueous phase was acidified with HCl (2N) and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give 68 (92 mg, 90%) as a white foam. 1 H NMR (400 MHz, CD 3 SOCD 3 ) δ 1.45 (m, 1H), 1.76 (m, 2H), 2.62 (m, 2H), 3.25 (m overlapping H 2 O, 2H), 4.01 (m, 1H), 4.59 (d, J = 15.0 Hz, 1H), 4.68 (d, J = 15.0 Hz, 1H), 4.96 (m, 1H), 5.97 (s, 2H), 6.24 (d, J = 6.6 Hz, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.75 (dd, 1H). J = 8.1, 1.5 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 1.5 Hz, 1H), 6.97 ( dd, J = 5.1, 3.3 Hz, 1H), 7.03 (dd, J = 3.3, 1.5 Hz, 1H), 7.42 (dd, J = 5.1, 1, 5 Hz, 1H), 12.06 (br, s, 1H).

Primer 17Example 17

Sinteza (3S)-3-(l,3-benzodioksol-5-il)-3-[({[(3S)-2-okso-l-(2tienilmetil)tetrahidro- lH-pirol-3-il]amino}karbonil)amino]propanojske kisline (74)Synthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[(3S) -2-oxo-1- (2-thienylmethyl) tetrahydro-1H-pyrrol-3-yl] amino} carbonyl) amino] propanoic acid (74)

Stopnja ena: K raztopini α-benzilestra N-terc.butoksikarbonil-L-aspartinske kisline (2,10 g, 6,5 mmol) v dimetoksietanu (15 ml), ohlajeni na -15 °C (temperatura kopeli), pod atmosfero suhega dušika zaporedoma dodamo z brizgo 4-metilmorfolin (0,71 ml,Step One: To a solution of N-tert.butoxycarbonyl-L-aspartic acid α-benzyl ester (2.10 g, 6.5 mmol) in dimethoxyethane (15 ml) cooled to -15 ° C (bath temperature) under a dry atmosphere of nitrogen was successively added with a syringe of 4-methylmorpholine (0.71 ml,

-104104-104104

6,5 mmol) in izobutil kloroformat (0,84 ml, 6,5 mmol). Dobljeno zmes mešamo 2 minuti, nato filtriramo, pri čemer izperemo trdno pogačo z dimetoksietanom (10 ml). Filtrat ponovno ohladimo na -15 °C (temperatura kopeli) in dodamo raztopino natrijevega borohidrida (370 mg, 9,7 mmol) v H2O (3 ml), čemur takoj sledi dodatek H2O (100 ml). Zmes ekstrahiramo z etil acetatom (3-krat), organske sloje združimo in izperemo s hladno (0 °C) HC1 (0,2 N), H2O, nasičenim NaHCO3 in slanico. Dobljeni organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 69 (2,50 g) kot brezbarvno olje. Ta material vsebuje nekaj nereduciranega mešanega anhidrida, vendar ga uporabimo brez čiščenja.6.5 mmol) and isobutyl chloroformate (0.84 ml, 6.5 mmol). The resulting mixture was stirred for 2 minutes, then filtered, washing the solid cake with dimethoxyethane (10 ml). The filtrate was cooled again to -15 ° C (bath temperature) and a solution of sodium borohydride (370 mg, 9.7 mmol) in H 2 O (3 ml) was added, followed immediately by the addition of H 2 O (100 ml). The mixture was extracted with ethyl acetate (3 times), the organic layers combined and washed with cold (0 ° C) HCl (0.2 N), H 2 O, saturated NaHCO 3 and brine. The resulting organic layer was dried over MgSO 4 , filtered and the filtrate was concentrated under reduced pressure to give 69 (2.50 g) as a colorless oil. This material contains some unreduced mixed anhydride, but it is used without purification.

Stopnja dve: K raztopini oksalil klorida (2,4 ml, 2,0 M v CH2C12, 4,8 mmol) v CH2C12 (30 ml), ohlajeni na -65 °C, pod atmosfero suhega dušika dodamo z brizgo raztopino metilsulfoksida (0,55 ml, 7,8 mmol) v CH2C12 (8 ml). Dobljeno zmes mešamo 15 minut pri -65 °C, nato dodamo raztopino alkohola 69 (1,00 g, 3,2 mmol) v CH2C12 (29 ml) s kanilo skupaj s CH2C12 (3 ml) splakovanjem. Zmes mešamo 3 ure pri -65 °C, nato pustimo ogreti na -20 °C (temperatura kopeli). Dodamo trietilamin (0,96 ml, 6,9 mmol), čemur sledi H2O (20 ml). Vodni sloj ekstrahiramo s CH2C12, združene organske faze sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo aldehid 70 kot belo trdno snov. Ta material uporabimo takoj brez čiščenja.Step two: To a solution of oxalyl chloride (2.4 ml, 2.0 M in CH 2 C1 2 , 4.8 mmol) in CH 2 C1 2 (30 ml) cooled to -65 ° C was added under dry nitrogen atmosphere with a syringe solution of methylsulfoxide (0.55 ml, 7.8 mmol) in CH 2 Cl 2 (8 ml). The resulting mixture was stirred for 15 minutes at -65 ° C, then a solution of alcohol 69 (1.00 g, 3.2 mmol) in CH 2 Cl 2 (29 ml) was cannulated with CH 2 Cl 2 (3 ml) flushing. The mixture was stirred for 3 hours at -65 ° C, then allowed to warm to -20 ° C (bath temperature). Triethylamine (0.96 ml, 6.9 mmol) was added followed by H 2 O (20 ml). The aqueous layer was extracted with CH 2 Cl 2 , the combined organic phases were dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give aldehyde 70 as a white solid. Use this material immediately without cleaning.

Stopnja tri: K raztopini surovega aldehida 70 (3,2 mmol teor.) in 2-aminometiltiofena (402 mg, 3,55 mmol) v dikloroetanu (13 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo natrijev triacetoksiborohidrid (959 mg, 4,5 mmol). Dobljeno zmes mešamo preko noči pri sobni temperaturi, nato razredčimo z etil acetatom ter izperemo z nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:1 heksani:etil acetatom, da dobimo laktam 71 (220 mg, 23 % za 3 stopnje) kot belo trdno snov.Step Three: To a solution of the crude aldehyde 70 (3.2 mmol. Theorem) and 2-aminomethylthiophene (402 mg, 3.55 mmol) in dichloroethane (13 ml) was added sodium triacetoxyborohydride (959 mg, 4 at room temperature under dry nitrogen atmosphere). , 5 mmol). The resulting mixture was stirred overnight at room temperature, then diluted with ethyl acetate and washed with saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 , filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1: 1 hexanes: ethyl acetate to give lactam 71 (220 mg, 23% for 3 steps) as a white solid.

-105105-105105

Stopnja štiri: K raztopini 71 (220 mg, 0,74 mmol) v dioksanu (1,5 ml), zaprti z gumijevim prekatom, pri sobni temperaturi pod atmosfero suhega dušika dodamo z brizgo HC1 (1,50 ml, 4,0M v dioksanu, 6,0 mmol). Dušikovo iglo odstranimo in zmes v zaprti buči mešamo 5 ur. Zmes razredčimo s CH2C12 in izperemo z nasičenim NaHCO3. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo amin 72 (129 mg, 89 %) kot svetlo rumeno olje. Ta material uporabimo brez čiščenja.Step four: To a solution of 71 (220 mg, 0.74 mmol) in dioxane (1.5 ml), sealed with a rubber chamber, was added at room temperature under a dry nitrogen atmosphere with a HC1 syringe (1.50 ml, 4.0M v dioxane, 6.0 mmol). The nitrogen needle was removed and the mixture was stirred in a closed flask for 5 hours. The mixture was diluted with CH 2 C1 2 and washed with saturated NaHCO 3 . The organic phase was dried over MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure to give amine 72 (129 mg, 89%) as a pale yellow oil. Use this material without cleaning.

Stopnja pet: K raztopini amina 72 (123 mg, 0,63 mmol) v CH2C12 (1,5 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo karbonildiimidazol (112 mg, 0,69 mmol). Dobljeno zmes mešamo pri sobni temperaturi 5 minut in dodamo raztopino βamino estra 60 (164 mg, 0,69 mmol) v CH2C12 (0,8 ml) s kanilo skupaj s CH2C12 (0,2 ml) splakovanjem. Dobljeno zmes mešamo pri sobni temperaturi preko noči, nato razredčimo z etil acetatom ter izperemo z 2N HC1 (2-krat), H2O, nasičenim NaHCO3 in slanico. Organsko fazo sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek filtriramo skozi silikagel z eluiranjem z 49:1 kloroformom:metanolom, da dobimo sečnino 73 (230 mg, 80 %) kot brezbarvno olje, ki se počasi strdi pri stanju.Step Five: To a solution of amine 72 (123 mg, 0.63 mmol) in CH 2 Cl 2 (1.5 mL) at room temperature under an atmosphere of dry nitrogen was added carbonyldiimidazole (112 mg, 0.69 mmol). The resulting mixture was stirred at room temperature for 5 minutes and a solution of βamino ester 60 (164 mg, 0.69 mmol) in CH 2 Cl 2 (0.8 ml) was added with cannula together with CH 2 Cl 2 (0.2 ml) rinsing. The resulting mixture was stirred at room temperature overnight, then diluted with ethyl acetate and washed with 2N HCl (2 times), H 2 O, saturated NaHCO 3 and brine. The organic phase was dried over MgSO 4 , filtered and the filtrate was concentrated under reduced pressure. The residue was filtered through silica gel eluting with 49: 1 chloroform: methanol to give urea 73 (230 mg, 80%) as a colorless, slowly solidifying oil.

Stopnja šest: K raztopini sečnine 73 (230 mg, 0,50 mmol) v THF (3 ml) pri sobni temperaturi dodamo NaOH (1 ml, 2N v H2O, 2 mmol) in metanol (1 ml). Dobljeno zmes mešamo 1 uro, nato razredčimo z vodo in ekstrahiramo z etrom. Vodno fazo nakisamo s HC1 (2N) in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo s slanico, sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 74 (181 mg, 84 %) kot belo peno. *H NMR (400 MHz, CD3SOCD3) δ 1,64 (m, IH), 2,30 (m, IH), 2,64 (m, 2H), 3,20 (m, 2H), 4,17 (dd, J =Step Six: To a solution of urea 73 (230 mg, 0.50 mmol) in THF (3 ml) at room temperature was added NaOH (1 ml, 2N in H 2 O, 2 mmol) and methanol (1 ml). The resulting mixture was stirred for 1 hour, then diluted with water and extracted with ether. The aqueous phase was acidified with HCl (2N) and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give 74 (181 mg, 84%) as a white foam. 1 H NMR (400 MHz, CD 3 SOCD 3 ) δ 1.64 (m, 1H), 2.30 (m, 1H), 2.64 (m, 2H), 3.20 (m, 2H), 4 , 17 (dd, J =

8,8, 8,4 Hz, IH), 4,56 (s, 2H), 4,96 (m, IH), 5,97 (s, 2H), 6,30 (d, J = 7,0 Hz, IH),8.8, 8.4 Hz, 1H), 4.56 (s, 2H), 4.96 (m, 1H), 5.97 (s, 2H), 6.30 (d, J = 7.0) Hz, 1H),

6,58 (d, J = 8,8 Hz, IH), 6,77 (m, IH), 6,80-6,90 (m, 2H), 6,96-7,04 (m, 2H), 7,45 (dd, J = 5,1, 0,7 Hz, IH), 12,10 (br, s, IH).6.58 (d, J = 8.8 Hz, 1H), 6.77 (m, 1H), 6.80-6.90 (m, 2H), 6.96-7.04 (m, 2H) , 7.45 (dd, J = 5.1, 0.7 Hz, 1H), 12.10 (br, s, 1H).

Primer 18Example 18

-106106-106106

Sinteza (3 S)-3- [( {[5-kloro-2-hidroksi-3 -(fenilmetil)fenil] amino} karbonil)amino]-3 -(4metilfenil)propanojske kislineSynthesis of (3S) -3 - [({[5-chloro-2-hydroxy-3- (phenylmethyl) phenyl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid

Stopnja ena: K zmesi 2-fenilmetil-3-klorofenola (5,00 g, 22,9 mmol) v Et2O (20 ml) in 6N HC1 (50 ml) zaporedoma dodamo KNO3 (2,30 g, 22,9 mmol) in NaNO2 (20 mg, katalitsko). Dobljeno zmes mešamo 2 uri, razredčimo z vodo in ekstrahiramo z etil acetatom. Organski sloj izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 99 (6,0 g, 100 %).Step One: To a mixture of 2-phenylmethyl-3-chlorophenol (5.00 g, 22.9 mmol) in Et 2 O (20 ml) and 6N HCl (50 ml) was added successively KNO 3 (2.30 g, 22. 9 mmol) and NaNO 2 (20 mg, catalytic). The resulting mixture was stirred for 2 hours, diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give 99 (6.0 g, 100%).

Stopnja dve: K raztopini 99 (6,0 g, 22,8 mmol) v metanolu (360 ml) dodamo cinkov prah (6,0 g, 92 mmol) in nasičeni vodni NH4C1 (6 ml). Dobljeno heterogeno zmes refluktiramo preko noči. Po filtraciji vroče zmesi in koncentriranju filtrata pod zmanjšanim tlakom ostanek raztopimo v etil acetatu ter izperemo z nasičenim vodnim NaHCO3 in slanico. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo spojino 100 (2,93 g, 55 %).Step two: To a solution of 99 (6.0 g, 22.8 mmol) in methanol (360 ml) was added zinc powder (6.0 g, 92 mmol) and saturated aqueous NH 4 C1 (6 ml). The resulting heterogeneous mixture was refluxed overnight. After filtration of the hot mixture and concentration of the filtrate under reduced pressure, the residue was dissolved in ethyl acetate and washed with saturated aqueous NaHCO 3 and brine. The organic layer was dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give compound 100 (2.93 g, 55%).

Stopnja tri: K raztopini 25 (0,20 g, 0,96 mmol) v CH2C12 pri 0 °C dodamo zaporedoma DIPEA (0,40 ml, 2,4 mmol) in fosgen (1,93 M v toluenu, 0,60 ml, 1,2 mmol). Dobljeno zmes pustimo ogreti na sobno temperaturo, mešamo 20 minut, nato ponovno ohladimo na 0 °C. K tej zmesi po kapljicah dodamo raztopino 100 (0,25 g, 1,1 mmol) v CH2C12. Dobljeno zmes pustimo ogreti na sobno temperaturo preko noči, razredčimo z vodo in ekstrahiramo s CH2C12. Organski sloj izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s silikagelno kromatografijo z eluiranjem z 9:1 in z naraščanjem do 5:1 heksani:etil acetatom, da dobimo 101 (60 mg, 12 %).Step three: To a solution of 25 (0.20 g, 0.96 mmol) in CH 2 Cl 2 at 0 ° C was added successively DIPEA (0.40 ml, 2.4 mmol) and phosgene (1.93 M in toluene, 0.60 ml, 1.2 mmol). The resulting mixture was allowed to warm to room temperature, stirred for 20 minutes, then cooled again to 0 ° C. To this mixture was added dropwise a solution of 100 (0.25 g, 1.1 mmol) in CH 2 Cl 2 . The resulting mixture was allowed to warm to room temperature overnight, diluted with water and extracted with CH 2 Cl 2 . The organic layer was washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue purified by silica gel chromatography eluting with 9: 1 and increasing to 5: 1 hexanes: ethyl acetate to give 101 (60 mg, 12%).

(3S)-3-[({[5-kloro-2-hidroksi-3-(fenilmetil)fenil]amino}karbonil)amino]-3-(4metilfenil)propanojsko kislino pripravimo iz 101 po postopkih, opisanih v primeru 1. *H NMR (400 MHz, CD3SO2CD3) δ 2,26 (s, 3H), 2,58 (dd, J = 15,8, 6,6 Hz, IH), 2,67 (dd, J = 15,8, 8,4 Hz, IH), 3,49 (s, 2H), 4,88 (m, IH), 7,00-7,70 (m, 13H), 11,95 (br. s, IH).(3S) -3 - [({[5-chloro-2-hydroxy-3- (phenylmethyl) phenyl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid was prepared from 101 according to the procedures described in Example 1. 1 H NMR (400 MHz, CD 3 SO 2 CD 3 ) δ 2.26 (s, 3H), 2.58 (dd, J = 15.8, 6.6 Hz, 1H), 2.67 (dd, J = 15.8, 8.4 Hz, 1H), 3.49 (s, 2H), 4.88 (m, 1H), 7.00-7.70 (m, 13H), 11.95 (br s, 1H).

-107107-107107

Primer 19Example 19

Sinteza (3S)-3-(l,3-benzodioksol-5-il)-3-[({butil[2,5-diokso-l(fenilmetil)tetrahidro-1 H-pirol-3 -il] amino} karbonil)amino]propanoj ske kislineSynthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({butyl [2,5-dioxo-1 (phenylmethyl) tetrahydro-1H-pyrrol-3-yl] amino} carbonyl ) amino] propanoic acid

Stopnja ena: Raztopino N-benzilmaleimida (2,60 g, 13,9 mmol) in n-butilamina (1,00 g, 13,7 mmol) v THF (15 ml) mešamo pri sobni temperaturi preko noči in koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem s 4:1 z naraščanjem do 2:1 heksani:etil acetatom, da dobimo 102 (3,25 g, 90 %).Step One: A solution of N-benzylmaleimide (2.60 g, 13.9 mmol) and n-butylamine (1.00 g, 13.7 mmol) in THF (15 ml) was stirred at room temperature overnight and concentrated under reduced pressure. . The residue was purified by silica gel chromatography eluting with 4: 1 increasing to 2: 1 hexanes: ethyl acetate to give 102 (3.25 g, 90%).

(3S)-3-(l,3-benzodioksol-5-il)-3-[({butil[2,5-diokso-l(fenilmetil)tetrahidro-lH-pirol-3-il]amino}karbonil)amino]propanojsko kislino pripravimo iz 102 po postopkih, opisanih v primeru 1. Tal.: 80-85 °C.(3S) -3- (1,3-benzodioxol-5-yl) -3 - [({butyl [2,5-dioxo-1 (phenylmethyl) tetrahydro-1H-pyrrol-3-yl] amino} carbonyl) amino ] propanoic acid was prepared from 102 according to the procedures described in Example 1. Melting point: 80-85 ° C.

Primer 20Example 20

Sinteza (3S)-3-(l,3-benzodioksol-5-il)-3-[({[l-(ciklopentilmetil)-2-okso-l,2dihidro-3-piridinil]amino}karbonil)amino]propanojske kislineSynthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[1- (cyclopentylmethyl) -2-oxo-1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] propanoic acid

Stopnja ena: K raztopini 2-hidroksi-3-nitropiridina (200 mg, 1,4 mmol) v CH2C12 (14 ml) pri 0 °C v atmosferi dušika dodamo ciklopentanmetanol (178 mg, 1,78 mmol), temu pa sledi trifenilfosfin (551 mg, 2,1 mmol). Raztopino mešamo pri 0 °C 15 minut in po kapljicah preko brizge dodamo dietil azodikarboksilat (366 mg, 2,1 mmol). Reakcijsko zmes pustimo mešati pri 0 °C 1 uro in nato pri sobni temperaturi preko noči. Zmes pogasimo z metanolom (20 ml) in izperemo z vodo (2-krat). Vodni sloj ekstrahiramo z diklorometanom ter združene organske sloje sušimo nad magnezijevim sulfatom in filtriramo. Filtrat koncentriramo in ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:1 heksani:etil acetatom, da dobimo 103 (299 mg, dobitek 96 %) kot rumeno trdno snov.Step One: To a solution of 2-hydroxy-3-nitropyridine (200 mg, 1.4 mmol) in CH 2 Cl 2 (14 ml) at 0 ° C under nitrogen atmosphere was added cyclopentanethanol (178 mg, 1.78 mmol) to this followed by triphenylphosphine (551 mg, 2.1 mmol). The solution was stirred at 0 ° C for 15 minutes and diethyl azodicarboxylate (366 mg, 2.1 mmol) was added dropwise via syringe. The reaction mixture was allowed to stir at 0 ° C for 1 hour and then at room temperature overnight. The mixture was quenched with methanol (20 ml) and washed with water (2 times). The aqueous layer was extracted with dichloromethane and the combined organic layers were dried over magnesium sulfate and filtered. The filtrate was concentrated and the residue purified by silica gel chromatography eluting with 1: 1 hexanes: ethyl acetate to give 103 (299 mg, 96% yield) as a yellow solid.

(3 S)-3-( 1,3-benzodioksol-5-il)-3-[({ [ 1 -(ciklopentilmetil)-2-okso-1,2-dihidro-3piridinil] amino }karbonil)amino]propanojsko kislino pripravimo iz 103 po postopkih,(3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[1- (cyclopentylmethyl) -2-oxo-1,2-dihydro-3pyridinyl] amino} carbonyl) amino] propanoic acid is prepared from 103 according to the procedures,

-108108 opisanih v primeru 1. 'H NMR (400 MHz, CDCl3) δ 1,2-1,7 (m, 8H), 2,34 (m, IH),-108108 described in Example 1. 1 H NMR (400 MHz, CDCl 3 ) δ 1.2-1.7 (m, 8H), 2.34 (m, 1H),

2,81 (dd, J = , IH), 2,95 (dd, J =, IH), 3,92 (d, J = 7,7 Hz, 2H), 5,30 (m, IH), 5,92 (m, 2H), 6,30 (t, J = 7,1 Hz, IH), 6,68-7,00 (m, 5H), 8,33 (d, J = 7,7 Hz, IH), 8,89 (s, IH).2.81 (dd, J =, 1H), 2.95 (dd, J =, 1H), 3.92 (d, J = 7.7 Hz, 2H), 5.30 (m, 1H), 5 , 92 (m, 2H), 6.30 (t, J = 7.1 Hz, 1H), 6.68-7.00 (m, 5H), 8.33 (d, J = 7.7 Hz, 1H), 8.89 (s, 1H).

Primer 21Example 21

Sinteza (3 S)-3 -(1,3 -benzodioksol-5-il)-3 - {[({3 - [(2-tiofenilmetil)amino] fenil} amino)karbonil] amino} propanojske kislineSynthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - {[({3 - [(2-thiophenylmethyl) amino] phenyl} amino) carbonyl] amino} propanoic acid

Stopnja ena: K raztopini 2-tiofenkarboksaldehida (0,48 g, 4,0 mmol) v diklorometanu dodamo 3-nitroanilin (0,51 g, 3,7 mmol). Raztopino koncentriramo do suhega in spravimo v 1,2-dikloroetan (16 ml). Dodamo molekulska sita (0,3 nm, 1,1 g) temu pa sledi NaBH(OAc)3, (1,01 g, 4,8 mmol). Raztopino mešamo preko noči pri sobni temperaturi, razredčimo s kloroformom in izperemo z vodo. Organski sloj sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 104 (0,72 g, 84%).Step One: To a solution of 2-thiophenecarboxaldehyde (0.48 g, 4.0 mmol) in dichloromethane was added 3-nitroaniline (0.51 g, 3.7 mmol). The solution was concentrated to dryness and taken up in 1,2-dichloroethane (16 ml). Molecular sieves (0.3 nm, 1.1 g) were added followed by NaBH (OAc) 3 , (1.01 g, 4.8 mmol). The solution was stirred overnight at room temperature, diluted with chloroform and washed with water. The organic layer was dried over MgSO 4 , filtered and the filtrate concentrated under reduced pressure to give 104 (0.72 g, 84%).

Stopnja dve: K raztopini 104 (0,30 g, 1,3 mmol) v CH2C12 (5,2 ml) in trietilamina (0,215 ml, 1,5 mmol) pri 0 °C dodamo trifluoracetanhidrid (0,193 ml, 1,4 mmol). Raztopino mešamo 15 minut pri 0 °C, kopel ledu odstranimo in zmes mešamo še 15 minut. Zmes razredčimo s CH2C12, izperemo z 2N HC1, vodo in slanico. Organski sloj sušimo nad Na2SO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 105 (0,38 g, 100 %) kot rumeno trdno snov.Step two: To a solution of 104 (0.30 g, 1.3 mmol) in CH 2 Cl 2 (5.2 ml) and triethylamine (0.215 ml, 1.5 mmol) at 0 ° C was added trifluoroacetic anhydride (0.193 ml, 1 , 4 mmol). The solution was stirred at 0 ° C for 15 minutes, the ice bath removed and the mixture stirred for another 15 minutes. The mixture was diluted with CH 2 C1 2 , washed with 2N HCl, water and brine. The organic layer was dried over Na 2 SO 4 , filtered and the filtrate concentrated under reduced pressure to give 105 (0.38 g, 100%) as a yellow solid.

Stopnja tri: K raztopini 105 (0,38 g, 1,4 mmol) v etanolu (2,6 ml) in ocetni kislini (2,6 ml) pri sobni temperaturi, dodamo Fe prah (0,36 g, 6,5 mmol) in suspenzijo močno mešamo pri 40 °C, dokler TLC ne pokaže kompletne porabe 105. Zmes filtriramo skozi celit, izperemo s kloroformom. Filtrat razredčimo z nasičenim natrijevim bikarbonatom in kloroformski sloj sušimo nad Na2SO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s kromatografijo na silikagelu (gradientno eluiranje 6:1 do 4:1 heksani:etil acetat), da dobimo spojino 106 (0,102 g, 25%).Step Three: To a solution of 105 (0.38 g, 1.4 mmol) in ethanol (2.6 ml) and acetic acid (2.6 ml) at room temperature was added Fe powder (0.36 g, 6.5 mmol) and the suspension was stirred vigorously at 40 ° C until TLC showed complete consumption of 105. The mixture was filtered through celite, washed with chloroform. The filtrate was diluted with saturated sodium bicarbonate and the chloroform layer was dried over Na 2 SO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (gradient elution 6: 1 to 4: 1 hexanes: ethyl acetate) to give compound 106 (0.102 g, 25%).

-109109 (3 S)-3 -(1,3 -benzodioksol-5 - i 1)-3 - {[( { 3 - [(2-tiofenilmetil)amino] fenil}amino)karbonil]amino}propanojsko kislino pripravimo iz 106 po postopkih, opisanih v primeru 1. ’H NMR (400 MHz, CD3SO2CD3) δ 2,50 (m, 2H prekrivajoč DMSO), 4,37 (d, J = 5,9 Hz, 2H), 4,94 (m, IH), 5,94 (m, 2H), 6,06 (t, J = 5,8 Hz, IH),-109109 (3S) -3- (1,3-benzodioxol-5-yl) -3 - {[({3 - [(2-thiophenylmethyl) amino] phenyl} amino) carbonyl] amino} propanoic acid is prepared from 106 according to the procedures described in Example 1. 1 H NMR (400 MHz, CD 3 SO 2 CD 3) δ 2.50 (m, 2H overlapping DMSO), 4.37 (d, J = 5.9 Hz, 2H), 4.94 ( m, 1H), 5.94 (m, 2H), 6.06 (t, J = 5.8 Hz, 1H),

6,16 (m, IH), 6,59 (d, J = 8,8 Hz, IH), 6,78 (m, 3H), 6,85 (dd, J = 8,8, 7,7 Hz, IH),6.16 (m, 1H), 6.59 (d, J = 8.8 Hz, 1H), 6.78 (m, 3H), 6.85 (dd, J = 8.8, 7.7 Hz) , IH),

6,90 (s, IH), 6,94 (dd, J = 5,2, 3,7 Hz, IH), 7,00 (d, J - 3,3 Hz, IH), 7,33 (dd, J = 5,1,6.90 (s, 1H), 6.94 (dd, J = 5.2, 3.7 Hz, 1H), 7.00 (d, J - 3.3 Hz, 1H), 7.33 (dd , J = 5.1,

1,1 Hz, IH), 8,5 (s, IH).1.1 Hz, 1H), 8.5 (s, 1H).

Primer 22Example 22

Sinteza 3-(l,3-benzodioksol-5-il)-2,2-difluoro-3-[({[2-okso-l-(2tiofenilmetil) 1,2-dihidro-3 -piridinil [amino} karbonil)amino]propanoj ske kislineSynthesis of 3- (1,3-benzodioxol-5-yl) -2,2-difluoro-3 - [({[2-oxo-1- (2-thiophenylmethyl) 1,2-dihydro-3-pyridinyl [amino} carbonyl) amino] propanoic acid

Stopnja ena: K raztopini (lS,2R,5S)-(+)-mentil (R)-p-toluensulfmata (3,00 g, 10,2 mmol) v THF (25,5 ml) ohlajeni na -78 °C, po kapljicah 15 minut dodajamo litijev bis(trimetilsilil)amid (1,0 M v THF, 15,3 ml). Dobljeno zmes mešamo pri sobni temperaturi 6 ur, nato ohladimo na 0 °C. Hitro dodamo piperonal (3,06 g, 20,4 mmol) in CsF (3,10 g, 20,4 mmol) in suspenzijo mešamo 36 ur pri sobni temperaturi. Reakcijo pogasimo z nasičenim NH4C1 in ekstrahiramo z etil acetatom. Organski sloj izperemo s slanico, sušimo nad Na2SO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek prekristaliziramo iz heksanov in diklorometana, da dobimo spojino 108 (1,36 g, 46 %).Step One: To a solution of (1S, 2R, 5S) - (+) - menthyl (R) -p-toluenesulphate (3.00 g, 10.2 mmol) in THF (25.5 ml) cooled to -78 ° C , lithium bis (trimethylsilyl) amide (1.0 M in THF, 15.3 ml) was added dropwise over 15 minutes. The resulting mixture was stirred at room temperature for 6 hours, then cooled to 0 ° C. Piperonal (3.06 g, 20.4 mmol) and CsF (3.10 g, 20.4 mmol) were added rapidly and the suspension stirred for 36 hours at room temperature. The reaction was quenched with saturated NH 4 Cl and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na 2 SO 4 , filtered and the filtrate concentrated under reduced pressure. The residue was recrystallized from hexanes and dichloromethane to give compound 108 (1.36 g, 46%).

Stopnja dve: Etil bromodifluoroacetat (0,78 ml, 6,1 mmol) dodamo k suspenziji Zn prahu (2,00 g, 30,5 mmol) v THF (20,2 ml) in refluktiramo 15 minut. Suspenzijo ohladimo na 0 °C in dodamo 108 (0,87 g, 3,0 mmol). Suspenzijo pustimo ogreti na sobno temperaturo in mešamo preko noči. Zmes pogasimo z minimalno količino nasičenega NH4C1 in ekstrahiramo z etil acetatom. Organski sloj izperemo z nasičenim vodnim NaHCO3 in slanico, sušimo nad Na2SO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s kromatografijo na silikagelu (gradientnoStep two: Ethyl bromodifluoroacetate (0.78 ml, 6.1 mmol) was added to a suspension of Zn powder (2.00 g, 30.5 mmol) in THF (20.2 ml) and refluxed for 15 minutes. The suspension was cooled to 0 ° C and 108 (0.87 g, 3.0 mmol) was added. Allow the suspension to warm to room temperature and stir overnight. The mixture was quenched with a minimal amount of saturated NH 4 Cl and extracted with ethyl acetate. The organic layer was washed with saturated aqueous NaHCO 3 and brine, dried over Na 2 SO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (gradient

-110110 eluiranje 6:1 do 4:1 heksani:etil acetat, da dobimo 109 (0,607 g, 61 % pri 80 % konverziji).-110110 eluting 6: 1 to 4: 1 hexanes: ethyl acetate to give 109 (0.607 g, 61% at 80% conversion).

Stopnja tri: K raztopini 109 (0,700 g, 1,70 mmol) v metanolu (4,3 ml) pri 0 °C dodamo trifluoroocetno kislino (0,26 ml, 3,4 mmol). Raztopino mešamo pri 0 “C 2 uri, nato koncentriramo do suhega pod zmanjšanim tlakom ob vzdrževanju zunanje temperature pod 30 °C. Ostanek prevzamemo v dietil eter in izperemo z 2N HC1 (2-krat). Združene vodne sloje skrbno naalkalimo s prebitnim nasičenim NaHCO3 in ekstrahiramo z dietil etrom. Etrski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 110 (0,326 g, 80 %).Step Three: To a solution of 109 (0.700 g, 1.70 mmol) in methanol (4.3 mL) at 0 ° C was added trifluoroacetic acid (0.26 mL, 3.4 mmol). The solution was stirred at 0 C C for 2 hours, then concentrated to dryness under reduced pressure while maintaining the ambient temperature below 30 ° C. The residue was taken up in diethyl ether and washed with 2N HCl (2 times). The combined aqueous layers were carefully basified with excess saturated NaHCO 3 and extracted with diethyl ether. The ether layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give 110 (0.326 g, 80%).

3-(1,3 -benzodioksol-5 -il)-2,2-difluoro-3 -[({[2-okso-1 -(2-tiofenilmetil)-1,2-dihidro-3 piridinil]amino}karbonil)amino]propanojsko kislino pripravimo iz 110 po postopkih, opisanih v primeru 1. MS: izrač.: (M-H)' = 476,07; ugot.: (M-H)' = 476,00.3- (1,3-benzodioxol-5-yl) -2,2-difluoro-3 - [({[2-oxo-1- (2-thiophenylmethyl) -1,2-dihydro-3 pyridinyl] amino} carbonyl ) amino] propanoic acid was prepared from 110 according to the procedures described in Example 1. MS: calc .: (MH) '= 476.07; found: (M-H) '= 476.00.

Primer 23Example 23

Sinteza (3S)-3-(l,3-benzodioksol-5-il)-3-({[9-okso-8-(fenilmetil)2,3,4,5,8,9-heksahidro-1 H-pirido[3,4-b]azepin-1-iljkarbonil} amino)propanoj ske kislineSynthesis of (3S) -3- (1,3-benzodioxol-5-yl) -3 - ({[9-oxo-8- (phenylmethyl) 2,3,4,5,8,9-hexahydro-1H- Pyrido [3,4-b] azepin-1-ylcarbonyl} amino) propanoic acid

Stopnja ena: K raztopini 3 (0,74 g, 3,6 mmol) v THF (14,4 ml) in TMEDA (1,60 ml, 10,8 mmol) pri -20 °C zaporedoma dodamo po kapljicah z brizgo n-butillitij (1,6 M v heksanih, 3,4 ml, 5,4 mmol) in terc.butillitij (1,7 M v pentanu, 2,5 ml, 4,3 mmol). Temperaturo pustimo zvišati na med -10 in 0 °C in vzdržujemo pri tem 2 uri. K dobljeni zmesi hitro dodamo 1,4-dibromobutan (1,75 ml, 14,7 mmol), raztopino pustimo ogreti na sobno temperaturo in mešamo 4 dni. Reakcijo pogasimo z vodo in ekstrahiramo s CHC13 (3-krat). Združene ekstrakte izperemo s slanico, sušimo nad NaSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s kromatografijo na silikagelu z eluiranjem s 4:1 heksani:etil acetatom, da dobimo 111 (0,41 g, 44 %).Step One: To a solution of 3 (0.74 g, 3.6 mmol) in THF (14.4 ml) and TMEDA (1.60 ml, 10.8 mmol) at -20 ° C was added successively dropwise with syringe n -butillithium (1.6 M in hexanes, 3.4 ml, 5.4 mmol) and tert.butillithium (1.7 M in pentane, 2.5 ml, 4.3 mmol). The temperature was raised to between -10 and 0 ° C and maintained for 2 hours. 1,4-dibromobutane (1.75 ml, 14.7 mmol) was rapidly added to the resulting mixture, the solution was allowed to warm to room temperature and stirred for 4 days. The reaction was quenched with water and extracted with CHC1 3 (3 times). The combined extracts were washed with brine, dried over our 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel eluting with 4: 1 hexanes: ethyl acetate to give 111 (0.41 g, 44%).

(3S)-3-(l,3-benzodioksol-5-il)-3-({[9-okso-8-(fenilmetil)-111111(3S) -3- (1,3-benzodioxol-5-yl) -3 - ({[9-oxo-8- (phenylmethyl) -111111

2,3,4,5,8,9-heksahidro-lH-pirido[3,4-b]azepin-l-il]karbonil}amino)propanojsko kislino pripravimo iz 111 po postopkih, opisanih v primeru 4. MS: izrač.: (M-H)' = 488,18; ugot.: (M-H)’= 488,21.2,3,4,5,8,9-Hexahydro-1H-pyrido [3,4-b] azepin-1-yl] carbonyl} amino) propanoic acid was prepared from 111 according to the procedures described in Example 4. MS: Calc. .: (MH) '= 488.18; found: (M-H) '= 488.21.

Primer 24Example 24

Sinteza (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso-l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4-hidroksifenil)propanojske kislineSynthesis of (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-hydroxyphenyl) propanoic acid

Stopnja ena: K raztopini 112 (pripravljeni po postopkih, opisanih v primeru 15, 0,19 g, 0,39 mmol) v CH2C12 pri 0 °C pod dušikom dodamo z brizgo BBr3 (1,0 M v CH2C12,Step One: To a solution of 112 (prepared according to the procedures described in Example 15, 0.19 g, 0.39 mmol) in CH 2 Cl 2 at 0 ° C under nitrogen was added with a BBr 3 syringe (1.0 M in CH 2 C1 2 ,

1,2 ml, 1,2 mmol). Zmes pustimo postopoma ogreti na sobno temperaturo in nato mešamo preko noči. Zmes razredčimo z vodo in mešamo 30 minut ter nadalje razredčimo z nasičenim vodnim NaHCO3. Organski sloj izperemo z vodo ter vodne sloje združimo in nakisamo z 2N HC1 in ekstrahiramo z etil acetatom (3-krat). Združene etil acetatne sloje sušimo nad MgSO4, filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso-l,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-hidroksifenil)propanojsko kislino (113, 120 mg, 70 %). *H NMR (400 MHz, CD3SO2CD3) δ 2,95 (d, J = 5,2 Hz, 2H), 5,28 (s, 2H), 5,35 (ddd, J = 9,2, 4,8, 4,4 Hz, IH), 6,33 (t, J = 7,1 Hz, IH), 6,60 (d, J = 8,8 Hz, 2H), 7,04 (m, 5H), 7,22 (m, 3H), 7,37 (dd, J = 7,7, 1,5 Hz, IH), 8,35 (dd, J = 7,6, 1,5 Hz, IH), 8,80 (s, IH).1.2 ml, 1.2 mmol). The mixture was gradually warmed to room temperature and then stirred overnight. The mixture was diluted with water and stirred for 30 minutes and further diluted with saturated aqueous NaHCO 3 . The organic layer was washed with water and the aqueous layers were combined and acidified with 2N HCl and extracted with ethyl acetate (3 times). The combined ethyl acetate layers were dried over MgSO 4 , filtered, and the filtrate concentrated under reduced pressure to give (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro3- pyridinyl} amino) carbonyl] amino} -3- (4-hydroxyphenyl) propanoic acid (113, 120 mg, 70%). 1 H NMR (400 MHz, CD 3 SO 2 CD 3 ) δ 2.95 (d, J = 5.2 Hz, 2H), 5.28 (s, 2H), 5.35 (ddd, J = 9. 2, 4.8, 4.4 Hz, 1H), 6.33 (t, J = 7.1 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 7.04 ( m, 5H), 7.22 (m, 3H), 7.37 (dd, J = 7.7, 1.5 Hz, 1H), 8.35 (dd, J = 7.6, 1.5 Hz) , 1H), 8.80 (s, 1H).

Primer 25Example 25

Sinteza (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3 ί 1] amino} karbonil)amino] -3 -(4-metilfenil)propanoj ske kisline, 119Synthesis of (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3 - (4-methylphenyl) propanoic acid, 119

Stopnja ena: K suspenziji natrijevega hidrida (3,6 g 60 % disperzija v mineralnem olju, 90 mmol) v THF (300 ml) v atmosferi suhega dušika dodamo TMEDA (13,2 ml,Step One: To a suspension of sodium hydride (3.6 g 60% dispersion in mineral oil, 90 mmol) in THF (300 ml) under dry nitrogen atmosphere was added TMEDA (13.2 ml,

87,5 mmol) in zmes ohladimo na -20 °C. Po kapljicah dodamo metil propionilacetat (9,60 ml, 76,5 mmol) in raztopino mešamo še 15 minut. Po kapljicah dodamo raztopino n-butillitija (90 ml, 1,6M v heksanih, 144 mmol) in dobljeno zmes mešamo87.5 mmol) and the mixture was cooled to -20 ° C. Methyl propionyl acetate (9.60 ml, 76.5 mmol) was added dropwise and the solution was stirred for another 15 minutes. A solution of n-butyllithium (90 ml, 1.6M in hexanes, 144 mmol) was added dropwise and the resulting mixture was stirred

-112112 minut pri -20 °C. Potem dodamo hitro metil format (6,0 ml, 97 mmol) in zmes pustimo mešati 15 minut pred pogasitvijo s HC1 (2 N, 250 ml). Reakcijo razredčimo z dietiletrom (150 ml) in organski sloj še 2-krat izperemo z vodo. Vodne sloje združimo in dodamo natrijev klorid do nasičenja. To zmes ekstrahiramo z etil acetatom (3-krat). Originalni etrski sloj izperemo z raztopino nasičenega natrijevega bikarbonata in vodo. Združene vodne izpiralne tekočine nakisamo s prebitno HC1 (2 N), nasitimo z natrijevim kloridom in ekstrahiramo z etil acetatom (3-krat). Vse od etil acetatnih ekstraktov združimo in sušimo nad MgSO4. Dobljeno zmes vakuumsko filtriramo skozi grob silikagel in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 114 (8,27 g, 68 %) kot svetlo rumeno olje. Ta material uporabimo brez nadaljnjega čiščenja.-112112 minutes at -20 ° C. Then methyl formate (6.0 ml, 97 mmol) was added rapidly and the mixture was allowed to stir for 15 minutes before quenching with HCl (2 N, 250 ml). The reaction was diluted with diethyl ether (150 ml) and the organic layer was washed twice more with water. The aqueous layers were combined and sodium chloride was added to saturation. This mixture was extracted with ethyl acetate (3 times). The original ether layer was washed with saturated sodium bicarbonate solution and water. The combined aqueous washings were acidified with excess HCl (2 N), saturated with sodium chloride, and extracted with ethyl acetate (3 times). All of the ethyl acetate extracts were combined and dried over MgSO 4 . The resulting mixture was vacuum filtered through coarse silica gel and the filtrate was concentrated under reduced pressure to give 114 (8.27 g, 68%) as a pale yellow oil. Use this material without further purification.

Stopnja dve: K raztopini 114 (3,95 g, 25,0 mmol) v brezvodnem metanolu (225 ml) pri sobni temperaturi dodajamo po kapljicah iz dodajalnega lija raztopino 2klorobenzilamina (4,2 g, 30 mmol) v brezvodnem metanolu (25 ml). Raztopino segrevamo pri 45 °C preko noči, nato refluktiramo 2 uri. Reakcijsko zmes ohladimo na sobno temperaturo in koncentriramo do suhega. Ostanek damo v diklormetan in filtriramo. Trdno snov zberemo in sušimo v vakuumu, da dobimo 115 (2,20 g, 35 %) kot svetlo rumeno trdno snov.Step two: To a solution of 114 (3.95 g, 25.0 mmol) in anhydrous methanol (225 ml) at room temperature was added dropwise a solution of 2chlorobenzylamine (4.2 g, 30 mmol) in anhydrous methanol (25 ml) at room temperature. ). The solution was heated at 45 ° C overnight, then refluxed for 2 hours. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was taken up in dichloromethane and filtered. The solid was collected and dried in vacuo to give 115 (2.20 g, 35%) as a pale yellow solid.

Stopnja tri: K suspenziji 115 (840 mg, 3,4 mmol) v ledoctu (11 ml) dodamo zaporedoma pri sobni temperaturi NaNO2 (46 mg, 0,67 mmol), vodo (0,92 ml) in HNO3 (70 %, 0,85 ml, 13,4 mmol). Dobljeno svetlo rumeno raztopino mešamo preko noči pri sobni temperaturi, nato razredčimo s CH2C12 in vodo. Vodno fazo ekstrahiramo s CH2C12, organske sloje združimo in izperemo z vodo (3-krat) in slanico. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 116 (910 mg, 92 %) kot svetlo rumeno trdno snov. Ta material uporabimo brez čiščenja.Step Three: Add NaNO 2 (46 mg, 0.67 mmol), water (0.92 ml) and HNO 3 (70) to a suspension of 115 (840 mg, 3.4 mmol) in ice (11 ml). %, 0.85 ml, 13.4 mmol). The resulting light yellow solution was stirred overnight at room temperature, then diluted with CH 2 Cl 2 and water. The aqueous phase was extracted with CH 2 Cl 2 , the organic layers were combined and washed with water (3 times) and brine. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give 116 (910 mg, 92%) as a pale yellow solid. Use this material without cleaning.

Stopnja štiri: K raztopini 116 (910 mg, 3,1 mmol) v DMF (10,3 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo Zn prah (909 mg, 13,9 mmol) inStep four: To a solution of 116 (910 mg, 3.1 mmol) in DMF (10.3 ml) at room temperature under an atmosphere of dry nitrogen was added Zn powder (909 mg, 13.9 mmol) and

-113113 trietilamin hidroklorid (2340 mg, 17,0 mmol). Dobljeno zmes segrevamo na 55 °C 2 uri, nato ohladimo na sobno temperaturo. K dobljeni zmesi dodamo CDI (1002 mg,-113113 triethylamine hydrochloride (2340 mg, 17.0 mmol). The resulting mixture was heated to 55 ° C for 2 hours, then cooled to room temperature. CDI (1002 mg,

6,18 mmol) kot trdno snov. Po dodatku pride do razvijanja plina. Zmes nato segrevamo 1 uro na 80 °C, ohladimo na sobno temperaturo ter razredčimo s CH2C12 in HC1 (2 N). Vodno fazo ekstrahiramo s CH2C12, organske sloje združimo ter izperemo z vodo (4-krat) in slanico. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 117 (920 mg) kot rumeno trdno snov. Ta material vsebuje majhno količino DMF in ga uporabimo brez čiščenja.6.18 mmol) as a solid. After the addition, gas develops. The mixture was then heated to 80 ° C for 1 hour, cooled to room temperature and diluted with CH 2 Cl 2 and HCl (2 N). The aqueous phase was extracted with CH 2 Cl 2 , the organic layers were combined and washed with water (4 times) and brine. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give 117 (920 mg) as a yellow solid. This material contains a small amount of DMF and can be used without cleaning.

Stopnja pet: Suspenzijo 117 (920 mg surovega materiala, 3,1 mmol teor.) in 8 (800 mg, 3,86 mmol) v 21 ml THF pod atmosfero suhega dušika segrevamo na 55 °C preko noči, ohladimo na sobno temperaturo in nato razredčimo z etil acetatom. Dobljeno zmes 2-krat izperemo s HC1 (2N) in slanico ter organski sloj sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in dobljeni ostanek čistimo s silikagelno kromatografijo ob eluiranju s 7:3 heksanketil acetatu, da dobimo 118 (1098 mg, 71 % za 2 stopnji) kot bledo rumeno peno.Step Five: A suspension of 117 (920 mg of crude material, 3.1 mmol of theory) and 8 (800 mg, 3.86 mmol) in 21 ml of THF under an atmosphere of dry nitrogen was heated to 55 ° C overnight, cooled to room temperature and then diluted with ethyl acetate. The resulting mixture was washed twice with HCl (2N) and the brine and the organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography eluting with 7: 3 hexanacetyl acetate to give 118 (1098 mg, 71% over 2 steps) as a pale yellow foam.

Stopnja šest: K raztopini 118 (1091 mg, 2,19 mmol) v THF (18 ml) pri sobni temperaturi dodamo natrijev hidroksid (2 N, 6 ml) in metanol (12 ml). Zmes mešamo 20 minut, nato razredčimo z vodo in ekstrahiramo z etil etrom. Vodno fazo nakisamo s HC1 (2 N) in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil-2-okso-l,2dihidropiridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino, 119, (1045 mg, kvantitativno) kot belo peno. MS: izrač.: (M-H)' - 468,13 m/z; ugot.: (ΜΗ)’ = 467,99 m/z.Step Six: To a solution of 118 (1091 mg, 2.19 mmol) in THF (18 ml) at room temperature was added sodium hydroxide (2 N, 6 ml) and methanol (12 ml). The mixture was stirred for 20 minutes, then diluted with water and extracted with ethyl ether. The aqueous phase was acidified with HCl (2 N) and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, 119, (1045 mg, quantitative) as a white foam. MS: calc .: (MH) - 468.13 m / z; found: (ΜΗ) '= 467.99 m / z.

Primer 26Example 26

Sinteza (3 S)-3 - [({[4-hidroksi-2-okso-1 -(piridin-2-ilmetil)-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojske kislineSynthesis of (3S) -3 - [({[4-hydroxy-2-oxo-1- (pyridin-2-ylmethyl) -1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid

-114114-114114

Stopnja ena: K raztopini 23 (0,50 g, 3,2 mmol) v DMSO (12,5 ml) pri sobni temperaturi dodamo uprašen KOH (0,89 g, 16 mmol) in zmes mešamo 1,5 ure. K dobljeni zmesi dodamo 2-pikolilklorid hidroklorid (0,63 g, 3,8 mmol) kot trdno snov in zmes mešamo preko noči. Pri tej točki dodamo trietilamin hidroklorid (3,52 g, 25,6 mmol) in DMF (5 ml), temu pa sledi cinkov prah (1,04 g, 16,0 mmol). Zmes segrevamo na 80 °C 2 uri, nato ohladimo na sobno temperaturo. K zmesi dodamo CDI (1,00 g, 6,2 mmol) in dobljeno zmes segrevamo na 80 °C preko noči. Zmes razredčimo z etil acetatom in nasičenim vodnim NaHCO3. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom. Ostanek filtriramo skozi blazinico silikagela z eluiranjem z 9:1 CHC13:CH3OH, da dobimo 120 (0,14 g, 18 %).Step One: To a solution of 23 (0.50 g, 3.2 mmol) in DMSO (12.5 ml) at room temperature was added powdered KOH (0.89 g, 16 mmol) and the mixture was stirred for 1.5 hours. To the resulting mixture was added 2-picolyl chloride hydrochloride (0.63 g, 3.8 mmol) as a solid and the mixture was stirred overnight. At this point, triethylamine hydrochloride (3.52 g, 25.6 mmol) and DMF (5 ml) were added, followed by zinc powder (1.04 g, 16.0 mmol). The mixture was heated to 80 ° C for 2 hours, then cooled to room temperature. CDI (1.00 g, 6.2 mmol) was added to the mixture and the resulting mixture was heated to 80 ° C overnight. The mixture was diluted with ethyl acetate and saturated aqueous NaHCO 3 . The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure. The residue was filtered through a pad of silica gel eluting with 9: 1 CHCl 3 : CH 3 OH to give 120 (0.14 g, 18%).

(3 S)-3 - [({[4-hidroksi-2-okso-1 -(piridin-2-ilmetil)-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino pripravimo iz 120 po postopkih, opisanih v primeru 25. MS: izrač.: (M-H)' = 421,15 m/z; ugot.: (M-H)' = 421,06 m/z.(3 S) -3 - [({[4-hydroxy-2-oxo-1- (pyridin-2-ylmethyl) -1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid was prepared from 120 according to the procedures described in Example 25. MS: calc .: (MH) '= 421.15 m / z; found: (M-H) '= 421.06 m / z.

Primer 27Example 27

Sinteza (3 S)-3 - {[({1 -[2-kloro-5-(metilsulfonil)benzil]-4-hidroksi-2-okso-1,2dihidropiridin-3 -il} amino)karbonil]amino} -3 -(4-metilfenil)propanoj ske kislineSynthesis of (3S) -3 - {[({1- [2-chloro-5- (methylsulfonyl) benzyl] -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl} amino) carbonyl] amino} - 3- (4-methylphenyl) propanoic acid

Stopnja ena: K raztopini 121 (pripravljeni iz 23 po postopkih, opisanih v primeru 4, 220 mg, 0,67 mmol) v brezvodnem CH2C12 (14 ml), ohlajeni na 0 °C, pod atmosfero suhega dušika dodamo m-CPBA (610 mg, 3,6 mmol). Dobljeno zmes pustimo ogreti na sobno temperaturo in mešamo 4 ure. Reakcijo razredčimo z vodo (50 ml) in vodno fazo ekstrahiramo s CH2C12 (2-krat). Združene organske sloje sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem z 9:1 CHCl3:MeOH, da dobimo 122 (219 mg, dobitek 91 %) kot rumeno trdno snov.Step One: To a solution of 121 (prepared from 23 according to the procedures described in Example 4, 220 mg, 0.67 mmol) in anhydrous CH 2 C1 2 (14 ml) cooled to 0 ° C, m- CPBA (610 mg, 3.6 mmol). The resulting mixture was allowed to warm to room temperature and stirred for 4 hours. The reaction was diluted with water (50 ml) and the aqueous phase extracted with CH 2 Cl 2 (2 times). The combined organic layers were dried over MgSO 4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 9: 1 CHCl 3 : MeOH to give 122 (219 mg, 91% yield) as a yellow solid.

(3S)-3-{[({l-[2-kloro-5-(metilsulfonil)benzil]-4-hidroksi-2-okso-l,2-dihidropiridin-3il}amino)karbonil]amino}-3-(4-metilfenil)propanojsko kislino pripravimo iz 122 po(3S) -3 - {[({1- [2-chloro-5- (methylsulfonyl) benzyl] -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid was prepared from 122 after

-115115 postopkih, opisanih v primeru 25. MS: izrač.: (M-H)' = 532,10 m/z; ugot.: (M-H)' =-115115 procedures described in Example 25. MS: Calc .: (M-H) '= 532.10 m / z; found: (M-H) '=

531,94 m/z.531.94 m / z.

Primer 28Example 28

Sinteza (3 S)-3 - [({[ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-i 1]amino}karbonil)amino]-3-(3-metilfenil)propanojske kislineSynthesis of (3S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (3-methylphenyl) propanoic acid

Stopnja ena: K raztopini 123 (70 mg, 0,13 mmol) v brezvodnem CH2C12 (3 ml), mešanje ob atmosferi dušika, dodamo ZnBr2 (200 mg, 0,82 mmol). Raztopino mešamo 1 uro pri 0 °C. Reakcijsko zmes pustimo ogreti na sobno temperaturo in mešamo preko noči. Pri tej točki dodamo vodo (50 ml) in zmes mešamo še 3 ure. Sloje ločimo in vodni sloj ekstrahiramo s CH2C12 (2-krat). Združene organske sloje sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3 S)-3-[({ [ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-metilfenil)propanojsko kislino 124 (60 mg, dobitek 95 %), MS: izrač.: (M-H)' = 484,13 m/z; ugot.: (M-H)' = 484,00 m/z.Step One: To a solution of 123 (70 mg, 0.13 mmol) in anhydrous CH 2 C1 2 (3 mL), stirring under a nitrogen atmosphere, ZnBr 2 (200 mg, 0.82 mmol) was added. The solution was stirred at 0 ° C for 1 hour. The reaction mixture was allowed to warm to room temperature and stirred overnight. Water (50 ml) was added at this point and the mixture was stirred for 3 hours. The layers were separated and the aqueous layer was extracted with CH 2 C1 2 (2 times). The combined organic layers were dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1 , 2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-methylphenyl) propanoic acid 124 (60 mg, 95% yield), MS: calc .: (MH) '= 484.13 m / z; found: (MH) '= 484.00 m / z.

Primer 29Example 29

Sinteza (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-5-propil-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojske kislineSynthesis of (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4 -methylphenyl) propanoic acid

Stopnja ena: Zmes malonil diklorida (25,0 g, 177 mmol) in valeronitrila (25,0 g, 300,7 mmol) v brezvodni atmosferi močno mešamo 24 ur pri sobni temperaturi. Dobljeni heterogeni zmesi dodamo dietil eter (50 ml). Oborino zberemo in izperemo z dietil etrom, da dobimo 125·ΗΟ kot belo trdno snov (20,2 g, 64 %).Step One: A mixture of malonyl dichloride (25.0 g, 177 mmol) and valeronitrile (25.0 g, 300.7 mmol) was stirred vigorously at room temperature for 24 hours. Diethyl ether (50 ml) was added to the resulting heterogeneous mixture. The precipitate was collected and washed with diethyl ether to give 125 · ΗΟ as a white solid (20.2 g, 64%).

Stopnja dve: K suspenziji 125·ΗΟ (6,10 g, 27,2 mmol) v EtOH (100 ml) dodamo trietilamin (5,8 g, 57,3 mmol) in paladij na oglju (10 % Pd na osnovi suhe mase, tip Degussa E101 NE/W, ~50% vodna vsebnost, 3,5 g, 1,6 mmol Pd). Atmosfero nadomestimo z vodikom (preklapljanje med vakuumom in vodikom iz balona 5-krat) in zmes mešamo preko noči, nato filtriramo. Filtrat koncentriramo pod zmanjšanimStep two: To a suspension of 125 · ΗΟ (6.10 g, 27.2 mmol) in EtOH (100 mL) was added triethylamine (5.8 g, 57.3 mmol) and palladium on charcoal (10% Pd on a dry weight basis) , Deguss type E101 NE / W, ~ 50% water content, 3.5 g, 1.6 mmol Pd). The atmosphere was replaced with hydrogen (switching between vacuum and hydrogen from the balloon 5 times) and the mixture was stirred overnight, then filtered. The filtrate was concentrated under reduced pressure

-116116 tlakom, da dobimo 126*2Et3NHCl (11,0 g, 94 %). Ta material uporabimo brez nadaljnjega čiščenja.-116116 pressure to give 126 * 2Et 3 NHCl (11.0 g, 94%). Use this material without further purification.

(3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-5 -propil-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino pripravimo iz 126*2Et3NHCl po postopkih, opisanih v primeru 25. MS: izrač.: (M-H)' = 496,16 m/z; ugot.: (M-H)' = 495,94 m/z.(3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- ( 4-methylphenyl) propanoic acid was prepared from 126 * 2Et 3 NHCl according to the procedures described in Example 25. MS: Calculated: (MH) '= 496.16 m / z; found: (MH) '= 495.94 m / z.

Primer 30Example 30

Sinteza (3S)-3-[({[l -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il] amino }karbonil)amino]-3 -(4-metilfenil) propanojske kislineSynthesis of (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid

Stopnja ena: K raztopini etil 2-oksociklopentankarboksilata (3,30 g, 21,1 mmol) v toluenu (45 ml) dodamo 4-klorobenzilamin (2,56 ml, 21,1 mmol). Dobljeno zmes refluktiramo preko noči z azeotropsko odstranitvijo vode preko Dean-Starkove pasti. Reakcijsko zmes koncentriramo pod zmanjšanim tlakom, da dobimo 127 (5,90 g, 99 %) kot rdeče olje. Ta material uporabimo brez čiščenja.Step One: To a solution of ethyl 2-oxocyclopentanecarboxylate (3.30 g, 21.1 mmol) in toluene (45 ml) was added 4-chlorobenzylamine (2.56 ml, 21.1 mmol). The resulting mixture was refluxed overnight by azeotropically removing water via a Dean-Stark trap. The reaction mixture was concentrated under reduced pressure to give 127 (5.90 g, 99%) as a red oil. Use this material without cleaning.

Stopnja dve: K raztopini 127 (11,0 g, 39,3 mmol) v brezvodnem THF (75 ml), ohlajeni na 0 °C, dodamo pod atmosfero suhega dušika NaH (60 % disperzija v mineralnem olju, 1,73 g, 43,2 mmol). Reakcijo mešamo 10 minut pri 0 °C, nato dodamo acetil klorid (3,9 ml, 55 mmol). Reakcijsko zmes pustimo, da se postopoma ogreje na sobno temperaturo, nato mešamo preko noči. Dobljeno zmes koncentriramo pod zmanjšanim tlakom in ostanku dodamo zmes ledene vode (200 ml) in HC1 (1 N, 200 ml). To zmes ekstrahiramo z etil acetatom (300 ml) ter etil acetatni sloj sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 128 (13,4 g) kot rjavo olje. Ta material vsebuje mineralno olje, vendar ga uporabimo brez čiščenja.Step two: To a solution of 127 (11.0 g, 39.3 mmol) in anhydrous THF (75 ml) cooled to 0 ° C was added under an atmosphere of dry nitrogen NaH (60% dispersion in mineral oil, 1.73 g, 43.2 mmol). The reaction was stirred for 10 minutes at 0 ° C, then acetyl chloride (3.9 ml, 55 mmol) was added. The reaction mixture was allowed to gradually warm to room temperature, then stirred overnight. The resulting mixture was concentrated under reduced pressure and a mixture of ice water (200 ml) and HCl (1 N, 200 ml) was added to the residue. This mixture was extracted with ethyl acetate (300 ml) and the ethyl acetate layer was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give 128 (13.4 g) as a brown oil. This material contains mineral oil, but it is used without cleaning.

-117117-117117

Stopnja tri: K raztopini surovega 128 (13,4 g, 39,3 mmol teor.) v brezvodnem THF (50 ml), ohlajeni na 0 °C, počasi preko brizge dodajamo pod atmosfero suhega dušika litijev bis(trimetilsilil)amid (1,0 M v THF, 125 ml, 125 mmol). Reakcijsko zmes pustimo ogreti na sobno temperaturo, nato mešamo preko noči. Zmes koncentriramo pod zmanjšanim tlakom in ostanek trituriramo z etil acetatom/heksanom in filtriramo. Trdno snov izperemo s HC1 (IN, 250 ml) in vodo (500 ml), da dobimo 129 (5,48 g, 48 % za dve stopnji) kot rjavo trdno snov.Step three: To a solution of crude 128 (13.4 g, 39.3 mmol. Theorem) in anhydrous THF (50 ml) cooled to 0 ° C was added slowly under a syringe of dry nitrogen an atmosphere of lithium bis (trimethylsilyl) amide (1 , 0 M in THF, 125 mL, 125 mmol). The reaction mixture was allowed to warm to room temperature, then stirred overnight. The mixture was concentrated under reduced pressure and the residue triturated with ethyl acetate / hexane and filtered. The solid was washed with HCl (1N, 250 ml) and water (500 ml) to give 129 (5.48 g, 48% in two steps) as a brown solid.

(3 S )-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino sintetiziramo iz 129 po postopkih, opisanih v primeru 25. MS: izrač.: (M+H)+= 496,16 m/z; ugot.: (M+H)+= 495,99 m/z.(3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl ) amino] -3- (4-methylphenyl) propanoic acid was synthesized from 129 according to the procedures described in Example 25. MS: calculated: (M + H) + = 496.16 m / z; found: (M + H) + = 495.99 m / z.

Primer 31Example 31

Sinteza (3 S)-3-[({ [4- {[(terc.-butilamino)karbonil] amino} -1 -(2-klorobenzil)-2-okso1,2-dihidropiridin-3-il ] amino} karbonil)amino]-3 -(4-metilfenil)propanoj ske kislineSynthesis of (3S) -3 - [({[4- {[(tert-butylamino) carbonyl] amino} -1- (2-chlorobenzyl) -2-oxo 1,2,2-dihydropyridin-3-yl] amino} carbonyl ) amino] -3- (4-methylphenyl) propanoic acid

Stopnja ena: K raztopini 46 (500 mg, 1,79 mmol) v brezvodnem THF (10 ml), ohlajeni na 0 °C, pod atmosfero suhega dušika dodamo NaH (60 % disperzija v mineralnem olju, 210 mg, 5,37 mmol) in dobljeno zmes mešamo 20 minut. K tej zmesi dodamo terc.butil izocianat (0,31 ml, 2,68 mmol) in reakcijsko zmes pustimo ogreti na sobno temperaturo, nato mešamo 2 dni. Reakcijsko zmes pogasimo z vodo in 2-krat ekstrahiramo z etil acetatom. Organske sloje združimo, sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 130 (660 mg, 97 %) kot rjavo trdno snov.Step One: To a solution of 46 (500 mg, 1.79 mmol) in anhydrous THF (10 ml) cooled to 0 ° C, NaH (60% mineral oil dispersion, 210 mg, 5.37 mmol) was added under dry nitrogen atmosphere. ) and the resulting mixture was stirred for 20 minutes. To this mixture was added tert-butyl isocyanate (0.31 ml, 2.68 mmol) and the reaction mixture was allowed to warm to room temperature, then stirred for 2 days. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The organic layers were combined, dried over MgSO 4 and filtered, and the filtrate was concentrated under reduced pressure to give 130 (660 mg, 97%) as a brown solid.

(3 S )-3 -[({[4- {[(terc.-butilamino)karbonil] amino } -1 -(2-klorobenzil)-2-okso-1,2dihidropiridin-3 -il] amino} karbonil)amino] -3 -(4-metilfenil)propanoj sko kislino pripravimo iz 130 po postopkih, opisanih v primeru 3. MS: izrač.: (M-H)' = 552,20 m/z; ugot.: (M-H)' = 551,89 m/z.(3 S) -3 - [({[4- {[(tert-butylamino) carbonyl] amino} -1- (2-chlorobenzyl) -2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid was prepared from 130 according to the procedures described in Example 3. MS: calc .: (MH) '= 552.20 m / z; found: (M-H) '= 551.89 m / z.

-118118-118118

Sintetske postopke, podobne tistim, opisanim zgoraj, lahko uporabimo, da dobimo spojine tabel 2, 3, 4 in 5.Synthetic procedures similar to those described above can be used to obtain compounds of Tables 2, 3, 4 and 5.

Primer 32Example 32

Sinteza (3S)-3-[({[5-kloro-l-(2-klorobenzil)-4-hidroksi-2-okso-l,2dihidropiridin-3 -il] amino } karbonil)amino] -3 -(4-metilfenil)propanoj ske kislineSynthesis of (3S) -3 - [({[5-chloro-1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3 - (4 -methylphenyl) propanoic acid

Stopnja ena: K raztopini 31 (350 mg, 0,72 mmol) v CH2C12 pri sobni temperaturi pod atmosfero suhega dušika dodamo z brizgo sulfurilklorid (1,0 M v CH2C12, 0,65 ml, 0,65 mmol). Dobljeno zmes mešamo 1 uro pri sobni temperaturi, nato porazdelimo med CH2C12 in vodo. Organski sloj izperemo s slanico, sušimo nad MgSO4 in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem z 8:1, nato 4:1 in končno 1:1 heksani:etil acetatu, da dobimo 131 (240 mg, 64 %).Step One: To a solution of 31 (350 mg, 0.72 mmol) in CH 2 Cl 2 at room temperature under a dry nitrogen atmosphere was added a syringe of sulfuryl chloride (1.0 M in CH 2 Cl 2 , 0.65 ml, 0.65 mmol). The resulting mixture was stirred for 1 hour at room temperature, then partitioned between CH 2 Cl 2 and water. The organic layer was washed with brine, dried over MgSO 4 and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 8: 1, then 4: 1 and finally 1: 1 hexanes: ethyl acetate to give 131 (240 mg, 64%).

(3 S)-3-[( {[5-kloro-1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4-metilfenil)propanojsko kislino sintetiziramo iz 131 po postopkih, opisanih v primeru 1. MS: izrač.: (M-H)' = 488,08; ugot.: (M-H)' = 487,97.(3 S) -3 - [({[5-chloro-1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- ( 4-methylphenyl) propanoic acid was synthesized from 131 according to the procedures described in Example 1. MS: calc .: (MH) '= 488.08; found: (M-H) '= 487.97.

Primer 33Example 33

Sinteza (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso1,2-dihidropiridin-3-il]amino}karbonil)amino]-3-(2',6'-dimetoksi-1,1'bifenil-4-il)propanojske kislineSynthesis of (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo 1,2,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- ( 2 ', 6'-dimethoxy-1,1'biphenyl-4-yl) propanoic acid

Stopnja ena: K raztopini (R)-(+)-N-benzil-a-metilbenzil amina (5,07 g, 24 mmol) v THF (85 ml) pod dušikom v buči, posušeni s plamenom, ohlajeni na -78 °C, dodajamo po kapljicah 30 minut sek.-butillitij (1,3 M raztopina v cikloheksanu, 18,0 ml, 23,4 mmol). Zmes mešamo še 30 minut pri -78 °C, nato po kapljicah dodamo raztopino tbutil 4-bromocinamata (5,1 g, 20 mmol) v THF (20 ml) in zmes pustimo, da pride na sobno temperaturo preko noči. Reakcijo pogasimo z dodatkom nasičenega amonijevega klorida (~50 ml) in organski sloj izperemo z nasičenim natrijevimStep One: To a solution of (R) - (+) - N-benzyl-α-methylbenzyl amine (5.07 g, 24 mmol) in THF (85 ml) under nitrogen in a flask, dried with flame, cooled to -78 ° C, 30-sec sec-butyllithium (1.3 M solution in cyclohexane, 18.0 mL, 23.4 mmol) was added dropwise. The mixture was stirred at -78 [deg.] C. for 30 minutes, then a solution of tbutyl 4-bromocinamate (5.1 g, 20 mmol) in THF (20 ml) was added dropwise and the mixture was allowed to come to room temperature overnight. The reaction was quenched by the addition of saturated ammonium chloride (~ 50 ml) and the organic layer was washed with saturated sodium

-119119 kloridom, sušimo nad MgSO4, nato filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s silikagelno kromatografijo z eluiranjem s heksani in naraščanjem na 3:1 heksanketil acetat, da dobimo 132 (4,33 g, 47 %) kot bledo rumeno olje.-119119 chloride, dried over MgSO 4 , then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with hexanes and increasing to 3: 1 hexanacetyl acetate to give 132 (4.33 g, 47%) as a pale yellow oil.

Stopnja dve: K raztopini 132 (7,4 g, 15 mmol) in 2,6-dimetoksifenil boronske kisline (4,9 g, 27 mmol) v DME (100 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo fino uprašen kalijev fosfat (8,0 g, 37,5 mM) in diklorobis(trifenilfosfin)paladij (0) (0,5 g, 0,75 mmol). Zmes deoksigeniramo (preklapljanje med vakuumom in dušikovim plinom 5-krat) in nato segrevamo na refluksu 8 ur. Zmes potem ohladimo in filtriramo skozi Celite® 521 in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem s heksani z naraščanjem na 3:1 heksanketil acetat, da dobimo 133 (7,8 g, dobitek 95 %).Step Two: Add finely powdered potassium phosphate to a solution of 132 (7.4 g, 15 mmol) and 2,6-dimethoxyphenyl boronic acid (4.9 g, 27 mmol) in DME (100 ml) at room temperature under a dry nitrogen atmosphere. (8.0 g, 37.5 mM) and dichlorobis (triphenylphosphine) palladium (0) (0.5 g, 0.75 mmol). The mixture was deoxygenated (switching between vacuum and nitrogen gas 5 times) and then refluxed for 8 hours. The mixture was then cooled and filtered through Celite® 521 and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with hexanes, increasing to 3: 1 hexanethyl acetate to give 133 (7.8 g, 95% yield).

Stopnja tri: K raztopini 133 (3,39 g, 6,1 mmol) v etanolu (80 ml) v 250 ml buči dodamo zaporedoma ocetno kislino (0,5 ml) in paladij na oglju (10 % Pd na osnovi suhe mase), vsebnost vode -50 %, Degussa tip E101 NE/W, 2,5 g, 1,2 mmol Pd). Zmes mešamo pod atmosfero dušika iz balona 36 ur. Reakcijsko zmes filtriramo skozi Celite® 521 in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek prekristaliziramo iz etil acetata, da dobimo 134*HOAc (1,0 g, 71 %) kot belo trdno snov.Step three: To a solution of 133 (3.39 g, 6.1 mmol) in ethanol (80 ml) in 250 ml of flask was added successively acetic acid (0.5 ml) and palladium on charcoal (10% Pd on a dry weight basis) , water content -50%, Degussa type E101 NE / W, 2.5 g, 1.2 mmol Pd). The mixture was stirred under an atmosphere of balloon nitrogen for 36 hours. The reaction mixture was filtered through Celite® 521 and the filtrate was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give 134 * HOAc (1.0 g, 71%) as a white solid.

(3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(2',6'-dimetoksi-l,r-bifenil-4-il)propanojsko kislino sintetiziramo iz 134*HOAc po postopkih, opisanih v primeru 25.(3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (2 ', 6'-Dimethoxy-1,1'-biphenyl-4-yl) propanoic acid was synthesized from 134 * HOAc according to the procedures described in Example 25.

MS: izmerj.: (M+H)+= 592,04; ugot.: (M+H)+= 592,19.MS: measured: (M + H) + = 592.04; found: (M + H) + = 592.19.

Primer 34Example 34

Sinteza (3S)-3-[({[2-(2-kloro-6-etoksibenzil)-5-hidroksi-6-metil-3-okso2,3-dihidropiridazin-4-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojske kislineSynthesis of (3S) -3 - [({[2- (2-chloro-6-ethoxybenzyl) -5-hydroxy-6-methyl-3-oxo2,3-dihydropyridazin-4-yl] amino} carbonyl) amino] - 3- (3-Ethoxyphenyl) propanoic acid

-120120-120120

Stopnja ena: K raztopini natrijevega t-butoksida (65 g, 0,642 mol) v THF (1 1) pri sobni temperaturi pod atmosfero suhega dušika dodajamo 10 minut etanol (250 ml,Step One: To a solution of sodium t-butoxide (65 g, 0.642 mol) in THF (1 L) at room temperature under an atmosphere of dry nitrogen was added ethanol (250 ml,

5,35 mol). K dobljeni raztopini dodamo po deležih 2-kloro-6-fluorobenzonitril (100 g, 0,642 mol). Reakcijsko zmes mešamo 30 minut pri sobni temperaturi in nato zmanjšamo na volumen približno 250 ml pod zmanjšanim tlakom. Dobljeno zmes zlijemo v kloroform in vodo ter sloje ločimo. Organski sloj izperemo z vodo (2-krat) in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo svetlo rumeno trdno snov. Ta material prekristaliziramo iz heksanov, da dobimo 2-kloro-6-etoksibenzonitril, 135 (101 g, dobitek 87 %) kot belo kristalno trdno snov.5.35 mol). 2-Chloro-6-fluorobenzonitrile (100 g, 0.642 mol) was added portionwise to the resulting solution. The reaction mixture was stirred for 30 minutes at room temperature and then reduced to a volume of about 250 ml under reduced pressure. The resulting mixture was poured into chloroform and water and the layers separated. The organic layer was washed with water (2 times) and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give a pale yellow solid. This material was recrystallized from hexanes to give 2-chloro-6-ethoxybenzonitrile, 135 (101 g, yield 87%) as a white crystalline solid.

Stopnja dve: K raztopini 2-kloro-6-etoksibenzonitrila, 135, (93,2 g, 0,513 mol) v THF (350 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo boran v THF (1,0 M, 620 ml, 0,62 mol). Dobljeno zmes segrevamo do refluksa 3 ure in nato ohladimo do sobne temperature. Vodo (250 ml) dodajamo zelo počasi k raztopini, pri čemer se razvija vodik. Nato več minut dodajamo koncentrirano HC1 (50 ml) in raztopino segrevamo na 50 °C 2 uri. Zmes ohladimo ter porazdelimo med kloroform in vodo. Vodni sloj izperemo 6-krat s kloroformom. Združene organske frakcije izperemo HC1 (1 M) in ta organski sloj zavržemo. Kloroform dodamo združenim vodnim slojem in trden KOH dodajamo, dokler vodna faza ni bazična (pH > 9). Vodni sloj še 5-krat izperemo s kloroformom. Organske frakcije združimo ter izperemo z vodo, slanico ter sušimo nad MgSO4 in silikagelom (2 g). Zmes filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 2-kloro-6-etoksibenzilamin, 136, (60,1 g, dobitek 64 %) kot svetlo rumeno olje.Step two: To a solution of 2-chloro-6-ethoxybenzonitrile, 135, (93.2 g, 0.513 mol) in THF (350 ml) at room temperature under an atmosphere of dry nitrogen was added borane in THF (1.0 M, 620 ml. 0.62 mol). The resulting mixture was heated to reflux for 3 hours and then cooled to room temperature. Water (250 ml) was added very slowly to the solution, developing hydrogen. Concentrated HCl (50 ml) was then added over several minutes and the solution heated to 50 ° C for 2 hours. The mixture was cooled and partitioned between chloroform and water. The aqueous layer was washed 6 times with chloroform. The combined organic fractions were washed with HCl (1 M) and discarded this organic layer. Chloroform was added to the combined aqueous layers and solid KOH was added until the aqueous phase was basic (pH> 9). The aqueous layer is washed with chloroform 5 more times. The organic fractions were combined and washed with water, brine and dried over MgSO 4 and silica gel (2 g). The mixture was filtered and the filtrate was concentrated under reduced pressure to give 2-chloro-6-ethoxybenzylamine, 136, (60.1 g, yield 64%) as a pale yellow oil.

Stopnja tri: K raztopini 2-kloro-6-etoksibenzilamina, 136, (7,30 g, 39,3 mmol) v ledoctu (50 ml) in acetanhidridu (50 ml) pri sobni temperaturi dodamo v majhnih deležih natrijev nitrit (6,00 g, 85,7 mmol). Dobljeno zmes mešamo pri sobni temperaturi preko noči, nato jo zlijemo na ledeno vodo in ekstrahiramo z etil acetatom. Organski sloj izperemo z vodnim NaOH (IN, 2 X 100 ml) in slanico (2-krat).Step three: To a solution of 2-chloro-6-ethoxybenzylamine, 136, (7.30 g, 39.3 mmol) in glacial (50 ml) and acetanhydride (50 ml) was added in small portions sodium nitrite (6, 00 g, 85.7 mmol). The resulting mixture was stirred at room temperature overnight, then poured onto ice water and extracted with ethyl acetate. The organic layer was washed with aqueous NaOH (IN, 2 X 100 ml) and brine (2 times).

-121121-121121

Organski sloj sušimo nad Na2SO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 137 (9,00 g, 100 %) kot svetlo rumeno trdno snov.The organic layer was dried over Na 2 SO 4 and filtered and the filtrate concentrated under reduced pressure to give 137 (9.00 g, 100%) as a pale yellow solid.

Stopnja štiri: K raztopini 137 (9,00 g, 39,3 mmol) in tetrabutilamonijevega bromida (1,0 g, 3,1 mmol) v THF (50 ml) pri sobni temperaturi počasi dodamo vodni NaOH (2N, 50 ml, 100 mmol) in zmes segrevamo na 45 °C preko noči. Reakcijsko zmes ohladimo na sobno temperaturo, nato razredčimo z vodo in ekstrahiramo z etil acetatom. Organski sloj izperemo s slanico, sušimo nad Na2SO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 138 (7,08 g, dobitek 96 %).Step four: To a solution of 137 (9.00 g, 39.3 mmol) and tetrabutylammonium bromide (1.0 g, 3.1 mmol) in THF (50 ml), aqueous NaOH (2N, 50 ml) was slowly added at room temperature. 100 mmol) and the mixture was heated to 45 ° C overnight. The reaction mixture was cooled to room temperature, then diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na 2 SO 4 and filtered, and the filtrate was concentrated under reduced pressure to give 138 (7.08 g, 96% yield).

Stopnja pet: K raztopini 138 (7,08 g, 37,9 mmol) v CH2C12 (55 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo po kapljicah raztopino SOC12 (9,0 ml, 120 mmol) v CH2C12 (30 ml). Dobljeno zmes mešamo pri sobni temperaturi preko noči, nato zlijemo v ledeno vodo. Vodni sloj ekstrahiramo s CH2C12 ter združene organske sloje izperemo z vodnim NaOH (IN, 2-krat), vodo (3-krat) in slanico (2krat). Organski sloj sušimo nad Na2SO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 2-kloro-6-etoksibenzilklorid 139 (6,69 g, dobitek 86 %) kot viskozno rjavo olje.Step Five: To a solution of 138 (7.08 g, 37.9 mmol) in CH 2 C1 2 (55 ml) at room temperature under a dry nitrogen atmosphere was added dropwise a solution of SOC1 2 (9.0 ml, 120 mmol) in CH 2 C1 2 (30 ml). The resulting mixture was stirred at room temperature overnight, then poured into ice water. The aqueous layer was extracted with CH 2 Cl 2 and the combined organic layers were washed with aqueous NaOH (IN, 2 times), water (3 times) and brine (2 times). The organic layer was dried over Na 2 SO 4 and filtered and the filtrate concentrated under reduced pressure to give 2-chloro-6-ethoxybenzyl chloride 139 (6.69 g, yield 86%) as a viscous brown oil.

Stopnja šest: Raztopino 2-kloro-6-etoksibenzilklorida, 139 (6,90 g, 33,7 mmol) in hidrazina (21,60 g, 673 mmol) v MeOH (22 ml) mešamo pri sobni temperaturi 3 ure. Zmes nato porazdelimo med CH2C12 in vodo. Organski sloj sušimo nad MgSO4, in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 140 (6,18 g, 92 %).Step Six: A solution of 2-chloro-6-ethoxybenzyl chloride, 139 (6.90 g, 33.7 mmol) and hydrazine (21.60 g, 673 mmol) in MeOH (22 ml) was stirred at room temperature for 3 hours. The mixture was then partitioned between CH 2 C1 2 and water. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure to give 140 (6.18 g, 92%).

Stopnja sedem: K suspenziji etil piruvata (3,85 ml, 33,7 mmol) in MgSO4 v CHC13 (65 ml) počasi dodamo raztopino 140 (6,14 g, 30,6 mmol) v CHC13 (30 ml). Dobljeno zmes mešamo preko noči pri sobni temperaturi. Dobljeno zmes filtriramo in filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 141 (8,43 g, 92 %). Ta material uporabimo v naslednji stopnji brez čiščenja.Step seven: To a suspension of ethyl pyruvate (3.85 ml, 33.7 mmol) and MgSO 4 in CHC1 3 (65 ml) was slowly added a solution of 140 (6.14 g, 30.6 mmol) in CHC1 3 (30 ml). . The resulting mixture was stirred overnight at room temperature. The resulting mixture was filtered and the filtrate was concentrated under reduced pressure to give 141 (8.43 g, 92%). Use this material in the next step without cleaning.

-122122-122122

Stopnja osem: K raztopini 141 (8,43 g, 28,2 mmol) v suhem THF (110 ml), ohlajeni na 0 °C, pod atmosfero suhega dušika, dodamo v enem deležu natrijev hidrid (60 % disperzija v mineralnem olju, 1,88 g, 47,1 mmol). Dobljeno zmes mešamo pri 0 °C 30 minut, nato počasi dodamo metil malonilklorid (6,63 g, 47,10 mmol). Zmes pustimo ogreti na sobno temperaturo, mešamo preko noči, skrbno pogasimo z vodo, nato ekstrahiramo z etil acetatom (2-krat). Organske sloje združimo, izperemo s slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 142 (14,29 g). Ta material uporabimo v naslednji stopnji brez nadaljnjega čiščenja.Step eight: To a solution of 141 (8.43 g, 28.2 mmol) in dry THF (110 ml) cooled to 0 ° C under an atmosphere of dry nitrogen, sodium hydride (60% dispersion in mineral oil, in one portion) was added. 1.88 g, 47.1 mmol). The resulting mixture was stirred at 0 ° C for 30 minutes, then methyl malonyl chloride (6.63 g, 47.10 mmol) was added slowly. The mixture was allowed to warm to room temperature, stirred overnight, carefully quenched with water, then extracted with ethyl acetate (2 times). The organic layers were combined, washed with brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give 142 (14.29 g). Use this material in the next step without further purification.

Stopnja devet: K raztopini surovega 142 (14,29 g) v suhem DMF (60 ml), ohlajeni na 0 °C, pod atmosfero suhega dušika dodamo v enem deležu natrijev hidrid (60 % disperzija v mineralnem olju, 2,90 g, 72,2 mmol). To raztopino segrevamo na 60 °C preko noči, ohladimo na ledeni kopeli, nato stresamo s heksanom. Sloje ločimo in DMF sloj zlijemo v ledeno vodo. Zmes nakisamo (pH 1) z dodatkom HC1 (2N). Oborino zberemo s filtracijo in raztopimo v etil acetatu. Organsko raztopino sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo, da dobimo 143 (8,42 g, dobitek 85 %) za dve stopnji.Step nine: To a solution of crude 142 (14.29 g) in dry DMF (60 ml) cooled to 0 ° C, sodium hydride (60% dispersion in mineral oil, 2.90 g, was added in one portion) under a dry nitrogen atmosphere. 72.2 mmol). This solution was heated to 60 ° C overnight, cooled in an ice bath, then shaken with hexane. The layers are separated and the DMF layer is poured into ice water. The mixture was acidified (pH 1) with the addition of HC1 (2N). The precipitate was collected by filtration and dissolved in ethyl acetate. The organic solution was dried over MgSO 4 and filtered and the filtrate concentrated to give 143 (8.42 g, 85% yield) in two steps.

Stopnja deset: Raztopino 143 (8,42 g, 23,9 mmol) v dioksanu (100 ml) in vodni HC1 (60 ml, 5,2 N) refluktiramo preko noči. Zmes ohladimo na sobno temperaturo, razredčimo z vodo in ekstrahiramo z etil acetatom. Organski sloj izperemo s slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:1 etil acetatom.heksani, nato etil acetatom in končno 9:1 etil acetatom:metanolu, da dobimo 144 (2,0 g, 28 %).Step Ten: A solution of 143 (8.42 g, 23.9 mmol) in dioxane (100 mL) and aqueous HCl (60 mL, 5.2 N) was refluxed overnight. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 1: 1 ethyl acetate.hexanes followed by ethyl acetate and finally 9: 1 ethyl acetate: methanol to give 144 (2.0 g, 28%).

(3S)-3-[({[2-(2-kloro-6-etoksibenzil)-5-hidroksi-6-metil-3-okso2,3-dihidropiridazin-4-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojsko kislino pripravimo iz 144 po postopkih, opisanih v primeru 25. MS: izmerj.: (M+H)+= 545,05; izrač.: (M+H)+= 545,18.(3S) -3 - [({[2- (2-chloro-6-ethoxybenzyl) -5-hydroxy-6-methyl-3-oxo2,3-dihydropyridazin-4-yl] amino} carbonyl) amino] -3 - (3-Ethoxyphenyl) propanoic acid was prepared from 144 according to the procedures described in Example 25. MS: Measure: (M + H) + = 545.05; Calcd. (M + H) + = 545.18.

-123123-123123

Primer 35Example 35

Sinteza (3 S )-3-(( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(l,3-dietil-2-okso-2,3-dihidro-lHbenzimidazol-5-il propanojske kislineSynthesis of (3S) -3 - (({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (1,3-diethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl propanoic acid)

Stopnja ena: Ledeno hladno zmes natrijevega hidrida (8,00 g, 60 % disperzija v mineralnem olju, 200 mmol) in 145 (8,94 g, 66,6 mmol) v DMF (250 ml) pod atmosfero suhega dušika pustimo počasi ogreti na sobno temperaturo. Dobljeni zmesi dodamo jodoetan (16 ml, 200 mmol) in zmes mešamo preko noči pri sobni temperaturi. Reakcijsko zmes zlijemo v led in ekstrahiramo z etil acetatom. Organski sloj izperemo z vodo in slanico, sušimo nad Na2SO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom ter ostanek prevzamemo v heksanih in filtriramo. Dobljeno rjavo trdno snov sušimo pod zmanjšanim tlakom, da dobimo 146 (9,00 g, dobitek 71 %). Ta material uporabimo brez čiščenja.Step One: The ice cold mixture of sodium hydride (8.00 g, 60% dispersion in mineral oil, 200 mmol) and 145 (8.94 g, 66.6 mmol) in DMF (250 ml) was allowed to warm slowly under a dry nitrogen atmosphere to room temperature. The resulting mixture was added iodoethane (16 ml, 200 mmol) and the mixture was stirred overnight at room temperature. The reaction mixture was poured into ice and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na 2 SO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was taken up in hexanes and filtered. The resulting brown solid was dried under reduced pressure to give 146 (9.00 g, 71% yield). Use this material without cleaning.

Stopnja dve: Zmes DMF (3,6 g, 49 mmol) in POC13 (9,6 ml, 100 mmol) mešamo pri sobni temperaturi pod atmosfero suhega dušika 1 uro. Bučo, ki vsebuje to zmes, nato damo v oljno kopel s 45 °C in v majhnih deležih dodamo 146 (7,6 g, 40 mmol). Temperaturo oljne kopeli dvignemo na 70 °C in zmes mešamo preko noči, nato ohladimo na sobno temperaturo. Zmes razredčimo z vodo in ekstrahiramo z etil acetatom. Organski sloj izperemo z vodo in slanico, sušimo nad Na2SO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 7:3 zmes 147:146 (6,69 g). Ta material uporabimo brez čiščenja.Step Two: A mixture of DMF (3.6 g, 49 mmol) and POCl 3 (9.6 ml, 100 mmol) was stirred at room temperature under a dry nitrogen atmosphere for 1 hour. The flask containing this mixture was then placed in an oil bath at 45 ° C and 146 (7.6 g, 40 mmol) was added in small portions. The oil bath temperature was raised to 70 ° C and the mixture was stirred overnight, then cooled to room temperature. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na 2 SO 4 and filtered. The filtrate was concentrated under reduced pressure to give a 7: 3 mixture of 147: 146 (6.69 g). Use this material without cleaning.

Stopnja tri: K raztopini zmesi 147:146, dobljeni zgoraj (2,2 g), v etanolu (2,2 ml) dodamo zaporedoma malonsko kislino (1,16 g, 11,2 mmol), piridin (0,44 ml) in piperidin (0,99 ml). Dobljeno zmes segrevamo do refluksa 6 ur, nato ohladimo na sobno temperaturo. Zmes razredčimo z vodnim NaOH (IN) in ekstrahiramo z etil acetatom (4-krat). Vodno fazo nakisamo na pH 3 s HC1 (IN) in dobljeno suspenzijo filtriramo, izpiranje trdne snovi z vodo. Belo trdno snov zberemo in sušimo pod zmanjšanim tlakom, da dobimo 148 (1,69 g, 49 % za dve stopnji).Step Three: To a solution of the 147: 146 mixture obtained above (2.2 g), in ethanol (2.2 ml) was added sequentially malonic acid (1.16 g, 11.2 mmol), pyridine (0.44 ml) and piperidine (0.99 ml). The resulting mixture was heated to reflux for 6 hours, then cooled to room temperature. The mixture was diluted with aqueous NaOH (IN) and extracted with ethyl acetate (4 times). The aqueous phase was acidified to pH 3 with HCl (IN) and the resulting suspension filtered, washing the solid with water. The white solid was collected and dried under reduced pressure to give 148 (1.69 g, 49% in two steps).

-124124 (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 -il] amino } karbonil)amino]-3 -(1,3 -dietil-2-okso2,3-dihidro-lH-benzimidazol-5-il)propanojsko kislino pripravimo iz 148 po postopkih, opisanih v primerih 33 in 25. MS: izmerj.: (M+H)+ = 594,05; izrač.: (M+H)+= 594,21.-124124 (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl] amino } carbonyl) amino] -3- (1,3-diethyl-2-oxo2,3-dihydro-1H-benzimidazol-5-yl) propanoic acid was prepared from 148 according to the procedures described in Examples 33 and 25. MS: meas. : (M + H) + = 594.05; Calcd. (M + H) + = 594.21.

Primer 36Example 36

Sinteza (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso1,2-dihidropiridin-3 -il] amino} karbonil)amino] -3 -(4-metilfenil)propanoj ske kisline, 153Synthesis of (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo 1,2,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3 - (4-methylphenyl) propanoic acid, 153

Stopnja ena: K raztopini 114 (20,3 g, 129 mmol) v brezvodnem metanolu (430 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo 2-kloro-6-etoksibenzilamin, 136 (31,1 g, 168 mmol). Raztopino segrevamo pri 45 °C 1 uro, nato refluktiramo preko noči. Reakcijsko zmes ohladimo na sobno temperaturo in koncentriramo do suhega. Ostanek prevzamemo v diklorometanu in filtriramo. Trdno snov zberemo in posušimo pod vakuumom, da dobimo 149 (14,7 g, 39 %).Step One: To a solution of 114 (20.3 g, 129 mmol) in anhydrous methanol (430 ml) at room temperature under an atmosphere of dry nitrogen was added 2-chloro-6-ethoxybenzylamine, 136 (31.1 g, 168 mmol). The solution was heated at 45 ° C for 1 hour, then refluxed overnight. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was taken up in dichloromethane and filtered. The solid was collected and dried under vacuum to give 149 (14.7 g, 39%).

Stopnja dve: K suspenziji 149 (11,02 g, 37,8 mmol) v ledoctu (126 ml) pri sobni temperaturi zaporedoma dodamo NaNO2 (522 mg, 7,6 mmol), vodo (10,5 ml) in HNO3 (70 %, 9,6 ml, 151,2 mmol). Dobljeno svetlo rumeno raztopino mešamo pri sobni temperaturi preko noči, nato razredčimo s CH2C12 in vodo. Vodno fazo ekstrahiramo s CH2C12, organske sloje združimo in izperemo z vodo (3-krat) in slanico. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom. Ostanek prekristaliziramo iz CH2Cl2/etil acetata, da dobimo 150 (10,9 g, 85 %) kot svetlo rumeno trdno snov.Step Two: NaNO 2 (522 mg, 7.6 mmol), water (10.5 ml) and HNO 3 were successively added to a suspension of 149 (11.02 g, 37.8 mmol) in ice (126 ml) at room temperature. (70%, 9.6 ml, 151.2 mmol). The resulting light yellow solution was stirred at room temperature overnight, then diluted with CH 2 Cl 2 and water. The aqueous phase was extracted with CH 2 Cl 2 , the organic layers were combined and washed with water (3 times) and brine. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure. The residue was recrystallized from CH 2 Cl 2 / ethyl acetate to give 150 (10.9 g, 85%) as a pale yellow solid.

Stopnja tri: K raztopini 150 (10,9 g, 32,2 mmol) v DMF (107 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo Zn prah (9,48 g, 145 mmol) in trietilaminhidroklorid (24,4 g, 177 mmol). Dobljeno zmes segrevamo na 55 °C 1 uro,Step Three: To a solution of 150 (10.9 g, 32.2 mmol) in DMF (107 ml) at room temperature under an atmosphere of dry nitrogen was added Zn powder (9.48 g, 145 mmol) and triethylamine hydrochloride (24.4 g, 177 mmol). The resulting mixture was heated to 55 ° C for 1 hour,

-125125 nato ohladimo na sobno temperaturo. K dobljeni zmesi dodamo CDI (10,4 g, 64,4 mmol) kot trdno snov. Po dodatku pride do razvijanja plina. Zmes nato segrevamo na 80 °C 2 uri, ohladimo na sobno temperaturo in zlijemo v HC1 (2 N, 1 1). Dobljeno suspenzijo mešamo 20 minut ter nato razredčimo z vodo (1 1) in filtriramo. Trdno snov resuspendiramo v vodi (1 1) in nato filtriramo. Trdno snov sušimo v vakuumu, da dobimo 151 (10,78 g, dobitek 100 %) kot bel prah.-125125 is then cooled to room temperature. CDI (10.4 g, 64.4 mmol) was added to the resulting mixture as a solid. After the addition, gas develops. The mixture was then heated to 80 ° C for 2 hours, cooled to room temperature and poured into HCl (2 N, 1 L). The resulting suspension was stirred for 20 minutes and then diluted with water (1 L) and filtered. The solid was resuspended in water (1 L) and then filtered. The solid was dried in vacuo to give 151 (10.78 g, 100% yield) as a white powder.

Stopnja štiri: Zmes 151 (10,68 g, 31,9 mmol) in 8 (8,27 g, 39,9 mmol) v DMF (64 ml) pod atmosfero suhega dušika segrevamo na 55 °C preko noči, ohladimo na sobno temperaturo in nato razredčimo z etil acetatom. Dobljeno zmes izperemo s HC1 (2N), vodo (4-krat) in slanico ter organski sloj sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in dobljeni ostanek čistimo s silikagelno kromatografijo, z eluiranjem s 7:3 heksanketil acetatu, da dobimo 152 (14,2 g, 82 %) kot bledo rumeno peno.Step four: A mixture of 151 (10.68 g, 31.9 mmol) and 8 (8.27 g, 39.9 mmol) in DMF (64 ml) was heated to 55 ° C overnight under dry nitrogen, cooled to room temperature temperature and then diluted with ethyl acetate. The resulting mixture was washed with HCl (2N), water (4 times) and brine, and the organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography eluting with 7: 3 hexanacetyl acetate to give 152 (14.2 g, 82%) as a pale yellow foam.

Stopnja pet: K raztopini 152 (11,60 g, 21,4 mmol) v THF (138 ml) pri sobni temperaturi dodamo vodni natrijev hidroksid (2 N, 46 ml) in metanol (92 ml). Zmes mešamo 20 minut, nato razredčimo z vodo ter ekstrahiramo z etil etrom. Vodno fazo nakisamo s HC1 (2 N) in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5metil-2-okso-1,2-dihidrop iri din-3-i 1] amino} karbonil)amino] -3 -(4metilfenil)propanojsko kislino, 153, (10,82, dobitek 98 %) kot svetlo rjavo peno. MS: izrač.: (M-H)' = 512,16; izmerj.: (M-H)' = 512,03.Step Five: To a solution of 152 (11.60 g, 21.4 mmol) in THF (138 ml) at room temperature was added aqueous sodium hydroxide (2 N, 46 ml) and methanol (92 ml). The mixture was stirred for 20 minutes, then diluted with water and extracted with ethyl ether. The aqueous phase was acidified with HCl (2 N) and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5methyl-2-oxo-1,2-dihydropyridine-3- i 1] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid, 153, (10.82, yield 98%) as a light brown foam. MS: calc .: (MH) '= 512.16; measured: (MH) '= 512.03.

Primer 37Example 37

Sinteza (3 S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-oksol,2-dihidropiridin-3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojske kisline, 156Synthesis of (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxole, 2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-Ethoxyphenyl) propanoic acid, 156

-126126-126126

Stopnja ena: Zmes 151 (8,40 g, 28,8 mmol) in 154 (8,2 g, 35 mmol) v DMF (100 ml) pod atmosfero suhega dušika segrevamo preko noči na 55 °C, ohladimo na sobno temperaturo in nato razredčimo z etil acetatom. Dobljeno zmes izperemo s HC1 (2N), vodo (4-krat) in slanico ter organski sloj sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in dobljeni ostanek očistimo s silikagelno kromatografijo, z eluiranjem z 8:2, ki naraste na 1:1, heksanketil acetatu, da dobimo 155(11,1 g, dobitek 67%).Step One: A mixture of 151 (8.40 g, 28.8 mmol) and 154 (8.2 g, 35 mmol) in DMF (100 ml) under dry nitrogen was heated to 55 ° C overnight, cooled to room temperature and then diluted with ethyl acetate. The resulting mixture was washed with HCl (2N), water (4 times) and brine, and the organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography eluting with 8: 2 increasing to 1: 1 hexanethyl acetate to give 155 (11.1 g, yield 67%).

Stopnja dve: K raztopini 155 (9,12 g, 15,9 mmol) v THF (100 ml) pri sobni temperaturi dodamo vodni natrijev hidroksid (1 N, 88 ml) in metanol (63 ml). Zmes mešamo 20 minut, nato razredčimo z vodo in ekstrahiramo z etil etrom. Ta etrski sloj zavržemo. Vodno fazo nakisamo s HC1 (2 N) in ekstrahiramo z etil etrom (4-krat). Organske sloje izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-[({[l-(2-kloro-6etoksibenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojsko kislino, 156 (8,13 g, 93 %) kot belo peno. MS: izrač.: (M+H)+= 544,19; izmerj.: (M+H)+= 544,04.Step two: To a solution of 155 (9.12 g, 15.9 mmol) in THF (100 ml) at room temperature was added aqueous sodium hydroxide (1 N, 88 ml) and methanol (63 ml). The mixture was stirred for 20 minutes, then diluted with water and extracted with ethyl ether. We discard this ether layer. The aqueous phase was acidified with HCl (2 N) and extracted with ethyl ether (4 times). The organic layers were washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - [({[1- (2-chloro-6ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, 156 (8.13 g, 93%) as a white foam. MS: calc .: (M + H) + = 544.19; measured: (M + H) + = 544.04.

Primer 38Example 38

Sinteza (3S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-oksol,2-dihidropiridin-3-il]amino}karbonil)amino]-3-(6-metoksi-2-naftil)propanojske kisline, 159.Synthesis of (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxol, 2-dihydropyridin-3-yl] amino} carbonyl) amino] - 3- (6-Methoxy-2-naphthyl) propanoic acid, 159.

Stopnja ena: Zmes 151 (110 mg, 0,29 mmol), 157 (130 mg, 0,34 mmol) in NMM (0,50 ml, 4,5 mmol) v DMF (1,0 ml) pod atmosfero suhega dušika segrejemo preko noči na 55 °C, ohladimo na sobno temperaturo in nato razredčimo z etil acetatom. Dobljeno zmes izperemo s HC1 (2N), vodo (4-krat) in slanico ter organski sloj sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in dobljeni ostanek čistimo s silikagelno kromatografijo, z eluiranjem z 1:1 heksanketil acetatu, da dobimo 158 (130 mg, dobitek 73 %).Step One: A mixture of 151 (110 mg, 0.29 mmol), 157 (130 mg, 0.34 mmol) and NMM (0.50 mL, 4.5 mmol) in DMF (1.0 mL) under a dry nitrogen atmosphere heated overnight to 55 ° C, cooled to room temperature and then diluted with ethyl acetate. The resulting mixture was washed with HCl (2N), water (4 times) and brine, and the organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography eluting with 1: 1 hexanethyl acetate to give 158 (130 mg, yield 73%).

-127127-127127

Stopnja dve: K raztopini 158 (130 mg, 0,21 mmol) v THF (3 ml) pri sobni temperaturi dodamo vodni natrijev hidroksid (2 N, 1 ml) in metanol (2 ml). Zmes mešamo 20 minut, nato razredčimo z vodo in ekstrahiramo z etil etrom. Vodno fazo nakisamo s HC1 (2 N) in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-oksol,2-dihidropiridin-3-il]amino}karbonil)amino]-3-(6-metoksi-2-naftil)propanojsko kislino, 159, (90 mg, dobitek 74 %). MS: izmerj.: (M+H)+ = 580,07; izrač.: (M+H)+ = 580,19.Step two: To a solution of 158 (130 mg, 0.21 mmol) in THF (3 ml) at room temperature was added aqueous sodium hydroxide (2 N, 1 ml) and methanol (2 ml). The mixture was stirred for 20 minutes, then diluted with water and extracted with ethyl ether. The aqueous phase was acidified with HCl (2 N) and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxol, 2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (6-methoxy-2-naphthyl) propanoic acid, 159, (90 mg, yield 74%). MS: measured: (M + H) + = 580.07; Calcd. (M + H) + = 580.19.

Primer 39Example 39

Sinteza (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il] amino} karbonil)amino] -3 -(3 izopropoksifenil)propanojske kisline, 164Synthesis of (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3 isopropoxyphenyl) propanoic acid, 164

Stopnja ena: K suspenziji 129 (5,30 g, 19,2 mmol) v ledoctu (64 ml) pri sobni temperaturi zaporedoma dodamo NaNO2 (266 mg, 3,9 mmol), vodo (5,3 ml) in HNO3 (70 %, 4,9 ml, 77 mmol). Dobljeno svetlo rumeno raztopino mešamo pri sobni temperaturi preko noči, nato zlijemo v vodo in filtriramo, izpiranje z vodo. Rumeno trdno snov sušimo pod zmanjšanim tlakom, da dobimo 160 (5,35 g, 87 %).Step One: To a suspension of 129 (5.30 g, 19.2 mmol) in ice (64 ml) at room temperature was added successively NaNO 2 (266 mg, 3.9 mmol), water (5.3 ml) and HNO 3. (70%, 4.9 ml, 77 mmol). The resulting light yellow solution was stirred at room temperature overnight, then poured into water and filtered, washing with water. The yellow solid was dried under reduced pressure to give 160 (5.35 g, 87%).

Stopnja dve: K raztopini 160 (5,35 g, 16,7 mmol) v DMF (56 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo Zn prah (4,88 g, 74,7 mmol) in trietilamin hidroklorid (12,6 g, 91,5 mmol). Dobljeno zmes segrevamo na 55 °C 1 h, nato ohladimo na sobno temperaturo. K dobljeni zmesi dodamo CDI (5,41 g, 33,4 mmol) kot trdno snov. Po dodatku pride do razvijanja plina. Zmes nato segrevamo na 80 °C 2 uri, ohladimo na sobno temperaturo in zlijemo v HC1 (2 N, 500 ml). Dobljeno suspenzijo mešamo 20 minut ter nato razredčimo z vodo (500 ml) in filtriramo. Trdno snov resuspendiramo v vodi (500 ml) in nato filtriramo. Trdno snov sušimo pod vakuumom, da dobimo 161 (5,0 g, dobitek 95 %) kot bel prah.Step two: To a solution of 160 (5.35 g, 16.7 mmol) in DMF (56 ml) at room temperature under an atmosphere of dry nitrogen was added Zn powder (4.88 g, 74.7 mmol) and triethylamine hydrochloride (12, 6 g, 91.5 mmol). The resulting mixture was heated to 55 ° C for 1 h, then cooled to room temperature. CDI (5.41 g, 33.4 mmol) was added to the resulting mixture as a solid. After the addition, gas develops. The mixture was then warmed to 80 ° C for 2 hours, cooled to room temperature and poured into HCl (2 N, 500 ml). The resulting suspension was stirred for 20 minutes and then diluted with water (500 ml) and filtered. The solid was resuspended in water (500 ml) and then filtered. The solid was dried in vacuo to give 161 (5.0 g, 95% yield) as a white powder.

-128128-128128

Stopnja tri: Zmes 161 (6,14 g, 19,4 mmol) in 162 (5,12 g, 20,3 mmol) v DMF (90 ml) pod atmosfero suhega dušika segrevamo preko noči na 80 °C, ohladimo na sobno temperaturo in nato razredčimo z etil acetatom. Dobljeno zmes izperemo s HC1 (2 N), vodo (4-krat) in slanico ter organski sloj sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in dobljeni ostanek čistimo s silikagelno kromatografijo, z eluiranjem s 7:3 heksani:etil acetatu, da dobimo 163 (8,90 g, 81 %) kot bledo rumeno peno.Step Three: A mixture of 161 (6.14 g, 19.4 mmol) and 162 (5.12 g, 20.3 mmol) in DMF (90 ml) under dry nitrogen was heated at 80 ° C overnight, cooled to room temperature temperature and then diluted with ethyl acetate. The resulting mixture was washed with HCl (2 N), water (4 times) and brine, and the organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue purified by silica gel chromatography eluting with 7: 3 hexanes: ethyl acetate to give 163 (8.90 g, 81%) as a pale yellow foam.

Stopnja štiri: K raztopini 163 (8,69 g, 15,3 mmol) v THF (35 ml) pri sobni temperaturi dodamo vodni natrijev hidroksid (2 N, 30 ml) in metanol (30 ml). Zmes mešamo preko noči, nato razredčimo z vodo in ekstrahiramo z etil etrom. Vodno fazo nakisamo s HC1 (2 N) in ekstrahiramo z etil acetatom. Etil acetatni sloj izperemo z vodo in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3izopropoksifenil)propanojsko kislino, 164, (7,50 g, dobitek 91 %). MS: izmerj.: (M+H)+ = 540,09; izrač.: (M+H)+ - 540,19.Step four: To a solution of 163 (8.69 g, 15.3 mmol) in THF (35 ml) at room temperature was added aqueous sodium hydroxide (2 N, 30 ml) and methanol (30 ml). The mixture was stirred overnight, then diluted with water and extracted with ethyl ether. The aqueous phase was acidified with HCl (2 N) and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridine- 3-yl] amino} carbonyl) amino] -3- (3isopropoxyphenyl) propanoic acid, 164, (7.50 g, 91% yield). MS: measured: (M + H) + = 540.09; Calcd. (M + H) + - 540.19.

Primer 40Example 40

Sinteza (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(4-kloro-3izopropoksifenil)propanoj ske kislineSynthesis of (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino} carbonyl ) amino] -3- (4-chloro-3isopropoxyphenyl) propanoic acid

Stopnja ena: K zmesi 162 (200 mg, 0,80 mmol) v ledoctu (1,65 ml) ohlajeni na 0 °C, pod atmosfero suhega dušika, dodamo po kapljicah z brizgo zmes SO2C12 (1,2 ml, 15 mmol) v ledoctu (1,0 ml). Dobljeno zmes mešamo pri 0 °C 30 minut, nato ogrejemo na sobno temperaturo. Po mešanju še 4 ure zmes ponovno ohladimo na 0 °C in pogasimo s skrbnim dodatkom nasičenega vodnega NaHCO3. Zmes ekstrahiramo z etil acetatom in organski sloj izperemo z nasičenim vodnim NaHCO3, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo sStep One: To a mixture of 162 (200 mg, 0.80 mmol) in ice (1.65 ml) cooled to 0 ° C under an atmosphere of dry nitrogen was added dropwise a syringe of a mixture of SO 2 C1 2 (1.2 ml, 15 mmol) in ice (1.0 ml). The resulting mixture was stirred at 0 ° C for 30 minutes, then warmed to room temperature. After stirring for another 4 hours, the mixture was cooled again to 0 ° C and quenched with the careful addition of saturated aqueous NaHCO 3 . The mixture was extracted with ethyl acetate and the organic layer was washed with saturated aqueous NaHCO 3 , dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by

-129129 silikagelno kromatografijo z eluiranjem z 2:1 heksaniretil acetatu, da dobimo 165 (148 mg, 65 %).-129129 silica gel chromatography eluting with 2: 1 hexanyreethyl acetate to give 165 (148 mg, 65%).

(3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(4-kloro-3izopropoksifenil)propanojsko kislino pripravimo iz 165 po postopkih, opisanih v primerih 25 in 30. MS: izrač.: (M-H)'= 586,15; ugot.: (M-H)'= 585,29.(3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino} carbonyl ) amino] -3- (4-chloro-3isopropoxyphenyl) propanoic acid was prepared from 165 according to the procedures described in Examples 25 and 30. MS: Calculated: (MH) '= 586.15; found: (M-H) '= 585.29.

Primer 41Example 41

Sinteza (3S)-3-({ [(1 - {[2-kloro-6-tetrahidro- l(2H)-piridinilfenil]metil}-4-hidroksi-5metil-2-okso-1,2-dihidro-3-piridinil)amino]karbonil} amino)-3-(4metilfenil)propanojske kislineSynthesis of (3S) -3 - ({[(1 - {[2-chloro-6-tetrahydro-1 (2H) -pyridinylphenyl] methyl} -4-hydroxy-5methyl-2-oxo-1,2-dihydro-3 -pyridinyl) amino] carbonyl} amino) -3- (4methylphenyl) propanoic acid

Stopnja ena: K suspenziji 166 (0,35 g, 1,06 mmol, pripravljeni po postopkih, opisanih v primerih 34 in 25) v metanolu (7 ml) in vodi (3,5 ml), ohlajeni na 0 °C, zaporedoma dodamo ledocet (189 pl, 3,2 mmol) in natrijev nitrit (178 mg, 2,65 mmol). Zmes pustimo počasi ogreti na sobno temperaturo preko noči ter nato razredčimo s kloroformom in vodo. pH vodne faze kontroliramo, da zagotovimo pH 4-5. Organski sloj izperemo s slanico, sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 167 (0,35 g, 92 %) kot rumeno trdno snov.Step One: To a suspension of 166 (0.35 g, 1.06 mmol, prepared according to the procedures described in Examples 34 and 25) in methanol (7 ml) and water (3.5 ml), cooled to 0 ° C, respectively. glacial acetic acid (189 pl, 3.2 mmol) and sodium nitrite (178 mg, 2.65 mmol) were added. The mixture was allowed to warm slowly to room temperature overnight and then diluted with chloroform and water. The pH of the aqueous phase is controlled to ensure a pH of 4-5. The organic layer was washed with brine, dried over MgSO 4 and filtered, and the filtrate was concentrated under reduced pressure to give 167 (0.35 g, 92%) as a yellow solid.

(3S)-3-({[(l-{[2-kloro-6-tetrahidro-l(2H)-piridinilfenil]metil}-4-hidroksi-5-metil-2okso-l,2-dihidro-3-piridinil)amino]karbonil}amino)-3-(4-metilfenil)propanojsko kislino sintetiziramo iz 167 po postopkih, opisanih v primeru 25. MS: izrač.: (M-H)'= 551,21; ugot.: (M-H)'= 551,06.(3S) -3 - ({[(1 - {[2-chloro-6-tetrahydro-1 (2H) -pyridinylphenyl] methyl} -4-hydroxy-5-methyl-2oxo-1,2-dihydro-3- pyridinyl) amino] carbonyl} amino) -3- (4-methylphenyl) propanoic acid was synthesized from 167 according to the procedures described in Example 25. MS: Calculated: (MH) '= 551.21; found: (M-H) '= 551.06.

Primer 42Example 42

Sinteza (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-5-metil-2-okso-l,2-dihidro-3piridinil} amino)karbonil]amino} -3 - [3 -(difluorometil)fenil]propanoj ske kislineSynthesis of (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - [3- (difluoromethyl) phenyl] propanoic acid

-130130-130130

Stopnja ena: K raztopini 3-bromobenzaldehida, 168, (3,00 g, 16,2 mmol) v DMF (69 ml), pod atmosfero suhega dušika, dodamo paladijev acetat (73 mg, 0,32 mmol), tri-otolilfosfin (197 mg, 0,65 mmol), etil akrilat (2,20 ml, 20,3 mmol) in trietilamin (4,50 ml, 32,4 mmol). Sistem deoksigeniramo (preklapljanje med vakuumom in dušikom 5krat), zmes segrevamo na 125 °C 19 ur in nato ohladimo na sobno temperaturo. Reakcijo zlijemo v vodo in ekstrahiramo z etrom. Organski sloj izperemo s HC1 (4N) in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom, da dobimo 169 (2,74 g, 83 %), ki ga uporabimo brez nadaljnjega čiščenja.Step One: To a solution of 3-bromobenzaldehyde, 168, (3.00 g, 16.2 mmol) in DMF (69 ml), under a dry nitrogen atmosphere, palladium acetate (73 mg, 0.32 mmol), tri-otolylphosphine was added. (197 mg, 0.65 mmol), ethyl acrylate (2.20 ml, 20.3 mmol) and triethylamine (4.50 ml, 32.4 mmol). The system was deoxygenated (switching between vacuum and nitrogen 5 times), the mixture was heated to 125 ° C for 19 hours and then cooled to room temperature. The reaction was poured into water and extracted with ether. The organic layer was washed with HCl (4N) and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure to give 169 (2.74 g, 83%), which was used without further purification.

Stopnja dve: V bučo, ki vsebuje 169 (1,00 g, 4,9 mmol), pod atmosfero suhega dušika dodamo z brizgo (dimetilamino)žveplov trifluorid (0,96 ml, 9,8 mmol). Zmes segrevamo na 90 °C za detonacijskim zaslonom 25 minut, nato ohladimo na sobno temperaturo. Dobljeno zmes razredčimo s CH2C12 in izperemo z nasičenim vodnim NaHCO3 in H2O. Organski sloj sušimo nad MgSO4 in filtriramo ter filtrat koncentriramo pod zmanjšanim tlakom. Ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:5 etil acetatom:heksani, da dobimo 170 (0,62 g, 56 %).Step two: To the flask containing 169 (1.00 g, 4.9 mmol), sulfur trifluoride (0.96 ml, 9.8 mmol) was added under a dry nitrogen atmosphere. The mixture was heated to 90 ° C behind the detonation screen for 25 minutes, then cooled to room temperature. The resulting mixture was diluted with CH 2 Cl 2 and washed with saturated aqueous NaHCO 3 and H 2 O. The organic layer was dried over MgSO 4 and filtered and the filtrate concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1: 5 ethyl acetate: hexanes to give 170 (0.62 g, 56%).

Stopnja tri: K raztopini (R)-(+)-N-benzil-a-metilbenzilamina (0,70 g, 3,3 mmol) v THF (6,7 ml), ohlajeni na -78 °C, pod atmosfero suhega dušika dodamo po kapljicah sek.BuLi (4,22 ml, 1,3M v cikloheksanu, 5,5 mmol). Dobljeno zmes mešamo pri -78 °C 30 minut in nato po kapljicah z brizgo dodamo raztopino 170 (0,62 g, 2,74 mmol) v THF (3,4 ml). Zmes mešamo 5 ur pri -78 °C in nato pogasimo z ledoctom AcOH (2 ml) v THF (5 ml). Reakcijsko zmes ogrejemo na sobno temperaturo, zlijemo v 1:1 zmes nasičenega vodnega NaHCO3:EtOAc. Organski sloj izperemo s H2O (2-krat) in slanico, sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:5 etil acetatom:heksani, da dobimo 171 (1,2 g, 100 %). Ta material še vsebuje malo nečistot, vendar ga uporabimo brez nadaljnjega čiščenja.Step Three: To a solution of (R) - (+) - N-benzyl-α-methylbenzylamine (0.70 g, 3.3 mmol) in THF (6.7 ml) cooled to -78 ° C under a dry atmosphere of nitrogen was added dropwise to sec.BuLi (4.22 ml, 1.3M in cyclohexane, 5.5 mmol). The resulting mixture was stirred at -78 ° C for 30 minutes and then a solution of 170 (0.62 g, 2.74 mmol) in THF (3.4 ml) was added dropwise with a syringe. The mixture was stirred for 5 hours at -78 ° C and then quenched with ice-cold AcOH (2 ml) in THF (5 ml). The reaction mixture was warmed to room temperature, poured into a 1: 1 mixture of saturated aqueous NaHCO 3 : EtOAc. The organic layer was washed with H 2 O (2 times) and brine, dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 1: 5 ethyl acetate: hexanes to give 171 (1.2 g, 100%). This material still contains a little impurity, but it is used without further purification.

Stopnja štiri: K raztopini 171 (0,50 g, 1,14 mmol) v EtOH (10 ml) pri sobni temperaturi pod atmosfero suhega dušika dodamo Pd/C (10 % Pd na osnovi suheStep four: To a solution of 171 (0.50 g, 1.14 mmol) in EtOH (10 ml) at room temperature under an atmosphere of dry nitrogen was added Pd / C (10% Pd on a dry basis)

-131131 mase, 50 mas.% vode, Degussa tip E101 NE/W, 0,25 g) in ledocet AcOH (0,5 ml). Atmosfero nadomestimo z vodikom (preklapljanje med vakuumom in vodikom iz balona 5-krat) in zmes segrevamo na 35 °C 6 ur. Reakcijo ohladimo na sobno temperaturo, filtriramo skozi zamašek Celite® 521 in filtrat koncentriramo pod zmanjšanim tlakom. Ostanek razredčimo s CHC13 in izperemo z nasičenim vodnim NaHCO3. Vodni sloj ekstrahiramo s CHC13 (2-krat) in združene organske sloje sušimo nad MgSO4 in filtriramo. Filtrat koncentriramo pod zmanjšanim tlakom in ostanek čistimo s silikagelno kromatografijo z eluiranjem z 1:10 MeOH:CHCl3, da dobimo 172 (180 mg, 67 %).-131131 wt, 50 wt% water, Degussa type E101 NE / W, 0.25 g) and glacial acOH (0.5 ml). The atmosphere was replaced with hydrogen (switching between vacuum and hydrogen from the balloon 5 times) and the mixture was heated to 35 ° C for 6 hours. The reaction was cooled to room temperature, filtered through a Celite® 521 stopper, and the filtrate was concentrated under reduced pressure. The residue was diluted with CHC1 3 and washed with saturated aqueous NaHCO 3 . The aqueous layer was extracted with CHCl 3 (2 times) and the combined organic layers were dried over MgSO 4 and filtered. The filtrate was concentrated under reduced pressure and the residue purified by silica gel chromatography eluting with 1:10 MeOH: CHCl 3 to give 172 (180 mg, 67%).

(3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-5-metil-2-okso-l,2-dihidro3 -piridinil} amino)karbonil]amino} -3 -[3-(difluorometil)fenil]propanoj sko kislino sintetiziramo iz 172 po postopkih, opisanih v primeru 25. MS: izrač.: (M-H)' = 504,11; ugot.: (M-H)'= 503,96.(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3 - [3- (difluoromethyl) phenyl] propanoic acid was synthesized from 172 according to the procedures described in Example 25. MS: calc .: (MH) '= 504.11; found: (M-H) &lt; + &gt; = 503.96.

Primer 43Example 43

Postopke, opisane v primerih 3, 4, 8, 25, 26, 27, 29, 30, 34, 36, 39 in 41, uporabimo za sintetiziranje številnih spojin s splošno formulo VII in s splošno formulo VIII z variiranjem izhodhih materialov. V spodaj prikazani tabeli 1 so navedeni karakterizacijski podatki za sintetizirane spojine.The procedures described in Examples 3, 4, 8, 25, 26, 27, 29, 30, 34, 36, 39 and 41 are used to synthesize a number of compounds of general formula VII and general formula VIII by varying the starting materials. Table 1 below shows the characterization data for the synthesized compounds.

Tabela 1Table 1

SpojinaCompound

-(2-klorobenzil)-3,5 dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion- (2-chlorobenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-klorobenzil)-6-metil3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion 'H NMR (400 MHz) (CD3SO2CD3) δ 5,27 (s, 2H), 6,67 (d, J = 7,4 Hz, IH),5- (2-chlorobenzyl) -6-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione 1 H NMR (400 MHz) (CD 3 SO 2 CD 3 ) δ 5.27 (s, 2H), 6.67 (d, J = 7.4 Hz, 1H),

6,88 (dd, J = 7,3, 1,4 Hz, IH), 7,27-7,37 (m, 2H), 7,51 (dd, J = 7,9, 1,5 Hz, IH), 7,65 (d, J = 7,4 Hz, IH), 12,01 (br. s, IH).6.88 (dd, J = 7.3, 1.4 Hz, 1H), 7.27-7.37 (m, 2H), 7.51 (dd, J = 7.9, 1.5 Hz, 1H), 7.65 (d, J = 7.4 Hz, 1H), 12.01 (br s, 1H).

(CD3SO2CD3) δ 2,27 (s, 3H), 5,36 (s, 2H), 6,60 (d, J =(CD 3 SO 2 CD 3 ) δ 2.27 (s, 3H), 5.36 (s, 2H), 6.60 (d, J =

7,3 Hz, IH), 6,63 (s, IH), 7,27-7,37 (m, 2H), 7,51 (d, J = 7,7 Hz, IH), 11,9 (br, s, IH).7.3 Hz, 1H), 6.63 (s, 1H), 7.27-7.37 (m, 2H), 7.51 (d, J = 7.7 Hz, 1H), 11.9 ( br, s, 1H).

-132132-132132

5-(2-fluorobenzil)-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion 5-(2-kloro-6-fluorobenzil)3,5-dihidro[l,3oksazolo[4,5 -c]piridin-2,4dion5- (2-fluorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-chloro-6-fluorobenzyl) 3,5-dihydro [1,3oxazolo [ 4,5-c] pyridine-2,4dione

5-benzil-6-metil-3,5dihidrof 1,3-oksazolo[4,5c]piridin-2,4-dion 5-benzil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion5-Benzyl-6-methyl-3,5-dihydro 1,3-oxazolo [4,5c] pyridine-2,4-dione 5-benzyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine- 2,4dion

5-(2,5 -dimetilbenzil)-3,5 dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion 5 -(2-metilbenzil)-3,5 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion5- (2,5-dimethylbenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-methylbenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2,4-diklorobenzil)-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion 5-(2-metoksibenzil)-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion5- (2,4-Dichlorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-methoxybenzyl) -3,5-dihydro [1,3-oxazolo [4 , 5c] pyridine-2,4-dione

5-(2,5-difluorobenzil)-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion 5-[2-kloro-5metiltio)benzil] -)-3,5(CD3SO2CD3) 8 5,26 (s, 2H), 6,65 (d, J = 7,3 Hz, IH), 6,88, 7,12-7,26 (m, 3H), 7,37 (m, IH), 7,69 (d, J = 7,3 Hz, IH), 11,93 (br, s, IH).5- (2,5-difluorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- [2-chloro-5methylthio) benzyl] -) - 3,5 (CD 3 SO 2 CD 3 ) 8 5.26 (s, 2H), 6.65 (d, J = 7.3 Hz, 1H), 6.88, 7.12-7.26 (m, 3H), 7 , 37 (m, 1H), 7.69 (d, J = 7.3 Hz, 1H), 11.93 (br, s, 1H).

(CD3SO2CD3) 8 5,30 (s, 2H), 6,56 (d, J = 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) 8 5.30 (s, 2H), 6.56 (d, J = 7.3 Hz, 1H),

7,25 (ddd, J = 9,4, 8,9, 1,1 Hz, IH), 7,37 (d, J = 8,0 Hz, IH) 7,43 (m, 2H), 11,93 (br. s, IH).7.25 (ddd, J = 9.4, 8.9, 1.1 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H) 7.43 (m, 2H), 11. 93 (No. s, 1H).

(CD3SO2CD3) δ 2,30 (s, 3H), 5,37 (s, 2H), 6,55 (s, IH),(CD 3 SO 2 CD 3 ) δ 2.30 (s, 3H), 5.37 (s, 2H), 6.55 (s, 1H),

7,10 (d, J = 7,0 Hz, 2H), 7,24-7,36 (m, 3H), 11,88 (br. s, IH).7.10 (d, J = 7.0 Hz, 2H), 7.24-7.36 (m, 3H), 11.88 (br s, 1H).

(CD3SO2CD3) δ 5,20 (s, 2H), 6,60 (d, J = 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.20 (s, 2H), 6.60 (d, J = 7.3 Hz, 1H),

7,28-7,36 (m, 5H), 7,72 (d, J = 7,3 Hz, IH), 11,97 (br. s,7.28-7.36 (m, 5H), 7.72 (d, J = 7.3 Hz, 1H), 11.97 (br. S.

IH).1H).

(CDC13) δ 2,27 (s, 3H), 2,32 (s, 3H), 5,27 (s, 2H), 6,42 (d, J - 7,3 Hz, IH), 6,90 (s, IH), 7,09 (m, 3H), 10,68 (br. s, IH).(CDCl 3 ) δ 2.27 (s, 3H), 2.32 (s, 3H), 5.27 (s, 2H), 6.42 (d, J - 7.3 Hz, 1H), 6. 90 (s, 1H), 7.09 (m, 3H), 10.68 (br s, 1H).

(CDC13) δ 2,30 (s, 3H), 5,28 (s, 2H), 6,39 (d, J = 7,3 Hz, IH), 7,06 (d, J = 7,3 Hz, IH), 7,09 (d, J = 7,7 Hz, IH),(CDCl 3 ) δ 2.30 (s, 3H), 5.28 (s, 2H), 6.39 (d, J = 7.3 Hz, 1H), 7.06 (d, J = 7.3) Hz, 1H), 7.09 (d, J = 7.7 Hz, 1H),

7,18 - 7,28 (m, 3H) 10,91 (br. s, IH).7.18 - 7.28 (m, 3H) 10.91 (br s, 1H).

(CDC13) δ 5,33 (s, 2H), 6,47 (d, J = 7,3 Hz, IH), 7,29 (m, IH), 7,38 (d, J = 7,3 Hz, IH), 7,42 - 7,48 (m, 2H), 10,77 (br. s, IH).(CDCl 3 ) δ 5.33 (s, 2H), 6.47 (d, J = 7.3 Hz, 1H), 7.29 (m, 1H), 7.38 (d, J = 7.3) Hz, 1H), 7.42 - 7.48 (m, 2H), 10.77 (br. S, 1H).

(CDC13) δ 3,87 (s, IH), 5,24 (s, 2H), 6,36 (d, J = 7,5 Hz, IH), 6,88 (d, J = 8,1 Hz, IH), 6,97 (m, IH), 7,30 (m, IH), 7,45 (d, J = 7,5 Hz, IH), 7,55 (m, IH), 10,75 (br. s, IH) (CDC13) δ 5,26 (s, 2H), 6,46 (d, J = 7,4 Hz, IH), 6,967,05 (m, 2H), 7,30-7,37 (m, IH), 7,39 (m, IH), 10,68 (br. s, IH) (CD3SO2CD3) δ 2,41 (s, 3H), 5,24 (s, 2H), 6,65 (d, J =(CDCl 3 ) δ 3.87 (s, 1H), 5.24 (s, 2H), 6.36 (d, J = 7.5 Hz, 1H), 6.88 (d, J = 8.1) Hz, 1H), 6.97 (m, 1H), 7.30 (m, 1H), 7.45 (d, J = 7.5 Hz, 1H), 7.55 (m, 1H), 10. 75 (br. S, 1H) (CDCl 3 ) δ 5.26 (s, 2H), 6.46 (d, J = 7.4 Hz, 1H), 6.967.05 (m, 2H), 7.30 -7.37 (m, 1H), 7.39 (m, 1H), 10.68 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 2.41 (s, 3H), 5.24 (s, 2H), 6.65 (d, J =

7,2 Hz, IH), 6,83 (d, J = 2,6 Hz, IH), 7,25 (dd, J = 8,0,7.2 Hz, 1H), 6.83 (d, J = 2.6 Hz, 1H), 7.25 (dd, J = 8.0,

-133133 dihidro [ 1,3-oksazolo[4,5c]piridin-2,4-dion-133133 Dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(4-fluorobenzil)-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion5- (4-Fluorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-kloro-5 -metoksibenzil)-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion )5-[3,5bis(trifluorometil)benzil]3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chloro-5-methoxybenzyl) -3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione) 5- [3,5bis (trifluoromethyl) benzyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(4-terc.-butilbenzil)-3,5dihidro[ 1,3 -oksazolo[4,5 c]piridin-2,4-dion5- (4-tert-butylbenzyl) -3,5-dihydro [1,3-oxazolo [4,5 c] pyridine-2,4-dione

-(3 -klorobenzil)-3,5 dihidro [ 1,3-oksazolo[4,5c]piridin-2,4-dion- (3-chlorobenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(4-klorobenzil)-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (4-chlorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

- [3 -(trifluorometil)benzil)3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion- [3- (trifluoromethyl) benzyl) 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

-(2-bromobenzil)-3,5 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion 5 -(3,4-diklorobenzil)-3,52,6 Hz, 2H), 7,45 (d, J = 8,0 Hz, IH), 7,62 (d, J = 7,2 Hz, IH), 12,01 (br. s, IH).- (2-bromobenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5 - (3,4-dichlorobenzyl) -3,52,6 Hz, 2H), 7 , 45 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 12.01 (br s, 1H).

(CD3SO2CD3) δ 5,18 (s, 2H), 6,61 (d, J = 7,4 Hz, IH), 7,14-7,2 (m, 2H), 7,35-7,39 (m, 2H), 7,74 (d, J = 7,3 Hz, IH), 11,96 (br. s, IH) (CD3SO2CD3) δ 3,69 (s, 3H), 5,22 (s, 2H), 6,42 (d, J =(CD 3 SO 2 CD 3 ) δ 5.18 (s, 2H), 6.61 (d, J = 7.4 Hz, 1H), 7.14-7.2 (m, 2H), 7.35 -7.39 (m, 2H), 7.74 (d, J = 7.3 Hz, 1H), 11.96 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 3.69 (s , 3H), 5.22 (s, 2H), 6.42 (d, J =

2,93 Hz, IH), 6,65 (d, J = 7,3 Hz, IH), 6,94 (dd, J = 8,8,2.93 Hz, 1H), 6.65 (d, J = 7.3 Hz, 1H), 6.94 (dd, J = 8.8,

2,9 Hz, IH), 7,43 (d, J = 8,8 Hz, IH), 7,62 (d, J = 7,3 Hz, IH), 12,05 (br. s, IH).2.9 Hz, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 7.3 Hz, 1H), 12.05 (br. S, 1H) .

(CD3SO2CD3) δ 5,36 (s, 2H), 6,69 (d, J = 7,5 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.36 (s, 2H), 6.69 (d, J = 7.5 Hz, 1H),

7,91 (d, J = 7,5 Hz, IH), 8,08 (s, 3H), 12,04 (br. s, IH).7.91 (d, J = 7.5 Hz, 1H), 8.08 (s, 3H), 12.04 (br s, 1H).

(CD3SO2CD3) δ 1,24 (s, 9H), 5,15 (s, 2H), 6,61 (d, J =(CD 3 SO 2 CD 3 ) δ 1.24 (s, 9H), 5.15 (s, 2H), 6.61 (d, J =

7,3 Hz, IH), 7,23 (d, J = 8,4 Hz, 2H), 7,35 (d, J = 8,4 Hz, 2H), 7,74 (d, J = 7,3 Hz, IH), 12,02 (br. s, IH) (CD3SO2CD3) δ 5,20 (s, 2H), 6,63 (d, J = 7,4 Hz, IH),7.3 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 7. 3 Hz, 1H), 12.02 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 5.20 (s, 2H), 6.63 (d, J = 7.4 Hz, 1H).

7,25 (m, IH), 7,35-7,39 (m, 3H), 7,76 (d, J = 7,4 Hz, IH), 11,97 (br. s, IH) (CD3SO2CD3) δ 5,19 (s, 2H), 6,62 (d, J = 7,3 Hz, IH),7.25 (m, 1H), 7.35-7.39 (m, 3H), 7.76 (d, J = 7.4 Hz, 1H), 11.97 (br s, 1H) (CD 3 SO 2 CD 3 ) δ 5.19 (s, 2H), 6.62 (d, J = 7.3 Hz, 1H),

7,29-7,33 (m, 2H), 7,37-7,42 (m, 2H), 7,73 (d, J = 7,3 Hz, IH), 11,97 (br. s, IH)7.29-7.33 (m, 2H), 7.37-7.42 (m, 2H), 7.73 (d, J = 7.3 Hz, 1H), 11.97 (br. S. IH)

n.d.n.d.

(CD3SO2CD3) δ 5,23 (s, 2H), 6,68 (d, J = 7,4 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.23 (s, 2H), 6.68 (d, J = 7.4 Hz, 1H),

6,79 (m, IH), 7,26 (m, IH), 7,34 (m, IH), 7,64 (d, J = 7,4 Hz, IH), 7,68 (m, IH), 12,02 (br. s, IH) (CD3SO2CD3) δ 5,19 (s, 2H), 6,64 (d, J = 7,3 Hz, IH),6.79 (m, 1H), 7.26 (m, 1H), 7.34 (m, 1H), 7.64 (d, J = 7.4 Hz, 1H), 7.68 (m, 1H) ), 12.02 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 5.19 (s, 2H), 6.64 (d, J = 7.3 Hz, 1H),

-134134 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion-134134 Dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

-(4-metilbenzil)-3,5 dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion- (4-methylbenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

-(2-kloro-6-metoksibenzil )-3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion- (2-chloro-6-methoxybenzyl) -3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-[4-trifluoronietil)benzil]3,5-dihidro[l,3oksazolo[4,5 -c]piridin-2,4dion5- [4-Trifluoroniethyl) benzyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(3 -metilbenzil)-3,5dihidro[ 1,3 -oksazolo [4,5c]piridin-2,4-dion5- (3-methylbenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(piridin-2-ilmetil)-3,5dihidro [ 1,3 -oksazolo [4,5c]piridin-2,4-dion5- (pyridin-2-ylmethyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-klorobenzil)-7-metil3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chlorobenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2,4-difluorobenzil)-3,5 dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (2,4-Difluorobenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2,6-difluorobenzil)-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (2,6-difluorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-[3(trifluorometoksi)benzil]7,29 (m, IH), 7,61 (m, 2H), 7,77 (d, J = 7,3 Hz, IH),5- [3 (trifluoromethoxy) benzyl] 7.29 (m, 1H), 7.61 (m, 2H), 7.77 (d, J = 7.3 Hz, 1H).

11,98 (br. s, IH) (CD3SO2CD3) δ 2,27 (s, 3H), 5,14 (s, 2H), 6,59 (d, J =11.98 (br. S, 1H) (CD3SO2CD3) δ 2.27 (s, 3H), 5.14 (s, 2H), 6.59 (d, J =

7,5 Hz, IH), 7,14 (d, J = 8,2 Hz, 2H), 7,20 (d, J = 8,2 Hz, 2H), 7,69 (d, J = 7,5 Hz, IH), 11,95 (br. s, IH) (CD3SO2CD3) δ 3,80 (s, 3H), 5,23 (s, 2H), 6,48 (d, J =7.5 Hz, 1H), 7.14 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 7. 5 Hz, 1H), 11.95 (br s, 1H) (CD 3 SO 2 CD 3 ) δ 3.80 (s, 3H), 5.23 (s, 2H), 6.48 (d, J =

7,4 Hz, IH), 7,05-7,15 (m, 3H), 7,42 (m, IH), 11,95 (br. s, IH) (CD3SO2CD3) δ 5,30 (s, 2H), 6,65 (d, J = 7,3 Hz, IH),7.4 Hz, 1H), 7.05-7.15 (m, 3H), 7.42 (m, 1H), 11.95 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 5 , 30 (s, 2H), 6.65 (d, J = 7.3 Hz, 1H),

7,48 (d, J = 8,0 Hz, 2H), 7,71 (d, J = 8,0 Hz, 2H), 7,76 (d, J = 7,3 Hz, IH), 11,96 (br. s, IH) (CD3SO2CD3) δ 2,27 (s, 3H), 5,15 (s, 2H), 6,62 (d, J =7.48 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 7.3 Hz, 1H), 11. 96 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 2.27 (s, 3H), 5.15 (s, 2H), 6.62 (d, J =

7,3 Hz, IH), 7,10 (m, 4H), 7,72 (d, J = 7,3 Hz, IH), 12,53 (br. s, IH) (CD3SO2CD3) δ 5,29 (s, 2H), 6,62 (d, J = 7,3 Hz, IH),7.3 Hz, 1H), 7.10 (m, 4H), 7.72 (d, J = 7.3 Hz, 1H), 12.53 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 5.29 (s, 2H), 6.62 (d, J = 7.3 Hz, 1H),

7.22- 7,33 (m, 2H), 7,71 (d, J = 7,3 Hz, IH), 7,79 (m, IH), 8,50 (m, IH), 11,96 (br. s, IH).7.22-7.33 (m, 2H), 7.71 (d, J = 7.3 Hz, 1H), 7.79 (m, 1H), 8.50 (m, 1H), 11.96 (br s, 1H).

(CD3SO2CD3) δ 2,10 (s, 3H), 5,23 (s, 2H), 6,86 (dd, J = 7,7, 1,5 Hz, IH), 7,31 (m, 2H), 7,50 (m, 2H), 12,01 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.10 (s, 3H), 5.23 (s, 2H), 6.86 (dd, J = 7.7, 1.5 Hz, 1H), 7.31 (m, 2H), 7.50 (m, 2H), 12.01 (br s, 1H).

(CD3SO2CD3) δ 5,21 (s, 2H), 6,63 (d, J = 7,3 Hz, IH), 7,02-7,07 (m, IH), 7,20-7,29 (m, 2H), 7,65 (d, J = 7,3 Hz, IH), 11,97 (br. s, IH) (CD3SO2CD3) δ 5,25 (s, 2H), 6,58 (d, J - 7,3 Hz, IH), 7,02-7,12 (m, 2H), 7,38-7,55 (m, IH), 7,63 (d, J = 7,3 Hz, IH), 11,91 (br. s, IH) (CD3SO2CD3) δ 5,24 (s, 2H), 6,64 (d, J - 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.21 (s, 2H), 6.63 (d, J = 7.3 Hz, 1H), 7.02-7.07 (m, 1H), 7.20 -7.29 (m, 2H), 7.65 (d, J = 7.3 Hz, 1H), 11.97 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 5.25 (s , 2H), 6.58 (d, J = 7.3 Hz, 1H), 7.02-7.12 (m, 2H), 7.38-7.55 (m, 1H), 7.63 ( d, J = 7.3 Hz, 1H), 11.91 (br. s, 1H) (CD 3 SO 2 CD 3 ) δ 5.24 (s, 2H), 6.64 (d, J - 7. 3 Hz, 1H),

7.22- 7,35 (m, 3H), 7,46 (t, J - 7,7 Hz, IH), 7,78 (d, J =7.22-7.35 (m, 3H), 7.46 (t, J = 7.7 Hz, 1H), 7.78 (d, J =

-135135-135135

3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-[4(trifluorometoksi)benzil]3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- [4 (Trifluoromethoxy) benzyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-[2-(trifluorometil)benzil]·5- [2- (Trifluoromethyl) benzyl] ·

3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(3-metoksibenzil)-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (3-methoxybenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2,3 -diklorobenzil)-3,5 dihidro[ 1,3 -oksazolo[4,5 c]piridin-2,4-dion5- (2,3-Dichlorobenzyl) -3,5 dihydro [1,3-oxazolo [4,5 c] pyridine-2,4-dione

5-(3,5 -dimetilbenzil)-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (3,5-dimethylbenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-klorobenzil)-7-pentil3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chlorobenzyl) -7-pentyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2,4-diklorobenzil)-7metil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion5- (2,4-Dichlorobenzyl) -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

-(2-klorobenzil)-7-etil3,5-dihidro[l,37,3 Hz, IH), ll,99(br. s, IH).- (2-chlorobenzyl) -7-ethyl3,5-dihydro [1,37.3 Hz, 1H), 11.99 (br. S, 1H).

(CD3SO2CD3) δ 5,23 (s, 2H), 6,63 (d, J = 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.23 (s, 2H), 6.63 (d, J = 7.3 Hz, 1H),

7,29-7,45 (m, 4H), 7,76 (d, J - 7,3 Hz, IH), 11,98 (br. s, IH) (CD3SO2CD3) δ 5,40 (s, 2H), 6,73 (d, J = 7,3 Hz, IH),7.29-7.45 (m, 4H), 7.76 (d, J = 7.3 Hz, 1H), 11.98 (br s, 1H) (CD 3 SO 2 CD 3 ) δ 5. 40 (s, 2H), 6.73 (d, J = 7.3 Hz, 1H),

6,81 (d, J = 7,5 Hz, IH), 7,51 (t, J = 7,5 Hz, IH), 7,61 (t, J = 7,5 Hz, IH), 7,70 (d, J = 7,3 Hz, IH), 7,80 (d, J - 7,5 Hz, IH), 12,04 (br. s, IH)6.81 (d, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7. 70 (d, J = 7.3 Hz, 1H), 7.80 (d, J - 7.5 Hz, 1H), 12.04 (br. S, 1H)

n.d.n.d.

n.d.n.d.

(CD3SO2CD3) δ 2,23 (s, 6H), 5,11 (s, 2H), 6,61 (d, J =(CD 3 SO 2 CD 3 ) δ 2.23 (s, 6H), 5.11 (s, 2H), 6.61 (d, J =

7.3 Hz, IH), 6,91 (m, 3H), 7,69 (d, J = 7,3 Hz, IH), 12,00 (br. s, IH) (CD3SO2CD3) δ 0,86 (t, J - 6,2 Hz, 3H), 1,27 (m, 6H),7.3 Hz, 1H), 6.91 (m, 3H), 7.69 (d, J = 7.3 Hz, 1H), 12.00 (br s, 1H) (CD 3 SO 2 CD 3 ) δ 0.86 (t, J = 6.2 Hz, 3H), 1.27 (m, 6H),

1,65 (t, J = 6,7 Hz, 2H), 5,24 (s, 2H), 6,83 (d, J = 6,6 Hz, IH), 7,24-7,34 (m, 2H), 7,48 (s, IH), 7,50 (d, J = 7,7 Hz, IH), 12,00 (br. s, IH) (CD3SO2CD3) δ 2,10 (s, 3H), 5,19 (s, 2H), 6,87 (d, J =1.65 (t, J = 6.7 Hz, 2H), 5.24 (s, 2H), 6.83 (d, J = 6.6 Hz, 1H), 7.24-7.34 (m , 2H), 7.48 (s, 1H), 7.50 (d, J = 7.7 Hz, 1H), 12.00 (br s, 1H) (CD 3 SO 2 CD 3 ) δ 2. 10 (s, 3H), 5.19 (s, 2H), 6.87 (d, J =

8.4 Hz, IH), 7,38 (dd, J = 8,4, 2,2 Hz, IH), 7,50 (s, IH), 7,69 (d, J = 2,2 Hz, IH), 12,02 (br. s, IH) (CD3SO2CD3) δ 1,17 (t, J = 7,5 Hz, 3H), 2,50 (m, 2H prekrivajoč DMSO), 5,25 (s, 2H), 6,84 (m, IH), 7,308.4 Hz, 1H), 7.38 (dd, J = 8.4, 2.2 Hz, 1H), 7.50 (s, 1H), 7.69 (d, J = 2.2 Hz, 1H) , 12.02 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 1.17 (t, J = 7.5 Hz, 3H), 2.50 (m, 2H overlapping DMSO), 5.25 (s, 2H), 6.84 (m, 1H), 7.30

-136136 oksazolo[4,5-c]piridin-2,4dion-136136 Oxazolo [4,5-c] pyridine-2,4dione

7-butil-5-(2-klorobenzil)3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion7-Butyl-5- (2-chlorobenzyl) 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-[2-kloro-5(trifluorometil)benzil] -3,5 dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- [2-chloro-5 (trifluoromethyl) benzyl] -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2,6-diklorobenzil)-3,5dihidro[l,3-oksazolo[4,5c] piridin-2,4-dion 5-(2-kloro-5-fluorobenzil)3.5dihidrof 1,3]oksazolo[4,5d] piridin-2,4-dion 5-(2-kloro-6-metilbenzil)7-metil-3,5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2,6-dichlorobenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-chloro-5-fluorobenzyl) 3.5-dihydro 1,3] oxazolo [ 4,5d] pyridine-2,4-dione 5- (2-chloro-6-methylbenzyl) 7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(4-klorobenzil)-7-metil3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (4-chlorobenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-klorobenzil)-5,6,7,8tetrahidro-2Hciklopenta[b][l,3oksazolo[5,4-d]piridin-2,4(3H)-dion5- (2-chlorobenzyl) -5,6,7,8tetrahydro-2Hcyclopenta [b] [1,3oxazolo [5,4-d] pyridine-2,4 (3H) -dione

7-metil-5-[4(m, 2H), 7,49 (m, 2H), 12,02 (br. s, IH) (CD3SO2CD3) δ 0,87 (t, J = 7,3 Hz, 3H), 1,28 (m, 4H),7-methyl-5- [4 (m, 2H), 7.49 (m, 2H), 12.02 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 0.87 (t, J = 7.3 Hz, 3H), 1.28 (m, 4H),

1,54 (t, J = 7,1 Hz, 2H), 5,24 (s, 2H), 6,83 (d, J = 6,8 Hz, IH), 7,24-7,34 (m, 2H), 7,48-7,56 (m, 2H), 12,00 (br. s, IH).1.54 (t, J = 7.1 Hz, 2H), 5.24 (s, 2H), 6.83 (d, J = 6.8 Hz, 1H), 7.24-7.34 (m , 2H), 7.48-7.56 (m, 2H), 12.00 (br s, 1H).

(CD3SO2CD3) δ 5,33 (s, 2H), 6,68 (d, J = 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.33 (s, 2H), 6.68 (d, J = 7.3 Hz, 1H),

7,35 (s, IH), 7,69-7,79 (m, 3H), 11,96 (br. s, IH).7.35 (s, 1H), 7.69-7.79 (m, 3H), 11.96 (br. S, 1H).

(CD3SO2CD3) δ 5,38 (s, 2H), 6,53 (d, J = 7,4 Hz, IH), 7,07 (d, J = 7,7, Hz, IH), 7,45-7,50 (m, IH), 7,52-7,59 (m, 2H), 11,99 (br. s, IH) (CD3SO2CD3) δ 5,27 (s, 2H), 6,67 (d, J - 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.38 (s, 2H), 6.53 (d, J = 7.4 Hz, 1H), 7.07 (d, J = 7.7, Hz, 1H) , 7.45-7.50 (m, 1H), 7.52-7.59 (m, 2H), 11.99 (br s, 1H) (CD 3 SO 2 CD 3 ) δ 5.27 ( s, 2H), 6.67 (d, J = 7.3 Hz, 1H),

6,72 (dd, J = 7,3, 3,2 Hz, IH), 7,21-7,23 (m, IH), 7,557,59 (m, IH), 7,65 (d, J = 7,3 Hz, IH), 12,00 (br. s, IH).6.72 (dd, J = 7.3, 3.2 Hz, 1H), 7.21-7.23 (m, 1H), 7,557.59 (m, 1H), 7.65 (d, J = 7.3 Hz, 1H), 12.00 (br s, 1H).

(CDC13) δ 2,07 (s, 3H), 2,29 (s, 3H), 5,48 (s, 2H), 6,63 (s, IH), 7,16 (d, J = 7,7 Hz, IH), 7,25 (t, J = 7,7 Hz, IH), 7,34 (d, J = 7,7 Hz, IH), 11,33 (br. s, IH).(CDCl 3 ) δ 2.07 (s, 3H), 2.29 (s, 3H), 5.48 (s, 2H), 6.63 (s, 1H), 7.16 (d, J = 7). , 7 Hz, 1H), 7.25 (t, J = 7.7 Hz, 1H), 7.34 (d, J = 7.7 Hz, 1H), 11.33 (br. S, 1H).

(CD3SO2CD3) δ 2,08 (s, 3H), 5,14 (s, 2H), 7,31 (d, J =(CD 3 SO 2 CD 3 ) δ 2.08 (s, 3H), 5.14 (s, 2H), 7.31 (d, J =

8,4 Hz, 2H), 7,41 (d, J = 8,4 Hz, 2H), 7,58 (s, IH), 12,03 (br. s, IH).8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.58 (s, 1H), 12.03 (br. S, 1H).

(CD3SO2CD3) δ 2,04 (m, 2H), 2,80 (m, 4H), 5,28 (s, 2H), 6,68 (d, J = 7,3 Hz, IH), 7,18-7,34 (m, 2H), 7,51 (d, J = 7,7 Hz, IH), 11,92 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.04 (m, 2H), 2.80 (m, 4H), 5.28 (s, 2H), 6.68 (d, J = 7.3 Hz, 1H ), 7.18-7.34 (m, 2H), 7.51 (d, J = 7.7 Hz, 1H), 11.92 (br s, 1H).

(CD3SO2CD3) δ 2,11 (s, 3H), 2,58 (s, 3H), 5,28 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.11 (s, 3H), 2.58 (s, 3H), 5.28 (s, 2H),

-137137 (metilsulfonil)benzil]-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion-137137 (Methylsulfonyl) benzyl] -3,5dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(4-metoksibenzil)-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion5- (4-methoxybenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-klorobenzil)-7-propil3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chlorobenzyl) -7-propyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

4- [(2,4-diokso-2,3dihidro[ 1,3]oksazolo[4,5c]piridin-5(4H)il)metil]N,Ndimetilbenzensulfon-amid 5 -(mezitilmetil)-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion4- [(2,4-dioxo-2,3dihydro [1,3] oxazolo [4,5c] pyridin-5 (4H) yl) methyl] N, N-dimethylbenzenesulfonamide 5 - (mesylmethyl) -3,5dihydro [1 , 3-Oxazolo [4,5c] pyridine-2,4-dione

5- (2-klorobenzil)3,5,6,7,8,9-heksahidro[l,3-oksazolo[4,5c]kinolin-2,4-dion 5-(2-klorobenzil)-7-etil-6metil-3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chlorobenzyl) 3,5,6,7,8,9-hexahydro [1,3-oxazolo [4,5c] quinoline-2,4-dione 5- (2-chlorobenzyl) -7-ethyl- 6methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

- [2-(metiltio)benzil-3,5 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion- [2- (methylthio) benzyl-3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

2-[(2,4-diokso-2,37,58 (d, J = 7,3 Hz, 2H), 7,64 (s, IH), 7,91 (d, J = 7,3 Hz, 2H), 12,06 (br. s, IH) (CD3SO2CD3) δ 3,73 (s, 3H), 5,10 (s, 2H), 6,56 (br. d, J = 5,9 Hz, IH), 6,89 (d, J = 8,8 Hz, 2H), 7,27 (d, J = 8,8 Hz, 2H), 7,67 (br. m, IH), 12,06 (br. s, IH). (CD3SO2CD3) δ 0,88 (t, J = 7,4 Hz, 3H), 1,57 (m, 2H), 2,46 (m, 2H), 5,24 (s, 2H), 6,84 (d, J = 6,2 Hz, IH), 7,26-7,38 (m, 2H), 7,48 (s, IH), 7,50 (d, J = 7,7 Hz, IH), 12,00 (br. s, IH).2 - [(2,4-dioxo-2,37,58 (d, J = 7.3 Hz, 2H), 7.64 (s, 1H), 7.91 (d, J = 7.3 Hz, 2H), 12.06 (br. S, 1H) (CD 3 SO 2 CD 3 ) δ 3.73 (s, 3H), 5.10 (s, 2H), 6.56 (br d, J = 5.9 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.67 (m, 1H). , 12.06 (br. S, 1H). (CD 3 SO 2 CD 3 ) δ 0.88 (t, J = 7.4 Hz, 3H), 1.57 (m, 2H), 2.46 ( m, 2H), 5.24 (s, 2H), 6.84 (d, J = 6.2 Hz, 1H), 7.26-7.38 (m, 2H), 7.48 (s, 1H ), 7.50 (d, J = 7.7 Hz, 1H), 12.00 (br s, 1H).

(CD3SO2CD3) δ 2,55 (s, 6H), 5,31 (s, 2H), 6,67 (d, J =(CD 3 SO 2 CD 3 ) δ 2.55 (s, 6H), 5.31 (s, 2H), 6.67 (d, J =

7,3 Hz, IH), 7,43-7,51 (m, 2H), 7,66-7,74 (m, 2H), 7,77 (d, J = 7,3 Hz, IH), 12,00 (br. s, IH).7.3 Hz, 1H), 7.43-7.51 (m, 2H), 7.66-7.74 (m, 2H), 7.77 (d, J = 7.3 Hz, 1H). 12.00 (br s, 1H).

(CDC13) δ 2,19 (s, 6H), 2,30 (s, 3H), 5,25 (s, 2H), 6,31 (d, J = 7,3 Hz, IH), 6,73 (d, J = 7,3 Hz, IH), 6,94 (s, 2H), 11,01 (br. s, IH).(CDCl 3 ) δ 2.19 (s, 6H), 2.30 (s, 3H), 5.25 (s, 2H), 6.31 (d, J = 7.3 Hz, 1H), 6. 73 (d, J = 7.3 Hz, 1H), 6.94 (s, 2H), 11.01 (br s, 1H).

(CD3SO2CD3) δ 1,64 (m, 4H), 2,50 (m, 4H), 5,34 (s, 2H), 6,59 (d, J = 8,1 Hz, IH), 7,25-7,34 (m, 2H), 7,51 (d, J-7,7 Hz, IH), 11,92 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 1.64 (m, 4H), 2.50 (m, 4H), 5.34 (s, 2H), 6.59 (d, J = 8.1 Hz, 1H ), 7.25-7.34 (m, 2H), 7.51 (d, J-7.7 Hz, 1H), 11.92 (br s, 1H).

(CD3SO2CD3) δ 1,10 (t, J = 7,4 Hz, 3H), 2,22 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.10 (t, J = 7.4 Hz, 3H), 2.22 (s, 3H),

2,56 (m, 2H), 5,40 (s, 2H), 6,58 (d, J = 7,0 Hz, IH),2.56 (m, 2H), 5.40 (s, 2H), 6.58 (d, J = 7.0 Hz, 1H),

7,23-7,34 (m, 2H), 7,52 (d, J - 8,1 Hz, IH), 11,92 (br. s, IH).7.23-7.34 (m, 2H), 7.52 (d, J = 8.1 Hz, 1H), 11.92 (br s, 1H).

(CD3SO2CD3) δ 2,52 (s, 3H), 5,19 (s, 2H), 6,63 (d, J =(CD 3 SO 2 CD 3 ) δ 2.52 (s, 3H), 5.19 (s, 2H), 6.63 (d, J =

7,3 Hz, IH), 6,76 (d, J = 7,7 Hz, IH), 7,09-7,17 (m, IH),7.3 Hz, 1H), 6.76 (d, J = 7.7 Hz, 1H), 7.09-7.17 (m, 1H),

7,29-7,37 (m, 2H), 7,55 (d, J - 7,3 Hz, IH), 11,99 (s, IH).7.29-7.37 (m, 2H), 7.55 (d, J = 7.3 Hz, 1H), 11.99 (s, 1H).

(CD3SO2CD3) δ 2,81 (s, 6H), 5,54 (s, 2H), 6,71 (d, J =(CD 3 SO 2 CD 3 ) δ 2.81 (s, 6H), 5.54 (s, 2H), 6.71 (d, J =

-138138 dihidro[l,3]oksazolo[4,5c]piridin-5(4H)il)metil]N,Ndimetilbenzensulfon-amid-138138 Dihydro [1,3] oxazolo [4,5c] pyridin-5 (4H) yl) methyl] N, N-dimethylbenzenesulfonamide

5-(2,6-dimetoksibenzil)3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2,6-dimethoxybenzyl) 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-[2(trifluorometoksi)benzil]3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- [2 (Trifluoromethoxy) benzyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(2-klorobenzil)-6,7dimetil-3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chlorobenzyl) -6,7-dimethyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-[2-kloro-5(metilsulfonil)benzil] -3,5 dihidro [1,3 -oksazolo[4,5 c]piridin-2,4-dion 5-(4-kloro-2metoksibenzil)-3,5dihidro[ 1,3 -oksazolo[4,5 c]piridin-2,4-dion 5-(2-klorobenzil)5,6,7,8,9,10-heksahidro2H-ciklohepta[b] [1,3oksazolo[5,4-d]piridin-2,4(3H)-dion5- [2-chloro-5 (methylsulfonyl) benzyl] -3,5 dihydro [1,3-oxazolo [4,5 c] pyridine-2,4-dione 5- (4-chloro-2methoxybenzyl) -3,5 dihydro [1,3-oxazolo [4,5 c] pyridine-2,4-dione 5- (2-chlorobenzyl) 5,6,7,8,9,10-hexahydro2H-cyclohepta [b] [1,3oxazolo [5 , 4-d] pyridine-2,4 (3H) -dione

5-[27,3 Hz, IH), 6,81 (d, J = 7,3 Hz, IH), 7,49-7,61 (m, 2H), 7,69 (d, J - 7,3 Hz, IH), 7,85 (d, J = 7,3 Hz, IH), 12,05 (br. s, IH).5- [27.3 Hz, 1H), 6.81 (d, J = 7.3 Hz, 1H), 7.49-7.61 (m, 2H), 7.69 (d, J - 7. 3 Hz, 1H), 7.85 (d, J = 7.3 Hz, 1H), 12.05 (br s, 1H).

(CD3SO2CD3) δ 3,76 (s, 6H), 5,07 (s, 2H), 6,43 (d, J =(CD3SO2CD3) δ 3.76 (s, 6H), 5.07 (s, 2H), 6.43 (d, J =

7,7 Hz, IH), 6,73 (d, J = 8,4 Hz, 2H), 7,00 (d, J = 7,7 Hz, IH), 7,37 (t, J = 8,4 Hz, IH), 11,92 (br. s, IH).7.7 Hz, 1H), 6.73 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 7.7 Hz, 1H), 7.37 (t, J = 8, 4 Hz, 1H), 11.92 (br s, 1H).

(CD3SO2CD3) δ 5,27 (s, 2H), 6,65 (d, J = 7,3 Hz, IH), 7,08 (dd, J = 7,3, 1,4 Hz, IH), 7,30-7,49 (m, 3H), 7,63 (d, J = 7,3 Hz, IH), 11,99 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 5.27 (s, 2H), 6.65 (d, J = 7.3 Hz, 1H), 7.08 (dd, J = 7.3, 1.4 Hz) , 1H), 7.30-7.49 (m, 3H), 7.63 (d, J = 7.3 Hz, 1H), 11.99 (br s, 1H).

(CD3SO2CD3) δ 2,12 (s, 3H), 2,19 (s, 3H), 5,40 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.12 (s, 3H), 2.19 (s, 3H), 5.40 (s, 2H),

6.59 (d, J = 6,6 Hz, IH), 7,25-7,34 (m, 2H), 7,52 (d, J =6.59 (d, J = 6.6 Hz, 1H), 7.25-7.34 (m, 2H), 7.52 (d, J =

7,7 Hz, IH), 11,91 (br. s, IH).7.7 Hz, 1H), 11.91 (br s, 1H).

(CD3SO2CD3) δ 3,20 (s, 3H), 5,35 (s, 2H), 6,70 (d, J =(CD 3 SO 2 CD 3 ) δ 3.20 (s, 3H), 5.35 (s, 2H), 6.70 (d, J =

7,3 Hz, IH), 7,55 (m, IH), 7,69 (m, IH), 7,90 (m, 2H), 12,04 (br. s, IH).7.3 Hz, 1H), 7.55 (m, 1H), 7.69 (m, 1H), 7.90 (m, 2H), 12.04 (br s, 1H).

(CD3SO2CD3) δ 3,86 (s, 3H), 5,09 (s, 2H), 6,60 (d, J =(CD 3 SO 2 CD 3 ) δ 3.86 (s, 3H), 5.09 (s, 2H), 6.60 (d, J =

7,3 Hz, IH), 6,90-6,98 (m, 2H), 7,12 (d, J = 2,2 Hz, IH),7.3 Hz, 1H), 6.90-6.98 (m, 2H), 7.12 (d, J = 2.2 Hz, 1H),

7.59 (d, J - 7,3 Hz, IH), 11,95 (br. s, IH).7.59 (d, J = 7.3 Hz, 1H), 11.95 (br s, 1H).

(CD3SO2CD3) δ 1,34 (m, 2H), 1,56 (m, 2H), 1,69 (m, 2H), 2,70 (m, 4H), 5,45 (s, 2H), 6,69 (d, J - 6,6 Hz, IH),(CD 3 SO 2 CD 3 ) δ 1.34 (m, 2H), 1.56 (m, 2H), 1.69 (m, 2H), 2.70 (m, 4H), 5.45 (s , 2H), 6.69 (d, J = 6.6 Hz, 1H),

7,24-7,35 (m, 2H), 7,52 (d, J = 7,7 Hz, IH), 11,91 (br. s, IH).7.24-7.35 (m, 2H), 7.52 (d, J = 7.7 Hz, 1H), 11.91 (br s, 1H).

(CD3SO2CD3) δ 5,21 (s, 2H), 6,64 (d, J = 7,3 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.21 (s, 2H), 6.64 (d, J = 7.3 Hz, 1H),

-139139 (difluorometoksi)benzil]3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion-139139 (Difluoromethoxy) benzyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

7-metil-5-[(lR)-l-feniletil]3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion7-methyl-5 - [(1R) -1-phenylethyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(4-klorobenzil)-7-propil3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (4-chlorobenzyl) -7-propyl 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

- [2-(metilsulfonil)benzil]3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion- [2- (methylsulfonyl) benzyl] 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

-(2,6-dimetilbenzil)-3,5 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion- (2,6-dimethylbenzyl) -3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

3-kloro-2-[(2,4-diokso-2,3dihidro[ 1,3]oksazolo[4,5c]piridin-5(4H)il)metil]benzonitril3-chloro-2 - [(2,4-dioxo-2,3dihydro [1,3] oxazolo [4,5c] pyridin-5 (4H) yl) methyl] benzonitrile

5-(2-kloro-6-metilbenzil)6,7-dimetil]-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (2-Chloro-6-methylbenzyl) 6,7-dimethyl] -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

2- [(2,4-diokso-2,3 dihidro [1,3] oksazolo [4,5c]piridin-5(4H)il)metil]benzonitril2 - [(2,4-dioxo-2,3 dihydro [1,3] oxazolo [4,5c] pyridin-5 (4H) yl) methyl] benzonitrile

7,02 (d, J = 7,3 Hz, IH), 7,20-7,25 (m, 2H), 7,27 (t, J = 74,0 Hz, IH), 7,62 (d, J = 7,3 Hz, IH), 12,00 (br. s, IH).7.02 (d, J = 7.3 Hz, 1H), 7.20-7.25 (m, 2H), 7.27 (t, J = 74.0 Hz, 1H), 7.62 (d , J = 7.3 Hz, 1H), 12.00 (br s, 1H).

(CD3SO2CD3) δ 1,72 (d, J = 7,3 Hz, 3H), 2,07 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.72 (d, J = 7.3 Hz, 3H), 2.07 (s, 3H),

6,27 (q, J = 7,3 Hz, IH), 7,27-7,40 (m, 6H), 11,95 (br. s, IH).6.27 (q, J = 7.3 Hz, 1H), 7.27-7.40 (m, 6H), 11.95 (br s, 1H).

(CD3SO2CD3) δ 0,89 (t, J = 7,3 Hz, IH), 1,54 (m, 2H),(CD 3 SO 2 CD 3 ) δ 0.89 (t, J = 7.3 Hz, 1H), 1.54 (m, 2H),

2,44 (t, J = 7,7 Hz, 2H), 5,15 (s, 2H), 7,30 (d, J = 8,4 Hz, 2H), 7,39 (d, J = 8,4 Hz, 2H), 7,57 (s, IH), 11,97 (br. s, IH).2.44 (t, J = 7.7 Hz, 2H), 5.15 (s, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8) , 4 Hz, 2H), 7.57 (s, 1H), 11.97 (br. S, 1H).

(CD3SO2CD3) δ 3,43 (s, 3H), 5,60 (s, 2H), 6,75 (d, J =(CD 3 SO 2 CD 3 ) δ 3.43 (s, 3H), 5.60 (s, 2H), 6.75 (d, J =

7,3 Hz, IH), 7,49-7,61 (m, 2H), 7,65-7,70 (m, 2H), 7,897,91 (m, IH), 12,02 (br. s, IH).7.3 Hz, 1H), 7.49-7.61 (m, 2H), 7.65-7.70 (m, 2H), 7.897.91 (m, 1H), 12.02 (no. S , 1H).

(CD3SO2CD3) δ 2,21 (s, 6H), 5,16 (s, 2H), 6,47 (d, J =(CD 3 SO 2 CD 3 ) δ 2.21 (s, 6H), 5.16 (s, 2H), 6.47 (d, J =

7,3 Hz, IH), 6,80 (d, J = 7,3 Hz, IH), 7,09-7,22 (m, 3H), 12,00 (br. s, IH).7.3 Hz, 1H), 6.80 (d, J = 7.3 Hz, 1H), 7.09-7.22 (m, 3H), 12.00 (br s, 1H).

(CD3SO2CD3) δ 5,38 (s, 2H), 6,61 (d, 7,4 Hz, IH), 7,55 (t, J = 8,0 Hz, IH), 7,62 (d, J = 7,4 Hz, IH), 7,82 (d, J = 8,0 Hz, IH), 7,87 (d, J = 8,0 Hz, IH), 11,96 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 5.38 (s, 2H), 6.61 (d, 7.4 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7. 62 (d, J = 7.4 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 11.96 ( No. s, 1H).

(CD3SO2CD3) δ 2,06 (s, 3H), 2,09 (s, 3H), 2,10 (s, 3H),(CD 3 SO 2 CD 3 ) δ 2.06 (s, 3H), 2.09 (s, 3H), 2.10 (s, 3H),

5,58 (s, 2H), 7,13 (d, J = 7,7 Hz, IH), 7,20 (t, J = 7,7 Hz, 2H), 7,27 (d, J = 7,7 Hz, IH), 11,84 (br. s, IH).5.58 (s, 2H), 7.13 (d, J = 7.7 Hz, 1H), 7.20 (t, J = 7.7 Hz, 2H), 7.27 (d, J = 7 , 7 Hz, 1H), 11.84 (br s, 1H).

(CD3SO2CD3) δ 5,40 (s, 2H), 6,70 (d, J = 7,4 Hz, IH),(CD 3 SO 2 CD 3 ) δ 5.40 (s, 2H), 6.70 (d, J = 7.4 Hz, 1H),

7,11 (d, J = 7,7 Hz, IH), 7,50 (t, J = 7,7 Hz, IH), 7,66 (td, J = 7,7, 1,1 Hz, IH), 7,74 (d, J = 7,4 Hz, IH), 7,88 (dd, J = 7,7, 1,1 Hz, IH), 12,01 (br. s, IH).7.11 (d, J = 7.7 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.66 (td, J = 7.7, 1.1 Hz, 1H ), 7.74 (d, J = 7.4 Hz, 1H), 7.88 (dd, J = 7.7, 1.1 Hz, 1H), 12.01 (br s, 1H).

-140140-140140

5-(2-kloro-6metoksibenzil)-7-metil5- (2-Chloro-6methoxybenzyl) -7-methyl

3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-[3-(metiltio)benzil]-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion5- [3- (methylthio) benzyl] -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-klorobenzil)-7ciklopropil-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (2-chlorobenzyl) -7cyclopropyl-3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(3 -klorobenzil)-7-metil3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (3-chlorobenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2,6-diklorobenzil)-7metil-3,5-dihidro[l,3oksazolo [4,5 -c]piridin-2,4dion5- (2,6-Dichlorobenzyl) -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

7-metil-5-(4-metilbenzil)3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion7-methyl-5- (4-methylbenzyl) 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(3,5-dimetoksibenzil)-7metil-3,5-dihidro [ 1,3oksazolo[4,5-c]piridin-2,4dion5- (3,5-dimethoxybenzyl) -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(2,6-difluorobenzil)-7metil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4(CD3SO2CD3) δ 2,01 (s, 3H), 3,81 (s, 3H), 5,21 (s, 2H),5- (2,6-difluorobenzyl) -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4 (CD 3 SO 2 CD 3 ) δ 2.01 (s, 3H) , 3.81 (s, 3H), 5.21 (s, 2H),

6,86 (s, IH), 7,11 (m, 2H), 7,41 (t, J = 8,2 Hz, IH), 11,96 (br. s, IH).6.86 (s, 1H), 7.11 (m, 2H), 7.41 (t, J = 8.2 Hz, 1H), 11.96 (br. S, 1H).

(CD3SO2CD3) δ 2,45 (s, 3H), 5,16 (s, 2H), 6,61 (d, J =(CD 3 SO 2 CD 3 ) δ 2.45 (s, 3H), 5.16 (s, 2H), 6.61 (d, J =

7,3 Hz, IH), 7,04 (d, J - 7,3 Hz, IH), 7,16-7,34 (m, 3H),7.3 Hz, 1H), 7.04 (d, J = 7.3 Hz, 1H), 7.16-7.34 (m, 3H),

7,73 (d, J = 7,3 Hz, IH), 11,97 (br. s, IH).7.73 (d, J = 7.3 Hz, 1H), 11.97 (br s, 1H).

(CD3SO2CD3) δ 0,70 (m, 2H), 0,87 (m, 2H), 1,79 (m, IH), 5,22 (s, 2H), 6,79 (d, J = 7,3 Hz, IH), 7,31 (m, IH),(CD 3 SO 2 CD 3 ) δ 0.70 (m, 2H), 0.87 (m, 2H), 1.79 (m, 1H), 5.22 (s, 2H), 6.79 (d , J = 7.3 Hz, 1H), 7.31 (m, 1H),

7,45 (s, IH), 7,50 (d, J = 7,7 Hz, IH), 12,01 (br. s, IH).7.45 (s, 1H), 7.50 (d, J = 7.7 Hz, 1H), 12.01 (br s, 1H).

(CD3SO2CD3) δ 2,09 (d, J = 1,1 Hz, 3H), 5,15 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.09 (d, J = 1.1 Hz, 3H), 5.15 (s, 2H),

7,26 (m, IH), 7,33-7,41 (m, 3H), 7,59 (q, J = 1,1 Hz, IH), 11,97 (br. s, IH).7.26 (m, 1H), 7.33-7.41 (m, 3H), 7.59 (q, J = 1.1 Hz, 1H), 11.97 (br. S, 1H).

(CD3SO2CD3) δ 2,03 (d, J = 1,1 Hz, 3H), 5,36 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.03 (d, J = 1.1 Hz, 3H), 5.36 (s, 2H),

6,87 (q, J = 1,1 Hz, IH), 7,46 (dd, J = 8,8, 7,4 Hz, IH),6.87 (q, J = 1.1 Hz, 1H), 7.46 (dd, J = 8.8, 7.4 Hz, 1H),

7,56 (d, J = 7,4 Hz, IH), 7,57 (d, J = 8,8 Hz, IH), 11,99 (br. s, IH).7.56 (d, J = 7.4 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 11.99 (br. S, 1H).

(CD3SO2CD3) δ 2,07 (s, 3H), 2,27 (s, 3H), 5,10 (s, 2H), 7,08-7,23 (m, 4H), 7,52 (s, IH), 11,95 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.07 (s, 3H), 2.27 (s, 3H), 5.10 (s, 2H), 7.08-7.23 (m, 4H), 7 , 52 (s, 1H), 11.95 (no s, 1H).

(CD3SO2CD3) δ 2,09 (s, 3H), 3,71 (s, 6H), 5,06 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.09 (s, 3H), 3.71 (s, 6H), 5.06 (s, 2H),

6,42 (t, J = 2,2 Hz, IH), 6,46 (d, J = 2,2 Hz, 2H), 7,51 (s, IH), 11,96 (br. s, IH).6.42 (t, J = 2.2 Hz, 1H), 6.46 (d, J = 2.2 Hz, 2H), 7.51 (s, 1H), 11.96 (br. S, 1H) ).

(CD3SO2CD3) δ 2,09 (d, J = 1,1 Hz, 3H), 5,21 (s, 2H), 7,04-7,13 (m, 2H), 7,38-7,47 (m, 2H), 11,91 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.09 (d, J = 1.1 Hz, 3H), 5.21 (s, 2H), 7.04-7.13 (m, 2H), 7.38 -7.47 (m, 2H), 11.91 (br s, 1H).

-141141 dion-141141 stocks

- [3 -(metilsulfonil)benzil] 3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion- [3- (methylsulfonyl) benzyl] 3.5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-kloro-6-etoksibenzil)3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chloro-6-ethoxybenzyl) 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(2-kloro-6-etoksibenzil)7-metil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion5- (2-chloro-6-ethoxybenzyl) 7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-fluoro-6metoksibenzil)-7-metil-3,5 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion 5-(2-kloro-6metoksibenzil)-7-propil3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-Fluoro-6methoxybenzyl) -7-methyl-3,5 dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-chloro-6methoxybenzyl) -7-propyl3. 5- dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(5-kloro-2-fluorobenzil)7-metil-3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (5-chloro-2-fluorobenzyl) 7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-klorobenzil)-7izopropil-3,5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion (CD3SO2CD3) δ 3,20 (s, 3H), 5,31 (s, 2H), 6,66 (d, J =5- (2-chlorobenzyl) -7isopropyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione (CD 3 SO 2 CD 3 ) δ 3.20 (s, 3H), 5 , 31 (s, 2H), 6.66 (d, J =

7,3 Hz, IH), 7,5-7,7 (m, 2H), 7,81 (d, J = 7,3 Hz, IH), 7,83-7,96 (m, 2H), 11,99 (br. s, IH).7.3 Hz, 1H), 7.5-7.7 (m, 2H), 7.81 (d, J = 7.3 Hz, 1H), 7.83-7.96 (m, 2H), 11.99 (br. S, 1H).

(CD3SO2CD3) δ 1,25 (t, J = 7,0 Hz, 3H), 4,05 (q, J = 7,0 Hz, 2H), 5,25 (s, 2H), 6,49 (d, J - 7,3 Hz, IH), 7,06 (d, J = 8,4 Hz, IH), 7,10 (d, J = 8,1 Hz, IH), 7,12 (d, J = 7,3 Hz, IH), 7,37 (dd, J = 8,4, 8,1 Hz, IH), 11,95 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 1.25 (t, J = 7.0 Hz, 3H), 4.05 (q, J = 7.0 Hz, 2H), 5.25 (s, 2H). 6.49 (d, J = 7.3 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7. 12 (d, J = 7.3 Hz, 1H), 7.37 (dd, J = 8.4, 8.1 Hz, 1H), 11.95 (br s, 1H).

(CD3SO2CD3) δ 1,25 (d, J = 7,0 Hz, 3H), 2,02 (s, 3H), 4,04 (q, J = 7,0 Hz, 2H), 5,23 (s, 2H), 6,97 (s, IH), 7,04 (d, J = 8,4 Hz, IH), 7,09 (d, J - 8,0 Hz, IH), 7,36 (dd, J = 8,4, 8,0 Hz, IH), 11,93 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 1.25 (d, J = 7.0 Hz, 3H), 2.02 (s, 3H), 4.04 (q, J = 7.0 Hz, 2H), 5.23 (s, 2H), 6.97 (s, 1H), 7.04 (d, J = 8.4 Hz, 1H), 7.09 (d, J - 8.0 Hz, 1H), 7.36 (dd, J = 8.4, 8.0 Hz, 1H), 11.93 (br s, 1H).

(CD3SO2CD3) δ 2,05 (s, 3H), 3,82 (s, 3H), 5,12 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.05 (s, 3H), 3.82 (s, 3H), 5.12 (s, 2H),

6,82 (dd, J = 9,5, 8,4 Hz, IH), 6,91 (d, J = 8,4 Hz, IH),6.82 (dd, J = 9.5, 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H),

7,18 (s, IH), 7,37 (td, J = 8,4, 6,6 Hz, IH), 11,89 (br. s, IH).7.18 (s, 1H), 7.37 (td, J = 8.4, 6.6 Hz, 1H), 11.89 (br. S, 1H).

(CD3SO2CD3) δ 0,82 (t, J = 7,3 Hz, 3H), 1,47 (sekstet, J = 7,3 Hz, 2H), 2,38 (t, J = 7,3 Hz, 2H), 3,80 (s, 3H), 5,21 (s, 2H), 6,89 (s, IH), 7,08-7,13 (m, 2H), 7,40 (t, J = 8,3 Hz, IH), 11,93 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 0.82 (t, J = 7.3 Hz, 3H), 1.47 (sextet, J = 7.3 Hz, 2H), 2.38 (t, J = 7 , 3 Hz, 2H), 3.80 (s, 3H), 5.21 (s, 2H), 6.89 (s, 1H), 7.08-7.13 (m, 2H), 7.40 (t, J = 8.3 Hz, 1H), 11.93 (br s, 1H).

(CD3SO2CD3) δ 2,10 (s, 3H), 5,18 (s, 2H), 7,20 (dd, J = 6,6, 3,0 Hz, IH), 7,29 (dd, J = 9,6, 8,8 Hz, IH), 7,42 (ddd, J - 8,8, 4,4, 3,0 Hz, IH), 7,51 (s, IH), 11,96 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.10 (s, 3H), 5.18 (s, 2H), 7.20 (dd, J = 6.6, 3.0 Hz, 1H), 7.29 (dd, J = 9.6, 8.8 Hz, 1H), 7.42 (ddd, J - 8.8, 4.4, 3.0 Hz, 1H), 7.51 (s, 1H), 11.96 (br. S, 1H).

(CD3SO2CD3) δ 1,23 (d, J = 7,0 Hz, 6H), 2,92 (m, IH),(CD 3 SO 2 CD 3 ) δ 1.23 (d, J = 7.0 Hz, 6H), 2.92 (m, 1H),

5,25 (s, 2H), 6,83 (dd, J = 7,4, 2,2 Hz, IH), 7,27-7,35 (m, 2H), 7,49 (s, IH), 7,51 (dd, J = 7,3, 1,8 Hz, IH), 12,01 (br. s, IH).5.25 (s, 2H), 6.83 (dd, J = 7.4, 2.2 Hz, 1H), 7.27-7.35 (m, 2H), 7.49 (s, 1H) , 7.51 (dd, J = 7.3, 1.8 Hz, 1H), 12.01 (br s, 1H).

-142142-142142

-(5 -fluoro-2-metilbenzil)7-metil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion- (5-Fluoro-2-methylbenzyl) 7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

7-metil-5-[( 1 S)-1 -feniletilf3.5- dihidro[l,3oksazolo [4,5 -c]piridin-2,4dion7-Methyl-5 - [(1S) -1-phenylethyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-kloro-5izopropoksibenzil)-7-metil3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chloro-5isopropoxybenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(5-acetil-2metoksibenzil)-3,5dihidro[ 1,3 -oksazolo [4,5c]piridin-2,4-dion 5-(2-klorobenzil)-7-metil3,5-dihidro[l,3oksazolo[4,5-djpiridazin2.4- dion5- (5-acetyl-2methoxybenzyl) -3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-chlorobenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-dpyridazine 2,4,4-dione

5-[2-fluoro-6(trifluorometil)benzil]-7metil-3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- [2-Fluoro-6 (trifluoromethyl) benzyl] -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-kloro-6-metilbenzil)5,6,7,8-tetrahidro-2Hciklopenta[b][l,3]oksazolo[5- (2-chloro-6-methylbenzyl) 5,6,7,8-tetrahydro-2Hcyclopenta [b] [1,3] oxazolo [

5.4- d]piridin-2,4(3H)-dion 5-(2-kloro-6-etoksibenzil)(CD3SO2CD3) δ 2,10 (d, J = 1,1 Hz, 3H), 2,30 (s, 3H),5.4- d] pyridine-2,4 (3H) -dione 5- (2-chloro-6-ethoxybenzyl) (CD 3 SO 2 CD 3 ) δ 2.10 (d, J = 1.1 Hz, 3H). 2.30 (s, 3H),

5,13 (s, 2H), 6,55 (dd, J = 9,9, 2,6 Hz, IH), 7,01 (td, J =5.13 (s, 2H), 6.55 (dd, J = 9.9, 2.6 Hz, 1H), 7.01 (td, J =

8,4, 2,6 Hz, IH), 7,25 (dd, J = 8,4, 5,9 Hz, IH), 7,42 (q,8.4, 2.6 Hz, 1H), 7.25 (dd, J = 8.4, 5.9 Hz, 1H), 7.42 (q,

1,1 Hz, IH), 11,99 (br. s, IH).1.1 Hz, 1H), 11.99 (br s, 1H).

(CD3SO2CD3) δ 1,72 (d, J = 7,3 Hz, IH), 2,07 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.72 (d, J = 7.3 Hz, 1H), 2.07 (s, 3H),

6,27 (q, J = 7,3 Hz, IH), 7,27-7,40 (m, 6H), 11,95 (br. s, IH).6.27 (q, J = 7.3 Hz, 1H), 7.27-7.40 (m, 6H), 11.95 (br s, 1H).

(CD3SO2CD3) δ 1,20 (d, J - 6,0 Hz, 6H), 2,11 (s, 3H), 4,50 (m, IH), 5,16 (s, 2H), 6,34 (d, J = 3,0 Hz, IH), 6,91 (dd, J - 8,8, 3,0 Hz, IH), 7,38 (d, J = 8,8 Hz, IH), 7,47 (s, IH), 12,01 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 1.20 (d, J - 6.0 Hz, 6H), 2.11 (s, 3H), 4.50 (m, 1H), 5.16 (s, 2H) ), 6.34 (d, J = 3.0 Hz, 1H), 6.91 (dd, J - 8.8, 3.0 Hz, 1H), 7.38 (d, J = 8.8 Hz) , 1H), 7.47 (s, 1H), 12.01 (br. S, 1H).

(CD3SO2CD3) δ 2,47 (s, 3H), 3,93 (s, 3H), 5,16 (s, 2H), 6,62 (d, J = 7,3 Hz, IH), 7,16 (d, J = 8,4 Hz, IH), 7,59 (d, J = 2,2 Hz, IH), 7,63 (d, J = 7,3 Hz, IH), 7,97 (dd, J = 8,4, 2,2 Hz, IH), 11,96 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.47 (s, 3H), 3.93 (s, 3H), 5.16 (s, 2H), 6.62 (d, J = 7.3 Hz, 1H ), 7.16 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 2.2 Hz, 1H), 7.63 (d, J = 7.3 Hz, 1H), 7.97 (dd, J = 8.4, 2.2 Hz, 1H), 11.96 (br s, 1H).

(CD3SO2CD3) δ 2,29 (s, 3H), 5,39 (s, 2H), 7,00 (d, J =(CD 3 SO 2 CD 3 ) δ 2.29 (s, 3H), 5.39 (s, 2H), 7.00 (d, J =

7,4 Hz, IH), 7,26-7,37 (m, 2H), 7,51 (d, J = 7,7 Hz, IH), 12,80 (br. s, IH).7.4 Hz, 1H), 7.26-7.37 (m, 2H), 7.51 (d, J = 7.7 Hz, 1H), 12.80 (br s, 1H).

(CD3SO2CD3) δ 2,04 (s, 3H), 5,33 (s, 2H), 7,05 (s, IH), 7,51-7,72 (m, 3H), 11,98 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.04 (s, 3H), 5.33 (s, 2H), 7.05 (s, 1H), 7.51-7.72 (m, 3H), 11 , 98 (No. s, 1H).

(CD3SO2CD3) δ 2,02 (m, 2H), 2,21 (s, 3H), 2,64-2,80 (m, 4H), 5,42 (s, 2H), 7,05-7,33 (m, 3H), 11,81 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.02 (m, 2H), 2.21 (s, 3H), 2.64-2.80 (m, 4H), 5.42 (s, 2H), 7 , 05-7.33 (m, 3H), 11.81 (br. S, 1H).

(CD3SO2CD3) δ 1,08 (t, J = 7,7 Hz, 3H), 1,25 (t, J = 7,0(CD 3 SO 2 CD 3 ) δ 1.08 (t, J = 7.7 Hz, 3H), 1.25 (t, J = 7.0

-143143-143143

7-etil-3,5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion7-ethyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(2-kloro-6propoksibenzil)-7-etil-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion5- (2-chloro-6-propoxybenzyl) -7-ethyl-3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-kloro-6izobutoksibenzil)-7-metil3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chloro-6-isobutoxybenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

-(2-kloro-6-etoksibenzil)5,6,7,8-tetrahidro-2Hciklopenta[b] [ 1,3]oksazolo[- (2-chloro-6-ethoxybenzyl) 5,6,7,8-tetrahydro-2Hcyclopenta [b] [1,3] oxazolo [

5.4- d]piridin-2,4(3H)-dion 5-(2-kloro-6izopropoksibenzil)-7-metil3.5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5.4- d] pyridine-2,4 (3H) -dione 5- (2-chloro-6isopropoxybenzyl) -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-[2-kloro-6-(2,2,2trifluoroetoksi)benzil]-7metil-3,5 -dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion5- [2-chloro-6- (2,2,2trifluoroethoxy) benzyl] -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(2-kloro-6-etoksibenzil)7-metil-3,5 -dihidro[ 1,3oksazolo [4,5 -d]piridazinHz, 3H), 2,44 (q, J = 7,7 Hz, 2H), 4,05 (q, J = 7,0 Hz, 2H), 5,23 (s, 2H), 6,99 (s, IH), 7,05 (d, J = 8,4 Hz, IH), 7,09 (d, J = 8,1 Hz, IH), 7,36 (dd, J = 8,4, 8,1 Hz, IH),5- (2-chloro-6-ethoxybenzyl) 7-methyl-3,5-dihydro [1,3oxazolo [4,5-d] pyridazineHz, 3H), 2.44 (q, J = 7.7 Hz, 2H ), 4.05 (q, J = 7.0 Hz, 2H), 5.23 (s, 2H), 6.99 (s, 1H), 7.05 (d, J = 8.4 Hz, 1H) ), 7.09 (d, J = 8.1 Hz, 1H), 7.36 (dd, J = 8.4, 8.1 Hz, 1H),

11.93 (br. s, IH).11.93 (No s, 1H).

(CD3SO2CD3) δ 0,88 (t, J = 7,3 Hz, 3H),(CD 3 SO 2 CD 3 ) δ 0.88 (t, J = 7.3 Hz, 3H),

1.66 (m, 2H), 2,01 (d, J = 1,1 Hz, 3H), 3,95 (t, J = 6,2 Hz, 2H), 5,24 (s, 2H), 6,91 (q, J = 1,1 Hz, IH), 7,03 (d, J = 8,4 Hz, IH), 7,10 (d, J = 8,1 Hz, IH), 7,37 (dd, J = 8,4,1.66 (m, 2H), 2.01 (d, J = 1.1 Hz, 3H), 3.95 (t, J = 6.2 Hz, 2H), 5.24 (s, 2H), 6. 91 (q, J = 1.1 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.37 ( dd, J = 8.4,

8,1 Hz, IH), 11,95 (br. s, IH).8.1 Hz, 1H), 11.95 (br s, 1H).

(CD3SO2CD3) δ 0,89 (d, J = 7,0 Hz, 6H), 1,95 (m, IH), 2,00 (s, 3H), 3,79 (d, J - 6,2 Hz, 2H), 5,25 (s, 2H), 6,85 (s, IH), 7,06 (d, J = 8,4 Hz, IH), 7,11 (d, J = 8,1 Hz, IH), 7,38 (dd, J = 8,4, 8,1 Hz, IH), 11,97 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 0.89 (d, J = 7.0 Hz, 6H), 1.95 (m, 1H), 2.00 (s, 3H), 3.79 (d, J - 6.2 Hz, 2H), 5.25 (s, 2H), 6.85 (s, 1H), 7.06 (d, J = 8.4 Hz, 1H), 7.11 (d, J) = 8.1 Hz, 1H), 7.38 (dd, J = 8.4, 8.1 Hz, 1H), 11.97 (br. S, 1H).

(CD3SO2CD3) δ 1,10 (t, J = 7,0 Hz, 3H), 2,06 (m, 2H), 2,70-2,92 (m, 4H), 3,90 (q, J = 7,0 Hz, 2H), 5,33 (s, 2H),(CD 3 SO 2 CD 3 ) δ 1.10 (t, J = 7.0 Hz, 3H), 2.06 (m, 2H), 2.70-2.92 (m, 4H), 3.90 (q, J = 7.0 Hz, 2H), 5.33 (s, 2H),

6.93 (d, J = 8,4 Hz, IH), 7,03 (d, J = 8,1 Hz, IH), 7,26 (dd, J = 8,4, 8,1 Hz, IH), 11,75 (br. s, IH).6.93 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H), 7.26 (dd, J = 8.4, 8.1 Hz, 1H), 11.75 (br. S, 1H).

(CD3SO2CD3) δ 1,16 (d, J = 6,2 Hz, 6H), 2,02 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.16 (d, J = 6.2 Hz, 6H), 2.02 (s, 3H),

4.67 (m, IH), 5,21 (s, 2H), 6,94 (s, IH), 7,07 (d, J = 8,0 Hz, 2H), 7,34 (t, J = 8,0 Hz, IH), 11,93 (br. s, IH).4.67 (m, 1H), 5.21 (s, 2H), 6.94 (s, 1H), 7.07 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 8) , 0 Hz, 1H), 11.93 (br s, 1H).

(CD3SO2CD3) δ 2,01 (s, 3H), 4,82 (q, J = 8,8 Hz, 2H),(CD 3 SO 2 CD 3 ) δ 2.01 (s, 3H), 4.82 (q, J = 8.8 Hz, 2H),

5,24 (s, 2H), 6,94 (s, IH), 7,19 (d, J = 8,4 Hz, IH), 7,22 (d, J = 8,1 Hz, IH), 7,43 (dd, J = 8,4, 8,1 Hz, IH), 11,92 (br. s, IH).5.24 (s, 2H), 6.94 (s, 1H), 7.19 (d, J = 8.4 Hz, 1H), 7.22 (d, J = 8.1 Hz, 1H). 7.43 (dd, J = 8.4, 8.1 Hz, 1H), 11.92 (br s, 1H).

(CD3SO2CD3) δ 1,19 (t, J = 7,0 Hz, 3H), 2,19 (s, 3H), 3,99 (q, J = 7,0 Hz, 2H), 5,41 (s, 2H), 6,98 (d, J = 8,4 Hz, IH), 7,05 d, J = 8,0 Hz, IH), 7,30 (dd, J = 8,4, 8,0 Hz,(CD 3 SO 2 CD 3 ) δ 1.19 (t, J = 7.0 Hz, 3H), 2.19 (s, 3H), 3.99 (q, J = 7.0 Hz, 2H), 5.41 (s, 2H), 6.98 (d, J = 8.4 Hz, 1H), 7.05 d, J = 8.0 Hz, 1H), 7.30 (dd, J = 8. 4, 8.0 Hz,

-144144-144144

2.4- dion2.4- Dion

5-(2-kloro-6-(2metoksietoksi)benzil)5,6,7,8-tetrahidro-2Hciklopenta[b][l,3]oksazolo[5- (2-chloro-6- (2methoxyethoxy) benzyl) 5,6,7,8-tetrahydro-2Hcyclopenta [b] [1,3] oxazolo [

5.4- d]piridin-2,4(3H)-dion 5-[2-kloro-6-etoksibenzil)6,7-dimetil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion5.4- d] pyridine-2,4 (3H) -dione 5- [2-chloro-6-ethoxybenzyl) 6,7-dimethyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2 , 4dion

5-[2-kloro-6-etoksibenzil)7-etil-6-metil-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- [2-chloro-6-ethoxybenzyl) 7-ethyl-6-methyl-3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-klorobenzil)-7-etil3.5- dihidro[l,3oksazolo[4,5-d]piridazin2.4- dion5- (2-chlorobenzyl) -7-ethyl3,5-dihydro [1,3oxazolo [4,5-d] pyridazine 2,4,4-dione

-(2-kloro-6-etoksibenzil)7-propil-3,5 -dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion- (2-chloro-6-ethoxybenzyl) 7-propyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-(2-kloro-6-etoksibenzil)7-ciklopropil-3,5dihidro[l,3-oksazolo[4,5c]piridin-2,4-dion5- (2-chloro-6-ethoxybenzyl) 7-cyclopropyl-3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2-kloro-5propoksibenzil)-7-metil3.5- dihidro[l,31H), 12,70 (br. s, IH).5- (2-chloro-5-propoxybenzyl) -7-methyl-3,5-dihydro [1,3H], 12.70 (br. S, 1H).

(CD3SO2CD3) δ 2,06 (m, 2H), 2,74-2,90 (m, 4H), 3,20 (s, 3H), 3,47 (t, J = 4,4 Hz, 2H), 4,01 (t, J = 4,4 Hz, 2H), 5,33 (s, 2H), 6,98 (d, J = 8,0 Hz, IH), 7,04 (d, J = 8,0 Hz, IH), 7,27 (t, J = 8,0 Hz, IH), (br. s, IH).(CD 3 SO 2 CD 3 ) δ 2.06 (m, 2H), 2.74-2.90 (m, 4H), 3.20 (s, 3H), 3.47 (t, J = 4, 4 Hz, 2H), 4.01 (t, J = 4.4 Hz, 2H), 5.33 (s, 2H), 6.98 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 7.27 (t, J = 8.0 Hz, 1H), (br. s, 1H).

(CD3SO2CD3) δ 1,03 (t, J = 7,0 Hz, 3H), 2,06 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.03 (t, J = 7.0 Hz, 3H), 2.06 (s, 3H),

2,22 (s, 3H), 3,84 (q, J = 7,0 Hz, 2H), 5,48 (s, 2H), 6,92 (d, J = 8,4 Hz, IH), 7,03 (d, J = 8,1 Hz, IH), 7,24 (dd, J = 8,4, 8,1 Hz, IH), 11,76 (br. s, IH).2.22 (s, 3H), 3.84 (q, J = 7.0 Hz, 2H), 5.48 (s, 2H), 6.92 (d, J = 8.4 Hz, 1H). 7.03 (d, J = 8.1 Hz, 1H), 7.24 (dd, J = 8.4, 8.1 Hz, 1H), 11.76 (br. S, 1H).

(CD3SO2CD3) δ 1,06 (m, 6H), 2,24 (s, 3H), 2,48-2,56 (m prekrivajoč DMSO, 2H) 3,85 (q, J = 7,0 Hz, 2H), 5,48 (s, 2H), 6,92 (d, 8,4 Hz, IH), 7,03 (d, J = 8,1 Hz, IH),(CD 3 SO 2 CD 3 ) δ 1.06 (m, 6H), 2.24 (s, 3H), 2.48-2.56 (m overlapping DMSO, 2H) 3.85 (q, J = 7 , 0 Hz, 2H), 5.48 (s, 2H), 6.92 (d, 8.4 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H),

7,24 (dd, J - 8,4, 8,1 Hz, IH), 11,77 (br. s, IH). (CD3SO2CD3) δ 1,18 (t, J = 7,5 Hz, 3H), 2,70 (q, J = 7,5 Hz, 2H), 5,38 (s, 2H), 7,0-7,6 (m, 4H), 12,77 (br. s, IH).7.24 (dd, J = 8.4, 8.1 Hz, 1H), 11.77 (br s, 1H). (CD 3 SO 2 CD 3 ) δ 1.18 (t, J = 7.5 Hz, 3H), 2.70 (q, J = 7.5 Hz, 2H), 5.38 (s, 2H). 7.0-7.6 (m, 4H), 12.77 (br s, 1H).

(CD3SO2CD3) δ 0,82 (t, J = 7,3 Hz, 3H), 1,24 (t, J = 7,0 Hz, 3H), 1,48 (m, 2H), 2,37 (t, J = 7,3 Hz, 2H), 4,05 (q, J = 7,0 Hz, 2H), 5,23 (s, 2H), 6,93 (s, IH), 7,05 (d, J = 8,4 Hz, IH), 7,09 (d, J - 8,1 Hz, IH), 7,36 (dd, J = 8,4, 8,1 Hz, IH), ll,94(br. s, IH).(CD 3 SO 2 CD 3 ) δ 0.82 (t, J = 7.3 Hz, 3H), 1.24 (t, J = 7.0 Hz, 3H), 1.48 (m, 2H), 2.37 (t, J = 7.3 Hz, 2H), 4.05 (q, J = 7.0 Hz, 2H), 5.23 (s, 2H), 6.93 (s, 1H). 7.05 (d, J = 8.4 Hz, 1H), 7.09 (d, J - 8.1 Hz, 1H), 7.36 (dd, J = 8.4, 8.1 Hz, 1H ), ll, 94 (br. s, 1H).

(CD3SO2CD3) δ 0,55 (m, 2H), 0,81 (m, 2H), 1,26 (t, J = 7,0 Hz, 3H), 1,72 (m, IH), 4,05 (q, J = 7,0 Hz, 2H), 5,22 (s, 2H), 6,95 (s, IH), 7,05 (d, J = 8,4 Hz, IH), 7,09 (d, J = 8,1 Hz, IH), 7,36 (dd, J = 8,4, 8,1 Hz, IH), 11,93 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 0.55 (m, 2H), 0.81 (m, 2H), 1.26 (t, J = 7.0 Hz, 3H), 1.72 (m, 1H ), 4.05 (q, J = 7.0 Hz, 2H), 5.22 (s, 2H), 6.95 (s, 1H), 7.05 (d, J = 8.4 Hz, 1H) ), 7.09 (d, J = 8.1 Hz, 1H), 7.36 (dd, J = 8.4, 8.1 Hz, 1H), 11.93 (br s, 1H).

(CD3SO2CD3) δ 0,92 (t, J = 7,3 Hz, 3H), 1,66 (m, 2H),(CD 3 SO 2 CD 3 ) δ 0.92 (t, J = 7.3 Hz, 3H), 1.66 (m, 2H),

2,10 (s, 3H), 3,85 (m, 2H), 5,17 (s, 2H), 6,41 (d, J = 3,3 Hz, IH), 6,91 (dd, J = 8,8, 3,3 Hz, IH), 7,39 (d, J = 8,82.10 (s, 3H), 3.85 (m, 2H), 5.17 (s, 2H), 6.41 (d, J = 3.3 Hz, 1H), 6.91 (dd, J = 8.8, 3.3 Hz, 1H), 7.39 (d, J = 8.8)

-145145 oksazolo[4,5-c]piridin-2,4dion-145145 Oxazolo [4,5-c] pyridine-2,4dione

5- (2-kloro-5metoksibenzil)-7-metil-3,5dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion 5 -(2-kloro-6-etoksibenzil)6- metil-3,5-dihidro[l,3oksazolo [4, 5 -c]piridin-2,4dion5- (2-chloro-5methoxybenzyl) -7-methyl-3,5-dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione 5- (2-chloro-6-ethoxybenzyl) 6- methyl- 3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4dione

5-(2-kloro-5-etoksibenzil)7- metil-3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- (2-chloro-5-ethoxybenzyl) 7- methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

- [2-kloro-5-(piperidin-1 ilsulfonil)benzil]-7-metil3,5-dihidro[l,3oksazolo[4,5-clpiridin-2,4dion- [2-chloro-5- (piperidin-1-ylsulfonyl) benzyl] -7-methyl-3,5-dihydro [1,3oxazolo [4,5-clpyridine-2,4-dione]

5-[2-kloro-5-(pirolidin-1 ilsulfonil)benzil] -7-metil3,5-dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- [2-chloro-5- (pyrrolidin-1-ylsulfonyl) benzyl] -7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-[2-kloro-6(ciklopentilmetoksi)benzil] 7-metil-3,5- dihidro[l,3oksazolo[4,5-c]piridin-2,4dion5- [2-chloro-6 (cyclopentylmethoxy) benzyl] 7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

5-[2-benziloksi)-6klorobenzil]-7-metil-3,5Hz, IH), 7,45 (s, IH), 12,00 (br. s, IH).5- [2-Benzyloxy) -6-chlorobenzyl] -7-methyl-3,5Hz, 1H), 7.45 (s, 1H), 12.00 (br. S, 1H).

(CD3SO2CD3) δ 2,10 (s, 3H), 3,9 (s, 3H), 5,18 (s, 2H),(CD 3 SO 2 CD 3 ) δ 2.10 (s, 3H), 3.9 (s, 3H), 5.18 (s, 2H),

6.42 (d, J = 3,0 Hz, IH), 6,93 (dd, J = 8,8, 3,0 Hz, IH),6.42 (d, J = 3.0 Hz, 1H), 6.93 (dd, J = 8.8, 3.0 Hz, 1H),

7.42 (d, J = 8,8 Hz, IH), 7,44 (s, IH), 12,00 (br. s, IH).7.42 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 12.00 (br s, 1H).

(CD3SO2CD3) δ 1,07 (t, J = 7,0 Hz, 3H), 2,32 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.07 (t, J = 7.0 Hz, 3H), 2.32 (s, 3H),

3,87 (q, J = 7,0 Hz, 2H), 5,42 (s, 2H), 6,44 (s, IH), 6,92 (d, J = 8,4 Hz, IH), 7,03 (d, J = 8,1 Hz, IH), 7,24 (dd, J = 8,4, 8,1 Hz, IH), 11,74 (br. s, IH).3.87 (q, J = 7.0 Hz, 2H), 5.42 (s, 2H), 6.44 (s, 1H), 6.92 (d, J = 8.4 Hz, 1H). 7.03 (d, J = 8.1 Hz, 1H), 7.24 (dd, J = 8.4, 8.1 Hz, 1H), 11.74 (br. S, 1H).

(CD3SO2CD3) δ 1,26 (t, J = 7,0 Hz, 3H), 2,10 (s, 3H),(CD 3 SO 2 CD 3 ) δ 1.26 (t, J = 7.0 Hz, 3H), 2.10 (s, 3H),

3,94 (q, J = 7,0 Hz, 2H), 5,17 (s, 2H), 6,38 (d, J = 2,9 Hz, IH), 6,91 (dd, J = 8,8, 2,9 Hz, IH), 7,39 (d, J = 8,8 Hz, IH), 7,44 (s, IH), 11,99 (br. s, IH).3.94 (q, J = 7.0 Hz, 2H), 5.17 (s, 2H), 6.38 (d, J = 2.9 Hz, 1H), 6.91 (dd, J = 8 , 8, 2.9 Hz, 1H), 7.39 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 11.99 (no s, 1H).

(CD3SO2CD3) δ 1,35 (m, 2H), 1,47 (m, 4H), 2,10 (s, 3H), 2,81 (m, 4H), 5,30 (s, 2H), 7,18 (d, J = 2,2 Hz, IH),(CD 3 SO 2 CD 3 ) δ 1.35 (m, 2H), 1.47 (m, 4H), 2.10 (s, 3H), 2.81 (m, 4H), 5.30 (s , 2H), 7.18 (d, J = 2.2 Hz, 1H),

7,57 (s, IH), 7,67 (dd, J = 8,4, 2,2 Hz, IH), 7,78 (d, J =7.57 (s, 1H), 7.67 (dd, J = 8.4, 2.2 Hz, 1H), 7.78 (d, J =

8,4 Hz, IH), 12,07 (br. s, IH).8.4 Hz, 1H), 12.07 (br. S, 1H).

(CD3SO2CD3) δ 1,62 (m, 4H), 2,11 (s, 3H), 3,05 (m, 4H), 5,30 (s, 2H), 7,30 (s, IH), 7,57 (s, IH), 7,75-7,82 (m, 2H), 12,08 (br. s, IH).(CD 3 SO 2 CD 3 ) δ 1.62 (m, 4H), 2.11 (s, 3H), 3.05 (m, 4H), 5.30 (s, 2H), 7.30 (s , 1H), 7.57 (s, 1H), 7.75-7.82 (m, 2H), 12.08 (br. S, 1H).

(CD3SO2CD3) δ 1,22 (m, 2H), 1,51 (m, 4H), 1,68 (m, 2H), 2,00 (s, 3H), 2,20 (m, IH), 3,89 (d, J = 7,0 Hz, 2H),(CD 3 SO 2 CD 3 ) δ 1.22 (m, 2H), 1.51 (m, 4H), 1.68 (m, 2H), 2.00 (s, 3H), 2.20 (m , 1H), 3.89 (d, J = 7.0 Hz, 2H),

5,24 (s, 2H), 6,86 (s, IH), 7,07 (d, J - 8,4 Hz, IH), 7,11 (d, J - 8,1 Hz, IH), 7,37 (dd, J = 8,4, 8,1 Hz, IH), 11,97 (br. s, IH).5.24 (s, 2H), 6.86 (s, 1H), 7.07 (d, J - 8.4 Hz, 1H), 7.11 (d, J - 8.1 Hz, 1H), 7.37 (dd, J = 8.4, 8.1 Hz, 1H), 11.97 (br s, 1H).

(CD3SO2CD3) δ 1,90 (s, 3H), 5,15 (s, 2H), 5,25 (s, 2H), 6,84 (s, IH), 7,13 (d, J = 8,1 Hz, IH), 7,19 (d, J = 7,7 Hz,(CD 3 SO 2 CD 3 ) δ 1.90 (s, 3H), 5.15 (s, 2H), 5.25 (s, 2H), 6.84 (s, 1H), 7.13 (d , J = 8.1 Hz, 1H), 7.19 (d, J = 7.7 Hz,

-146146 dihidro[ 1,3-oksazolo[4,5c]piridin-2,4-dion-146146 Dihydro [1,3-oxazolo [4,5c] pyridine-2,4-dione

5-(2,3-dikloro-6etoksibenzil)-5,6,7,8tetrahidro-2Hciklopenta[b] [ 1,3 ]oksazolo[5- (2,3-dichloro-6ethoxybenzyl) -5,6,7,8tetrahydro-2Hcyclopenta [b] [1,3] oxazolo [

5,4-d]piridin-2,4(3H)-dion5,4-d] pyridine-2,4 (3H) -dione

5-[2-kloro-5(trifluorometil)benzil]-7metil-3,5 -dihidro [1,3oksazolo[4,5-c]piridin-2,4dion5- [2-chloro-5 (trifluoromethyl) benzyl] -7methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

-(2-kloro-5 -fluorobenzil)7-metil-3,5-dihidro[ 1,3oksazolo[4,5-c]piridin-2,4dion- (2-chloro-5-fluorobenzyl) 7-methyl-3,5-dihydro [1,3oxazolo [4,5-c] pyridine-2,4-dione

IH), 7,30-7,37 (m, 5H), 7,39 (dd, J = 8,1, 7,7 Hz, IH),1H), 7.30-7.37 (m, 5H), 7.39 (dd, J = 8.1, 7.7 Hz, 1H),

11,91 (br. s, IH).11.91 (br. S, 1H).

(CD3SO2CD3) δ 1,10 (t, J = 7,0 Hz, 3H), 2,09 (m, 2H),(CD3SO2CD3) δ 1.10 (t, J = 7.0 Hz, 3H), 2.09 (m, 2H),

2,80 (m, 2H), 2,89 (m, 2H), 3,92 (q, J = 7,0 Hz, 2H), 5,33 (s, 2H), 6,98 (d, J = 8,8 Hz, IH), 7,50 (d, J = 8,8 Hz, IH), 11,71 (br. s, IH).2.80 (m, 2H), 2.89 (m, 2H), 3.92 (q, J = 7.0 Hz, 2H), 5.33 (s, 2H), 6.98 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 11.71 (br s, 1H).

(CD3SO2CD3) δ 2,11 (s, 3H), 5,29 (s, 2H), 7,34 (s, IH),(CD 3 SO 2 CD 3 ) δ 2.11 (s, 3H), 5.29 (s, 2H), 7.34 (s, 1H),

7,54 (s, IH), 7,72-7,79 (m, 2H), 12,00 (br. s, IH).7.54 (s, 1H), 7.72-7.79 (m, 2H), 12.00 (br s, 1H).

(CD3SO2CD3) δ 2,11 (s, 3H), 5,20 (s, 2H), 6,71 (dd, J =(CD 3 SO 2 CD 3 ) δ 2.11 (s, 3H), 5.20 (s, 2H), 6.71 (dd, J =

9,4, 2,9 Hz, IH), 7,22 (td, J = 8,4, 2,9 Hz, IH), 7,49 (s, IH), 7,57 (dd, J = 8,4, 5,2 Hz, IH), 11,99 (br. s, IH).9.4, 2.9 Hz, 1H), 7.22 (td, J = 8.4, 2.9 Hz, 1H), 7.49 (s, 1H), 7.57 (dd, J = 8) , 4, 5.2 Hz, 1H), 11.99 (br. S, 1H).

Primer 42Example 42

Za določitev učinkovitosti sintetiziranih spojin uporabimo postopek, pri katerem 26amino kislinski peptid, ki vsebuje CS1 sekvenco fibronektina z N-terminalnim Cys (CDE LPQ LVT LPH PNL HGP EIL DVP ST), pripajamo na ovalbumin, aktiviran z maleimidom. Goveji serumski albumin (BSA) in CS1 konjugiran ovalbumin preslojimo na polistirenske plošče s 96 vdolbinami pri 0,5 pg/ml v TBS (50 mM TRIS, pH 7,5; 150 mM NaCl) pri 4 °C v teku 16 ur. Plošče 3-krat izperemo s TBS in blokiramo s TBS, ki vsebuje 3 % BSA, pri sobni temperaturi 4 ure. Blokirane ploščeTo determine the effectiveness of the synthesized compounds, we use a process in which a 26amino acid peptide containing a CS1 sequence of fibronectin with N-terminal Cys (CDE LPQ LVT LPH PNL HGP EIL DVP ST) is attached to maleimide-activated ovalbumin. Bovine serum albumin (BSA) and CS1 conjugated ovalbumin were coated onto 96-well polystyrene plates at 0.5 pg / ml in TBS (50 mM TRIS, pH 7.5; 150 mM NaCl) at 4 ° C for 16 hours. The plates were washed 3 times with TBS and blocked with TBS containing 3% BSA at room temperature for 4 hours. Blockboards

3-krat izperemo v vezavnem pufru TBS; 1 mM MgCl2; 1 mM CaCl2; 1 mM MnCl2 pred testom. Ramosove celice, fluorescenčno markirane s calcein AM, resuspendiramo v vezavnem pufru (107 celic/ml) in razredčimo 1:2 z istim pufrom z ali brez spojine. Dodamo 100 μΜ spojine. Celice dodamo takoj v vdolbine (2,5 χ 105 celic/vdolbino) in inkubiramo 30 minut pri 37 °C. Po treh izpiranjih z vezavnim pufrom liziramo adherentne celice in kvantificiramo ob uporabi fluorometra. RezultatiWash 3 times in TBS binding buffer; 1 mM MgCl 2 ; 1 mM CaCl 2 ; 1 mM MnCl 2 before the test. Ramos cells fluorescently labeled with calcein AM were resuspended in binding buffer (10 7 cells / ml) and diluted 1: 2 with the same buffer with or without compound. Add 100 μΜ of compound. The cells were immediately added to the wells (2.5 χ 10 5 cells / well) and incubated for 30 minutes at 37 ° C. After three washes with binding buffer, adherent cells were lysed and quantified using a fluorometer. Results

-147147 so prikazani v tabelah 2-7. IC50 je definiran kot doza, ki je potrebna, da daje 50 % inhibicijo, merjeno v μΜ za tabeli 2 in 4. Nižja kot je IC50 vrednost in večji kot je odstotek inhibicije, bolj je spojina učinkovita pri preprečevanju celične adhezije.-147147 are shown in Tables 2-7. IC50 is defined as the dose required to give 50% inhibition measured in μΜ for Tables 2 and 4. The lower the IC 50 value and the greater the percentage inhibition, the more effective the compound is in preventing cell adhesion.

Tabela 2Table 2

Ime (3 S)-3 -(1,3-benzodioksol-5 -il)-3 [({[(3S)2-okso-1 -(2-tienilmetil)heksahidro-3piridinil]-amino}karbonil)amino]propanojska kislina (3 S )-3 -(1,3 -benzodioksol-5 -il)-3 [({[(3S)2-okso-1 -(2-tienilmetil)tetrahidro-1Hpirol-3 -il] -amino } karbonil)amino]propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3-[({[(3R)2-okso-1 -(2-tienilmetil)heksahidro-3piridinil]-amino}karbonil)amino]propanojska kislina (3 S)-3-(1,3-benzodioksol-5-il)-3-[({ [2okso-1 -(2-tienilmetil)-1,2-dihidro-3 p iridinil] -amino } karbonil)amino]propanojska kislinaName (3S) -3- (1,3-benzodioxol-5-yl) -3 [({[(3S) 2-oxo-1- (2-thienylmethyl) hexahydro-3pyridinyl] -amino} carbonyl) amino] (3S) -3- (1,3-benzodioxol-5-yl) -3 [({[(3S) 2-oxo-1- (2-thienylmethyl) tetrahydro-1H-pyrrol-3-yl] -amino) propanoic acid } carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[(3R) 2-oxo-1- (2-thienylmethyl) hexahydro-3pyridinyl] - (amino) carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[2-oxo-1- (2-thienylmethyl) -1,2-dihydro-3 pyridinyl] -amino} carbonyl) amino] propanoic acid

IC50 masni spektralni podatki (m/z)IC50 mass spectral data (m / z)

0,2 izrač.: (M-H)'= 444,12; ugot.: (M-H)' = 444,08 izrač.: (M-H)'= 430,11; ugot.: (M-H)'= 430,06 izrač.: (M-H)'= 444,12; ugot.: (M-H)' =444,050.2 Calc .: (M-H) '= 444.12; found: (M-H) '= 444.08 Calc .: (M-H)' = 430.11; found: (M-H) '= 430.06 calculated: (M-H)' = 444.12; found: (M-H) &lt; + &gt; = 444.05

0,9 izrač.: (M-H)' = 440,09; ugot.: (M-H)'= 439,980.9 Calc .: (M-H) '= 440.09; found: (M-H) '= 439.98

-148148 (3S)-3-(l,3-benzodioksol-5-il)-3-[({[(3S)2-okso-1 - {4- [(2-toluidinokarbonil)amino] benzil} heksahidro-3 -piridinil]-amino} karbonil)amino]-propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3-[({[2okso-1 - {4-[(2- toluidinokarbonil)amino]benzil} -1,2-dihidro-3-piridinil] amino}karbonil)amino]propanoj ska kislina (3 S)-3-( 1,3-benzodioksol-5-il)-3-({ [((3 S)1 - {4-[(2-metilbenzil)amino]benzil}-2oksoheksahidro-piridinil)amino]karbonil}amino)propanojska kislina (3 S)-3 -(1,3 -benzodioksol-5-il)-3 - [({ butil[2-okso- l-(2-tienilmetil)-1,2-dihidro-3p iridini 1] amino } karbonil)amino]propanojska kislina (3 S)-3-( 1,3-benzodioksol-5-il)-3-[( {[(3 S)2-okso-1 -(2-tienilmetil)azepanil] amino}karbonil)amino]propanoj ska kislina-148148 (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[(3S) 2-oxo-1- {4- [(2-toluidinocarbonyl) amino] benzyl} hexahydro- 3-Pyridinyl] -amino} carbonyl) amino] -propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[2oxo-1- {4 - [(2-toluidinocarbonyl) ) amino] benzyl} -1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - ({[( (3 S) 1- {4 - [(2-methylbenzyl) amino] benzyl} -2-oxohexahydro-pyridinyl) amino] carbonyl} amino) propanoic acid (3 S) -3- (1,3-benzodioxol-5-yl) -3 - [({butyl [2-oxo-1- (2-thienylmethyl) -1,2-dihydro-3β-iridines 1] amino} carbonyl) amino] propanoic acid (3 S) -3- (1,3- benzodioxol-5-yl) -3 - [({[(3 S) 2-oxo-1- (2-thienylmethyl) azepanyl] amino} carbonyl) amino] propanoic acid

Tabela 3Table 3

Spojina (3 S)-3 - [({ [2-metil-4-(2-metilpropil)6-okso-1 -(fenilmetil)-1,6-dihidro-5pirimidinil]-amino} karbonil)amino]-3 0,0003 izrač.: (M-H)' = 586,23;Compound (3S) -3 - [({[2-methyl-4- (2-methylpropyl) 6-oxo-1- (phenylmethyl) -1,6-dihydro-5-pyrimidinyl] -amino} carbonyl) amino] -3 0.0003 calcd .: (MH) '= 586.23;

ugot.: (M-H)'= 586,17found: (M-H) '= 586.17

0,001 izrač.: (M-H)' = 582,20;0.001 Calc .: (M-H) '= 582.20;

ugot.: (M-H) = 582,20 nd nd izrač.: (M-H)' -496,15;found: (M-H) = 582.20 nd a nd calc .: (M-H) '-496.15;

ugot.: (M-H)'= 496,10found: (M-H) '= 496.10

0,015 izrač.: (M-H)'= 458,13;0.015 Calc .: (M-H) '= 458.13;

ugot.: (M-H)'=458,09found: (M-H) '= 458.09

IC5o Masni spektralni podatki (nM) izrač.: (M-H)' = 475,23 m/z; ugot.: (M-H)'= 475,02 m/zIC 5 o Mass spectral data (nM) calculated: (MH) '= 475.23 m / z; found: (MH) '= 475.02 m / z

-149149 (4-metilfenil)propanojska kislina (3 S)-3-( 1,3-benzodioksol-5-il)-3-[({ [2okso-1 -(fenilmetil)-4-propil-1,2dihidro-3-piridinil]-amino }karbonil)amino]propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3-({[9okso-8-(fenilmetil)-2,3,4,5,8,9-heksahidro-1 H-pirido[3,4-b]azepin-1 -il] karbonil}amino)propanojska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-4etil-2-okso-1,2-dihidro-3 piridinil} -amino)karbonil]amino} -3 (4-metilfenil)propanojska kislina (3S)-3-{[({l - [(2-klorofenil)metil] -2-okso4-propil-1,2-dihidro-3-piridinil }-amino)~ karbonil] amino } -3 -(4-metilfenil)propanojska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-4metil-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} -3 (4-metilfenil)propanojska kislina (3 S)-3 - {[({ 6-metil-2-okso-1 -(fenilmetil)-4-[(fenilmetil)oksi]-l,2-dihidro3 -piridinil} -amino)karbonil] amino} -3 (4-metilfenil)propanoj ska kislina izrač.: (M-H)' — 476,18 m/z; ugot.: (M-H)'= 475,99 m/z-149149 (4-Methylphenyl) propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({[2-oxo-1- (phenylmethyl) -4-propyl-1,2-dihydro- 3-Pyridinyl] -amino} carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - ({[9oxo-8- (phenylmethyl) -2,3,4, 5,8,9-Hexahydro-1H-pyrido [3,4-b] azepin-1-yl] carbonyl} amino) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl ] -4ethyl-2-oxo-1,2-dihydro-3 pyridinyl} -amino) carbonyl] amino} -3 (4-methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) ) methyl] -2-oxo-4-propyl-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid (3S) -3 - {[({1- [(2-chlorophenyl) methyl] -4methyl-2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3 (4-methylphenyl) propanoic acid (3 S) -3 - {[({ 6-Methyl-2-oxo-1- (phenylmethyl) -4 - [(phenylmethyl) oxy] -1,2-dihydro3-pyridinyl} -amino) carbonyl] amino} -3 (4-methylphenyl) propanoic acid calcd. : (MH) - 476.18 m / z; found: (M-H) '= 475.99 m / z

4000 izrač.: (M-H)' = 488,18 m/z; ugot.: (M-H)' = 488,19 m/z izrač.: (M-H)' = 466,15 m/z; ugot.: (M-H)'= 465,95 m/z izrač.: (M-H)' = 480,17 m/z; ugot.: (M-H)'= 480,00 m/z izrač.: (M+H)' = 454,15 m/z; ugot.: (M+H)' = 454,09 m/z izrač.: (M-H)' = 524,22 m/z; ugot.: (M-H)'= 524,02 m/z4000 calc .: (M-H) '= 488.18 m / z; found: (M-H) '= 488.19 m / z calc .: (M-H)' = 466.15 m / z; found: (M-H) '= 465.95 m / z calc .: (M-H)' = 480.17 m / z; found: (M-H) '= 480.00 m / z calc .: (M + H)' = 454.15 m / z; found: (M + H) '= 454.09 m / z calc .: (M-H)' = 524.22 m / z; found: (M-H) '= 524.02 m / z

-150150 (3S)-3-{[({l-[(2-klorofenil)metil]-2,4dimetil-6-okso-1,6-dihidro-5-pirimidinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina (3 S)-3 - {[({ 1 -[(2,4-diklorofenil)metil] -4metil-2-okso-1,2-dihidro-3 piridinil}-amino)karbonil]amino}-3-(4metilfenil)propanojska kislina (3 S)-3 - {[({4-amino-1 -[(2-klorofenil)metil] 6-metil-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} -3 -(4metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -[(2-klorofenil)metil]-4(metiloksi)-2-okso-1,2-dihidro-3piridinil]-amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3 - {[({4-kloro-1 - [(2-klorofenil)-metil]2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} -3 -(4metilfenil)propanojska kislina izrač.: (M-H)' = 467,15 m/z; ugot.: (M-H)' = 467,00 m/z izrač.: (M-H)' = 486,10 m/z; ugot.: (M-H)' = 485,95 m/z izrač.: (M-H)' = 467,15 m/z; ugot.: (M-H)'= 467,14 m/z izrač.: (M-H)' = 468,13 m/z; ugot.: (M-H)'= 467,97 m/z izrač.: (M-H)' = 472,08 m/z; ugot.: (M-H)' = 471,91 m/z (3S)-3-{[({ l-[(2-klorofenil)-metil]- 15-150150 (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2,4 dimethyl-6-oxo-1,6-dihydro-5-pyrimidinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid (3 S) -3 - {[({1 - [(2,4-dichlorophenyl) methyl] -4methyl-2-oxo-1,2-dihydro-3 pyridinyl} -amino) carbonyl ] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] 6-methyl-2-oxo-1,2-dihydro- 3-pyridinyl} -amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1 - [(2-chlorophenyl) methyl] -4 (methyloxy) -2-oxo-1, 2-Dihydro-3-pyridinyl] -amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid (3 S) -3 - {[({4-chloro-1 - [(2-chlorophenyl) -methyl] 2-oxo) -1,2-Dihydro-3-pyridinyl} -amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid calc .: (MH) '= 467.15 m / z; found: (M-H) '= 467.00 m / z calc .: (M-H)' = 486.10 m / z; found: (M-H) '= 485.95 m / z calc .: (M-H)' = 467.15 m / z; found: (M-H) '= 467.14 m / z calc .: (M-H)' = 468.13 m / z; found: (M-H) '= 467.97 m / z calc .: (M-H)' = 472.08 m / z; found: (M-H) '= 471.91 m / z (3S) -3 - {[({1 - [(2-chlorophenyl) -methyl] - 15

4-metil-2-okso-1,2-dihidro-3 piridinil} -amino)karbonil]amino} -3 [3 -metil-4-metiloksi)fenil]propanoj ska kislina izrač.: (M-H)' = 482,15 m/z; ugot.: (M-H)'= 481,93 m/z4-Methyl-2-oxo-1,2-dihydro-3 pyridinyl} -amino) carbonyl] amino} -3 [3-methyl-4-methyloxy) phenyl] propanoic acid calc .: (MH) '= 482. 15 m / z; found: (M-H) '= 481.93 m / z

-151151 (3 S )-3 - {[({1 -[(2-klorofenil)-metil]4-metil-2-okso-l ,2-dihidro-3piridinil} -amino)karbonil] amino} -3 [4-metiloksi)fenil]propanoj ska kislina (3 S)-3- {[({1 - [(2-klorofenil)-metil]4-metil-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} -3 [3,4-dimetilfenil)propanojska kislina (3 S)-3 - {[({4-amino-1 -[(2-klorofenil)metil]-2-okso-1,2-dihidro-3 piridinil}-amino)karbonil]amino}-3[4-metilfenil)propanojska kislina (3 S)-3 - {[({1 -[(2-klorofenil)metil] -4fluoro-2-okso-1,2-dihidro-3piridinil} -amino)karbonil]amino} -3 [4-metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -[(2-klorofenil)metil]2-okso-4-(fenilamino)-1,2-dihidro-3 piridinil]-amino}karbonil)amino]-3[4-metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -[(2-klorofenil)metil]2- okso-4-(2-piridinilamino)-1,2-dihidro-3 -piridinil] -amino} karbonil)amino]3- (4-metilfenil)propanojska kislina (3 S)-3 - {[({1 -[(2-klorofenil)metil]-43 izrač.: (M+H) = 470,15 m/z;-151151 (3 S) -3 - {[({1 - [(2-chlorophenyl) -methyl] 4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3 [ 4-Methyloxy) phenyl] propanoic acid (3S) -3- {[({1 - [(2-chlorophenyl) -methyl] 4-methyl-2-oxo-1,2-dihydro-3pyridinyl} -amino) carbonyl] amino} -3 [3,4-dimethylphenyl) propanoic acid (3 S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro -3-pyridinyl} -amino) carbonyl] amino} -3 [4-methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4fluoro-2-oxo-1, 2-Dihydro-3-pyridinyl} -amino) carbonyl] amino} -3 [4-methylphenyl) propanoic acid (3 S) -3 - [({[1 - [(2-chlorophenyl) methyl] 2-oxo-4- ( phenylamino) -1,2-dihydro-3 pyridinyl] -amino} carbonyl) amino] -3 [4-methylphenyl) propanoic acid (3 S) -3 - [({[1 - [(2-chlorophenyl) methyl] 2 - oxo-4- (2-pyridinylamino) -1,2-dihydro-3-pyridinyl] -amino} carbonyl) amino] 3- (4-methylphenyl) propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -43 calculated: (M + H) = 470.15 m / z;

ugot.: (M+H) = 470,01 m/z izrač.: (M+H)+ = 468,17 m/z; ugot.: (M+H)+= 468,05 m/z izrač.: (M-H) = 453,13 m/z; ugot.: (M-H) = 453,01 m/z izrač.: (M-H) = 456,12 m/z; ugot.: (M-H) = 455,94 m/z izrač.: (M-H) = 529,16 m/z; ugot.: (M-H)' = 529,02 m/z izrač.: (M-H) = 530,16 m/z; ugot.: (M-H) = 529,99 m/z izrač.: (M-H) = 454,11 m/z;found: (M + H) = 470.01 m / z calc .: (M + H) + = 468.17 m / z; found: (M + H) + = 468.05 m / z calcd: (MH) = 453.13 m / z; found: (MH) = 453.01 m / z calc .: (MH) = 456.12 m / z; found: (MH) = 455.94 m / z calc .: (MH) = 529.16 m / z; found: (MH) '= 529.02 m / z calc .: (MH) = 530.16 m / z; found: (MH) = 529.99 m / z calc .: (MH) = 454.11 m / z;

-152152 hidroksi-2-okso-1,2-dihidro-3piridinil} -amino)karbonil]amino} -3 (4-metilfenil)propanojska kislina ugot.: (M-H)'= 454,05 m/z-152152 hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3 (4-methylphenyl) propanoic acid found: (M-H) '= 454.05 m / z

(3S)-3-{[({l-[(2-klorofenil)metil]- 2-okso-4-[(2-piridinilmetil)amino]- l,2-dihidro-3-piridinil}-amino)karbonil]- amino}-3-(4-metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] - 2-oxo-4 - [(2-pyridinylmethyl) amino] - 1,2-dihydro-3-pyridinyl} -amino) carbonyl] - amino} -3- (4-methylphenyl) propanoic acid 15 15 izrač.: (M-H)' = 544,17 m/z; ugot.: (M-H)'= 544,03 m/z Calcd. (M-H) '= 544.17 m / z; found: (M-H) '= 544.03 m / z (3 S)-3 - {[({1 -[(2-klorofenil)metil] - 2-okso-4- [(3 -piridinilmetil)amino]- l,2-dihidro-3-piridinil}-amino)karbonil]- amino} -3 -(4-metilfenil)propanoj ska kislina (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] - 2-oxo-4- [(3-pyridinylmethyl) amino] - 1,2-dihydro-3-pyridinyl} -amino) carbonyl] - amino} -3- (4-methylphenyl) propanoic acid 20 20 izrač.: (M-H)'= 544,17 m/z; ugot.: (M-H)’= 544,02 m/z Calcd. (M-H) '= 544.17 m / z; found: (M-H) '= 544.02 m / z (3 S)-3-[( {[ 1 -[(2-klorofenil)metil]- -4-( 1,4-oksazinan-4-il)-2-okso-1,2- dihidro-3 -piridinil] amino { karbonil)amino] -3 - (4-metilfenil)propanojska kislina (3 S) -3 - [({[1 - [(2-chlorophenyl) methyl] - -4- (1,4-Oxazinan-4-yl) -2-oxo-1,2- dihydro-3-pyridinyl] amino {carbonyl) amino] -3 - (4-methylphenyl) propanoic acid 1 1 izrač.: (M-H)’ = 523,17 m/z; ugot.: (M-H)= 523,02 m/z Calcd .: (M-H) '= 523.17 m / z; found: (M-H) = 523.02 m / z (3S)-3-[({[l-[(2-klorofenil)metil]- 2- okso-4-(propilamino)-1,2- dihidro- 3- piridinil]amino}karbonil)amino]-3- (4-metilfenil)propanojska kislina (3S) -3 - [({[1 - [(2-chlorophenyl) methyl] - 2- oxo-4- (propylamino) -1,2-dihydro- 3- pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid 10 10 izrač.: (M-H)' = 495,18 m/z; ugot: (M-H)'= 495,04 m/z Calcd. (M-H) '= 495.18 m / z; found: (M-H) '= 495.04 m / z (3S)-3-{[({l-[(2-fluorofenil)metil]-4- metil-2-okso-1,2-dihidro-3 -piridinil} - amino)karbonil]-amino}-3-(4-metilfenil)- propanojska kislina (3S) -3 - {[({1 - [(2-fluorophenyl) methyl] -4- methyl-2-oxo-1,2-dihydro-3-pyridinyl} - amino) carbonyl] -amino} -3- (4-methylphenyl) - propanoic acid 20 20 izrač.: (M-H)' = 436,17 m/z; ugot.: (M-H)' = 435,99 m/z Calcd. (M-H) '= 436.17 m / z; found: (M-H) '= 435.99 m / z (3S)-3-{[({l-[(2,6-diklorofenil)metil]-4- metil-2-okso-1,2-dihidro-3 -piridinil} - (3S) -3 - {[({1 - [(2,6-dichlorophenyl) methyl] -4- methyl-2-oxo-1,2-dihydro-3-pyridinyl} - 20 20 izrač.: (M-H)' = 486,10 m/z; ugot.: (M-H)'= 485,95 m/z Calcd. (M-H) '= 486.10 m / z; found: (M-H) '= 485.95 m / z

-153153 amino)karbonil] -amino} -3 -(4-metilfenil)propanojska kislina (3 R)-3 - {[({1 - [(2-klorofenil)metil]-4metil-2-okso-1,2-dihidro-3 - piridinil} amino)karbonil] -amino } butanoj ska kislina (3 S)-3 - {[({1 -[(2-bromofenil)metil-4metil-2-okso-l,2-dihidro-3-piridinil}amino)karbonil]-amino}-3(4-metilfenil)propanojska kislina (3S)-3-[({ [4-metil-2-okso-1 -(fenilmetil)l,2-dihidro-3-piridinil]amino}karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina-153153 amino) carbonyl] -amino} -3- (4-methylphenyl) propanoic acid (3 R) -3 - {[({1 - [(2-chlorophenyl) methyl] -4methyl-2-oxo-1,2 -Dihydro-3-pyridinyl} amino) carbonyl] -amino} butanoic acid (3S) -3 - {[({1 - [(2-bromophenyl) methyl-4methyl-2-oxo-1,2-dihydro- 3-Pyridinyl} amino) carbonyl] -amino} -3 (4-methylphenyl) propanoic acid (3S) -3 - [({[4-methyl-2-oxo-1- (phenylmethyl) 1,2,2-dihydro-3 -pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid

300 izrač.: (M-H) = 376,11 m/z; ugot.: (M-H)'=376,00 m/z izrač.: (M-H) = 496,09 m/z; ugot.: (M-H) = 495,87 m/z izrač.: (M-H) = 418,17 m/z; ugot.: (M-H) = 417,96 m/z izrač.: (M-H) = 484,12 m/z; ugot.: (M-H) = 484,03 m/z (3 S)-3-{ [({l-[2-klorofenil)metil)-4- 8 hidroksi-2-okso-l,2-dihidro-3piridinil} amino)karbonil] amino} -3[3-metil-4-(metiloksi)fenil]propanojska kislina (3 S)-3- {[({1 -[2-klorofenil)metil]-2-okso-4fenil-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 (4-metilfenil]propanojska kislina (3 S)-3- {[({4-bromo-1 -[(2-klorofenil)metil] -2-okso-1,2-dihidro-3 piridinil} amino)karbonil] amino} -3 (4-metilfenil]propanojska kislina izrač.: (M-H) = 514,15 m/z; ugot.: (M-H)= 514,00 m/z izrač.: (M-H) = 516,03 m/z; ugot.: (M-H)'= 515,90 m/z300 calc .: (M-H) = 376.11 m / z; found: (M-H) '= 376.00 m / z calc .: (M-H) = 496.09 m / z; found: (M-H) = 495.87 m / z calc .: (M-H) = 418.17 m / z; found: (M-H) = 417.96 m / z calc .: (M-H) = 484.12 m / z; found: (MH) = 484.03 m / z (3S) -3- {[({1- [2-chlorophenyl) methyl) -4-8 hydroxy-2-oxo-1,2-dihydro-3pyridinyl } amino) carbonyl] amino} -3 [3-methyl-4- (methyloxy) phenyl] propanoic acid (3 S) -3 - {[({1- [2-chlorophenyl) methyl] -2-oxo-4phenyl- 1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} -3 (4-methylphenyl] propanoic acid (3 S) -3 - {[({4-bromo-1 - [(2-chlorophenyl) methyl] -2 -oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3 (4-methylphenyl] propanoic acid calc .: (MH) = 514.15 m / z found: (MH) = 514, 00 m / z calc .: (MH) = 516.03 m / z; found: (MH) '= 515.90 m / z

-154154 (3S)-3-(l,3-benzodioksol-5-il)-3-{[({l[(2-klorofenil)metil]-4-hidroksi2-okso-1,2-dihidro-3-piridinil }amino)karbonil]amino}propanojska kislina izrač.: (M-H)' = 484,09 m/z; ugot.: (M-H)'= 484,03 m/z (3 S)-3-{ [({l-[(2-klorofenil)metil-4- 2 [(2- {[2-(metiloksi)etil] oksi} etil)oksi]2-okso-1,2-dihidro-3-piridinil}amino)karbonil]amino} 3-(4-metilfenil)propanojska kislina izrač.: (M-H)' = 556,18 m/z; ugot.: (M-H)'= 556,03 m/z (3 S)-3 - {[({1 - [(2-klorofenil)metil-4hidroksi-6-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino } 3 (4-metilfenil)propanoj ska kislina izrač.: (M-H)' = 468,13 m/z; ugot.: (M-H)'= 468,05 m/z (3S)-3-{[({l-[(2-klorofenil)metil-4[(1,1 -dimetiletil)amino] -2-okso-1,2dihidro-3 -piridinil} amino)karbonil] amino} 3-(4-metilfenil)propanojska kislina (3 S)-3 - {[({1 -[(2-klorofenil)metil-4hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} 3-fenilpropanojska kislina izrač.: (M-H)' = 509,20 m/z; ugot.: (M-H)'= 509,06 m/z izrač.: (M-H)' = 440,10 m/z;-154154 (3S) -3- (1,3-benzodioxol-5-yl) -3 - {[({1 [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3- pyridinyl} amino) carbonyl] amino} propanoic acid calc .: (MH) '= 484.09 m / z; found: (MH) '= 484.03 m / z (3 S) -3- {[({1 - [(2-chlorophenyl) methyl-4- 2 [(2 - {[2- (methyloxy) ethyl) ] oxy} ethyl) oxy] 2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} 3- (4-methylphenyl) propanoic acid calc .: (MH) '= 556.18 m / z ; found: (MH) '= 556.03 m / z (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydro -3-pyridinyl} amino) carbonyl] amino} 3 (4-methylphenyl) propanoic acid calc .: (MH) '= 468.13 m / z; found: (MH) '= 468.05 m / z (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-4 [(1,1-dimethylethyl) amino] -2-oxo- 1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} 3- (4-methylphenyl) propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4-hydroxy-2-oxo- 1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} 3-phenylpropanoic acid calc .: (MH) '= 509.20 m / z; found: (M-H) '= 509.06 m / z calc .: (M-H)' = 440.10 m / z;

ugot.: (M-H) = 440,04 m/z (3S)-3-{[({ l-[(2-klorofenil)metil-4- 3 [4-metiltetrahidro-1 (2H)-pirazinil2-okso-1,2-dihidro-3-piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina izrač.: (M-H)' = 536,20 m/z; ugot.: (M-H)'= 536,12 m/zfound: (MH) = 440.04 m / z (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-4- 3 [4-methyltetrahydro-1 (2H) -pyrazinyl2-oxo- 1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid calc .: (MH) '= 536.20 m / z; found: (M-H) '= 536.12 m / z

-155155 (3 S)-3 - {[({1 -[(2-klorofenil)metil-4hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 - [4 (metiloksi)fenil]propanoj ska kislina izrač.: (M-H)' - 470,11 m/z; ugot.: (M-H)'= 470,05 m/z (3 S)-3 - {[({1 - [(2-klorofenil)metil-4hidroksi-2-okso-1,2-dihidro-3 piridinil} amino)karbonil] amino} -3 - [3,4,5 tris((metiloksi)fenil]propanojska kislina izrač.: (M-H)' = 530,13 m/z; ugot.: (M-H)'= 530,05 m/z (3 S)-3 - {[({1 - [(2-klorofenil)metil-4hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 - [3,5 dimetil)fenil]propanoj ska kislina izrač.: (M-H)' = 468,13 m/z; ugot.: (M-H)'= 468,08 m/z (3S)-3-{[({ l-[(2-klorofenil)metil-4- 15 [(3 -metil- 5 -izoksazolil)amino] 2-okso-1,2-dihidro-3 -piridinil} amino) karbonil]amino} -3 -(4-metilfenil)propanoj ska kislina izrač.: (M-H)' = 534,15 m/z; ugot.: (M-H)'= 534,01 m/z (3 S)-3 - {[({1 - [(2-klorofenil)metil-4hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino } -3 - [3 metilfenil)propanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil-4hidroksi-2-okso-l,2-dihidro-3piridinil} amino)karbonil] amino} -3 - [3metiloksi)fenil]propanojska kislina (3 S)-3 - [3,5 -bis(metiloksi)fenil] -3 20 izrač.: (M-H)' = 454,17 m/z; ugot.: (M-H)'= 454,04 m/z izrač.: (M-H)' = 470,11 m/z; ugot.: (M-H)'= 470,03 m/z izrač.: (M-H)' = 500,12 m/z;-155155 (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- [4 (methyloxy ) phenyl] propanoic acid calcd .: (MH) - 470.11 m / z; found: (MH) '= 470.05 m / z (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- [3,4,5 tris ((methyloxy) phenyl] propanoic acid calc .: (MH) '= 530.13 m / z found: (MH)' = 530.05 m / z (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - [3. 5 dimethyl) phenyl] propanoic acid calcd: (MH) '= 468.13 m / z; found: (MH) '= 468.08 m / z (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-4- 15 [(3-methyl-5-isoxazolyl) amino] 2 -oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid calc .: (MH) '= 534.15 m / z; found: (MH) '= 534.01 m / z (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino ) carbonyl] amino} -3- [3 methylphenyl) propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) ) carbonyl] amino} -3- [3methyloxy) phenyl] propanoic acid (3 S) -3- [3,5-bis (methyloxy) phenyl] -3 20 calcd. (MH) '= 454.17 m / z ; found: (M-H) '= 454.04 m / z calc .: (M-H)' = 470.11 m / z; found: (M-H) '= 470.03 m / z calc .: (M-H)' = 500.12 m / z;

-156156 {[({l-[(2- klorofenil)metil-4-hidroksi2-okso-1,2-dihidro-3- piridinil }amino)karbonil]amino}-propanojska kislina ugot.: (M-H)' = 500,07 m/z-156156 {[({1 - [(2-chlorophenyl) methyl-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -propanoic acid found: (MH) '= 500 , 07 m / z

(3 S)-3 - {[({1 - [(2-klorofenil)metil-4- hidroksi-2-okso-l,2-dihidro-3- kinolinil} amino)karbonil] amino } -3 - [4- metilfenil)propanojska kislina (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4- hydroxy-2-oxo-1,2-dihydro-3- quinolinyl} amino) carbonyl] amino} -3- [4- methylphenyl) propanoic acid 8 8 izrač.: (M-H)‘ = 504,13 m/z; ugot.: (M-H)' = 504,06 m/z Calc'd: (M-H) '= 504.13 m / z; found: (M-H) '= 504.06 m / z (3 S)-3 - {[({1 -[(2-klorofenil)metil-4- hidroksi-2-okso-1,2-dihidro-3- piridinil} amino)karbonil] amino } -3 -[3 - (trifluorometil)fenil]propanoj ska kislina (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl-4- hydroxy-2-oxo-1,2-dihydro-3- pyridinyl} amino) carbonyl] amino} -3 - [3 - (trifluoromethyl) phenyl] propanoic acid 20 20 izrač.: (M-H)' = 508,04 m/z; ugot.: (M-H)'= 508,09 m/z Calcd. (M-H) '= 508.04 m / z; found: (M-H) '= 508.09 m / z (3S)-3-{[({l-[(2-klorofenil)metil-4- [({ etil [(etilamino)karbonil] amino} - karbonil)amino} -2-okso-1,2-dihidro-3 - piridinil} amino)karbonil] amino} -3 - [4- metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2-chlorophenyl) methyl-4- [({ethyl [(ethylamino) carbonyl] amino} - carbonyl) amino} -2-oxo-1,2-dihydro-3 - pyridinyl} amino) carbonyl] amino} -3- [4- methylphenyl) propanoic acid 2 2 izrač.: (M-H)' = 595,21 m/z; ugot.: (M-H)'= 594,97 m/z Calcd .: (M-H) '= 595.21 m / z; found: (M-H) '= 594.97 m / z (3 S)-3- {[({4-( 1 -azetanil)-1 -[(2- klorofenil)metil]-2-okso-1,2-dihidro-3- piridinil} amino)karbonil] amino } -3 - [4- metilfenil)propanojska kislina (3 S) -3- {[({4- (1-azetanyl) -1 - [(2- chlorophenyl) methyl] -2-oxo-1,2-dihydro-3- pyridinyl} amino) carbonyl] amino} -3- [4- methylphenyl) propanoic acid 5 5 izrač.: (M-H)' = 493,16 m/z; ugot.: (M-H) = 493,05 m/z Calcd. (M-H) '= 493.16 m / z; found: (M-H) = 493.05 m / z (3 S)-3- {[({1 -[(2-klorofenil)metil]-4- hidroksi-2-okso-1,2-dihidro-3- piridinil} amino)karbonil] amino} -3 - [4fluorofenil)propanojska kislina (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4- hydroxy-2-oxo-1,2-dihydro-3- pyridinyl} amino) carbonyl] amino} -3- [4fluorophenyl) propanoic acid 30 30 izrač.: (M-H)' = 458,09 m/z; ugot.: (M-H)' = 458,03 m/z Calcd. (M-H) '= 458.09 m / z; found: (M-H) '= 458.03 m / z (3 S)-3- {[({1 -[(2-klorofenil)metil]-4- (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4- 40 40 izrač.: (M-H)' = 458,09 m/z; Calcd. (M-H) '= 458.09 m / z;

-157157 hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino}-3-[3fluorofenil)propanojska kislina (3 S)-3 -[({[ 1 -[(2- klorofenil)metil]-4-( {2-[(2{[2-(metiloksi)etil]oksi}etil)oksi]etil}oksi)2-okso-1,2-dihidro-3piridinil]amino} karbonil)amino } -3 -(4metilfenil)propanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil] -4hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino}-3-[4trifluorometil)fenil]propanojska kislina (3 S)-3 - {[({1 - [(2-fluorofenil)metil]-4hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino }-3-[4metilfenil)propanojska kislina (3S)-3-{[({l-[(2-kloro-6-fluorofenil)metil]4-hidroksi-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 - [4metilfenil)propanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4hidroksi-2-okso-l ,2-dihidro-3piridinil}amino)karbonil] amino} -3-[4-( 1,1dimetiletil)fenil]propanojska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-5ugot.: (M-H) = 458,06 m/z izrac.: (M-H) = 600,21 m/z; ugot.: (M-H) = 600,10 m/z izrač.: (M-H) = 508,09 m/z; ugot.: (M-H)'= 508,02 m/z izrač.: (M-H) = 438,15 m/z; ugot.: (M-H) = 438,07 m/z izrač.: (M-H) = 472,11 m/z; ugot.: (M-H) = 472,06 m/z-157157 Hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- [3fluorophenyl) propanoic acid (3S) -3 - [({[1 - [(2-chlorophenyl) methyl] ] -4- ({2 - [(2 {[2- (methyloxy) ethyl] oxy} ethyl) oxy] ethyl} oxy) 2-oxo-1,2-dihydro-3pyridinyl] amino} carbonyl) amino} -3 - (4methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - [4trifluoromethyl) phenyl] propanoic acid (3S) -3 - {[({1 - [(2-fluorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- [4methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chloro-6-fluorophenyl) methyl] 4-hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- [4methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- [4- (1,1-dimethylethyl) phenyl] propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -5%: (MH) = 458.06 m / z calc .: (MH) = 600.21 m / z; found: (MH) = 600.10 m / zi radi .: (M-H) = 508.09 m / z; found: (M-H) '= 508.02 m / z calc .: (M-H) = 438.15 m / z; found: (M-H) = 438.07 m / z calc .: (M-H) = 472.11 m / z; found: (M-H) = 472.06 m / z

400 izrač.: (M-H) = 496,16 m/z;400 Calc .: (M-H) = 496.16 m / z;

ugot.: (M-H) = 496,11 m/z izrač.: (M-H) = 452,14 m/z;found: (M-H) = 496.11 m / z calc .: (M-H) = 452.14 m / z;

-158158 metil-2-okso- l,2-dihidro-3piridinil}amino)karbonil]amino}-3-(4metilfenil)propanojska kislina-158158 Methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid

3- (4-klorofenil)-3-{[({l-[(2klorofenil)metil]-4-hidroksi2- okso-1,2-dihidro-3 -piridinil} amino)karbonil] amino }propanoj ska kislina (3 S)-3 -[({[2-metil-6-okso-1 -(fenilmetil)4- (2-piridinil)-1,6-dihidro-5-pirimidinil]amino} karbonil)amino]-3 -(4-metilfeniI)propanojska kislina3- (4-chlorophenyl) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid (3 S) -3 - [({[2-methyl-6-oxo-1- (phenylmethyl) 4- (2-pyridinyl) -1,6-dihydro-5-pyrimidinyl] amino} carbonyl) amino] -3 - ( 4-methylphenyl) propanoic acid

3- (3-klorofenil)-3-{[({ l-[(2klorofenil)metil]-4-hidroksi2-okso-1,2-dihidro-3-piridinil}amino)karbonil] amino} propanojska kislina ugot.: (M-H)'= 451,99 m/z izrač.: (M-H)’ = 474,06 m/z; ugot.: (M-H) = 474,07 m/z izrač.: (M+H)+ = 498,22 m/z; ugot.: (M+H)+= 498,10 m/z izrač.: (M-H)' = 474,06 m/z; ugot.: (M-H)'=474,03 m/z3- (3-chlorophenyl) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid found: (MH) '= 451.99 m / z calc .: (MH)' = 474.06 m / z; found: (MH) = 474.07 m / z calc .: (M + H) + = 498.22 m / z; found: (M + H) + = 498.10 m / z calcd: (MH) '= 474.06 m / z; found: (MH) '= 474.03 m / z

3-{[({l-[(2-klorofenil)metil]-4-hidroksi- 40 izrač,3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-40 calc.

2-okso-1,2-dihidro-3 -piridinil} amino)- ugot.2-oxo-1,2-dihydro-3-pyridinyl} amino) - found.

karbonil]amino}-3-(3,4-diklorofenil)propanojska kislina (M-H)' = 508,02 m/z; (M-H)'=507,97 m/zcarbonyl] amino} -3- (3,4-dichlorophenyl) propanoic acid (M-H) = 508.02 m / z; (M-H) '= 507.97 m / z

Tabela 4Table 4

Ime (3S)-3-(l,3-benzodioksol-5-il)-3[({[2-okso-1 -(fenilmetil)-3 azepanil] amino } karbonilamino] propanojska kislinaName (3S) -3- (1,3-benzodioxol-5-yl) -3 [({[2-oxo-1- (phenylmethyl) -3 azepanyl] amino} carbonylamino] propanoic acid

IC50 Masni spektralni podatkiIC 50 Mass spectral data

0,015 izrač.: (M-H) = 452,18 m/z; ugot.: (M-H)'= 452,10 m/z0.015 Calc .: (M-H) = 452.18 m / z; found: (M-H) '= 452.10 m / z

-159159 (3S)-3-(l,3-benzodioksol-5-il)-3-{[({l-[(3cianofenil)metil] -2-okso-3 azepanil]amino}karbonilamino]propanojska kislina (3 S)-3 -(4-metilfenil)-3 -[( {[2-okso-1 (2-tiofenilmetil)-l,2-dihidro-3piridinil]amino } karbonil)amino]propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3[({[2-okso-1 - (fenilmetil)-1,2-dihidro3 -p ir i din il] amino } karbonil)amino] propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3{[({l-[(4-metilfenil)metil]2-okso-1,2-dihidro-3 -piridinil} amino)karbonil]amino}propanojska kislina (3 S )-3-(1,3-benzodioksol-5-il)-3({[(!-{[4-(metiloksi)fenil]metil} 2-okso-1,2-dihidro-3-piridinil)amino]karbonil} aminopropanoj ska kislina (3S)-3-(l,3-benzodioksol-5-il)-3{[({l-[(3-metilfenil)metil]2-okso-1,2-dihidro-3 -piridinil} amino)karbonil] amino} propanoj ska kislina-159159 (3S) -3- (1,3-benzodioxol-5-yl) -3 - {[({1 - [(3cyanophenyl) methyl] -2-oxo-3 azepanyl] amino} carbonylamino] propanoic acid (3 S) -3- (4-methylphenyl) -3 - [({[2-oxo-1 (2-thiophenylmethyl) -1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 [({[2-oxo-1- (phenylmethyl) -1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 {[({1 - [(4-methylphenyl) methyl] 2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 ({[(1 - {[4- (methyloxy) phenyl] methyl} 2-oxo-1,2-dihydro-3 -pyridinyl) amino] carbonyl} aminopropanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 {[({1 - [(3-methylphenyl) methyl] 2-oxo-1,2 -Dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid

0,04 izrač.: (M-H)' = 477,18 m/z; ugot.: (M-H)'= 477,14 m/z0.04 Calc .: (M-H) '= 477.18 m / z; found: (M-H) '= 477.14 m / z

0,6 izrač.: (M-H)' = 410,11 m/z;0.6 Calc .: (M-H) '= 410.11 m / z;

ugot.: (M-H)'= 410,00 m/zfound: (M-H) '= 410.00 m / z

0,5 izrač.: (M-H)' = 434,13 m/z; ugot.: (M-H)'= 434,05 m/z izrač.: (M-H)'= 448,14 m/z; ugot.: (M-H) = 448,02 m/z izrač.: (M-H)' = 464,14 m/z; ugot.: (M-H)'= 464,03 m/z0.5 Calc .: (M-H) '= 434.13 m / z; found: (M-H) '= 434.05 m / z calc .: (M-H)' = 448.14 m / z; found: (M-H) = 448.02 m / z calc .: (M-H) '= 464.14 m / z; found: (M-H) '= 464.03 m / z

1,5 izrač.: (M-H)' = 448,15 m/z; ugot.: (M-H)'= 448,04 m/z1.5 calc .: (M-H) '= 448.15 m / z; found: (M-H) '= 448.04 m / z

-160160 (3S)-3-[3,5-bis(metiloksi)fenil]-3-[({[2okso-1 -(2-tiofenilmetil)-1,2-dihidro-3piridinil]amino}karbonil)amino]propanojska kislina (3 S)-3 - [4-metiloksi)fenil]-3 -[({[2-okso1 -(2-tiofenilmetil)-1,2-dihidro-3p ir idini 1] amino } karbonil)amino] propanojska kislina (3 S)-3 - [({[2-okso-1 -(2-tiofenilmetil)1.2- dihidro- 3 -piridinil] amino } karbonil)amino]-3-[3-trifluorometil)fenil]propanojska kislina (3S)-3-( 1,3-benzodioksol-5-il)-3[({[3-(feniloksi)fenil]amino}karbonil) amino]propanojska kislina (3 S)-3-( 1,3-benzodioksol-5-il)-3{[({3-[(2-tiofenilmetil)amino]fenil {amino)karbonil]amino} propanojska kislina (3 S)-3 -(1,3 -benzodioksol- 5 - il) - 3 {[({l-[(3-klorofenil)metil]-2-okso1.2- dihidro-3 -piridinil} amino)karbonil]amino}propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3-({[(20,7 izrač.: (M-H)'= 456,12 m/z; ugot.: (M-H)'= 456,00 m/z-160160 (3S) -3- [3,5-bis (methyloxy) phenyl] -3 - [({[2-oxo-1- (2-thiophenylmethyl) -1,2-dihydro-3pyridinyl] amino} carbonyl) amino] propanoic acid (3S) -3- [4-methyloxy) phenyl] -3 - [({[2-oxo 1- (2-thiophenylmethyl) -1,2-dihydro-3pyrimidine 1] amino} carbonyl) amino] (3S) -3 - [({[2-oxo-1- (2-thiophenylmethyl) 1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] -3- [3-trifluoromethyl) phenyl] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 [({[3- (phenyloxy) phenyl] amino} carbonyl) amino] propanoic acid (3 S) -3- (1,3- benzodioxol-5-yl) -3 {[({3 - [(2-thiophenylmethyl) amino] phenyl {amino) carbonyl] amino} propanoic acid (3 S) -3- (1,3-benzodioxol-5-yl) - 3 {[({1 - [(3-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid (3S) -3- (1,3-benzodioxole- 5-yl) -3 - ({[(20.7 calc .: (MH) '= 456.12 m / z; found: (MH)' = 456.00 m / z

0,8 izrač.: (M-H)' = 426,11 m/z; ugot.: (M-H)’= 426,00 m/z0.8 Calc .: (M-H) '= 426.11 m / z; found: (M-H) '= 426.00 m / z

2,5 izrač.: (M-H)'= 464,09 m/z; ugot.: (M-H)'= 463,99 m/z izrač.: (M-H)' = 419,12 m/z; ugot.: (M-H)'= 418,97 m/z izrač.: (M-H)' = 438,11 m/z; ugot.: (M-H)'= 438,00 m/z2.5 calc .: (M-H) '= 464.09 m / z; found: (M-H) '= 463.99 m / z calc .: (M-H)' = 419.12 m / z; found: (M-H) '= 418.97 m / z calc .: (M-H)' = 438.11 m / z; found: (M-H) '= 438.00 m / z

0,8 izrač.: (M-H)' = 468,09 m/z; ugot.: (M-H)'= 468,01 m/z0.8 Calc .: (M-H) '= 468.09 m / z; found: (M-H) '= 468.01 m / z

0,8 izrač.: (M-H)' = 502,12 m/z;0.8 Calc .: (M-H) '= 502.12 m / z;

-161--161-

161 161 okso-1 - {[3-trifluorometil)fenil]metil} - 1,2-dihidro-3 -piridinil)amino]karbonil} - amino)propanojska kislina oxo-1 - {[3-trifluoromethyl) phenyl] methyl} - 1,2-dihydro-3-pyridinyl) amino] carbonyl} - amino) propanoic acid ugot.: (M-H)'= 502,03 m/z found: (M-H) '= 502.03 m / z (3 S)-3 -(4-fluorofenil)-3 -[({[2-okso-1 -(2- m/z; tiofenilmetil)-1,2-dihidro-3- piridinil] amino } karbonil)amino] - propanojska kislina (3 S) -3 - (4-fluorophenyl) -3 - [({[2-oxo-1 - (2- m / z; Thiophenylmethyl) -1,2-dihydro-3- pyridinyl] amino} carbonyl) amino] - propanoic acid 1,6 izrač.: (M-H)‘ = 414,09 ugot.: (M-H)' = 414,01 m/z 1.6 Calc .: (M-H) '= 414.09 found: (M-H) '= 414.01 m / z (3S)-3-(l,3-benzodioksol-5-il)-3-{[({-l- [(4-klorofenil)metil]-2-okso-1,2-dihidro- 3 -piridinil} amino)karbonil]amino} - propanojska kislina (3S) -3- (1,3-benzodioxol-5-yl) -3 - {[({- 1- [(4-chlorophenyl) methyl] -2-oxo-1,2-dihydro- 3-pyridinyl} amino) carbonyl] amino} - propanoic acid 3 3 izrač.: (M-H)' = 468,09 m/z; ugot.: (M-H)' = 467,99 m/z Calcd. (M-H) '= 468.09 m / z; found: (M-H) '= 467.99 m / z (3 S)-3 -(1,3 -benzodioksol-5 -il)-3 -({[(1 - {[2- (metiloksi)fenil]metil} -2-okso-1,2-di- hidro-3 -piridinil)amino]karbonil} aminopropanojska kislina (3 S) -3 - (1,3-benzodioxol-5-yl) -3 - ({[(1 - {[2- (methyloxy) phenyl] methyl} -2-oxo-1,2-di- hydro-3-pyridinyl) amino] carbonyl} aminopropanoic acid 0,5 0.5 izrač.: (M-H)' = 464,14 m/z; ugot.: (M-H)'= 464,04 m/z Calcd. (M-H) '= 464.14 m / z; found: (M-H) '= 464.04 m / z (3S)-3-[3-(metiloksi)fenil]-3-[({[-2- okso-1 -(2-tiofenilmetil)-1,2-dihidro-3 piridinil] -amino} karbonil)amino] - propanojska kislina (3S) -3- [3- (methyloxy) phenyl] -3 - [({[- 2- oxo-1- (2-thiophenylmethyl) -1,2-dihydro-3 pyridinyl] -amino} carbonyl) amino] - propanoic acid 1,4 1.4 izrač.: (M-H)' = 426,11 m/z; ugot.: (M-H)' = 426,02 m/z Calcd. (M-H) '= 426.11 m / z; found: (M-H) '= 426.02 m / z (3 S)-3 -[( {[2-okso-1 -(2-tiofenilmetil)- 1,2-dihidro-3 -piridinil] -amino} karbonil)- amino]-3-fenilpropanojska kislina (3 S) -3 - [({[2-oxo-1- (2-thiophenylmethyl) - 1,2-dihydro-3-pyridinyl] -amino} carbonyl) - amino] -3-phenylpropanoic acid 1 1 izrač.: (M-H)' = 396,10 m/z; ugot.: (M-H)'= 396,01 m/z Calcd. (M-H) '= 396.10 m / z; found: (M-H) '= 396.01 m / z (3 S)-3 -[( {[2-okso-1 -(2-tiofenilmetil)1,2-dihidro-3 -piridinil] amino} karbonil)- (3 S) -3 - [({[2-oxo-1- (2-thiophenylmethyl) 1,2-dihydro-3-pyridinyl] amino} carbonyl) - 0,3 0.3 izrač.: (M-H)' = 486,13 m/z; ugot.: (M-H)'= 485,98 m/z Calcd. (M-H) '= 486.13 m / z; found: (M-H) '= 485.98 m / z

-162162 amino]-3-[3,4,5-tris(metiloksi)fenil]propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3-{[({l[(2-klorofenil)metil]-2-okso-1,2-dihidro3 -piridinil} amino)karbonil] amino} propanoj ska kislina-162162 amino] -3- [3,4,5-tris (methyloxy) phenyl] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - {[({l [(2 -chlorophenyl) methyl] -2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} propanoic acid

0,3 izrač.: (M-H)' = 468,08 m/z; ugot.: (M-H)'= 468,03 m/z (3 S) - 3 -(1,3 -benzodioksol-5 -il)-3 - {[({1 [(4-fluorofenil)metil]-2-okso-1,2-dihidro-3 -piridinil} amino)karbonil]-aminopropanojska kislina izrač.: (M-H)' = 452,12 m/z; ugot.: (M-H) = 452,00 m/z0.3 Calc .: (M-H) '= 468.08 m / z; found: (MH) '= 468.03 m / z (3 S) -3- (1,3-benzodioxol-5-yl) -3 - {[({1 [(4-fluorophenyl) methyl] -2 -oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] -aminopropanoic acid calc .: (MH) '= 452.12 m / z; found: (M-H) = 452.00 m / z

-(1,3 -benzodioksol-5 -il)-2,2-di - >100 fluoro-3 -[({[2-okso-1 -(2-tiofenilmetil)1,2-dihidro-3 -piridinil] amino} karbonil)amino]propanojska kislina izrač.: (M-H)' = 476,07 m/z; ugot.: (M-H)' = 476,00 m/z (3 S)-3 -(1,3 -benzodioksol-5-il)-3 - {[({2okso-1 -[3-(feniloksi)propil]-1,2-dihidro3 -piridinil} amino)karbonil] amino} propanoj ska kislina izrač.: (M-H)' = 478,16 m/z; ugot.: (M-H) = 478,09 m/z (3 S)-3 -(1,3 -benzodioksol-5 - il)-3 - {[({1 - 5 [(3,5-diklorofenil)metil]-2-okso-1,2-dihidro-3 -piridinil} amino)karbonil]amino} propanoj ska kislina izrač.: (M-H)' = 502,05 m/z; ugot.: (M-H)'= 501,94 m/z (3 S)-3-( 1,3-benzodioksol-5-il)-3-[({ [ 1 (ciklopentilmetil)-2-okso-1,2-dihidro-3p ir idini 1] -amino} karbonil)amino]6 izrač.: (M-H) = 426,16 m/z; ugot.: (M-H)'= 426,09 m/z- (1,3-benzodioxol-5-yl) -2,2-di -> 100 fluoro-3 - [({[2-oxo-1- (2-thiophenylmethyl) 1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] propanoic acid calc .: (MH) '= 476.07 m / z; found: (MH) '= 476.00 m / z (3 S) -3- (1,3-benzodioxol-5-yl) -3 - {[({2oxo-1- [3- (phenyloxy) propyl) ] -1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid calc .: (MH) '= 478.16 m / z; found: (MH) = 478.09 m / z (3 S) -3- (1,3-benzodioxol-5-yl) -3 - {[({1- 5 [(3,5-dichlorophenyl) methyl ] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid calcd: (MH) '= 502.05 m / z; found: (MH) '= 501.94 m / z (3 S) -3- (1,3-benzodioxol-5-yl) -3 - [({[1 (cyclopentylmethyl) -2-oxo-1, 2-Dihydro-3pyrimidine 1] -amino} carbonyl) amino] Calcd for (MH) = 426.16 m / z; found: (M-H) '= 426.09 m / z

-163163-163163

propanojska kislina propanoic acid (3 S)-3-( 1,3-benzodioksol-5-il)-3- {[({2- okso-l-[2-(2-tiofenil)etil]-l,2-dihidro-3piridinil} aminojkarbonil] amino } - propanojska kislina (3S) -3- (1,3-benzodioxol-5-yl) -3- {[({2- oxo-1- [2- (2-thiophenyl) ethyl] -1,2-dihydro-3-pyridinyl} aminocarbonyl] amino} - propanoic acid 15 15 izrač.: (M-H) = 454,09 m/z; ugot.: (M-H) = 453,99 m/z Calcd. (M-H) = 454.09 m / z; found: (M-H) = 453.99 m / z (3 S )-3 - {[({1 - [(2-klorofenil)metil]-2-okso- l,2-dihidro-3- piridinil}amino)karbonil]amino}-3-(4metilfeniljpropanojska kislina (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo- 1,2-dihydro-3- pyridinyl} amino) carbonyl] amino} -3- (4methylphenylpropanoic acid) 0,1 0.1 izrač.: (M+H)+ = 440,14 m/z; ugot.: (M+H)+= 440,09 m/zCalcd .: (M + H) + = 440.14 m / z; found: (M + H) + = 440.09 m / z (3 S)-3 -(2,3-dihidro-1 -benzofuran-5-il)-3 - [({[2-okso-1 -(2-tiofenilmetil)-1,2-dihidro-3 - piridinil] -amino } karbonil)amino] - propanojska kislina (3S) -3- (2,3-dihydro-1-benzofuran-5-yl) -3 - [({[2-oxo-1- (2-thiophenylmethyl) -1,2-dihydro-3 - pyridinyl] -amino} carbonyl) amino] - propanoic acid 0,14 0.14 izrač.: (M-H) = 438,11 m/z; ugot.: (M-H) = 437,99 m/z Calcd. (M-H) = 438.11 m / z; found: (M-H) = 437.99 m / z (3 S)-3-(3 -fluorofenil)-3-[( {[2-okso-1 -(2- tiofenilmetil)-1,2-dihidro-3 - piridinil] -amino} karboniljamino]- propanojska kislina (3 S) -3- (3-fluorophenyl) -3 - [({[2-oxo-1 - (2- thiophenylmethyl) -1,2-dihydro-3 - pyridinyl] -amino} carbonylamino] - propanoic acid 3 3 izrač.: (M-H) = 414,09 m/z; ugot.: (M-H) = 413,99 m/z Calcd. (M-H) = 414.09 m / z; found: (M-H) = 413.99 m / z (3 S)-3-[( {[2-okso-1 -(2-tiofenilmetil)-1,2- dihidro-3-piridinil]-amino}karbonil)amino]- -3-[4-trifluorometil)fenil]propanojska kislina (3 S) -3 - [({[2-oxo-1- (2-thiophenylmethyl) -1,2- dihydro-3-pyridinyl] -amino} carbonyl) amino] - -3- [4-Trifluoromethyl) phenyl] propanoic acid 1,5 1.5 izrač.: (M-H) = 464,09 m/z; ugot.: (M-H) = 463,99 m/z Calcd. (M-H) = 464.09 m / z; found: (M-H) = 463.99 m / z (3 S)-3 -(1,3 -benzodioksol-5-il)-3- [({[6-okso-1 -(fenilmetil)-1,6-dihidro-3 - piridinil] -amino} karboni l)amino] - (3S) -3- (1,3-benzodioxol-5-yl) -3- [({[6-oxo-1- (phenylmethyl) -1,6-dihydro-3 - pyridinyl] -amino} carbonyl (1) amino] - 0,5 0.5 izrač.: (M-H) = 434,13 m/z; ugot.: (M-H) = 434,02 m/z Calcd .: (M-H) = 434.13 m / z; found: (M-H) = 434.02 m / z

propanojska kislinapropanoic acid

-164164 (3S)-3-[4-fluoro-3-(trifluorometil)fenil]-3[({[2-okso-1 -(2-tiofenilmetil)-1,2-dihidro3-piridinil]-amino}karbonil)amino]propanojska kislina (3 S)-3 -[4-( 1,1 -dimetiletil)fenil] -3 - [( {[2okso-1 -(2-tiofenilmetil)-1,2-dihidro-3pir i din i 1] amino } karbonil)amino] propanojska kislina (3S)-3-(l,3-benzodioksol-5-il)-3-[({butil[2,5diokso-1-(fenilmetil)tetrahidro-1 H-pirol-3il] amino} karbonil)amino]propanoj ska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso1,2-dihidro-3 -piridinil} amino)karbonil]amino}-3-[3,4,5-tris(metiloksi)fenil]propanojska kislina-164164 (3S) -3- [4-Fluoro-3- (trifluoromethyl) phenyl] -3 [({[2-oxo-1- (2-thiophenylmethyl) -1,2-dihydro3-pyridinyl] -amino} carbonyl ) amino] propanoic acid (3S) -3- [4- (1,1-dimethylethyl) phenyl] -3 - [({[2-oxo-1- (2-thiophenylmethyl) -1,2-dihydro-3pyridine] and 1] amino} carbonyl) amino] propanoic acid (3S) -3- (1,3-benzodioxol-5-yl) -3 - [({butyl [2,5-dioxo-1- (phenylmethyl) tetrahydro-1H- pyrrol-3yl] amino} carbonyl) amino] propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo 1,2,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- [3,4,5-tris (methyloxy) phenyl] propanoic acid

0,35 izrač.: (M-H)' = 482,08 m/z; ugot.: (M-H)' = 481,97 m/z izrač.: (M-H)'= 452,16 m/z; ugot.: (M-H)' = 452,02 m/z.0.35 Calc .: (M-H) '= 482.08 m / z; found: (M-H) '= 481.97 m / z calc .: (M-H)' = 452.16 m / z; found: (M-H) '= 452.02 m / z.

izrač.: (M-H)‘ = 494,19 m/z; ugot.: (M-H)'= 494,12 m/z.Calcd. (M-H) '= 494.19 m / z; found: (M-H) '= 494.12 m / z.

0,04 izrač.: (M+H)+ = 516,16 m/z; izrač.: (M+H)+ = 516,02 m/z;0.04 Calc .: (M + H) + = 516.16 m / z; Calc'd: (M + H) + = 516.02 m / z;

(3S)-3-{[({l-[(2,6-diklorofenil)metil]-2-okso- 0,2(3S) -3 - {[({1 - [(2,6-dichlorophenyl) methyl] -2-oxo-0,2

1,2-dihidro-3 -piridinil} amino)karbonil]amino} -3 -(4-metilfeniljpropanojska kislina izrač.: (M+H)+ = 474,10 m/z; izrač.: (M+H)+ = 474,04 m/z;1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenylpropanoic acid calc .: (M + H) + = 474.10 m / z; calc .: (M + H) + = 474.04 m / z;

(3 S)-3- {[({1 -[(2-klorofenil)metil]-2-okso1,2-dihidro-3 -piridinil} amino)karbonil]amino } -3 - [4-fluoro-3 -(trifluorometil) fenil] propanojska kislina(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3 - [4-fluoro-3 - (trifluoromethyl) phenyl] propanoic acid

0,2 izrač.: (M+H)+ = 512,10 m/z; izrač.: (M+H)+ = 512,04 m/z;0.2 Calc .: (M + H) + = 512.10 m / z; Calcd .: (M + H) + = 512.04 m / z;

(3S)-3-{[({ l-[(2-fluorofenil)metil]-2-okso- 0,1 l,2-dihidro-3-piridinil }amino)karbonil]izrač.: (M-H)' = 422,15 m/z; izrač.: (M-H)' = 422,01 m/z;(3S) -3 - {[({1 - [(2-fluorophenyl) methyl] -2-oxo-0,1,1,2-dihydro-3-pyridinyl} amino) carbonyl] calc .: (MH) '= 422.15 m / z; Calc'd: (M-H) '= 422.01 m / z;

-165165 amino } -3 - [4-metilfenil)propanojska kislina (3S)-3-(4-metilfenil)-3-{[({l-[(2metilfenil)metil]-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} propanojska kislina (3S)-3- {[({1 -[(2-bromofenil)metil]-2-okso1,2-dihidro-3 -piridinil} amino)karbonil] amino}-3-(4-metilfenil)propanojska kislina (3 S)-3- {[({1 -[(2,4-diklorofenil)metil]-2okso-1,2-dihidro-3-piridinil }amino)karbonil] -amino } -3 -(4-metilfenil)propanojska kislina-165165 amino} -3- [4-methylphenyl) propanoic acid (3S) -3- (4-methylphenyl) -3 - {[({1 - [(2methylphenyl) methyl] -2-oxo-1,2-dihydro -3-pyridinyl} amino) carbonyl] amino} propanoic acid (3S) -3- {[({1 - [(2-bromophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid (3S) -3- {[({1 - [(2,4-dichlorophenyl) methyl] -2oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] -amino} -3- (4-methylphenyl) propanoic acid

0,1 izrač.: (M-H)' = 418,18 m/z;0.1 Calc .: (M-H) '= 418.18 m / z;

ugot.: (M-H)'= 418,02 m/z;found: (M-H) '= 418.02 m / z;

0,05 izrač.: (M+H)+ = 484,09 m/z; ugot.: (M+H)+ = 484,03 m/z;0.05 Calc .: (M + H) + = 484.09 m / z; found: (M + H) + = 484.03 m / z;

0,4 izrač.: (M+H)+ = 474,10 m/z; ugot.: (M+H)+ = 474,05 m/z;0.4 Calc .: (M + H) + = 474.10 m / z; found: (M + H) + = 474.05 m / z;

(3S)-3-{[({ l-[(2-klorofenil)metil]-2- 0,04 okso-1,2-dihidro-3 -piridinil} amino)karbonil]amino}-3-(2,3dihidro- l-benzofuran-5-il)-propanojska kislina izrač.: (M-H)'= 466,11 m/z; ugot.: (M-H)'= 466,00 m/z;(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-0.04 oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2, 3dihydro-1-benzofuran-5-yl) -propanoic acid calc .: (MH) '= 466.11 m / z; found: (M-H) '= 466.00 m / z;

(3r)-3 -(1,3 -benzodioksol-5-il)-3- {[({1 -[(2 klorofenil)metil] -2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}propanojska kislina (3 S)-3 -(4-metilfenil)-3 -({[(2-okso-1 - {[2(trifluorometil)fenil]metil} -1,2-dihidro-3 piridinil)amino]karbonil} amino)propanojska kislina izrač.: (M-H)' = 468,09 m/z;(3r) -3- (1,3-benzodioxol-5-yl) -3 - {[({1 - [(2 chlorophenyl) methyl] -2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} propanoic acid (3 S) -3- (4-methylphenyl) -3 - ({[(2-oxo-1 - {[2 (trifluoromethyl) phenyl] methyl} -1,2-dihydro-3 pyridinyl) amino ] carbonyl} amino) propanoic acid calc .: (MH) '= 468.09 m / z;

ugot.: (M-H)'= 467,97 m/z izrač.: (M+H)+ = 474,10 m/z; ugot.: (M+H)+= 474,09 m/zfound: (MH) '= 467.97 m / z calc .: (M + H) + = 474.10 m / z; found: (M + H) + = 474.09 m / z

-166166-166166

(3S)-3-{[({ l-[(2,5-diklorofenil)metil]-2- okso-1,2-dihidro-3 - piridinil} -amino)karbonil] amino} -3 -(4- metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2,5-dichlorophenyl) methyl] -2- oxo-1,2-dihydro-3 - pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 0,15 0.15 izrač.: (M+H)+ = 474,10 m/z; ugot.: (M+H)+= 474,04 m/zCalcd. (M + H) + = 474.10 m / z; found: (M + H) + = 474.04 m / z (2R)-2- {[({1 -[(2-klorofenil)metil]-2-okso- l,2-dihidro-3- piridinil} -amino)karbonil] amino} -3 - fenilpropanojska kislina (2R) -2- {[({1 - [(2-chlorophenyl) methyl] -2-oxo- 1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- phenylpropanoic acid 50 50 izrač.: (M-H)' = 424,10 m/z; ugot.: (M-H)'=423,99 m/z Calcd. (M-H) '= 424.10 m / z; found: (M-H) '= 423.99 m / z (2R)-2- {[({1 -[(2-klorofenil)metil]-2-okso- l,2-dihidro-3- piridinil} -amino)karbonil]amino} -2- feniletanojska kislina (2R) -2- {[({1 - [(2-chlorophenyl) methyl] -2-oxo- 1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -2- phenylethanoic acid 80 80 izrač.: (M-H)' = 410,08 m/z; ugot.: (M-H)'= 409,95 m/z Calcd .: (M-H) '= 410.08 m / z; found: (M-H) '= 409.95 m / z (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso- l,2-dihidro-3- piridinil} -amino)karbonil]amino}-3-(3,5dimetilfenil)propanojska kislina (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo- 1,2-dihydro-3- Pyridinyl} -amino) carbonyl] amino} -3- (3,5-dimethylphenyl) propanoic acid 0,1 0.1 izrač.: (M-H)' = 452,14 m/z; ugot.: (M-H)' = 451,96 m/z Calcd. (M-H) '= 452.14 m / z; found: (M-H) '= 451.96 m / z (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso- l,2-dihidro-3- piridinil} -amino)karbonil] amino} -3 - fenilpropanojska kislina (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo- 1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- phenylpropanoic acid 0,1 0.1 izrač.: (M-H)' = 424,10 m/z; ugot.: (M-H)'= 424,07 m/z Calcd. (M-H) '= 424.10 m / z; found: (M-H) '= 424.07 m / z (3 S)-3 - {[({1 - [(2-klorofenil)metil]-2-okso- l,2-dihidro-3- piridinil} -amino)karbonil]amino}-3-[4(metiloksi)fenil]propanoj ska kislina (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo- 1,2-dihydro-3- Pyridinyl} -amino) carbonyl] amino} -3- [4 (methyloxy) phenyl] propanoic acid 0,1 0.1 izrač.: (M-H)' = 454,11 m/z; ugot.: (M-H)' = 454,01 m/z Calcd. (M-H) '= 454.11 m / z; found: (M-H) '= 454.01 m / z

-167167 (3 S)-3 - {[({1 - [(2-klorofenil)metil] -2-okso- 0,1 l,2-dihidro-3-piridinil}amino)karbonil]amino}-3-(4-hidroksifenil)propanojska kislina (3 S)-3 -({[(1 - {[3 -(metiloksi)fenil]metil} -2- 0,2 okso-1,2-dihidro-3-piridinil)amino]karbonil}amino)-3-(4-metilfenil)propanoj ska kislina (3 S)-3 - {[({1 -[(2-bromofenil)metil]-2-okso1,2 - dihidro-3 -pir idini 1} amino)karbonil] amino}-3-(3,4,5-tris(metiloksi)fenil]propanojska kislina-167167 (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-0,1, 2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-Hydroxyphenyl) propanoic acid (3 S) -3 - ({[(1 - {[3- (methyloxy) phenyl] methyl} -2,2,2 oxo-1,2-dihydro-3-pyridinyl) amino ] carbonyl} amino) -3- (4-methylphenyl) propanoic acid (3 S) -3 - {[({1 - [(2-bromophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridine] 1} amino) carbonyl] amino} -3- (3,4,5-tris (methyloxy) phenyl] propanoic acid

0,08 izrač.: (M-H) = 558,09 m/z; ugot.: (M-H) = 557,87 m/z;0.08 Calc .: (M-H) = 558.09 m / z; found: (M-H) = 557.87 m / z;

(3 S)-3-{[({l-[(2-klorofenil)metil]-2-okso- 0,09(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-0.09

1,2-dihidro-3 -piridinil} amino)karbonil]amino}-3-(3,4-dimetilfenil)propanojska kislina (3 S)-3 -[( {[5-kloro-2-hidroksi-3 -(fenilmetil)- 8 fenil]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina (3 S)-3 -(4-metilfenil)-3 - [({[3 -(fenilmetil)- 10 fenil]amino}karbonil)amino]propanojska kislina izrač.: (M-H) = 440,10 m/z; ugot.: (M-H) = 440,00 m/z;1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3,4-dimethylphenyl) propanoic acid (3 S) -3 - [({[5-chloro-2-hydroxy-3 - ( phenylmethyl) -8 phenyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid (3 S) -3- (4-methylphenyl) -3 - [({[3- (phenylmethyl) - 10 phenyl] amino} carbonyl) amino] propanoic acid calc .: (MH) = 440.10 m / z; found: (M-H) = 440.00 m / z;

izrač.: (M-H) = 434,17 m/z; ugot.: (M-H) = 434,01 m/z;Calcd. (M-H) = 434.17 m / z; found: (M-H) = 434.01 m / z;

izrač.: (M+H)+ = 454,15 m/z; ugot.: (M+H)+ = 454,07 m/z;Calcd .: (M + H) + = 454.15 m / z; found: (M + H) + = 454.07 m / z;

izrač.: (M-H) = 437,12 m/z; ugot.: (M-H) = 437,06 m/z;Calcd. (M-H) = 437.12 m / z; found: (M-H) = 437.06 m / z;

izrač.: (M-H) = 387,17 m/z; ugot.: (M-H) = 387,00 m/z;Calcd. (M-H) = 387.17 m / z; found: (M-H) = 387.00 m / z;

(3 S)-3 - {[({1 - [(2-klorofenil)metil]-2-okso1.2- dihidro-3-piridinil}amino)karbonil]amino } -3 -[3 -metil-4-(metiloksi)fenil] propanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil]-2-okso1.2- dihidro-3 -piridinil} amino)karbonil] 0,04 izrač.: (M-H) = 468,13 m/z; ugot.: (M-H) = 468,01 m/z;(3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3 - [3-methyl-4- (methyloxy) phenyl] propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridinyl} amino) carbonyl] 0.04 calc. : (MH) = 468.13 m / z; found: (M-H) = 468.01 m / z;

0,07 izrač.: (M-H) = 454,11 m/z; ugot.: (M-H) = 454,00 m/z;0.07 Calc .: (M-H) = 454.11 m / z; found: (M-H) = 454.00 m / z;

-168168 amino } -3 -(4-hidroksi-3 -metilfenil)propanojska kislina (3S)-3-{[({l-[(2,3-diklorofenil)metil]-2-okso- 0,35-168168 amino} -3- (4-hydroxy-3-methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2,3-dichlorophenyl) methyl] -2-oxo-0,35

1,2-dihidro-3 -piridinil} amino)karbonil] amino}-3-[4-metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -([ 1,1 '-bifenil]-2-ilmetil)-2- 2,5 okso-1,2-dihidro-3 -piridinil]amino} karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso1,2-dihidro-3 -piridinil} amino)karbonil] amino } -3 -(3 -metilfenil)propanojska kislina1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} -3- [4-methylphenyl) propanoic acid (3 S) -3 - [({[1 - ([1,1 '-biphenyl] -2) -ylmethyl) -2-2.5 oxo-1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid (3S) -3 - {[({1- [(2-chlorophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3-methylphenyl) propanoic acid

0,2 izrač.: (M-H)' = 438,12 m/z; ugot.: (M-H)' = 438,00 m/z;0.2 Calc .: (M-H) '= 438.12 m / z; found: (M-H) '= 438.00 m / z;

(3S)-3-{[({ l-[(2-klorofenil)metil]-2-okso- 3(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-3

1,2-dihidro-3 -piridinil} amino)karbonil] amino} -3 -(2-metilfenil)propanojska kislina izrač.: (M-H)' = 472,08 m/z; ugot.: (M-H)'= 471,94 m/z;1,2-Dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2-methylphenyl) propanoic acid calc .: (M-H) '= 472.08 m / z; found: (M-H) '= 471.94 m / z;

izrač.: (M-H)' = 480,19 m/z; ugot.: (M-H)' = 480,05 m/z.Calcd .: (M-H) '= 480.19 m / z; found: (M-H) '= 480.05 m / z.

izrač.: (M-H) = 438,12 m/z; ugot.: (M-H)' = 437,99 m/z;Calcd. (M-H) = 438.12 m / z; found: (M-H) '= 437.99 m / z;

(3S)-3-{[({ 1 -[(2-klorofenil)metil]-2-okso1,2-dihidro-3 -piridinil} amino)karbonil] amino}-3-(2,3-dihidro-lH-inden-5-il)propanojska kislina(3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2,3-dihydro-1H -inden-5-yl) propanoic acid

0,3 izrač.: (M-H)' = 464,13 m/z; ugot.: (M-H)' = 464,03 m/z;0.3 Calc .: (M-H) '= 464.13 m / z; found: (M-H) '= 464.03 m / z;

(3 S)-3 - {[({1 - [(2-cianofenil)metil]-2-okso1,2-dihidro-3-piridinil} amino)karbonil]amino } -3 -(4-metilfenil)propanojska kislina(3 S) -3 - {[({1 - [(2-cyanophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3 - (4-methylphenyl) propanoic acid

0,1 izrač.: (M+H)+ = 431,18 m/z; ugot.: (M+H)+ = 431,09 m/z;0.1 Calc .: (M + H) + = 431.18 m / z; found: (M + H) + = 431.09 m / z;

-169169 (3 S)-3-[2,6-bis(metiloksi)fenil]-3-{[({l-[(2- 6 klorofenil)metil]-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} propanoj ska kislina izrač.: (M-H)'= 484,14 m/z; ugot.: (M-H)' = 483,96 m/z;-169169 (3S) -3- [2,6-bis (methyloxy) phenyl] -3 - {[({1 - [(2-6 chlorophenyl) methyl] -2-oxo-1,2-dihydro-3pyridinyl } amino) carbonyl] amino} propanoic acid calcd: (MH) '= 484.14 m / z; found: (M-H) '= 483.96 m / z;

(3S)-3-{[({1-[(3-hidroksifenil)metil]-2-okso- 0,2 izrač.: (M+H)+ = 420,18 m/z;(3S) -3 - {[({1 - [(3-hydroxyphenyl) methyl] -2-oxo-0.2 calc .: (M + H) + = 420.18 m / z;

l,2-dihidro-3-piridinil}amino)karbonil]amino}- ugot.: (M+H)+ = 422,05 m/z.1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} - found (M + H) + = 422.05 m / z.

3-(4-metilfenil)propanojska kislina (3 S)-3 - [({ [(2-metil-6-okso-1 -(fenilmetil)l,6-dihidro-5-pirimidinil]amino}karbonil)amino] -3 -(4-metilfenil)propanoj ska kislina3- (4-methylphenyl) propanoic acid (3 S) -3 - [({[(2-methyl-6-oxo-1- (phenylmethyl) 1,6-dihydro-5-pyrimidinyl] amino} carbonyl) amino] -3- (4-Methylphenyl) propanoic acid

0,1 izrač.: (M-H)' = 419,17 m/z; ugot.: (M-H)' = 419,03 m/z;0.1 Calc .: (M-H) '= 419.17 m / z; found: (M-H) '= 419.03 m / z;

(3 S)-3-{ [({l-[(2-klorofenil)metil]-4-okso- 0,1(3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4-oxo-0,1

1,4-dihidro-3 -piridinil} amino)karbonil] amino} 3-(4-metilfenil)propanojska kislina (3S)-3-(4-metilfenil)-3-{[({l-[(2nitrofenil)metil]-2-okso-1,2-dihidro-3piridinil} -amino)karbonil]amino} propanoj ska kislina (3S)-3-(4-metilfenil)-3-{[({l-[(4nitrofenil)metil]-2-okso-1,2-dihidro-3piridinil} -amino)karbonil]amino} propanoj ska kislina izrač.: (M-H)'= 438,12 m/z; ugot.: (M-H)' = 438,10 m/z.1,4-Dihydro-3-pyridinyl} amino) carbonyl] amino} 3- (4-methylphenyl) propanoic acid (3S) -3- (4-methylphenyl) -3 - {[({1 - [(2nitrophenyl) methyl) ] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} propanoic acid (3S) -3- (4-methylphenyl) -3 - {[({1 - [(4nitrophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} propanoic acid calcd: (MH) '= 438.12 m / z; found: (M-H) '= 438.10 m / z.

izrač.: (M+H)+ = 451,17 m/z; ugot.: (M+H)+ = 451,07 m/z izrač.: (M+H)+ = 451,17 m/z; ugot.: (M+H)+ = 451,09 m/z (3 S)-3 - {[({1 - [(2-klorofenil)metil] -2-okso l,2-dihidro-3piridinil} -amino)karbonil]amino} -3 -(2,6dihidroksifenil)propanojska kislina izrač.: (M-H)' = 456,10 m/z; ugot.: (M-H)'= 456,04 m/zCalcd .: (M + H) + = 451.17 m / z; found: (M + H) + = 451.07 m / z calc .: (M + H) + = 451.17 m / z; found: (M + H) + = 451.09 m / z (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo 1,2,2-dihydro-3pyridinyl} - amino) carbonyl] amino} -3- (2,6dihydroxyphenyl) propanoic acid calc .: (MH) '= 456.10 m / z; found: (MH) '= 456.04 m / z

-170170-170170

(3S)-3-{[({l-[(2,6-difluorofenil)metil]-2- okso-1,2-dihidro-3 - piridinil} -amino)karbonil]amino}-3-(4metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2,6-difluorophenyl) methyl] -2- oxo-1,2-dihydro-3 - Pyridinyl} -amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid 0,3 0.3 izrač.: (M-H) = 440,14 m/z; ugot.: (M-H)'= 440,00 m/z Calcd. (M-H) = 440.14 m / z; found: (M-H) '= 440.00 m / z (3S)-3-{[({l-[(2,4-difluorofenil)metil]-2- okso-1,2-dihidro-3- piridinil} -amino)karbonil]amino} -3 -(4- metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2,4-difluorophenyl) methyl] -2- oxo-1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 1,3 1.3 izrač.: (M-H) = 440,14 m/z; ugot.: (M-H) = 439,96 m/z Calcd. (M-H) = 440.14 m / z; found: (M-H) = 439.96 m / z (3 S)-3- {[({1 -[(2,5-difluorofenil)metil]-2- okso-1,2-dihidro-3 - piridinil} -amino)karbonil] amino} -3-(4- metilfenil)propanojska kislina (3 S) -3- {[({1 - [(2,5-difluorophenyl) methyl] -2- oxo-1,2-dihydro-3 - pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 0,8 0.8 izrač.: (M-H) = 440,14 m/z; ugot.: (M-H)-439,96 m/z Calcd. (M-H) = 440.14 m / z; found: (M-H) -439.96 m / z (3 S)-3- {[({1 -[(2-klorofenil)metil]-2- metil-6-okso-1,6-dihidro-5- pirimidinil} -amino)karbonil]amino} -3 -(4- metilfenil)propanojska kislina (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -2- methyl-6-oxo-1,6-dihydro-5- pyrimidinyl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 0,09 0.09 izrač.: (M-H) = 453,13 m/z; ugot.: (M-H)'= 453,00 m/z Calcd. (M-H) = 453.13 m / z; found: (M-H) '= 453.00 m / z (3S)-3-{[({l-[(2-kloro-6- fluorofenil)metil]-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} -3-(4metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2-chloro-6-) fluorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid 0,1 0.1 izrač.: (M-H)' - 456,11 m/z; ugot.: (M-H)'= 455,94 m/z Calcd. (M-H) - 456.11 m / z; found: (M-H) '= 455.94 m / z (3S)-3-{[({l-[(2-bromo-5- fluorofenil)metil]-2-okso-1,2-dihidro-3- piridinil} -amino)karbonil]amino} -3 -(4- metilfenil)propanojska kislina (3S) -3 - {[({l - [(2-bromo-5- fluorophenyl) methyl] -2-oxo-1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 0,5 0.5 izrač.: (M-H)' = 500,06 m/z; ugot.: (M-H)'= 499,91 m/z Calcd .: (M-H) '= 500.06 m / z; found: (M-H) '= 499.91 m / z

-171171-171171

(3S)-3-{[({l-[(2-kloro-4- fluorofenil)metil]-2-okso-1,2-dihidro-3- piridinil} -amino)karbonil]amino} -3 -(4metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2-chloro-4- fluorophenyl) methyl] -2-oxo-1,2-dihydro-3- Pyridinyl} -amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid 0,35 0.35 izrač.: (M-H) = 456,11 m/z; ugot.: (M-H) = 455,93 m/z Calcd. (M-H) = 456.11 m / z; found: (M-H) = 455.93 m / z (3S)-3-{[({l-[(2-bromofenil)metil]-2-okso- l,2-dihidro-3- piridinil} -amino)karbonil] amino} -3-(3 -metil- 4-(metiloksi)fenil]propanojska kislina (3S) -3 - {[({1 - [(2-bromophenyl) methyl] -2-oxo- 1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- (3-methyl- 4- (methyloxy) phenyl] propanoic acid 0,2 0.2 izrač.: (M-H) = 512,08 m/z; ugot.: (M-H) = 511,96 m/z Calcd. (M-H) = 512.08 m / z; found: (M-H) = 511.96 m / z (3 S)-3- {[({1 -[(3,5-dimetil-4- izoksazolil)metil]-2-okso-1,2-dihidro-3piridinil}-amino)karbonil]amino}-3-(4- metilfenil)propanojska kislina (3 S) -3- {[({1 - [(3,5-dimethyl-4- isoxazolyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 3 3 izrač.: (M-H) = 423,17 m/z; ugot.: (M-H) = 423,02 m/z Calcd. (M-H) = 423.17 m / z; found: (M-H) = 423.02 m / z (3 S)-3 -(4-metilfenil)-3 - {[({2-okso-1 - [(2,4,6-trimetilfenil)metil]-l,2-dihidro-3- piridinil} -amino)karbonil] amino} - propanojska kislina (3S) -3- (4-methylphenyl) -3 - {[({2-oxo-1 - [(2,4,6-trimethylphenyl) methyl] -1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} - propanoic acid 2,5 2.5 izrač.: (M-H) = 446,21 m/z; ugot.: (M-H) = 446,08 m/z Calcd. (M-H) = 446.21 m / z; found: (M-H) = 446.08 m / z (3S)-3-(4-metilfenil)-3-{[({l-[(2-metil- 1,3 -tiazol-4-il)metil] -2-okso-1,2-dihidro-3 - piridinil} -amino)karbonil] amino} - propanojska kislina (3S) -3- (4-methylphenyl) -3 - {[({1 - [(2-methyl- 1,3-thiazol-4-yl) methyl] -2-oxo-1,2-dihydro-3 - pyridinyl} -amino) carbonyl] amino} - propanoic acid 1 1 izrač.: (M-H) = 425,13 m/z; ugot.: (M-H) = 424,99 m/z Calcd. (M-H) = 425.13 m / z; found: (M-H) = 424.99 m / z (3S)-3-({[(l-{[4-l,l dimetiletil)fenil]metil} -2-okso-1,2- dihidro-3 -piridinil)amino]karbonil} amino)-3 - (4-metilfenil)propanojska kislina (3S) -3 - ({[(l - {[4-l, l dimethylethyl) phenyl] methyl} -2-oxo-1,2- dihydro-3-pyridinylamino] carbonyl} amino) -3 - (4-methylphenyl) propanoic acid 6 6 izrač.: (M-H) = 460,22 m/z; ugot.: (M-H) = 460,07 m/z Calcd. (M-H) = 460.22 m / z; found: (M-H) = 460.07 m / z (3 S )-3 - [({[ 1 -(1,3 -benzoksazol-2-ilmetil)-2- (3 S) -3 - [({[1- (1,3-benzoxazol-2-ylmethyl) -2- >10 > 10 izrač.: (M-H) = 445,15 m/z; Calcd. (M-H) = 445.15 m / z;

-172172-172172

okso-1,2-dihidro-3 - piridinil] -amino} karbonil)amino] -3 -(4- metilfenil)propanojska kislina oxo-1,2-dihydro-3 - pyridinyl] -amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid ugot.: (M-H)'= 445,01 m/z found: (M-H) '= 445.01 m / z (3 S)-3 -({[(1 - { 2-[(2-hidroksifenil)amino] -2- oksoetil {-2-okso-1,2-dihidro-3 - piridinil)-amino]karbonil} amino)-3 -(4- metilfenil)propanojska kislina (3 S) -3 - ({[(1 - {2 - [(2-hydroxyphenyl) amino] -2- oxoethyl {-2-oxo-1,2-dihydro-3 - pyridinyl) amino] carbonyl} amino) -3- (4- methylphenyl) propanoic acid >10 > 10 izrač.: (M-H)' = 463,16 m/z; ugot.: (M-H)' = 463,06 m/z Calcd. (M-H) '= 463.16 m / z; found: (M-H) '= 463.06 m / z (3 S)-3- {[({1 -[(2-kloro-6-nitrofenil)metil]- 2-okso-1,2-dihidro-3 - piridinil} -amino)karbonil] amino} -3 -(4metilfenil)propanojska kislina (3 S) -3- {[({1 - [(2-chloro-6-nitrophenyl) methyl] - 2-oxo-1,2-dihydro-3 - Pyridinyl} -amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid 4 4 izrač.: (M-H)' = 483,11 m/z; ugot.: (M-H)' = 483,01 m/z Calcd. (M-H) '= 483.11 m / z; found: (M-H) '= 483.01 m / z (3 S)-3 - {[({1 - [(5 -kloro-2-fluorofenil)metil]- 2-okso-l,2-dihidro-3- piridinil} -amino)karbonil] amino} -3 -(4- metilfenil)propanojska kislina (3 S) -3 - {[({1 - [(5-chloro-2-fluorophenyl) methyl] - 2-oxo-1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 2,5 2.5 izrač.: (M-H)' = 456,11 m/z; ugot.: (M-H)'= 456,00 m/z Calcd. (M-H) '= 456.11 m / z; found: (M-H) '= 456.00 m / z (3S)-3-{[({l-[(2-amino-6- klorofenil)metil]-2-okso-1,2-dihidro-3- piridinil} -amino)karbonil]amino} -3 -(4metilfenil)propanojska kislina (3S) -3 - {[({1 - [(2-amino-6- chlorophenyl) methyl] -2-oxo-1,2-dihydro-3- Pyridinyl} -amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid 2 2 izrač.: (M-H)' = 453,13 m/z; ugot.: (M-H)'= 453,02 m/z Calcd. (M-H) '= 453.13 m / z; found: (M-H) '= 453.02 m / z (3S)-3-({[(l-{[2-fluoro-4- (trifluorometil)fenil]metil} -2-okso-1,2- dihidro-3 -piridinil)amino]karbonil} amino)-3 - (4-metilfenil)propanojska kislina (3S) -3 - ({[(l - {[2-fluoro-4- (trifluoromethyl) phenyl] methyl} -2-oxo-1,2- dihydro-3-pyridinylamino] carbonyl} amino) -3 - (4-methylphenyl) propanoic acid 3 3 izrač.: (M-H)' = 490,14 m/z; ugot.: (M-H)'= 489,99 m/z Calcd. (M-H) '= 490.14 m / z; found: (M-H) '= 489.99 m / z (3S)-3-{[({l-[(5-kloro-2-tiofenil)metil]- 2-okso-1,2-dihidro-3- (3S) -3 - {[({1 - [(5-chloro-2-thiophenyl) methyl] - 2-oxo-1,2-dihydro-3- 1,3 1.3 izrač.: (M-H)' = 444,08 m/z; ugot.: (M-H)’= 443,97 m/z Calcd. (M-H) '= 444.08 m / z; found: (M-H) '= 443.97 m / z

-173173-173173

piridinil} -amino)karbonil] amino } -3 -(4- metilfenil)propanojska kislina pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid (3 S)-3 - {[({1 -[(2-bromo-5 -nitrofenil)metil]- 2-okso-1,2-dihidro-3- piridinil} -amino)karbonil] amino} -3 -(4- metilfenil)propanojska kislina (3 S) -3 - {[({1 - [(2-bromo-5-nitrophenyl) methyl] - 2-oxo-1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 2 2 izrač.: (M-H)' = 527,06 m/z; ugot.: (M-H)' = 526,95 m/z Calcd. (M-H) '= 527.06 m / z; found: (M-H) '= 526.95 m / z 3-(4-klorofenil)-3-{[({ l-[(2- klorofenil)metil]-4-hidroksi-2-okso-1,2- dihidro-3 - piridinil} -amino)karbonil]amino } - propanojska kislina 3- (4-chlorophenyl) -3 - {[({l - [(2- chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2- dihydro-3-pyridinyl} -amino) carbonyl] amino} - propanoic acid 0,03 0.03 izrač.: (M-H)' = 474,06 m/z; ugot.: (M-H)’= 474,07 m/z Calcd. (M-H) '= 474.06 m / z; found: (M-H) '= 474.07 m / z (3 S)-3 - [( {[2-metil-6-okso-1 -(fenilmetil)-4- (2-piridinil)-l,6-dihidro-5- pirimidinil] -amino} karbonil)amino] -3-(4- metilfenil)propanojska kislina (3 S) -3 - [({[2-methyl-6-oxo-1- (phenylmethyl) -4- (2-pyridinyl) -1,6-dihydro-5- pyrimidinyl] -amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid 0,025 0.025 izrač.: (M+H)+ = 498,22 m/z; ugot.: (M+H)+= 498,10 m/zCalcd .: (M + H) + = 498.22 m / z; found: (M + H) + = 498.10 m / z (3S)-3-{[({l-[(5-amino-2- bromofenil)metil]-2-okso-1,2-dihidro-3 - piridinil} -amino)karbonil] amino} -3-(4- metilfenil)propanojska kislina (3S) -3 - {[({1 - [(5-amino-2- bromophenyl) methyl] -2-oxo-1,2-dihydro-3 - pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 0,08 0.08 izrač.: (M-H)' = 497,08 m/z; ugot.: (M-H)'=497,02 m/z Calcd. (M-H) '= 497.08 m / z; found: (M-H) '= 497.02 m / z (3 S)-3 - {[({1 -[(2,5-dimetilfenil)metil]-2- okso-1,2-dihidro-3- piridinil} -amino)karbonil] amino } -3 -(4- metilfenil)propanojska kislina (3 S) -3 - {[({1 - [(2,5-dimethylphenyl) methyl] -2- oxo-1,2-dihydro-3- pyridinyl} -amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 0,15 0.15 izrač.: (M-H)' = 432,19 m/z; ugot.: (M-H)' = 432,04 m/z Calc'd: (M-H) '= 432.19 m / z; found: (M-H) '= 432.04 m / z 3-(3-klorofenil)-3-{[({ l-[(2- klorofenil)metil]-4-hidroksi-2-okso-1,2- dihidro-3 -piridinil} amino) 3- (3-chlorophenyl) -3 - {[({l - [(2- chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2- dihydro-3-pyridinyl} amino) 0,03 0.03 izrač.: (M-H)' = 474,06 m/z; ugot.: (M-H)‘= 474,03 m/z Calcd. (M-H) '= 474.06 m / z; found: (M-H) '= 474.03 m / z

-174174 karbonil]amino}propanojska kislina-174174 carbonyl] amino} propanoic acid

3- {[({1 -[(2-klorofenil)metil]-4-hidroksi-2okso-1,2-dihidro-3 piridinil}-amino)karbonil]amino}-3-(3,4diklorofenil)propanojska kislina (3 S)-3 -({[(1 - {[5 -(acetilamino)-2bromofenil]metil}-2-okso-l,2-dihidro-3piridinil)amino]karbonil} amino)-3 -(4metilfenil)propanojska kislina3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl} -amino) carbonyl] amino} -3- (3,4-dichlorophenyl) propanoic acid ( 3 S) -3 - ({[(1 - {[5- (acetylamino) -2bromophenyl] methyl} -2-oxo-1,2-dihydro-3-pyridinyl) amino] carbonyl} amino) -3- (4methylphenyl) propanoic acid

0,04 izrač.: (M-H)' = 508,02 m/z; ugot.: (M-H)’= 507,97 m/z0.04 Calc .: (M-H) '= 508.02 m / z; found: (M-H) '= 507.97 m / z

0,2 izrač.: (M-H)' = 539,09 m/z; ugot.: (M-H)' = 539,02 m/z (3S)-3-[({[l-({2-bromo-5- 0,25 [(metilsulfonil)amino]fenil}metil)-2-okso1,2-dihidro-3 -piridinil] -amino } karbonil)amino]3-(4-metilfenil)propanojska kislina izrač.: (M-H)' = 575,06 m/z; ugot.: (M-H)'= 575,01 m/z0.2 Calc .: (M-H) '= 539.09 m / z; found: (MH) '= 539.02 m / z (3S) -3 - [({[1 - ({2-bromo-5- 0.25 [(methylsulfonyl) amino] phenyl} methyl) -2- oxo 1,2-dihydro-3-pyridinyl] -amino} carbonyl) amino] 3- (4-methylphenyl) propanoic acid calc .: (MH) '= 575.06 m / z; found: (M-H) '= 575.01 m / z

3-(4-klorofenil)-3-{[({ l-[(2klorofenil)metil]-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} propanoj ska kislina3- (4-chlorophenyl) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} propanoic acid

3-(3-klorofenil)-3-{[({l-[(2klorofenil)metil]-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} propanoj ska kislina3- (3-chlorophenyl) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} propanoic acid

0,4 izrač.: (M-H)' = 458,07 m/z; ugot.: (M-H)'= 457,96 m/z izrač.: (M-H)' = 458,07 m/z; ugot.: (M-H)'= 457,93 m/z0.4 Calc .: (M-H) '= 458.07 m / z; found: (M-H) '= 457.96 m / z calc .: (M-H)' = 458.07 m / z; found: (M-H) '= 457.93 m / z

3-{[({ l-[(2-klorofenil)metil]-2-okso-l,2- 1 dihidro-3 -piridinil} -amino)karbonil] amino } -3 (3,4-diklorofenil)propanojska kislina izrač.: (M-H)' = 492,03 m/z; ugot.: (M-H)'= 491,85 m/z3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-1 dihydro-3-pyridinyl} -amino) carbonyl] amino} -3 (3,4-dichlorophenyl) propanoic acid Calc'd: (MH) '= 492.03 m / z; found: (M-H) '= 491.85 m / z

-175175 (3S)-3-{[({l-[(2-bromo-4klorofenil)metil]-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino} -3 -(4metilfenil)propanojska kislina izrač.: (M-H)' = 516,03 m/z; ugot.: (M-H)'= 515,91 m/z (3S)-3-{[({l - [(4-klorofenil)metil]-2-okso l,2-dihidro-3piridinil} -amino)karbonil] amino} -3 -(4metilfenil)propanojska kislina izrač.: (M-H)' = 438,12 m/z; ugot.: (M-H)'= 437,88 m/z (3S)-3-{[({l-[(2-klorofenil)metil]-4hidroksi-2-okso-1,2-dihidro-3piridinil}-amino)karbonil]amino}-3-(2,3-dimetil)-4-(metiloksi)fenil]propanoj ska kislina-175175 (3S) -3 - {[({1 - [(2-bromo-4-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} -amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid calc .: (MH) '= 516.03 m / z; found: (MH) '= 515.91 m / z (3S) -3 - {[({1 - [(4-chlorophenyl) methyl] -2-oxo 1,2-dihydro-3-pyridinyl} -amino) carbonyl ] amino} -3- (4methylphenyl) propanoic acid calc .: (MH) '= 438.12 m / z; found: (MH) '= 437.88 m / z (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4hydroxy-2-oxo-1,2-dihydro-3pyridinyl} - amino) carbonyl] amino} -3- (2,3-dimethyl) -4- (methyloxy) phenyl] propanoic acid

0,035 izrač.: (M-H)' = 498,14 m/z; ugot.: (M-H)'= 498,05 m/z (3 S)-3 - {[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-1,2-dihidro-3piridinil} -amino)karbonil] amino }-3 -(4[(trifluorometil)oksi]fenil]propanoj ska kislina0.035 Calc .: (M-H) '= 498.14 m / z; found: (MH) '= 498.05 m / z (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3pyridinyl} -amino) carbonyl] amino} -3- (4 [(trifluoromethyl) oxy] phenyl] propanoic acid

0,015 izrač.: (M-H)'= 524,08 m/z; ugot.: (M-H)'= 524,03 m/z (3R)-3 -[({[ 1 - [(2-klorofenil)metil]-4-( 1,4 oksazinan-4-il)-2-okso-1,2-dihidro-3 piridinil] -amino } karbonil)amino] - 5 metilheksanojska kisline0.015 Calc .: (M-H) '= 524.08 m / z; found: (MH) '= 524.03 m / z (3R) -3 - [({[1 - [(2-chlorophenyl) methyl] -4- (1,4 oxazinan-4-yl) -2- oxo-1,2-dihydro-3 pyridinyl] -amino} carbonyl) amino] -5 methylhexanoic acid

0,1 izrač.: (M-H)' = 489,19 m/z; ugot.: (M-H)'= 489,13 m/z (3 S)-3 - [({ [4-hidroksi-6-metil] m/z;0.1 Calc .: (M-H) '= 489.19 m / z; found: (M-H) '= 489.13 m / z (3 S) -3 - [({[4-hydroxy-6-methyl] m / z;

2-okso-1 -(fenilmetil)-1,2-dihidro-3 piridinil] -amino } karbonil)amino]-3 -(4metilfenil)propanojska kislina2-Oxo-1- (phenylmethyl) -1,2-dihydro-3 pyridinyl] -amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid

0,035 izrač.: (M-H)' = 434,17 ugot.: (M-H)'= 434,08 m/z0.035 Calc .: (M-H) '= 434.17 Found: (M-H)' = 434.08 m / z

-176\Ί6 (3 S)-3- {[({1 -[(2-klorofenil)metil]-2-okso-4[(propilsulfonil)amino]-1,2-dihidro-3piridinil} -amino)karbonil] amino}-3-(4metilfenil)propanojska kislina-176 \ Ί6 (3S) -3- {[({1 - [(2-chlorophenyl) methyl] -2-oxo-4 [(propylsulfonyl) amino] -1,2-dihydro-3pyridinyl} -amino) carbonyl ] amino} -3- (4methylphenyl) propanoic acid

0,030 izrač.: (M-H) = 559,14 m/z; ugot.: (M-H)' = 559,04 m/z (3 S)-3- {[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-1,2-dihidro-3piridinil} -amino)karbonil]amino} -3 -(4etilfenil)propanojska kislina (3 S)-3 - {[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-1,2-dihidro-3piridinil}-amino)karbonil]amino}-3-(4(etiloksi)fenil]propanojska kislina0.030 calc .: (M-H) = 559.14 m / z; found: (MH) '= 559.04 m / z (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3pyridinyl} -amino) carbonyl] amino} -3- (4-ethylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl } -amino) carbonyl] amino} -3- (4 (ethyloxy) phenyl] propanoic acid

0,025 izrač.: (M-H) = 468,13 m/z; ugot.: (M-H) = 468,06 m/z0.025 Calc .: (M-H) = 468.13 m / z; found: (M-H) = 468.06 m / z

0,02 izrač.: (M-H) = 484,13 m/z; ugot.: (M-H) = 484,06 m/z (3S)-3-[({[4-hidroksi-2-okso-l(fenilmetil)-1,2-dihidro-3piridinil]-amino } karbonil)amino]-3 -(4metilfenil)propanojska kislina0.02 Calc .: (M-H) = 484.13 m / z; found: (MH) = 484.06 m / z (3S) -3 - [({[4-hydroxy-2-oxo-1 (phenylmethyl) -1,2-dihydro-3pyridinyl] -amino} carbonyl) amino ] -3- (4methylphenyl) propanoic acid

Tabela 5Table 5

Ime (3S)-3-[({[l-(3-terc.-butil-2metoksibenzil)-2-okso-1,2-dihidropiridin3 - il] amino} karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(4-fluorobenzil)2-okso-1,2dihidropiridin-3i 1] amino] }karbonil)amino-3 -(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4- hidroksi-2okso-1,2-dihidropiridin-3 0,030 izrač.: (M-H) = 420,16 m/z; ugot.: (M-H) = 420,08 m/zName (3S) -3 - [({[1- (3-tert-butyl-2methoxybenzyl) -2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (4-fluorobenzyl) 2-oxo-1,2-dihydropyridin-3I] amino]} carbonyl) amino-3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine-3 0.030 calc .: (MH) = 420.16 m / z; found: (MH) = 420.08 m / z

IC5o (μΜ) Masni spektralni podatkiIC 5 o (μΜ) Mass spectral data

2,5 izrač.: (M-H) =2.5 Calc .: (M-H) =

490,23 m/z; ugot.: (M-H) = 490,11 m/z.490.23 m / z; found: (M-H) = 490.11 m / z.

izrač.: (M-H) =Calcd. (M-H) =

422,12 m/z; ugot.: (M-H) = 422,00 m/z.422.12 m / z; found: (M-H) = 422.00 m / z.

0,025 izrač.: (M-H) =0.025 Calcd .: (M-H) =

526,08 m/z; ugot.: (M-H)526.08 m / z; found: (M-H)

-177177 il] amino} karbonil)amino]-3 -(4-iluoro-3 (trifluorometil)fenil]propanojska kislina (3 S)-3 - [({[ 1 -(2,5 -dimetilbenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3 - [({[4-hidroksi-1 -(2-metilbenzil)-2okso-1,2-dihidropiridin-3 illamino}karbonil)amino}-3-(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-hidroksibenzil)-2-okso1,2-dihidropiridin-3i 1] amino} karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -(3-klorobenzil)-2-okso-1,2dihidropiridin-3il] amino } karbonil)amino } -3 -(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-2okso-1,2-dihidropiridin-3 il]amino} karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 illamino} karbonil)amino]-3 -(4-metoksi3,5-dimetilfenil)propanojska kislina-177177 yl] amino} carbonyl) amino] -3- (4-fluoro-3 (trifluoromethyl) phenyl] propanoic acid (3 S) -3 - [({[1- (2,5-dimethylbenzyl) -4-hydroxy-2 -oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[4-hydroxy-1- (2-methylbenzyl) -2oxo] 1,2-Dihydropyridin-3-ylamino} carbonyl) amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-hydroxybenzyl) -2-oxo 1,2-dihydropyridin-3i 1 ] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (3-chlorobenzyl) -2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -2oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3 - (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-ylamino} carbonyl) amino] -3 - (4- methoxy 3,5-dimethylphenyl) propanoic acid

4- {[3 -[({[(1 S)-2-karboksi-1 -(4metilfenil)etil]amino}karbonil)amino]-1 (2-klorobenzil)-2-okso-1,2-dihidropiridin4-il]amino}benzojska kislina (3S)-3-{[({l -(2-klorobenzil)-4- [(2,2- 526,01 m/z.4- {[3 - [({[(1S) -2-carboxy-1- (4methylphenyl) ethyl] amino} carbonyl) amino] -1 (2-chlorobenzyl) -2-oxo-1,2-dihydropyridine 4 - yl] amino} benzoic acid (3S) -3 - {[({1- (2-chlorobenzyl) -4 - [(2,2- 526,01 m / z.

0,02 izrač.: (M-H)' =0.02 Calc .: (M-H) '=

448,19 m/z; ugot.: (M-H)' = 448,00 m/z.448.19 m / z; found: (M-H) '= 448.00 m / z.

0,02 izrač.: (M-H)'=0.02 Calc .: (M-H) '=

434,17 m/z; ugot.: (M-H)' = 434,05 m/z.434.17 m / z; found: (M-H) '= 434.05 m / z.

0,2 izrač.: (M-H)' =0.2 calcd: (M-H) '=

420,16 m/z; ugot.: (M-H)' = 420,09 m/z.420.16 m / z; found: (M-H) '= 420.09 m / z.

0,5 izrač.: (M-H)' =0.5 Calc .: (M-H) '=

438.12 m/z; ugot.: (M-H)' = 438,01 m/z.438.12 m / z; found: (M-H) '= 438.01 m / z.

0,1 izrač.: (M-H)'=0.1 Calc .: (M-H) '=

468.13 m/z; ugot.: (M-H)' = 468,08 m/z.468.13 m / z; found: (M-H) '= 468.08 m / z.

0,035 izrač.: (M-H)'=0.035 calcd .: (M-H) '=

498.14 m/z; ugot.: (M-H)' = 497,94 m/z.498.14 m / z; found: (M-H) '= 497.94 m / z.

0,004 izrač.: (M-H)' =0.004 calc .: (M-H) '=

573.15 m/z; ugot.: (M-H)' = 572,92 m/z.573.15 m / z; found: (M-H) '= 572.92 m / z.

0,01 izrač.: (M-H)' =0.01 Calc .: (M-H) '=

-178178 dimetilpropanoil)amino]2-okso-1,2dihidropiridin-3il }amino)karbonil] amino}-3-(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-5 -metoksibenzil)-2okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3R)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3il] amino } karbonil)amino]butanoj ska kislina (3S)-3-[({[4-{[terc.butilamino)karbonil] amino} -1 -(2klorobenzil)-2-okso-1,2-dihidropiridin-3 iljamino } karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2-kloro-5 -hidroksibenzil)-2okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3S)-3-[({[l -(2-cianobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3S)-3-[({[l-(2,4-diklorobenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3-[( {[4-hidroksi-1 -(2-metoksibenzil)2-okso-1,2-dihidropiridin-3 537,19 m/z; ugot.: (M-H) = 536,88 m/z.-178178 dimethylpropanoyl) amino] 2-oxo-1,2-dihydropyridin-3yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-5 - methoxybenzyl) -2oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo] -1,2-Dihydropyridin-3yl] amino} carbonyl) amino] butanoic acid (3S) -3 - [({[4 - {[tert-butylamino) carbonyl] amino} -1- (2-chlorobenzyl) -2-oxo -1,2-Dihydropyridin-3-ylamino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-5-hydroxybenzyl) -2oxo-1,2] -dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (2-cyanobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine- 3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (2,4-dichlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] ] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[4-hydroxy-1- (2-methoxybenzyl) 2-oxo-1,2-dihydropyridine-3 537, 19 m / z ; found: (M-H) = 536.88 m / z.

0,09 izrač.: (M-H)' =0.09 Calc .: (M-H) '=

468,13 m/z; ugot.: (M-H)' = 467,99 m/z.468.13 m / z; found: (M-H) '= 467.99 m / z.

0,19 izrač.: (M-H)'=0.19 calcd. (M-H) '=

378,09 m/z; ugot.: (M-H)' = 378,01 m/z.378.09 m / z; found: (M-H) '= 378.01 m / z.

0,01 izrač.: (M-H)'=0.01 Calc .: (M-H) '=

552,20 m/z; ugot.: (M-H)' = 551,89 m/z.552.20 m / z; found: (M-H) '= 551.89 m / z.

0,25 izrač.: (M-H)'=0.25 Calc .: (M-H) '=

454,12 m/z; ugot.: (M-H)' = 454,03 m/z.454.12 m / z; found: (M-H) '= 454.03 m / z.

0,009 izrač.: (M-H)' =0.009 calc .: (M-H) '=

445,15 m/z; ugot.: (M-H)‘ = 445,01 m/z.445.15 m / z; found: (M-H) '= 445.01 m / z.

0,06 izrač.: (M-H)'=0.06 Calc .: (M-H) '=

488,08 m/z; ugot.: (M-H)' = 487,96 m/z.488.08 m / z; found: (M-H) '= 487.96 m / z.

0,08 izrač.: (M-H)'=0.08 Calc .: (M-H) '=

450,17 m/z; ugot.: (M-H)'450.17 m / z; found: (M-H) '

-179179-179179

il] amino }karbonil)amino]-3 -(4- yl] amino} carbonyl) amino] -3- (4- = 450,02 m/z. = 450.02 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,08 0.08 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 498,14 m/z; ugot.: (M-H)' 498.14 m / z; found: (M-H) ' il]amino} karbonil)amino] -3 -(4-metoksi- yl] amino} carbonyl) amino] -3- (4-methoxy- = 497,95 m/z. = 497.95 m / z. 2,5-dimetilfenil)propanojska kislina 2,5-dimethylphenyl) propanoic acid (3 S)-3 -[({[ 1 -(2-kloro-6-hidroksibenzil)-2- (3 S) -3 - [({[1- (2-chloro-6-hydroxybenzyl) -2- 0,1 0.1 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 454,12 m/z; ugot.: (M-H)' 454.12 m / z; found: (M-H) ' il] amino} karbonil)amino] -3-(4- yl] amino} carbonyl) amino] -3- (4- = 454,05 m/z. = 454.05 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3S)-3-[({[l-(3-terc.-butil-2- (3S) -3 - [({[1- (3-tert-butyl-2- 4 4 izrač.: (M-H)' = calcd. (M-H) '= hidroksibenzil)-2-okso-1,2-dihidropiridin- hydroxybenzyl) -2-oxo-1,2-dihydropyridine- 476,02 m/z; ugot.: (M-H)' 476.02 m / z; found: (M-H) ' 3-il]amino}karbonil)amino]-3-((4- 3-yl] amino} carbonyl) amino] -3 - ((4- = 476,00 m/z. = 476.00 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3R)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,3 0.3 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 454,17 m/z; ugot.: (M-H)' 454.17 m / z; found: (M-H) ' il] amino} karbonil)amino]-3 -(4- yl] amino} carbonyl) amino] -3- (4- = 454,05 m/z. = 454.05 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,015 0.015 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 468,13 m/z; ugot.: (M-H)' 468.13 m / z; found: (M-H) ' il] amino} karbonil)amino]-3-(3- yl] amino} carbonyl) amino] -3- (3- = 467,95 m/z. = 467.95 m / z. etilfenil)propanojska kislina ethylphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,01 0.01 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 498,10 m/z; ugot.: (M-H)' 498.10 m / z; found: (M-H) ' il] amino }karbonil)amino]-3 -(2,3 -dihidro- yl] amino} carbonyl) amino] -3- (2,3-dihydro- = 497,85 m/z. = 497.85 m / z. 1,4-benzodioksin-6-il)propanojska kislina 1,4-Benzodioxin-6-yl) propanoic acid (3S)-3-[({[l-(2,5-difluorobenzil)-4- (3S) -3 - [({[1- (2,5-difluorobenzyl) -4- 0,015 0.015 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-1,2-dihidropiridin-3 - hydroxy-2-oxo-1,2-dihydropyridine-3 - 456,14 m/z; ugot.: (M-H)' 456.14 m / z; found: (M-H) ' il]amino} karbonil)amino]-3 -(4- yl] amino} carbonyl) amino] -3- (4- = 455,96 m/z. = 455.96 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 30 30 izrač.: (M-H)' = calcd. (M-H) '=

-180180-180180

okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 468,13 m/z; ugot.: (M-H)' 468.13 m / z; found: (M-H) ' il]amino}karbonil)amino]-4-(4- yl] amino} carbonyl) amino] -4- (4- = 467,87 m/z. = 467.87 m / z. metilfenil)butanojska kislina methylphenyl) butanoic acid (3S)-3-[({[l-[2-kloro-5-(metiltio)benzil]4- (3S) -3 - [({[1- [2-chloro-5- (methylthio) benzyl] 4- 0,015 0.015 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-1,2-dihidropiridin-3 - hydroxy-2-oxo-1,2-dihydropyridine-3 - 500,10 m/z; ugot.: (M-H)' 500.10 m / z; found: (M-H) ' il}amino)karbonil]amino}-3-(4- yl} amino) carbonyl] amino} -3- (4- = 499,92 m/z. = 499.92 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,005 0,005 izrač.: (M-H)’ = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 514,10 m/z; ugot.: (M-H)' 514.10 m / z; found: (M-H) ' il] amino} karbonil)amino] -3 -(7 -metoksi- yl] amino} carbonyl) amino] -3- (7-methoxy- = 513,86 m/z. = 513.86 m / z. 1,3-benzodioksol-5-il)propanojska kislina 1,3-benzodioxol-5-yl) propanoic acid (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,002 0.002 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 514,13 m/z; ugot.: (M-H)' 514.13 m / z; found: (M-H) ' il] amino} karbonil)amino] -3 -(3 -etoksi-4- yl] amino} carbonyl) amino] -3- (3-ethoxy-4- = 513,90 m/z. = 513.90 m / z. metoksifenil)-propanoj ska kislina methoxyphenyl) -propionic acid (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,015 0.015 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 488,10 m/z; ugot.: (M-H)' 488.10 m / z; found: (M-H) ' il] amino } karbonil)amino]-3 -(3 -fluoro-4- yl] amino} carbonyl) amino] -3- (3-fluoro-4- = 487,92 m/z. = 487.92 m / z. metoksifenil)-propanoj ska kislina methoxyphenyl) -propionic acid (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,002 0.002 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 500,12 m/z; ugot.: (M-H)' 500.12 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(3,4- yl] amino} carbonyl) amino] -3- (3,4- = 500,01 m/z. = 500.01 m / z. dimetoksifenil)-propanoj ska kislina dimethoxyphenyl) -propionic acid (3S)-3-[({[l -(4-fluorobenzil)-4-hidroksi-2- (3S) -3 - [({[1- (4-fluorobenzyl) -4-hydroxy-2- 0,022 0.022 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 438,18 m/z; ugot.: (M-H)' 438.18 m / z; found: (M-H) ' il] amino } karbonil)amino] -3-(4- yl] amino} carbonyl) amino] -3- (4- = 438,00 m/z. = 438.00 m / z. metilfenil)-propanojska kislina methylphenyl) -propanoic acid (3 S)-3 -[({[ 1 -(2-metoksibenzil)-2-okso- (3 S) -3 - [({[1- (2-methoxybenzyl) -2-oxo- 0,25 0.25 izrač.: (M-H)' = calcd. (M-H) '= 1,2-dihidropiridin-3 - 1,2-Dihydropyridine-3 - 434,17 m/z; ugot.: (M-H)‘ 434.17 m / z; found: (M-H) ' il] amino }karbonil)amino] -3 -(4- yl] amino} carbonyl) amino] -3- (4- = 433,95 m/z. = 433.95 m / z. metilfenil)-propanojska kislina methylphenyl) -propanoic acid

-181181 (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 11] amino} karbonil)amino] -3 -(2,5 dimetilfenil)-propanojska kislina (3 S)-3-[( {[ 1 -(2-kloro-5-metoksibenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il]amino} karbonil)amino]-3 -(4metilfenil)-propanojska kislina (3S)-3-{[({ l-[3,5bis(trifluorometil)benzil]-4-hidroksi-2okso-1,2-dihidropiridin-3 il] aminojkarbonil] amino } -3 -(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(4-terc.-butilbenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il] amino}karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 - [({ [ 1 -(3-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il] amino} karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(4-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3 - {[({4-hidroksi-2-okso-1 - [3 (trifluorometil)benzil]-1,2-dihidropiridin3 -il} aminojkarbonil] amino} -3 -(4metilfeniljpropanojska kislina (3 S)-3 - [({[ 1 -(2-bromobenzil)-4-hidroksi2-okso-1,2-dihidropiridin-3 0,05 izrač.: (M-H) =-181181 (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 11] amino} carbonyl) amino] -3- (2,5 dimethylphenyl ) -propanoic acid (3S) -3 - [({[1- (2-chloro-5-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 - (4methylphenyl) -propanoic acid (3S) -3 - {[({1- [3,5bis (trifluoromethyl) benzyl] -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] aminocarbonyl] amino} -3 - (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (4-tert-butylbenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 - (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (3-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) ) propanoic acid (3S) -3 - [({[1- (4-chlorobenzyl) -4-hydroxy-2oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - {[({4-hydroxy-2-oxo-1- [3 (trifluoromethyl) benzyl] -1,2-dihydropyridin3-yl} amino) carbonyl] amino} -3 - (4methylphenylpropanoic acid (3 S ) -3 - [({[1- (2-bromobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine-3 0.05 calculated: (M-H) =

468.13 m/z; ugot.: (M-H) = 467,94 m/z.468.13 m / z; found: (M-H) = 467.94 m / z.

0,012 izrač.: (M-H)' =0.012 Calc .: (M-H) '=

484.13 m/z; ugot.: (M-H)' = 484,03 m/z.484.13 m / z; found: (M-H) '= 484.03 m / z.

0,3 izrač.: (M-H)‘ =0.3 Calc .: (M-H) '=

556.13 m/z; ugot.: (M-H) = 555,95 m/z.556.13 m / z; found: (M-H) = 555.95 m / z.

0,03 izrač.: (M-H)' =0.03 Calc .: (M-H) '=

476,22 m/z; ugot.: (M-H) = 476,05 m/z.476.22 m / z; found: (M-H) = 476.05 m / z.

0,015 izrač.: (M-H)’=0.015 Calc .: (M-H) '=

454,12 m/z; ugot.: (M-H) = 453,99 m/z.454.12 m / z; found: (M-H) = 453.99 m / z.

0,007 izrač.: (M-H)’ =0.007 calc .: (M-H) '=

454,12 m/z; ugot.: (M-H) = 454,00 m/z.454.12 m / z; found: (M-H) = 454.00 m / z.

0,017 izrač.: (M-H)’=0.017 Calc .: (M-H) '=

488,14 m/z; ugot.: (M-H) = 487,99 m/z.488.14 m / z; found: (M-H) = 487.99 m / z.

0,015 izrač.: (M-H)’=0.015 Calc .: (M-H) '=

498,07 m/z; ugot.: (M-H)498.07 m / z; found: (M-H)

-182182-182182

il] amino} karbonil)amino]-3 -(4- yl] amino} carbonyl) amino] -3- (4- = 497,97 m/z. = 497.97 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3S)-3-[({[l-(3,4-diklorobenzil)-4- (3S) -3 - [({[1- (3,4-dichlorobenzyl) -4- 0,045 0.045 izrač.: (M-H) = Calcd. (M-H) = hidroksi-2-okso-1,2-dihidropiridin-3 - hydroxy-2-oxo-1,2-dihydropyridine-3 - 488,08 m/z; ugot.: (M-H) 488.08 m / z; found: (M-H) il] amino } karbonil)amino] -3 -(4- yl] amino} carbonyl) amino] -3- (4- = 487,96 m/z. = 487.96 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 - [({ [4-hidroksi-1 -(4-metilbenzil)-2- (3 S) -3 - [({[4-hydroxy-1- (4-methylbenzyl) -2- 0,025 0.025 izrač.: (M-H) = Calcd. (M-H) = okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 434,17 m/z; ugot.: (M-H) 434.17 m / z; found: (M-H) il]amino}karbonil)amino]-3-(4- yl] amino} carbonyl) amino] -3- (4- = 434,05 m/z. = 434.05 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3-[({[ 1 -(2-kloro-6-metoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4- 0,003 0.003 izrač.: (M-H) = Calcd. (M-H) = hidroksi-2-okso-1,2-dihidropiridin-3- hydroxy-2-oxo-1,2-dihydropyridine-3- 484,13 m/z; ugot.: (M-H) 484.13 m / z; found: (M-H) il] amino} karbonil)amino] -3 -(4- yl] amino} carbonyl) amino] -3- (4- = 484,02 m/z. = 484.02 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3- {[({4-hidroksi-2-okso-1 - [4- (3S) -3- {[({4-hydroxy-2-oxo-1- [4- 0,02 0.02 izrač.: (M-H) = Calcd. (M-H) = (trifluorometil)benzil]-1,2-dihidropiridin- (trifluoromethyl) benzyl] -1,2-dihydropyridine- 488,14 m/z; ugot.: (M-H) 488.14 m / z; found: (M-H) 3-il} amino)karbonil]amino} -3 -(4- 3-yl} amino) carbonyl] amino} -3- (4- = 487,99 m/z. = 487.99 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,02 0.02 izrač.: (M-H) = Calcd. (M-H) = okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 524,08 m/z; ugot.: (M-H) 524.08 m / z; found: (M-H) il] amino } karbonil)amino] -3 - [3 - yl] amino} carbonyl) amino] -3- [3 - = 523,91 m/z. = 523.91 m / z. (trifluorometoksi)fenil]propanoj ska kislina (trifluoromethoxy) phenyl] propanoic acid (3 S)-3-[({ [4-hidroksi-1 -(3-metilbenzil)-2- (3 S) -3 - [({[4-hydroxy-1- (3-methylbenzyl) -2- 0,055 0,055 izrač.: (M-H) = Calcd. (M-H) = okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 434,17 m/z; ugot.: (M-H) 434.17 m / z; found: (M-H) il] amino} karbonil)amino] -3-(4- yl] amino} carbonyl) amino] -3- (4- = 433,99 m/z. = 433.99 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3S)-3-[({[4-hidroksi-2-okso-l-(piridin-2- (3S) -3 - [({[4-hydroxy-2-oxo-1- (pyridin-2- 0,045 0.045 izrač.: (M-H)' = calcd. (M-H) '= ilmetil)-1,2-dihidropiridin-3- ylmethyl) -1,2-dihydropyridin-3- 421,15 m/z; ugot.: (M-H) 421.15 m / z; found: (M-H) il] amino} karbonil)amino] -3-(4- yl] amino} carbonyl) amino] -3- (4- = 421,06 m/z. = 421.06 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 - (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 - 0,005 0,005 izrač.: (M-H) = Calcd. (M-H) =

-183183 metil-2-okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2,4-difluorobenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3i 1] amino} karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2,6-difluorobenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 - {[({4-hidroksi-2-okso-1 - [3 (trifluorometoksi)benzil]-1,2dihidropiridin-3il] amino)karbonil] amino } -3 -(4metilfenil)propanojska kislina (3 S)-3 - {[({4-hidroksi-2-okso-1 - [4(trifluorometoksi)benzil]-1,2dihidropiridin-3il] amino)karbonil] amino}-3-(4metilfenil)propanojska kislina (3 S)-3 -[( {[ 1 -(2-kloro-6-metoksibenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il] amino } karbonil)amino] -3-(3,5dimetoksifenil)propanojska kislina-183183 Methyl-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2,4-difluorobenzyl) ) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid (3 S) -3 - [({[1- (2,6-difluorobenzyl)) ) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - {[({4-hydroxy-2-oxo- 1- [3 (trifluoromethoxy) benzyl] -1,2-dihydropyridin-3yl] amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - {[({4-hydroxy-2-oxo-1 - [4 (trifluoromethoxy) benzyl] -1,2-dihydropyridin-3yl] amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) ) -4hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,5 dimethoxyphenyl) propanoic acid

3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso1,2-dihidropiridin-3il] amino } karbonil)amino]-3 -(2furil)propanojska kislina (3 S)-3 - {[({4-hidroksi-2-okso-1 - [2(trifluorometil)benzil]-1,2-dihidropiridin468.13 m/z; ugot.: (M-H)' = 467,99 m/z.3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo 1,2,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (2-furyl) propanoic acid (3 S) -3 - { [({4-hydroxy-2-oxo-1- [2 (trifluoromethyl) benzyl] -1,2-dihydropyridine468.13 m / z; found: (MH) '= 467.99 m / z.

0,03 izrač.: (M-H)'=0.03 Calc .: (M-H) '=

456.14 m/z; ugot.: (M-H)' = 456,01 m/z.456.14 m / z; found: (M-H) '= 456.01 m / z.

0,008 izrač.: (M-H)' =0.008 calc .: (M-H) '=

456.14 m/z; ugot.: (M-H)' = 456,01 m/z.456.14 m / z; found: (M-H) '= 456.01 m / z.

0,045 izrač.: (M-H)' =0.045 calc .: (M-H) '=

504.14 m/z; ugot.: (M-H) = 503,98 m/z.504.14 m / z; found: (M-H) = 503.98 m / z.

0,025 izrač.: (M-H)' =0.025 calcd. (M-H) '=

504,14 m/z; ugot.: (M-H) = 503,98 m/z.504.14 m / z; found: (M-H) = 503.98 m / z.

0,0015 izrač.: (M-H)' =0.0015 calc .: (M-H) '=

530.13 m/z; ugot.: (M-H) = 529,91 m/z.530.13 m / z; found: (M-H) = 529.91 m / z.

0,05 izrač.: (M-H)'=0.05 Calc .: (M-H) '=

430,08 m/z; ugot.: (M-H)' = 429,94 m/z.430.08 m / z; found: (M-H) '= 429.94 m / z.

0,02 izrač.: (M-H)’=0.02 Calc .: (M-H) '=

488.14 m/z; ugot.: (M-H)488.14 m / z; found: (M-H)

-184184-184184

3 -il} amino)karbonil])amino} -3 -(4- 3-yl} amino) carbonyl] amino} -3- (4- = 487,96 m/z. = 487.96 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3R)-3-[({ [l-(2-klorobenzil)-4-hidroksi-2- (3R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,15 0.15 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 468,13 m/z; ugot.: (M-H)' 468.13 m / z; found: (M-H) ' il]amino}karbonil)amino]-4-(4- yl] amino} carbonyl) amino] -4- (4- = 467,99 m/z. = 467.99 m / z. metilfenil)butanojska kislina methylphenyl) butanoic acid (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,0008 0,0008 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 528,15 m/z; ugot.: (M-H)' 528.15 m / z; found: (M-H) ' il]amino} karbonil)amino]-3 -(3,4- yl] amino} carbonyl) amino] -3- (3,4- = 527,96 m/z. = 527.96 m / z. dietoksifenil)propanoj ska kislina diethoxyphenyl) propanoic acid (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,003 0.003 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 484,12 m/z; ugot.: (M-H)' 484.12 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(3- yl] amino} carbonyl) amino] -3- (3- = 483,94 m/z. = 483.94 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3 - [( {[4-hidroksi-1 -(3 -metoksibenzil)- (3 S) -3 - [({[4-hydroxy-1- (3-methoxybenzyl) - 0,04 0.04 izrač.: (M-H)' = calcd. (M-H) '= 2-okso-1,2-dihidropiridin-3 - 2-oxo-1,2-dihydropyridine-3 - 450,17 m/z; ugot.: (M-H)' 450.17 m / z; found: (M-H) ' iljamino } karbonil)amino] -3 -(4- islamino} carbonyl) amino] -3 - (4- = 450,00 m/z. = 450.00 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2,3 -diklorobenzil)-4- (3 S) -3 - [({[1 - (2,3-dichlorobenzyl) -4- 0,13 0.13 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-1,2-dihidropiridin-3- hydroxy-2-oxo-1,2-dihydropyridine-3- 488,08 m/z; ugot.: (M-H)' 488.08 m / z; found: (M-H) ' i 1] amino } karbonil)amino] -3-(4- and 1] amino} carbonyl) amino] -3- (4- = 487,92 m/z. = 487.92 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3S)-3-[({[l-benzil-2-okso-5- (3S) -3 - [({[1-benzyl-2-oxo-5- 1,5 1.5 izrač.: (M-H)' = calcd. (M-H) '= (trifluorometil)-1,2-dihidropiridin-3- (trifluoromethyl) -1,2-dihydropyridine-3- 472,15 m/z; ugot.: (M-H)' 472.15 m / z; found: (M-H) ' il] amino } karbonil)amino] -3 -(4- yl] amino} carbonyl) amino] -3- (4- = 471,89 m/z. = 471.89 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3S)-3-[({[l-3,5-dimetilbenzil)-4-hidroksi- (3S) -3 - [({[1-3,5-dimethylbenzyl) -4-hydroxy- 0,06 0.06 izrač.: (M-H)' = calcd. (M-H) '= 2-okso-1,2-dihidropiridin-3- 2-oxo-1,2-dihydropyridine-3- 448,19 m/z; ugot.: (M-H)' 448.19 m / z; found: (M-H) ' i 1] amino} karbonil)amino] -3-(4- and 1] amino} carbonyl) amino] -3- (4- = 448,02 m/z. = 448.02 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3-[( {[ 1 -(2-kloro-6-metoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4- 0,04 0.04 izrač.: (M-H)' = calcd. (M-H) '=

-185185-185185

hidroksi-2-okso-1,2-dihi drop iridin-3 - hydroxy-2-oxo-1,2-dihydro-iridine-3 - 554,09 m/z; ugot.: (M-H)' 554.09 m / z; found: (M-H) ' i 1] amino } karbonil)amino] -3 - [4- trifluorometoksi)fenil]propanojska kislina and 1] amino} carbonyl) amino] -3- [4- trifluoromethoxy) phenyl] propanoic acid = 553,98 m/z. = 553.98 m / z. (3 S)-3- [({[ 1 -(2-klorobenzil)-4-hidroksi-2- okso-1,2-dihidropiridin-3- il]amino} karbonil)amino]-3 -(3 -metoksi-4- metilfenil)propanojska kislina (3S) -3- [({[1- (2-chlorobenzyl) -4-hydroxy-2- oxo-1,2-dihydropyridine-3- yl] amino} carbonyl) amino] -3- (3-methoxy-4- methylphenyl) propanoic acid 0,003 0.003 izrač.: (M-H)' = 484,13 m/z; ugot.: (M-H)' = 483,95 m/z. calcd. (M-H) '= 484.13 m / z; found: (M-H) ' = 483.95 m / z. (3 S)-3 -[({[ 1 -(2-klorobenzil-4-hidroksi-2- okso-1,2-dihidropiridin-3 - il] amino} karbonil)amino] -3 -(3,5- dimetoksi-4-metilfenil)propanojska kislina (3S) -3 - [({[1- (2-chlorobenzyl-4-hydroxy-2- oxo-1,2-dihydropyridine-3 - yl] amino} carbonyl) amino] -3- (3,5- dimethoxy-4-methylphenyl) propanoic acid 0,003 0.003 izrač.: (M-H)' = 514,14 m/z; ugot.: (M-H)' = 513,95 m/z. calcd. (M-H) '= 514.14 m / z; found: (M-H) ' = 513.95 m / z. (3 S)-3-[({ [ l-(2-klorobenzil)-4-hidroksi-2- okso-5-pentil-1,2-dihidropiridin-3il] amino } karbonil)amino] -3 -(4- metilfenil)propanojska kislina (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- oxo-5-pentyl-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid 0,04 0.04 izrač.: (M-H)' = 524,20 m/z; ugot.: (M-H)' = 523,98 m/z. calcd. (M-H) '= 524.20 m / z; found: (M-H) ' = 523.98 m / z. (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2- okso-1,2-dihidrop iridin-3 - il]amino}karbonil)amino]-3-(3,4- dimetilfenil)propanojska kislina (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- oxo-1,2-dihydrop iridin-3 - yl] amino} carbonyl) amino] -3- (3,4- dimethylphenyl) propanoic acid 0,005 0,005 izrač.: (M+H) = 468,13 m/z; ugot.: (M+H)+ = 467,99 m/z.Calcd. (M + H) = 468.13 m / z; found: (M + H) + = 467.99 m / z. (3 S)-3-[({ [ 1 -(2,4-diklorobenzil)-4- hidroksi-5-metil-2-okso-1,2- dihidropiridin-3- il]amino}karbonil)amino]-3-(4- metilfenil)propanojska kislina (3 S) -3 - [({[1 - (2,4-dichlorobenzyl) -4- hydroxy-5-methyl-2-oxo-1,2- dihydropyridine-3- yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid 0,02 0.02 izrač.: (M-H)‘ = 502,09 m/z; ugot.: (M-H)' = 501,89 m/z. calcd. (M-H) '= 502.09 m / z; found: (M-H) ' = 501.89 m / z. [2-( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso1,2 - dihidrop ir idin-3 - il] amino} karbonil)-1 - (4-metilfenil)hidrazino] ocetna kislina [2- ({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) -1- (4-methylphenyl) hydrazino] acetic acid >10 > 10 izrač.: (M-H)' = 455,11 m/z; ugot.: (M-H)' = 454,97 m/z. calcd. (M-H) '= 455.11 m / z; found: (M-H) ' = 454.97 m / z. (3 S)-3 -[({[ 1 -(2-klorobenzil)-5-etil-4hidroksi-2-okso-1,2-dihidropiridin-3 il] amino } karbonil)amino] -3-(4metilfenil)propanojska kislina (3S) -3 - [({[1- (2-chlorobenzyl) -5-ethyl-4hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid 0,01 0.01 izrač.: (M-H)' = 482,15 m/z; ugot.: (M-H)' = 482,00 m/z. calcd. (M-H) '= 482.15 m / z; found: (M-H) ' = 482.00 m / z.

-186186-186186

3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso1,2-dihidropiridin-3i 1] amino} karbonil)amino] -3-piridin-3 -il propanojska kislina (3S)-3-[({ [5-butil-1 -(2-klorobenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3-(4metilfenil)propanojska kislina (3S)-3-{[({l-(2-kloro-5(trifluorometil)benzil]-4-hidroksi-2-okso1,2-dihidropiridin-3il]amino)karbonil]amino}-3-(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il] amino} karbonil)amino] -3 -(3 metilfenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2,6-diklorobenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3S)-3-[({[l-(2-kloro-5-fluorobenzil)-4hidroksi-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il] amino} karbonil)amino]-3 -(4metilfenil)propanojska kislina (3S)-3-[({[l-(4-klorobenzil)-4-hidroksi-50,05 izrač.: (M-H)' =3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo,2,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3-pyridin-3-yl propanoic acid (3S) -3 - [({[5-butyl-1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) - 3 - {[({1- (2-chloro-5 (trifluoromethyl) benzyl] -4-hydroxy-2-oxo 1,2,2-dihydropyridin-3yl] amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3 methylphenyl) propanoic acid (3 S) -3 - [({[1- (2,6-dichlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid ( 3S) -3 - [({[1- (2-chloro-5-fluorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid ( 3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid (3S) -3 - [({[1- (4-chlorobenz yl) -4-hydroxy-50.05 calculated: (M-H) '=

441,09 m/z; ugot.: (M-H) = 441,00 m/z.441.09 m / z; found: (M-H) = 441.00 m / z.

0,025 izrač.: (M-H) =0.025 Calcd .: (M-H) =

510,18 m/z; ugot.: (M-H) = 509,98 m/z.510.18 m / z; found: (M-H) = 509.98 m / z.

0,01 izrač.: (M-H) =0.01 Calc .: (M-H) =

522,10 m/z; ugot.: (M-H) = 521,97 m/z.522.10 m / z; found: (M-H) = 521.97 m / z.

0,005 izrač.: (M-H) =0.005 calc .: (M-H) =

484,13 m/z; ugot.: (M-H) = 484,00 m/z.484.13 m / z; found: (M-H) = 484.00 m / z.

0,013 izrač.: (M-H) =0.013 Calcd .: (M-H) =

488,08 m/z; ugot.: (M-H)' = 487,91 m/z.488.08 m / z; found: (M-H) '= 487.91 m / z.

0,014 izrač.: (M-H) =0.014 Calc .: (M-H) =

472,11 m/z; ugot.: (M-H)' = 471,96 m/z.472.11 m / z; found: (M-H) '= 471.96 m / z.

0,01 izrač.: (M-H) =0.01 Calc .: (M-H) =

482,15 m/z; ugot.: (M-H) = 481,98 m/z.482.15 m / z; found: (M-H) = 481.98 m / z.

0,02 izrač.: (M-H) =0.02 Calc .: (M-H) =

-187187 metil-2-okso-1,2-dihidropiridin-3 iljamino } karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3S)-3-{[({4-hidroksi-5-metil-l-[4(metilsulfonil)benzil]-2-okso-1,2dihidropiridin-3il} amino)karbonil]amino} -3 -(4metilfenil)propanojska kislina (3 S)-3 -[( {[4-hidroksi-1 -(4-metoksibenzil)2-okso-l,2-dihidropiridin-3i 1] amino} karbonil)amino]-3 -(4metilfenil)propanojska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2okso-5 -propil-1,2-dihidropiridin-3 ί 1] amino } karbonil)amino] -3 -(4metilfenil)propanojska kislina (3S)-3-({[(l-{4[(dimetilamino)sulfonil]benzil}-4hidroksi-2-okso-l,2-dihidropiridin-3il]amino]karbonil} amino)-3 -(4metilfenil)propanojska kislina (3 S)-3-[({ [4-hidroksi-1 -(mezitilmetil)-2okso-1,2-dihidropiridin-3il]amino } karbonil)amino]-3 -(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2468,13 m/z; ugot.: (M-H)‘ = 467,94 m/z.-187187 Methyl-2-oxo-1,2-dihydropyridin-3 ylamino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-2oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - {[({4-hydroxy) -5-methyl-1- [4 (methylsulfonyl) benzyl] -2-oxo-1,2-dihydropyridin-3yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[ 4-Hydroxy-1- (4-methoxybenzyl) 2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo-5-propyl-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - ({[( 1- {4 [(dimethylamino) sulfonyl] benzyl} -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino] carbonyl} amino) -3- (4methylphenyl) propanoic acid (3 S) -3 - [( {[4-hydroxy-1- (mesylmethyl) -2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1 - ( 2-chlorobenzyl) -4 -hydroxy-2468.13 m / z; found: (M-H) '= 467.94 m / z.

0,003 izrač.: (M+H)+ =0.003 calc .: (M + H) + =

496,16 m/z; ugot.: (M+H)+ = 495,99 m/z.496.16 m / z; found: (M + H) + = 495.99 m / z.

0,02 izrač.: (M-H)' =0.02 Calc .: (M-H) '=

512,15 m/z; ugot.: (M-H)' = 511,96 m/z.512.15 m / z; found: (M-H) '= 511.96 m / z.

0,02 izrač.: (M-H)' =0.02 Calc .: (M-H) '=

450,17 m/z; ugot.: (M-H) = 449,99 m/z.450.17 m / z; found: (M-H) = 449.99 m / z.

0,02 izrač.: (M-H)' =0.02 Calc .: (M-H) '=

496.16 m/z; ugot.: (M-H)’ = 495,94 m/z.496.16 m / z; found: (M-H) '= 495.94 m / z.

0,035 izrač.: (M-H)' =0.035 calcd .: (M-H) '=

527.16 m/z; ugot.: (M-H)’ = 526,96 m/z.527.16 m / z; found: (M-H) '= 526.96 m / z.

0,06 izrač.: (M-H)' =0.06 Calc .: (M-H) '=

462,20 m/z; ugot.: (M-H) = 462,02 m/z.462.20 m / z; found: (M-H) = 462.02 m / z.

0,02 izrač.: (M-H)' =0.02 Calc .: (M-H) '=

-188188 okso-1,2,5,6,7,8-heksahidrokinolin-311] amino } karbonil)amino]-3 -(4metilfenil)propanojska kislina (3S)-3-[({[l -(2-klorobenzil)-5-etil-4hidroksi-6-metil-2-okso-1,2dihidropiridin-3il] amino} karbonil)amino]-3 -(4metilfenil)propanojska kislina (3 S )-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3il]amino}karbonil)(metil)amino]-3-(4metilfenil)propanojska kislina (3S)-3-{[({4-hidroksi-l-[2(metiltio)benzil]-2-okso-1,2dihidropiridin-3il]amino)karbonil]amino}-3-(4-metilfenil) (3S)-3-({[(l-{2[(dimetilamino)sulfonil]benzil} -4hidroksi-2-okso-1,2-dihidropiridin-3il] amino]karbonil} amino)-3 -(4metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2,6-dimetoksibenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3il] amino} karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3 - {[({4-hidroksi-2-okso-1 [2(trifluorometoksi)benzil]-1,2dihidropiridin-3il}amino)karbonil]amino}-3-(4metilfenil)propanojska kislina (3 R)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2508.16 m/z; ugot.: (M-H) = 507,96 m/z.-188188 Oxo-1,2,5,6,7,8-hexahydroquinoline-311] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) ) -5-ethyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1 - ( 2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) (methyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - {[({4-hydroxy- 1- [2 (methylthio) benzyl] -2-oxo-1,2-dihydropyridin-3yl] amino) carbonyl] amino} -3- (4-methylphenyl) (3S) -3 - ({[(1- {2 [( dimethylamino) sulfonyl] benzyl} -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino] carbonyl} amino) -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1 - (2 , 6-dimethoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - {[({4-hydroxy-2 -oxo-1 [2 (trifluoromethoxy) benzyl] -1,2-dihydropyridin-3yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2508.16 m / z found: (MH ) = 507.96 m / z.

0,025 izrač.: (M-H)’=0.025 Calc .: (M-H) '=

496.16 m/z; ugot.: (M-H) = 495,96 m/z.496.16 m / z; found: (M-H) = 495.96 m / z.

0,4 izrač.: (M-H)' =0.4 Calc .: (M-H) '=

468.13 m/z; ugot.: (M-H)' = 467,85 m/z.468.13 m / z; found: (M-H) '= 467.85 m / z.

0,02 izrač.: (M-H)' =0.02 Calc .: (M-H) '=

466.14 m/z; ugot.: (M-H)' = 465,97 m/z.466.14 m / z; found: (M-H) '= 465.97 m / z.

0,03 izrač.: (M-H)' =0.03 Calc .: (M-H) '=

527,16 m/z; ugot.: (M-H)' = 526,97 m/z.527.16 m / z; found: (M-H) '= 526.97 m / z.

0,01 izrač.: (M-H)' =0.01 Calc .: (M-H) '=

480,18 m/z; ugot.: (M-H) = 480,00 m/z.480.18 m / z; found: (M-H) = 480.00 m / z.

0,025 izrač.: (M-H)'=0.025 calcd. (M-H) '=

504,14 m/z; ugot.: (M-H) = 503,96 m/z.504.14 m / z; found: (M-H) = 503.96 m / z.

0,35 izrač.: (M-H)'=0.35 Calcd .: (M-H) '=

-189189 okso-1,2-dihidropiridin-3il]amino } karbonil)amino]-4- [3 (trifluorometil)fenil]butanojska kislina (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2- 0,003 okso-1,2-dihidrop iridin-3il]amino}karbonil)amino]-3'(3propoksifenil)propanoj ska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- 0,003 okso-5-propil-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3etoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi- 0,006-189189 Oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -4- [3 (trifluoromethyl) phenyl] butanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4 -hydroxy-2- 0.003 oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 '(3propoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) - 4-hydroxy-2- 0,003 oxo-5-propyl-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3ethoxyphenyl) propanoic acid (3 S) -3 - [({[1 - (2 -chlorobenzyl) -4-hydroxy- 0.006

5,6-dimetil-2-okso-1,2-dihidrop iridin-3il] amino} karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- 0,005 okso-5-propil-1,2-dihidropiridin-3i 1 ] amino }karbonil)amino] -3 -(3,4dietoksifenil)propanojska kislina (3S)-3-(3-butoksifenil)-3-[({ [ 1 -(2- 0,005 klorobenzil)-4-hidroksi-2-okso-1,2dihidropiridin-3il] amino } karbonil)amino]propanoj ska kislina (3S)-3-{[({l-[2-kloro-5- 0,003 (metilsulfonil)benzil]-4-hidroksi-2-oksol,2-dihidropiridin-3il} amino)karbonil]amino} 3 -(4metilfenil)propanojska kislina (3R)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- 0,08 okso-1,2-dihidropiridin-3522.10 m/z; ugot.: (M-H) = 521,95 m/z.5,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) ) -4-hydroxy-2- 0,005 oxo-5-propyl-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4diethoxyphenyl) propanoic acid (3S) -3- (3-butoxyphenyl) ) -3 - [({[1- (2- 0.005 chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] propanoic acid (3S) -3 - {[({ 1- [2-chloro-5- 0,003 (methylsulfonyl) benzyl] -4-hydroxy-2-oxole, 2-dihydropyridin-3yl} amino) carbonyl] amino} 3- (4methylphenyl) propanoic acid (3R) -3 - [ ({[1- (2-chlorobenzyl) -4-hydroxy-2- 0.08 oxo-1,2-dihydropyridine-3522.10 m / z; found: (MH) = 521.95 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

498.14 m/z; ugot.: (M-H) = 497,97 m/z.498.14 m / z; found: (M-H) = 497.97 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

528.19 m/z; ugot.:528.19 m / z; found:

(M+H)+ = 528,02 m/z. izrač.: (M-H) =(M + H) + = 528.02 m / z. Calcd. (MH) =

482.15 m/z; ugot.: (M-H)' = 481,95 m/z.482.15 m / z; found: (M-H) '= 481.95 m / z.

izrač.: (M-H) =Calcd. (M-H) =

570.20 m/z; ugot.: (M-H)' = 569,98 m/z.570.20 m / z; found: (M-H) '= 569.98 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

514,17 m/z; ugot.:514.17 m / z; found:

(M+H)+ = 514,00 m/z.(M + H) + = 514.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

532.10 m/z; ugot.: (M-H)' = 531,94 m/z.532.10 m / z; found: (M-H) '= 531.94 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

468,13 m/z; ugot.: (M-H)'468.13 m / z; found: (M-H) '

-190190 i 1] amino } karbonil)amino] -4-(2metilfenil)butanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-[3-(2metoksietoksi)fenil]propanojska kislina (3 S)-3-[( {[ 1 -(4-kloro-2-metoksibenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3 il] amino } karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3i 1] amino }karbonil)amino] -3 -(3,4dipropoksifenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2-5,6,7,8,9-heksahidro-lHciklohepta[b]piridin-3il] amino } karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-4,4difenilbutanojska kislina (3 S)-3- {[({1 -[2-difluorometoksi)benzil]-4hidroksi-2-okso-1,2-dihidropiridin-3 il} amino)karbonil] amino } -3 -(4metilfenil)propanojska kislina (3 S)-3 - {[({4-hidroksi-5 -metil-2-okso-1 [(1 R)-1 - feniletil] -1,2-dihidropiridin-3il} amino)karbonil]amino } -3 -(4metilfenil)propanojska kislina = 468,03 m/z.-190190 and 1] amino} carbonyl) amino] -4- (2methylphenyl) butanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine- 3yl] amino} carbonyl) amino] -3- [3- (2methoxyethoxy) phenyl] propanoic acid (3 S) -3 - [({[1- (4-chloro-2-methoxybenzyl) -4-hydroxy-2-oxo- 1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1, 2-Dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4-dipropoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2- 5,6,7,8,9-Hexahydro-1Hcyclohepta [b] pyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2- chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -4,4-diphenylbutanoic acid (3 S) -3 - {[({1- [2-difluoromethoxy) benzyl] - 4hydroxy-2-oxo-1,2-dihydropyridin-3 yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - {[({4-hydroxy-5-methyl-2- oxo-1 [(1 R) -1 - phenylethyl] -1,2-dihydropyridin-3-yl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid = 468.03 m / z.

0,003 izrač.: (M-H) =0.003 calc .: (M-H) =

514,14 m/z; ugot.: (M-H) = 513,95 m/z.514.14 m / z; found: (M-H) = 513.95 m / z.

0,025 izrač.: (M-H) =0.025 Calcd .: (M-H) =

484,13 m/z; ugot.: (M-H) = 483,93 m/z.484.13 m / z; found: (M-H) = 483.93 m / z.

0,003 izrač.: (M-H) =0.003 calc .: (M-H) =

556,18 m/z; ugot.: (M-H) = 555,94 m/z.556.18 m / z; found: (M-H) = 555.94 m / z.

0,12 izrač.: (M-H) =0.12 Calc .: (M-H) =

522; 18 m/z; ugot.: (M-H)' = 521,98 m/z.522 Hours; 18 m / z; found: (M-H) '= 521.98 m / z.

izrač.: (M-H) =Calcd. (M-H) =

530.15 m/z; ugot.: (M-H) = 529,92 m/z.530.15 m / z; found: (M-H) = 529.92 m / z.

0,075 izrač.: (M-H) =0.075 calc .: (M-H) =

486.15 m/z; ugot.: (M-H) = 486,00 m/z.486.15 m / z; found: (M-H) = 486.00 m / z.

izrač.: (M-H) =Calcd. (M-H) =

448,19 m/z; ugot.: (M-H) = 447,99 m/z.448.19 m / z; found: (M-H) = 447.99 m / z.

-191191-191191

(3 S)-3-[( {[ 1 -(4-klorobenzil)-4-hidroksi-2- (3S) -3 - [({[1- (4-chlorobenzyl) -4-hydroxy-2- 0,03 0.03 izrač.: (M-H)' = calcd. (M-H) '= okso-5-propil-1,2-dihidropiridin-3- oxo-5-propyl-1,2-dihydropyridine-3- 496,16 m/z; ugot.: (M-H)' 496.16 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(4- yl] amino} carbonyl) amino] -3- (4- = 495,96 m/z. = 495.96 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,05 0.05 izrač.: (M-H) = Calcd. (M-H) = okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 496,16 m/z; ugot.: (M-H)' 496.16 m / z; found: (M-H) ' i 1] amino} karbonil)amino] -3 -(3,4- and 1] amino} carbonyl) amino] -3- (3,4- = 495,98 m/z. = 495.98 m / z. dietilfenil)propanojska kislina diethylphenyl) propanoic acid (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,05 0.05 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 476,08 m/z; ugot.: (M-H)' 476.08 m / z; found: (M-H) ' il] amino } karbonil)amino] -3 -(3,5 - yl] amino} carbonyl) amino] -3- (3,5 - = 475,93 m/z. = 475.93 m / z. difluorofenil)propanojska kislina difluorophenyl) propanoic acid 3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso- 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 0,02 0.02 izrač.: (M-H)' = calcd. (M-H) '= 1,2-dihidropiridin-3 - 1,2-Dihydropyridine-3 - 490,12 m/z; ugot.: (M-H) 490.12 m / z; found: (M-H) il] amino }karbonil)amino] -3-(2- yl] amino} carbonyl) amino] -3- (2- = 489,97 m/z. = 489.97 m / z. naftil)propanojska kislina naphthyl) propanoic acid 3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso- 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 0,025 0.025 izrač.: (M+H)+ =calcd. (M + H) + = 1,2-dihidropiridin-3 - 1,2-Dihydropyridine-3 - 446,11 m/z; 446.11 m / z; il]amino} karbonil)amino] -3 -(5-metil-2- yl] amino} carbonyl) amino] -3- (5-methyl-2- ugot.: found: furil)propanojska kislina furyl) propanoic acid (M+H)+ = 446,08 m/z.(M + H) + = 446.08 m / z. (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 0,025 0.025 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 584,21 m/z; ugot.: (M-H)' 584.21 m / z; found: (M-H) ' il] amino } karbonil)amino] -3 -(3,4- yl] amino} carbonyl) amino] -3- (3,4- = 583,98 m/z. = 583.98 m / z. dibutoksifenil)propanojska kislina dibutoxyphenyl) propanoic acid (3S)-3-{[({4-hidroksi-l-[2- (3S) -3 - {[({4-hydroxy-1- [2- 0,035 0.035 izrač.: (M+H)+ =calcd. (M + H) + = (metilsulfonil)benzil]-2-okso-1,2- (methylsulfonyl) benzyl] -2-oxo-1,2- 500,15 m/z; 500.15 m / z; dihidropiridin-3- dihydropyridine-3- ugot.: found: il} amino)karbonil] amino } -3 -(4- yl} amino) carbonyl] amino} -3- (4- (M+H)+ = 500,01 m/z.(M + H) + = 500.01 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid 3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso- 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 0,2 0.2 izrač.: (M-H)' = calcd. (M-H) '= 1,2-dihidropiridin-3- 1,2-dihydropyridine-3- 490,12 m/z; ugot.: (M-H)' 490.12 m / z; found: (M-H) '

-192192 il]amino}karbonil)amino]-3-(lnaftil)propanojska kislina (3 S)-3-[({ [ 1 -(4-klorobenzil)-4-hidroksi-2okso-5-propil-1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3 -(3 etoksifenil)propanojska kislina (3 S)-3-[({ [ 1 -(4-klorobenzil)-4-hidroksi-2okso-5-propil-l,2-dihidropiridin-3il] amino} karbonil)amino] -3-(3,4dietoksifenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2,6-dimetilbenzil)-4hidroksi-2-okso-1,2-dihidropiridin-3iljamino} karbonil)amino]-3 -(4metilfenil)propanojska kislina (3S)-3-[3,5-bis(trifluorometil)fenil]-3[({[ 1 -(2-klorobenzil)-4-hidroksi-2-oksol,2-dihidropiridin-3il] amino } karbonil)amino] -propanoj ska kislina (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il] amino} karbonil)amino] -3 - [3 (difluorometoksi)fenil]propanoj ska kislina (3R)-3-[({[l-(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il] amino }karbonil)amino] -4-piridin-2ilbutanojska kislina (3 S)- 3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi- 5 metil-2-okso-1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3-(3,4dietoksifenil)propanoj ska kislina = 489,91 m/z.-192192 yl] amino} carbonyl) amino] -3- (naphthyl) propanoic acid (3S) -3 - [({[1- (4-chlorobenzyl) -4-hydroxy-2oxo-5-propyl-1,2] -dihydropyridine-3I] amino} carbonyl) amino] -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (4-chlorobenzyl) -4-hydroxy-2-oxo-5-propyl- 1,2-Dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,4diethoxyphenyl) propanoic acid (3S) -3 - [({[1- (2,6-dimethylbenzyl) -4hydroxy-2- oxo-1,2-dihydropyridin-3ylamino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3- [3,5-bis (trifluoromethyl) phenyl] -3 [({[1- (2- chlorobenzyl) -4-hydroxy-2-oxol, 2-dihydropyridin-3yl] amino} carbonyl) amino] -propionic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 2-Oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- [3 (difluoromethoxy) phenyl] propanoic acid (3R) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -4-pyridin-2-ylbutanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5] methyl-2-oxo-1,2-dihydropyr idin-3 and 1] amino} carbonyl) amino] -3- (3,4diethoxyphenyl) propanoic acid = 489.91 m / z.

0,03 izrač.: (M-H)' =0.03 Calc .: (M-H) '=

526,17 m/z; ugot.: (M-H)' = 525,95 m/z.526.17 m / z; found: (M-H) '= 525.95 m / z.

0,015 izrač.: (M-H)'=0.015 Calc .: (M-H) '=

570,20 m/z; ugot.: (M-H)' = 569,97 m/z.570.20 m / z; found: (M-H) '= 569.97 m / z.

0,035 izrač.: (M-H)'=0.035 calcd .: (M-H) '=

448,19 m/z; ugot.: (M-H) = 448,02 m/z.448.19 m / z; found: (M-H) = 448.02 m / z.

0,22 izrač.: (M-H)' =0.22 calcd. (M-H) '=

576,08 m/z; ugot.: (M-H)' = 575,91 m/z.576.08 m / z; found: (M-H) '= 575.91 m / z.

0,006 izrač.: (M-H)'=0.006 calc .: (M-H) '=

506,09 m/z; ugot.: (M-H) = 505,93 m/z.506.09 m / z; found: (M-H) = 505.93 m / z.

0,225 izrač.: (M-H)'=0.225 calcd. (M-H) '=

455,11 m/z; ugot.: (M-H)' = 455,09 m/z.455.11 m / z; found: (M-H) '= 455.09 m / z.

0,0006 izrač.: (M-H)'=0.0006 calcd. (M-H) '=

542,17 m/z; ugot.: (M-H)’ = 542,06 m/z.542.17 m / z; found: (M-H) '= 542.06 m / z.

-193193 (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi- 5 - 0,002 metil-2-okso-1,2-dihidropiridin-3il] amino} karbonil)amino] -3-(3etoksifenil)propanojska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5- 0,020 metil-2-okso-l,2-dihidropiridin-3i 1] amino } karbonil) amino] - 3 -(3 -metoksi-4metilfenil)propanojska kislina-193193 (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 - 0.002 methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 - (3ethoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 0,020 methyl-2-oxo-1,2-dihydropyridine-3i] amino} carbonyl) amino] -3- (3-methoxy-4methylphenyl) propanoic acid

3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil- 0,0303 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-0.030

2-okso-1,2-dihidropiridin-3il] amino }karbonil)amino] -3 -(2naftil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4- 0,015 hidroksi-5,6-dimetil-2-okso-1,2dihidropiridin-3il] amino } karbonil)amino]-3 -(3 etoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metilbenzil)-4- 0,025 hidroksi-5,6-dimetil-2-okso-1,2dihidropiridin-3il] amino} karbonil)amino] -3 -(3 -metoksi-4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4- 0,004 hidroksi-5,6-dimetil-2-okso-1,2dihidropiridin-3il] amino } karbonil)amino]-3 -(3,4dietoksifenil)propanojska kislina (3 S)-3-[( {[ 1 -(2-kloro-6-cianobenzil)-4- 0,007 hidroksi-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina izrač.: (M-H)' =2-Oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (2-naphthyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4 - 0.015 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1 - (2 -chloro-6-methylbenzyl) -4-0,025 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-methoxy-4methylphenyl) propanoic acid (3 S ) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- 0.004 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 - (3,4diethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-cyanobenzyl) -4-0,007 hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl ) amino] -3- (4methylphenyl) propanoic acid calcd: (MH) '=

499.15 m/z; ugot.: (M-H)' = 498,07 m/z.499.15 m / z; found: (M-H) '= 498.07 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

500.16 m/z;500.16 m / z;

ugot.:found:

(M+H)+ = 500,02 m/z. izrač.: (M-H)' =(M + H) + = 500.02 m / z. Calcd. (MH) '=

504,13 m/z; ugot.: (M-H)' = 504,04 m/z.504.13 m / z; found: (M-H) '= 504.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

526.17 m/z; ugot.: (M-H)' = 525,95 m/z.526.17 m / z; found: (M-H) '= 525.95 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

526,17 m/z; ugot.: (M-H) = 525,97 m/z.526.17 m / z; found: (M-H) = 525.97 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

570,20 m/z; ugot.: (M-H) = 570,00 m/z.570.20 m / z; found: (M-H) = 570.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

479,11 m/z; ugot.: (M-H) = 478,90 m/z.479.11 m / z; found: (M-H) = 478.90 m / z.

-194194-194194

(3 S)-3 -[({[ 1 -(2-kloro-6-metilbenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- 0,03 0.03 izrač.: (M-H)’ = calcd. (M-H) '= hidroksi-5,6-dimetil-2-okso-1,2- hydroxy-5,6-dimethyl-2-oxo-1,2- 496,16 m/z; ugot.: (M-H)' 496.16 m / z; found: (M-H) ' dihidropiridin-3- dihydropyridine-3- = 495,97 m/z. = 495.97 m / z. il]amino} karbonil)amino]-3 -(4- yl] amino} carbonyl) amino] -3- (4- metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 0,015 0.015 izrač.: (M-H)' = calcd. (M-H) '= 5,6-dimetil-2-okso-l,2-dihidropiridin-3- 5,6-dimethyl-2-oxo-1,2-dihydropyridine-3- 512,16 m/z; ugot.: (M-H)' 512.16 m / z; found: (M-H) ' il]amino} karbonil)amino] -3-(3 -metoksi-4- yl] amino} carbonyl) amino] -3- (3-methoxy-4- = 511,95 m/z. = 511.95 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 0,003 0.003 izrač.: (M-H)' = calcd. (M-H) '= 5,6-dimetil-2-okso-l,2-dihidropiridin-3- 5,6-dimethyl-2-oxo-1,2-dihydropyridine-3- 556,18 m/z; ugot.: (M-H)' 556.18 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(3,4- yl] amino} carbonyl) amino] -3- (3,4- = 555,99 m/z. = 555.99 m / z. dietoksifenil)propanoj ska kislina diethoxyphenyl) propanoic acid Tabela 6 Table 6 Spojina Compound IC5o(nM)IC 5 o (nM) Masni spektralni podatki Mass spectral data (m/z) (m / z) (3R)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 2500 2500 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 504,13 m/z; ugot.: (M-H)’ 504.13 m / z; found: (M-H) ' il]amino}karbonil)amino]-4-( 1 - yl] amino} carbonyl) amino] -4- (1- = 503,97 m/z. = 503.97 m / z. naftil)butanojska kislina naphthyl) butanoic acid (3 S )-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 30 30 izrač.: (M-H)' = calcd. (M-H) '= 5,6-dimetil-2-okso-1,2-dihidropiridin-3- 5,6-dimethyl-2-oxo-1,2-dihydropyridine-3- 512,16 m/z; ugot.: (M-H) 512.16 m / z; found: (M-H) i 1] amino} karbonil)amino] -3-(3- and 1] amino} carbonyl) amino] -3- (3- = 511,99 m/z. = 511.99 m / z. etoksifeniljpropanojska kislina ethoxyphenylpropanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 40 40 izrač.: (M-H)' = calcd. (M-H) '= 5,6-dimetil-2-okso-1,2-dihidropiridin-3- 5,6-dimethyl-2-oxo-1,2-dihydropyridine-3- 496,16 m/z; ugot.: (M-H)' 496.16 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(3,4- yl] amino} carbonyl) amino] -3- (3,4- = 496,05 m/z. = 496.05 m / z. dimetilfeniljpropanojska kislina dimethylphenylpropanoic acid (3 S)-3 - [({[ 1 -(2-kloro-6-metoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4- 5 5 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 498,15 m/z; ugot.: (M-H)‘ 498.15 m / z; found: (M-H) '

-195195 dihidropiridin-311] amino} karbonil)amino } -3 -(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il]amino}karbonil)amino}-3-(3,4dietoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il] amino}karbonil)amino } -3 -(3 -metoksi-4metilfenil)propanojska kislina (3S)-3-[({[l-(2-kloro-6-metoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il]amino} karbonil)amino } -3 -(3 etoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il]amino } karbonil)amino]-3 - [3-(1,1,2,2tetrafluoroetoksi)fenil]propanoj ska kislina (3R)-3-[({[l-(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-4-(2klorofenil]butanojska kislina (3S)-3-{[({4-hidroksi-l-[3(metiltio)benzil]-2-okso-1,2dihidropiridin-3il}amino)karbonil]amino}-3-(4metilfenil)propanojska kislina-195195 Dihydropyridine-311] amino} carbonyl) amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4hydroxy-5-methyl-2 -oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino} -3- (3,4diethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4hydroxy- 5-Methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino} -3- (3-methoxy-4methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-6 -methoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino} -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1 - (2 -chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- [3- (1,1,2,2tetrafluoroethoxy) phenyl] propanoic acid (3R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -4- (2-chlorophenyl] butanoic acid (3S) -3 - {[( {4-hydroxy-1- [3 (methylthio) benzyl] -2-oxo-1,2-dihydropyridin-3yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid

- 497,91 m/z.- 497.91 m / z.

izrač.: (M-H) 572,18 m/z; ugot.: (M-H) = 571,96 m/z.Calcd. (M-H) 572.18 m / z; found: (M-H) = 571.96 m / z.

izrač.: (M-H) =Calcd. (M-H) =

528,15 m/z; ugot.: (M-H) = 527,95 m/z.528.15 m / z; found: (M-H) = 527.95 m / z.

izrač.: (M-H) =Calcd. (M-H) =

528,15 m/z; ugot.: (M-H) = 527,99 m/z.528.15 m / z; found: (M-H) = 527.99 m / z.

izrač.: (M-H) =Calcd. (M-H) =

556,09 m/z; ugot.: (M-H) = 555,97 m/z.556.09 m / z; found: (M-H) = 555.97 m / z.

700 izrač.: (M-H) =700 Calc .: (M-H) =

488,08 m/z; ugot.: (M-H) = 487,96 m/z.488.08 m / z; found: (M-H) = 487.96 m / z.

izrač.: (M-H) =Calcd. (M-H) =

466,14 m/z; ugot.: (M-H) = 466,04 m/z.466.14 m / z; found: (M-H) = 466.04 m / z.

-196196 (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 - 15 metil-2-okso-1,2-dihidropiridin-3il] amino} karbonil)amino]-3 -(3,4dimetilfenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2-kloro-6-metoksibenzil)-4- 3 hidroksi-5-metil-2-okso-l,2dihidropiridin-3il]amino} karbonil)amino]-3 -(3,4dimetilfenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2-klorobenzil)- 5 -ciklopropil- 20-196196 (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5--15 methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 - (3,4dimethylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-3 hydroxy-5-methyl-2-oxo-1,2 dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,4-dimethylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -5-cyclopropyl-20]

4-hidroksi-2-okso-1,2-dihidropiridin-3i 1] amino} karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(4-klorobenzil)-4-hidroksi-2- 5 0 okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3il] amino } karbonil)amino] -3-(4metilfenil)propanojska kislina (3S)-3-[({[l-(3-klorobenzil)-4-hidroksi-5- 20 metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil))propanojska kislina (3 S)-3 - [({[ 1 -(2,6-diklorobenzil)-4- 20 hidroksi-5-metil-2-okso-1,2dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil))propanojska kislina (3 S)-3-[( {[4-hidroksi-5-metil-1 -(4- 150 metilbenzil)-2-okso-1,2-dihidropiridin-3i 1] amino} karbonil)amino]-3 -(4metilfenil)propanojska kislina izrač.: (M-H) =4-hydroxy-2-oxo-1,2-dihydropyridin-3i] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (4-chlorobenzyl) - 4-hydroxy-2- 5 O oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [( {[1- (3-chlorobenzyl) -4-hydroxy-5- 20 methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl)) propanoic acid (3 S) -3 - [({[1- (2,6-dichlorobenzyl) -4-20 hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl)) propanoic (3 S) -3 - [({[4-hydroxy-5-methyl-1- (4- 150 methylbenzyl) -2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3 acid - (4methylphenyl) propanoic acid calc .: (MH) =

482.15 m/z; ugot.: (M-H) = 482,02 m/z.482.15 m / z; found: (M-H) = 482.02 m / z.

izrač.: (M-H) =Calcd. (M-H) =

512.16 m/z; ugot.: (M-H) = 512,03 m/z.512.16 m / z; found: (M-H) = 512.03 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

496.16 m/z; ugot.:496.16 m / z; found:

(M+H)+ = 496,05 m/z. izrač.: (M-H)' =(M + H) + = 496.05 m / z. Calcd. (MH) '=

494,15 m/z; ugot.: (M-H)' = 494,02 m/z.494.15 m / z; found: (M-H) '= 494.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

468,13 m/z; ugot.: (M-H) = 468,02 m/z.468.13 m / z; found: (M-H) = 468.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

502,09 m/z; ugot.: (M-H)' = 501,92 m/z.502.09 m / z; found: (M-H) '= 501.92 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

448,19 m/z; ugot.: (M-Hj = 448,05 m/z.448.19 m / z; found: (M-Hj = 448.05 m / z.

-197197-197197

3-(1 -benzofuran-2-il)-3-[( {[ 1 -(2- 140 klorobenzil)-4-hidroksi-2-okso-1,2dihidropiridin-3il]amino} karbonil)amino]propanoj ska kislina (3 S )-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- 3 okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 iljamino} karbonil)amino]-3 -(3 etoksifenil)propanojska kislina3- (1-Benzofuran-2-yl) -3 - [({[1- (2- 140 chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 3 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 ylamino} carbonyl) amino ] -3- (3 ethoxyphenyl) propanoic acid

3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2-okso- 153 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-15

1,2-dihidropiridin-3 il] amino } karbonil)amino]-3 -(6-metoksi-2naftil)propanojska kislina (3 S)-3 -[({[ 1 -(3,5-dimetoksibenzil)-4- 7 0 hidroksi-5-metil-2-okso-1,2dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2,6-difluorobenzil)-4- 25 hidroksi-5-metil-2-okso-1,2dihidropiridin-3il] amino } karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -((2-klorobenzil)-4-hidroksi-2- 3 okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3il]amino} karbonil)amino] -3 -(3,4dietoksifenil)propanojska kislina (3S)-3-{[({4-hidroksi-l-[3- 25 (metilsulfonil)benzil]-2-okso-1,2izrač.: (M-H)' =1,2-Dihydropyridin-3 yl] amino} carbonyl) amino] -3- (6-methoxy-2naphthyl) propanoic acid (3 S) -3 - [({[1- (3,5-dimethoxybenzyl) -4- 7 0 hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1 - (2,6- difluorobenzyl) -4-25 hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1 - ( (2-chlorobenzyl) -4-hydroxy-2- 3 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (3,4diethoxyphenyl) propanoic acid ( 3S) -3 - {[({4-hydroxy-1- [3- 25 (methylsulfonyl) benzyl] -2-oxo-1,2 calcd. (MH) '=

480,10 m/z; ugot.: (M-H)' = 479,96 m/z.480.10 m / z; found: (M-H) '= 479.96 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

524,16 m/z; ugot.: (M-H)’ = 523,95 m/z.524.16 m / z; found: (M-H) '= 523.95 m / z.

izrač.: (M-H)~ 520,13 m/z; ugot.: (M-H) = 520,00 m/z.Calcd. (M-H) ~ 520.13 m / z; found: (M-H) = 520.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

494,19 m/z; ugot.: (M-H)' = 494,04 m/z.494.19 m / z; found: (M-H) '= 494.04 m / z.

izrač.: (M-H)‘ —Calc .: (M-H) '-

470,15 m/z; ugot.: (M-H)' = 470,03 m/z.470.15 m / z; found: (M-H) '= 470.03 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

570,20 m/z; ugot.:570.20 m / z; found:

(M+H)+ = 570,00 m/z.(M + H) + = 570.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

498,13 m/z; ugot.: (M-H)'498.13 m / z; found: (M-H) '

-198198 dihidropiridin-3il}amino)karbonil]amino}-3-(4metilfenil)propanojska kislina (3 S)-3 -[( {[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il]amino}karbonil)amino]-3-(3,4dietoksifenil)propanoj ska kislina (3 S)-3 -[({[ 1 ~(2-kloro-6-metilbenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3i 1] amino} karbonil)amino] -3 -(3 etoksifenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3iljamino } karbonil)amino] -3 -(3,4dimetilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il] amino }karbonil)amino] -3 -(3-metoksi-4metilfenil)propanojska kislina-198198 Dihydropyridin-3yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-5-methyl-2 -oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,4diethoxyphenyl) propanoic acid (3 S) -3 - [({[1 ~ (2-chloro-6-methylbenzyl) -4hydroxy] -5-Methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6 -methylbenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-ylamino} carbonyl) amino] -3- (3,4-dimethylphenyl) propanoic acid (3 S) -3 - [({[1- (2- chloro-6-methylbenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-methoxy-4methylphenyl) propanoic acid

3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3 -(4,5 -dimetil2- furil)propanojska kislina3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4,5-dimethyl-2-furyl) propanoic acid

3- [({[l-(2-klorobenzil)-4-hidroksi-2-okso1,2-dihidropiridin-3il] amino } karbonil)amino] -3 -(4-metoksi-1 naftil)propanojska kislina = 498,01 m/z.3- [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo 1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methoxy-1 naphthyl) propanoic acid = 498, 01 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

556,19 m/z; ugot.: (M-H) = 556,02 m/z.556.19 m / z; found: (M-H) = 556.02 m / z.

izrač.: (M-H)’=calcd. (M-H) '=

512,16 m/z; ugot.: (M-H)' = 512,02 m/z.512.16 m / z; found: (M-H) '= 512.02 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

496,16 m/z; ugot.: (M-H) = 496,01 m/z.496.16 m / z; found: (M-H) = 496.01 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

512,16 m/z; ugot.: (M-H) = 511,97 m/z.512.16 m / z; found: (M-H) = 511.97 m / z.

115 izrač.: (M-H)'=115 Calc .: (M-H) '=

458,11 m/z; ugot.: (M-H) = 457,99 m/z.458.11 m / z; found: (M-H) = 457.99 m / z.

160 izrač.: (M-H)'=160 calcd. (M-H) '=

520,13 m/z; ugot.: (M-H) = 519,97 m/z.520.13 m / z; found: (M-H) = 519.97 m / z.

-199199-199199

(3R)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- (3R) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 115 115 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 468,13 m/z; ugot.: (M-H)' 468.13 m / z; found: (M-H) ' iljamino} karbonil)aminoj- 5 - islamino} carbonyl) amino- 5 - = 467,98 m/z. = 467.98 m / z. fenilpentanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- phenylpentanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 12 12 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidrokinolin-3- oxo-1,2-dihydroquinoline-3- 534,14 m/z; ugot.: (M-H)' 534.14 m / z; found: (M-H) ' ilj amino} karbonil)amino]-3 -(3 - or amino} carbonyl) amino] -3- (3 - = 533,94 m/z. = 533.94 m / z. etoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 18 18 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro-1H- oxo-2,5,6,7-tetrahydro-1H- 510,18 m/z; ugot.: (M+H)+ 510.18 m / z; found: (M + H) + ciklopenta[bJpiridin-3- cyclopenta [bJpyridine-3- = 510,06 m/z. = 510.06 m / z. ilj amino} karbonil)aminoj-3 -(3,4dimetilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4- or amino} carbonyl) amino-3- (3,4-dimethylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 7 7 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-1,2-dihidropiridin-3 - hydroxy-2-oxo-1,2-dihydropyridine-3 - 500,16 m/z; 500.16 m / z; ilJamino}karbonil)amino]-3-(4- ylamino} carbonyl) amino] -3- (4- ugot.: found: metilfenil)propanojska kislina methylphenyl) propanoic acid (M+H)+ = 500,06 m/z.(M + H) + = 500.06 m / z. (3S)-3-[({[l -(2-kloro-6-etoksibenzil)-4- (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 512,16 m/z; ugot.: (M-H)' 512.16 m / z; found: (M-H) ' dihidropiridin-3- X dihydropyridine-3- X = 512,03 m/z. = 512.03 m / z. \ il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3S)-3-[({[l-(2-klorobenzil)-5-ciklopropil- \ yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -5-cyclopropyl- 14 14 izrač.: (M+H)+ =calcd. (M + H) + = 4-hidroksi-2-okso-l,2-dihidropiridin-3- 4-hydroxy-2-oxo-1,2-dihydropyridine-3- 526,17 m/z; 526.17 m / z; il]amino}karbonil)amino]-3-(3- yl] amino} carbonyl) amino] -3- (3- ugot.: found: etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (M+H)+ = 526,01 m/z.(M + H) + = 526.01 m / z. (3S)-3-[({[l-(2-klorobenzil)-5-ciklopropil- (3S) -3 - [({[1- (2-chlorobenzyl) -5-cyclopropyl- 6 6 izrač.: (M+H)+ =calcd. (M + H) + = 4-hidroksi-2-okso-1,2-dihidropiridin-3- 4-hydroxy-2-oxo-1,2-dihydropyridine-3- 570,20 m/z; 570.20 m / z; il] amino }karbonil)aminoj-3-(3,4- yl] amino} carbonyl) amino-3- (3,4- ugot.: found: dietoksifenil)propanojska kislina diethoxyphenyl) propanoic acid (M+H)+ = 570,04 m/z.(M + H) + = 570.04 m / z. (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 30 30 izrač.: (M-H)' - calcd. (M-H) '-

-200200-200200

okso-1,2-dihidrop iridin-3 - oxo-1,2-dihydrop iridin-3 - 506,09 m/z; ugot.: (M-H)' 506.09 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(4- yl] amino} carbonyl) amino] -3- (4- = 505,96 m/z. = 505.96 m / z. difluorometoksi)fenil]propanoj ska kislina 3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso- difluoromethoxy) phenyl] propanoic acid 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 105 105 izrač.: (M-H)' = calcd. (M-H) '= 1,2-dihidropiridin-3 - 1,2-Dihydropyridine-3 - 491,11 m/z; ugot.: (M-H)' 491.11 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-kinolin-2- yl] amino} carbonyl) amino] -3-quinoline-2- = 490,96 m/z. = 490.96 m / z. ilpropanojska kislina (3S)-3-[({[l-(2-fluoro-6-metoksibenzil)-4- ilpropanoic acid (3S) -3 - [({[1- (2-fluoro-6-methoxybenzyl) -4- 10 10 izrač.: (M-H)‘ = calcd. (M-H) '= hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 482,17 m/z; ugot.: (M-H) 482.17 m / z; found: (M-H) dihidropiridin-3- dihydropyridine-3- = 482,02 m/z. = 482.02 m / z. il]amino}karbonil)amino]-3-(4- metilfenil)propanojska kislina (3S)-3-[({ [ 1 -(2-kloro-6-metoksibenzil)-4- yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4- 15 15 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-5-propil-1,2- hydroxy-2-oxo-5-propyl-1,2- 528,19 m/z; 528.19 m / z; dihidropiridin-3- dihydropyridine-3- ugot.: found: i 1] amino} karbonil)amino] -3-(4- and 1] amino} carbonyl) amino] -3- (4- (M+H)+ = 528,04 m/z.(M + H) + = 528.04 m / z. metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4- methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4- 7 7 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-5-propil-1,2- hydroxy-2-oxo-5-propyl-1,2- 558,20 m/z; 558.20 m / z; dihidropiridin-3- dihydropyridine-3- ugot.: found: il]amino}karbonil)amino]-3-(3- yl] amino} carbonyl) amino] -3- (3- (M+H)+ = 558,07 m/z.(M + H) + = 558.07 m / z. etoksifenil)propanojska kislina (3 S)-3-[({ [ 1 -(5-kloro-2-fluorobenzil)-4- ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (5-chloro-2-fluorobenzyl) -4- 15 15 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 486,12 m/z; ugot: (M-H)' 486.12 m / z; found: (M-H) ' dihidropiridin-3- dihydropyridine-3- = 486,00 m/z. = 486.00 m / z. il] amino} karbonil)amino] -3 -(4- metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2- yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 14 14 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidrokinolin-3 - oxo-1,2-dihydroquinoline-3 - 534,14 m/z; ugot: (M-H)' 534.14 m / z; found: (M-H) ' il] amino} karbonil)amino] -3 -(3 -metoksi-4- yl] amino} carbonyl) amino] -3- (3-methoxy-4- = 533,95 m/z. = 533.95 m / z.

metilfenil)propanojska kislinamethylphenyl) propanoic acid

-201201-201201

(3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 4 4 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidrokinolin-3- oxo-1,2-dihydroquinoline-3- 578,17 m/z; ugot.: (M-H)' 578.17 m / z; found: (M-H) ' i 1] amino} karbonil)amino] -3 -(3,4- and 1] amino} carbonyl) amino] -3- (3,4- = 577,99 m/z. = 577.99 m / z. dietoksifenil)propanoj ska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- diethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 25 25 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidrokinolin-3- oxo-1,2-dihydroquinoline-3- 518,15 m/z; ugot.: (M-H)' 518.15 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(3,4- yl] amino} carbonyl) amino] -3- (3,4- = 517,96 m/z. = 517.96 m / z. dimetilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2- dimethylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 150 150 izrač.: (M+H)+ =calcd. (M + H) + = okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 443,11 m/z; 443.11 m / z; il] amino } karbonil)amino] -3 -pirid-2- yl] amino} carbonyl) amino] -3-pyrid-2- ugot.: found: il)propanojska kislina il) propanoic acid (M+H)+ = 443,03 m/z.(M + H) + = 443.03 m / z. (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 3 3 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 498,14 m/z; ugot.: (M-H) 498.14 m / z; found: (M-H) il]amino}karbonil)amino]-3-(3- yl] amino} carbonyl) amino] -3- (3- = 498,04 m/z. = 498.04 m / z. izopropoksifenil)propanojska kislina isopropoxyphenyl) propanoic acid (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 7 7 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 528,15 m/z; ugot.: (M-H)' 528.15 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(3,5- yl] amino} carbonyl) amino] -3- (3,5- = 528,02 m/z. = 528.02 m / z. dietoksifenil)propanojska kislina (3 S )-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-5- diethoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 60 60 izrač.: (M+H)+ =calcd. (M + H) + = izopropil-2-okso-1,2-dihidropiridin-3- isopropyl-2-oxo-1,2-dihydropyridine-3- 498,18 m/z; 498.18 m / z; il]amino}karbonil)amino]-3-(4- yl] amino} carbonyl) amino] -3- (4- ugot.: found: metilfenil)propanojska kislina methylphenyl) propanoic acid (M+H)+ = 498,05 m/z.(M + H) + = 498.05 m / z. (3 S)-3-[( {[ 1 -(5-fluoro-2-metilbenzil)-4- (3S) -3 - [({[1- (5-fluoro-2-methylbenzyl) -4- 20 20 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 468,19 m/z; 468.19 m / z; dihidropiridin-3 - dihydropyridine-3 - ugot.: found: i 1] amino } karbonil)amino] -3 -(4- and 1] amino} carbonyl) amino] -3- (4- (M+H)+ = 468,07 m/z.(M + H) + = 468.07 m / z. metilfenil)propanojska kislina (3 S)-3 - {[({4-hidroksi-5 -metil-2-okso-1 - methylphenyl) propanoic acid (3S) -3 - {[({4-hydroxy-5-methyl-2-oxo-1 - 1500 1500 izrač.: (M+H)+ =calcd. (M + H) + = ](1 S)-1 -feniletil-1,2-dihidropiridin-3 - ] (1S) -1-Phenylethyl-1,2-dihydropyridine-3 - 450,20 m/z; 450.20 m / z;

-202202 il] amino} karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2-kloro-6-metoksibenzil)-4- 3 hidroksi-2-okso-5-propil-1,2dihidropiridin-3il] amino }karbonil)amino] -3 -(3,4dietoksifenil)propanojska kislina (3S)-3-[({[l-(2-kloro-5- 7 izopropoksibenzil)-4-hidroksi-5-metil-2okso-1,2-dihidropiridin-3il] amino} karbonil)amino]-3 -(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metoksibenzil)-4- 15 hidroksi-2-okso-5-propil-1,2dihidropiridin-3il]amino } karbonil)amino]-3 -(3 -metoksi-4metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4- 2 hidroksi-5-metil-2-okso-l,2dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(5 -acetil-2-metoksibenzil)-4- 3 3 hidroksi-2-okso-1,2-dihidropiridin-3 il] amino} karbonil)amino] -3-(4metilfenil)propanojska kislina 3 -[({[ 1 -(2-kloro-6-metilbenzil)-4-hidroksi- 3 5-202202 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-3 hydroxy-2-oxo- 5-Propyl-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,4diethoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-5-7 isopropoxybenzyl) -4 -hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6 -methoxybenzyl) -4-15 hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-methoxy-4methylphenyl) propanoic acid (3 S) -3 - [( {[1- (2-Chloro-6-ethoxybenzyl) -4-2 hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid ( 3 S) -3 - [({[1- (5-acetyl-2-methoxybenzyl) -4- 3 3 hydroxy-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid 3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy- 3 5

5-metil-2-okso-l,2-dihidropiridin-3i 1] amino} karbonil)amino]-3 -(6-metoksi-2naftil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metoksibenzil)-4- 17 ugot.:5-Methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (6-methoxy-2-naphthyl) propanoic acid (3 S) -3 - [({[1 - (2 -chloro-6-methoxybenzyl) -4-17 found:

(M+H)+ = 450,07 m/z. izrač.: (M+H)+ =(M + H) + = 450.07 m / z. calcd. (M + H) + =

602,23 m/z; ugot.:602.23 m / z; found:

(M+H)+ = 602,04 m/z.(M + H) + = 602.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

526.17 m/z; ugot.: (M-H) = 526,04 m/z.526.17 m / z; found: (M-H) = 526.04 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

558,20 m/z; ugot.:558.20 m / z; found:

(M+H)+ = 558,05 m/z.(M + H) + = 558.05 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

544,19 m/z; ugot.:544.19 m / z; found:

(M+H)+ = 544,04 m/z.(M + H) + = 544.04 m / z.

izrač.: (M-H) =Calcd. (M-H) =

492.18 m/z; ugot.: (M-H) - 492,04 m/z.492.18 m / z; found: (M-H) - 492.04 m / z.

izrač.: (M-H) =Calcd. (M-H) =

548,16 m/z; ugot.: (M-H) = 548,01 m/z.548.16 m / z; found: (M-H) = 548.01 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

-203203-203203

hidroksi-2-okso-5-propil-1,2- hydroxy-2-oxo-5-propyl-1,2- 542,21 m/z; 542.21 m / z; dihidropiridin-3- dihydropyridine-3- ugot.: found: il]amino}karbonil)amino]-3-(3,4- yl] amino} carbonyl) amino] -3- (3,4- (M+H)+ = 542,05 m/z.(M + H) + = 542.05 m / z. dimetilfenil)propanojska kislina dimethylphenyl) propanoic acid (3 S )-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 3 3 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 493,13 m/z; ugot.: (M-H)' 493.13 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-( 1 -metil- 1H- yl] amino} carbonyl) amino] -3- (1-methyl-1H- = 492,95 m/z. = 492.95 m / z. indol-5-il)propanojska kislina indol-5-yl) propanoic acid (3S)-3-[({[2-(2-klorobenzil)-5-hidroksi-6- (3S) -3 - [({[2- (2-chlorobenzyl) -5-hydroxy-6- 18 18 izrač.: (M+H)+ =calcd. (M + H) + = metil-3-okso-2,3-dihidropiridazin-4- methyl-3-oxo-2,3-dihydropyridazine-4- 471,14 m/z; 471.14 m / z; il]amino} karbonil)amino]-3 -(4-metil- yl] amino} carbonyl) amino] -3- (4-methyl- ugot.: found: fenil)propanojska kislina phenyl) propanoic acid (M+H)+ = 471,00 m/z.(M + H) + = 471.00 m / z. (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 5 5 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-l,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 534,14 m/z; ugot.: (M-H) 534.14 m / z; found: (M-H) il]amino} karbonil)amino] -3 -(6-metoksi-2- yl] amino} carbonyl) amino] -3- (6-methoxy-2- = 533,91 m/z. = 533.91 m / z. naftil)propanojska kislina naphthyl) propanoic acid (3S)-3-[({[2-(2-klorobenzil)-5-hidroksi-6- (3S) -3 - [({[2- (2-chlorobenzyl) -5-hydroxy-6- 5 5 izrač.: (M+H)+ =calcd. (M + H) + = metil-3 -okso-2,3 -dihidropiridazin-4- methyl-3-oxo-2,3-dihydropyridazine-4- 501,15 m/z; 501.15 m / z; il]amino} karbonil)amino] -3 -(3 -etoksi- yl] amino} carbonyl) amino] -3- (3-ethoxy- ugot.: found: fenil)propanojska kislina phenyl) propanoic acid (M+H)+ = 501,01 m/z.(M + H) + = 501.01 m / z. 3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso- 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 30 30 izrač.: (M+H)+ =calcd. (M + H) + = 1,2-dihidropiridin-3- 1,2-dihydropyridine-3- 448,07 m/z; 448.07 m / z; i 1] amino} karbonil)amino]-3 -tien-2- and 1] amino} carbonyl) amino] -3-thien-2- ugot.: found: ilpropanojska kislina ilpropanoic acid (M+H)+ = 447,97 m/z.(M + H) + = 447.97 m / z. (3 S)-3-[({[5-kloro-1-(2-klorobenzil)-4- (3 S) -3 - [({[5-chloro-1- (2-chlorobenzyl) -4- 6 6 izrač.: (M-H) = Calcd. (M-H) = hidroksi-2-okso-1,2-dihidropiridin-3- hydroxy-2-oxo-1,2-dihydropyridine-3- 488,08 m/z; ugot.: (M-H) 488.08 m / z; found: (M-H) il] amino }karbonil)amino] -3 -(4-metil- yl] amino} carbonyl) amino] -3- (4-methyl- = 487,97 m/z. = 487.97 m / z. fenil)propanojska kislina phenyl) propanoic acid (3S)-3-(3-butoksifenil)-3-[({[l-(2- (3S) -3- (3-butoxyphenyl) -3 - [({[1- (2- 20 20 izrač.: (M-H) = Calcd. (M-H) = klorobenzil)-4-hidroksi-2-okso-2,5,6,7- chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7- 552,19 m/z; ugot.: (M-H) 552.19 m / z; found: (M-H) tetrahidro-1 H-ciklopenta[b]piridin-3 - tetrahydro-1H-cyclopenta [b] pyridine-3 - ~ 552,01 m/z. ~ 552.01 m / z.

-204204-204204

il] amino} karbonil)amino] -propanoj ska yl] amino} carbonyl) amino] -propanoic acid kislina acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 5 5 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3 - oxo-1,2-dihydropyridine-3 - 524,16 m/z; ugot.: (M-H)' 524.16 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-[3- yl] amino} carbonyl) amino] -3- [3- = 524,00 m/z. = 524.00 m / z. (ciklopentiloksi)fenil]propanojska kislina (cyclopentyloxy) phenyl] propanoic acid (3 S)-3 - [({[2-(2-klorobenzil)-5-hidroksi-6- (3S) -3 - [({[2- (2-chlorobenzyl) -5-hydroxy-6- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = metil-3-okso-2,3-dihidropiridazin-4- methyl-3-oxo-2,3-dihydropyridazine-4- 545,18 m/z; ugot.: (M+H) 545.18 m / z; found: (M + H) il]amino}karbonil)amino]-3-[3,4- yl] amino} carbonyl) amino] -3- [3,4- = 544,98 m/z. = 544.98 m / z. dietoksifenil]propanoj ska kislina diethoxyphenyl] propanoic acid (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 3 3 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-l,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 507,14 m/z; ugot.: (M-H)' 507.14 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-( 1 -metil- 1H- yl] amino} carbonyl) amino] -3- (1-methyl-1H- = 506,94 m/z. = 506.94 m / z. indol-5-il)propanojska kislina indol-5-yl) propanoic acid (3 S)-3 - [({[2-(2-klorobenzil)-5 -hidroksi-6- (3 S) -3 - [({[2- (2-chlorobenzyl) -5-hydroxy-6- 10 10 izrač.: (M+H)+ =calcd. (M + H) + = metil-3-okso-2,3-dihidropiridazin-4- methyl-3-oxo-2,3-dihydropyridazine-4- 545J 8 m/z; 545J 8 m / z; il [amino } karbonil)amino] -3-(3,5- yl [amino} carbonyl) amino] -3- (3,5- ugot.: found: dietoksifenil)propanojska kislina diethoxyphenyl) propanoic acid (M+H)+ = 545,01 m/z.(M + H) + = 545.01 m / z. (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi- 5 - (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 5 - 70 70 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-1,2-dihidropiridin-3 - methyl-2-oxo-1,2-dihydropyridine-3 - 538,10 m/z; ugot.: (M-H)' 538.10 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-[4- yl] amino} carbonyl) amino] -3- [4- = 537,95 m/z. = 537.95 m / z. (trifluorometoksi)fenil]propanojska kislina (trifluoromethoxy) phenyl] propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 - (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 - 10 10 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 538,10 m/z; ugot.: (M-H)' 538.10 m / z; found: (M-H) ' il] amino} karbonil)amino]-3 -[3 - yl] amino} carbonyl) amino] -3- [3 - = 537,95 m/z. = 537.95 m / z. (trifluorometoksi)fenil]propanoj ska kislina (trifluoromethoxy) phenyl] propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 - (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 - 4 4 izrač.: (M+H)+ =calcd. (M + H) + = metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 486,14 m/z; 486.14 m / z; il] amino} karbonil)amino] -3 -(4- yl] amino} carbonyl) amino] -3- (4- ugot.: found: metoksifenil)propanojska kislina methoxyphenyl) propanoic acid (M+H)+ = 486,04 m/z.(M + H) + = 486.04 m / z. (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 15 15 izrač.: (M-H) = Calcd. (M-H) =

-205205 okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(6-metoksi-2naftil)propanojska kislina (3S)-3-{[({l-(2-fluoro-6- 100 (trifluorometil)benzil]-4-hidroksi-5-metil2-okso-1,2-dihidropiridin-3 il}amino)karbonil] amino}-3-(4metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-5- 10 metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-[3(trifluorometil)fenil]propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5- 3 metil-2-okso-1,2-dihidropiridin-3il]amino } karbonil)amino] -3-(3 metoksifenil)propanojska kislina (3S)-3-[({[l-(2-kloro-6-metilbenzil)- 4- 20 hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -(4il]amino}karbonil)amino]-3metilfenil)propanojska kislina (3 S)-3-[({ [ 1 -(2-kloro-6-metilbenzil)-4- 4 hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il] amino} karbonil)amino] -3 -(3 etoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- 3 okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il] amino } karbonil)amino] -3 -(3 izopropoksifenil)propanoj ska kislina-205205 Oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (6-methoxy-2naphthyl) propanoic acid (3S) -3 - {[({1- (2-fluoro-6- 100 (trifluoromethyl) benzyl] -4-hydroxy-5-methyl2-oxo-1,2-dihydropyridin-3 yl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[ 1- (2-chlorobenzyl) -4-hydroxy-5- 10 methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- [3 (trifluoromethyl) phenyl] propanoic acid (3 S ) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 3 methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3 methoxyphenyl) (3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- 20 hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 propanoic acid - (4yl] amino} carbonyl) amino] -3methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-4 hydroxy-2-oxo-2,5 , 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) - 4-hydroxy-2- 3 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (3 isopropoxyphenyl) propanoic acid

520,13 m/z; ugot.: (M-H) = 520,03 m/z.520.13 m / z; found: (M-H) = 520.03 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

520,15 m/z; ugot.: (M-H) - 519,97 m/z.520.15 m / z; found: (M-H) - 519.97 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

522,10 m/z; ugot.: (M-H) = 521,96 m/z.522.10 m / z; found: (M-H) = 521.96 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

484,13 m/z; ugot.: (M-H) = 484,00 m/z.484.13 m / z; found: (M-H) = 484.00 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

510.18 m/z; ugot.:510.18 m / z; found:

(M+H)+ = 510,05 m/z.(M + H) + = 510.05 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

540.19 m/z; ugot.:540.19 m / z; found:

(M+H)+ = 540,10 m/z.(M + H) + = 540.10 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

540,19 m/z; ugot.:540.19 m / z; found:

(M+H)+ = 540,09 m/z.(M + H) + = 540.09 m / z.

-206206-206206

(3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 3 3 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-1,2-dihidropiridin-3 - methyl-2-oxo-1,2-dihydropyridine-3 - 542,17 m/z; ugot.: (M-H)' 542.17 m / z; found: (M-H) ' il] amino} karbonil)amino] -3 -(3,5 - yl] amino} carbonyl) amino] -3- (3,5 - = 542,00 m/z. = 542.00 m / z. dietoksifenil)propanoj ska kislina diethoxyphenyl) propanoic acid (3S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-5- (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5- 4 4 izrač.: (M-H) = Calcd. (M-H) = etil-4-hidroksi-2-okso-1,2-dihidropiridin- ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine- 556,19 m/z; ugot.: (M-H)' 556.19 m / z; found: (M-H) ' 3 -il] amino } karbonil)amino] -3 -(3 - 3-yl] amino} carbonyl) amino] -3- (3- = 556,01 m/z. = 556.01 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-1,2-dihidropiridin-3- hydroxy-2-oxo-1,2-dihydropyridine-3- 530,17 m/z; 530.17 m / z; il] amino } karbonil)amino] -3-(3- yl] amino} carbonyl) amino] -3- (3- ugot.: found: etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (M+H)+ = 530,04 m/z.(M + H) + = 530.04 m / z. (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 15 15 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 538,17 m/z; ugot.: (M-H)' 538.17 m / z; found: (M-H) ' il] amino } karbonil)amino] - 3 - [3 - yl] amino} carbonyl) amino] -3- [3 - = 538,03 m/z. = 538.03 m / z. (ciklopentiloksi)fenil]propanoj ska kislina (cyclopentyloxy) phenyl] propanoic acid 3 -(1,1 ’ -bifenil-4-il)-3 -[({[ 1 -(2- 3 - (1,1 '-biphenyl-4-yl) -3 - [({[1 - (2- 130 130 izrač.: (M-H)' = calcd. (M-H) '= klorobenzil)-4-hidroksi-5-metil-2-okso- chlorobenzyl) -4-hydroxy-5-methyl-2-oxo- 530,15 m/z; ugot.: (M-H)' 530.15 m / z; found: (M-H) ' 1,2-dihidropiridin-3- 1,2-dihydropyridine-3- = 529,96 m/z. = 529.96 m / z. il] amino} karbonil)amino]propanoj ska yl] amino} carbonyl) amino] propane kislina acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 30 30 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro-1H- oxo-2,5,6,7-tetrahydro-1H- 580,15 m/z; 580.15 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il]amino} karbonil)amino]-3 - [3 -(2,2,2- yl] amino} carbonyl) amino] -3- [3- (2,2,2- (M+H)+ = 580,02 m/z.(M + H) + = 580.02 m / z. trifluoroetoksi)fenil)propanoj ska kislina trifluoroethoxy) phenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 - (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 - 15 15 izrač.: (M+H)+ =calcd. (M + H) + = metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 554,13 m/z; 554.13 m / z; il]amino}karbonil)amino]-3-[3-(2,2,2- yl] amino} carbonyl) amino] -3- [3- (2,2,2- ugot.: found: trifluoroetoksi)fenil)propanojska kislina trifluoroethoxy) phenyl) propanoic acid (M+H)+ = 554,00 m/z.(M + H) + = 554.00 m / z. (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 - (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 - 3 3 izrač.: (M+H)+ =calcd. (M + H) + =

-207207 metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3izopropoksifenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il] amino} karbonil)amino] -3-(3izopropoksifenil)propanoj ska kislina-207207 Methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3isopropoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6 -ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3isopropoxyphenyl) propanoic acid

Tabela 7Table 7

Spojina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5metil-2-okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metoksi-3metilfenil)propanojska kislina (3 S)-3 -[( {[ 1 -(2-kloro-6metilbenzil)-4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 iljamino }karbonil)amino] -3 -(3 izopropoksifenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3i 1] amino } karbonil)amino]-3 -(6-metoksi-2naftil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5 metil-2-okso-l,2-dihidropiridin-3il]amino }karbonil)amino] -3-(3,5dimetoksi-4-metilfenilpropanojska kislinaCompound (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methoxy (3-methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6methylbenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 ylamino } carbonyl) amino] -3- (3 isopropoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1, 2-Dihydropyridin-3-yl] amino} carbonyl) amino] -3- (6-methoxy-2-naphthyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5 methyl-2 -oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3,5-dimethoxy-4-methylphenylpropanoic acid

514,17 m/z; ugot.:514.17 m / z; found:

(M+H)+= 514,05 m/z. 4 izrač.: (M+H)+ =(M + H) + = 514.05 m / z. 4 calc .: (M + H) + =

558,20 m/z; ugot.:558.20 m / z; found:

(M+H)+ = 558,05 m/z.(M + H) + = 558.05 m / z.

IC50 (nM) Masni spektralni podatki (m/z) izrač.: (M+H)+=IC 50 (nM) Mass spectral data (m / z) calcd: (M + H) + =

500.16 m/z; ugot.:500.16 m / z; found:

(M+H)+ = 500,01 m/z.(M + H) + = 500.01 m / z.

izrač.: (M+H)+=calcd. (M + H) + =

554,21 m/z; ugot.:554.21 m / z; found:

(M+H)+ = 554,06 m/z.(M + H) + = 554.06 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

580,19 m/z; ugot.:580.19 m / z; found:

(M+H)+ = 580,07 m/z.(M + H) + = 580.07 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

530.17 m/z; ugot.:530.17 m / z; found:

(M+H)+ = 530,00 m/z.(M + H) + = 530.00 m / z.

-208208 (3 S)-3-[({[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il] amino } karbonil)amino] -3 -(3 propoksifenil)propanojska kislina (3 S)-3 - [({ [ 1 -(2-kloro-6-propoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3 il] amino } karbonil)amino] -3-(4metilfenil)propanojska kislina (3 S)-3-[({[ 1 -(2-kloro-6-izobutoksibenzil)4-hidroksi-5-metil-2-okso-l,2dihidropiridin-3il]amino }karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il] amino } karbonil)amino] -3 -(3 propoksifenil)propanoj ska kislina (3 S)-3-[({[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il] amino } karbonil)amino]-3 -(4metilfenil)propanojska kislina (3 S)-3-[({[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il ] amino} karbonil)amino] -3 -(3 izopropoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-5 12 izrač.: (M+H)+ = 554,21; ugot.:-208208 (3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (3-propoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-6-propoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1, 2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-isobutoxybenzyl) 4-hydroxy-5-methyl-2 -oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo-2, 5,6,7-Tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (3 propoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro- 6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3 - (3 isopropoxyphenyl) propanoic acid (3 S) -3 - [({[ 1- (2-chlorobenzyl) -4-hydroxy-5 12 calcd: (M + H) + = 554.21; found:

(M+H)+ = 554,05.(M + H) + = 554.05.

izrač.: (M+H)+= 528,19; ugot.:Calcd. (M + H) + = 528.19; found:

(M+H)+ = 528,06 m/z.(M + H) + = 528.06 m / z.

izrač.: (M+H)+ = 540,19 m/z; ugot.:Calcd .: (M + H) + = 540.19 m / z; found:

(M+H)+ = 540,07 m/z.(M + H) + = 540.07 m / z.

izrač.: (M+H)+= 540,19 m/z; ugot.:Calcd .: (M + H) + = 540.19 m / z; found:

(M+H)+ = 540,04 m/z.(M + H) + = 540.04 m / z.

izrač.: (M+H)+= 584,22 m/z; ugot.:Calcd. (M + H) + = 584.22 m / z; found:

(M+H)+ = 584,05 m/z.(M + H) + = 584.05 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

-209209-209209

metil-2-okso-l,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 592,19 m/z; 592.19 m / z; il ] amino} karboni l)amino] -3 -(2 ’ ,6 ’ - yl] amino} carbonyl) amino] -3 - (2 ', 6' - ugot.: found: dimetoksi-1,1 ’-bifenil-4-il)propanojska dimethoxy-1,1'-biphenyl-4-yl) propanoic (M+H)+ = 592,04 m/z.(M + H) + = 592.04 m / z. kislina acid (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 30 30 izrač.: (M+H)+ =calcd. (M + H) + = metil-2-okso-1,2-dihidropiridin-3-il] methyl-2-oxo-1,2-dihydropyridin-3-yl] 509,16 m/z; 509.16 m / z; amino } karbonil)amino]-3 -(1 -metil-1H- amino} carbonyl) amino] -3- (1-methyl-1H- ugot.: found: indol-7-il)propanojska kislina indol-7-yl) propanoic acid (M+H)+ = 509,03 m/z.(M + H) + = 509.03 m / z. (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 570,20 m/z; 570.20 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino } karbonil)amino] -3-(3- yl] amino} carbonyl) amino] -3- (3- (M+H)+ = 570,09 m/z.(M + H) + = 570.09 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-kloro-6-propoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-propoxybenzyl) -4- 5 5 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 558,20 m/z; 558.20 m / z; dihidropiridin-3-il] dihydropyridin-3-yl] ugot.: found: amino } karbonil)amino] -3-(3- amino} carbonyl) amino] -3- (3- (M+H)+ = 558,03 m/z.(M + H) + = 558.03 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3-[({ [ 1 -(2-kloro-6-izobutoksibenzil)- (3 S) -3 - [({[1- (2-chloro-6-isobutoxybenzyl) - 14 14 izrač.: (M+H)+ =calcd. (M + H) + = 4-hidroksi-5-metil-2-okso-1,2- 4-hydroxy-5-methyl-2-oxo-1,2- 572,22 m/z; 572.22 m / z; dihidropiridin-3-il] dihydropyridin-3-yl] ugot.: found: amino} karbonil)amino]-3 -(3 - amino} carbonyl) amino] -3- (3 - (M+H)+ = 572,05 m/z.(M + H) + = 572.05 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3S)-3-[({[l-(2-kloro-6- (3S) -3 - [({[1- (2-chloro-6-) 7 7 izrač.: (M+H)+ =calcd. (M + H) + = izopropoksibenzil)-4-hidroksi-5-metil-2- isopropoxybenzyl) -4-hydroxy-5-methyl-2- 558,20 m/z; 558.20 m / z; okso-1,2-dihidropiridin-3 -il] oxo-1,2-dihydropyridin-3-yl] ugot.: found: amino} karbonil)amino] -3 -(3 - amino} carbonyl) amino] -3- (3 - (M+H)+ = 558,03 m/z.(M + H) + = 558.03 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3S)-3-{[({l-[2-kloro-6-(2,2,2- (3S) -3 - {[({1- [2-chloro-6- (2,2,2- 4 4 izrač.: (M+H)+ =calcd. (M + H) + = trifluoroetoksi)benzil-4-hidroksi-5-metil- trifluoroethoxy) benzyl-4-hydroxy-5-methyl- 598,16 m/z; 598.16 m / z; 2-okso-1,2-dihidropiridin-3- 2-oxo-1,2-dihydropyridine-3- ugot.: found:

-210210-210210

il} amino)karbonil]amino}-3-(3- yl} amino) carbonyl] amino} -3- (3- (M+H)+ = 597,99 m/z.(M + H) + = 597.99 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid 3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-5-metil- 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl- 15 15 izrač.: (M+H)+ =calcd. (M + H) + = 2-okso-1,2-dihidropiridin-3- 2-oxo-1,2-dihydropyridine-3- 502,12 m/z; 502.12 m / z; il]amino}karbonil)amino]-3-[4- yl] amino} carbonyl) amino] -3- [4- ugot.: found: (metiltio)feniljpropanoj ska kislina (methylthio) phenylpropanoic acid (M+H)+ = 501,98 m/z.(M + H) + = 501.98 m / z. (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 606,20 m/z; 606.20 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il]amino} karbonil)amino]-3 -(6-metoksi-2- yl] amino} carbonyl) amino] -3- (6-methoxy-2- (M+H)+ = 606,04 m/z.(M + H) + = 606.04 m / z. naftil)propanojska kislina naphthyl) propanoic acid (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 6 6 izrač.: (M+H)+ =calcd. (M + H) + = metil-2-okso-1,2-dihidropiridin-3-il] methyl-2-oxo-1,2-dihydropyridin-3-yl] 498,14 m/z; 498.14 m / z; amino} karbonil)amino] -3 -(2,3 -dihidro-1 - amino} carbonyl) amino] -3- (2,3-dihydro-1 - ugot.: found: benzofuran-5-il)propanojska kislina benzofuran-5-yl) propanoic acid (M+H)+ = 498,02 m/z.(M + H) + = 498.02 m / z. (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4- (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 553,19 m/z; 553.19 m / z; dihidropiridin-3 -il] dihydropyridin-3-yl] ugot.: found: amino}karbonil)amino]-3-(l-metil-lH- amino} carbonyl) amino] -3- (1-methyl-1H- (M+H)+ = 553,05 m/z.(M + H) + = 553.05 m / z. indol-5-il)propanojska kislina indol-5-yl) propanoic acid (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-5-metil-2-okso-l ,2- hydroxy-5-methyl-2-oxo-1,2 542,17 m/z; 542.17 m / z; dihidropiridin-3-il] dihydropyridin-3-yl] ugot.: found: amino} karbonil)amino] -3 -(2,3 -dihidro-1 - amino} carbonyl) amino] -3- (2,3-dihydro-1 - (M+H)+ = 542,06 m/z.(M + H) + = 542.06 m / z. benzofuran-5-il)propanojska kislina benzofuran-5-yl) propanoic acid (3 S)-3- [( {[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3- [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 614,22 m/z; 614.22 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il]amino}karbonil)amino]-3-(3,5- yl] amino} carbonyl) amino] -3- (3,5- (M+H)+ = 614,11 m/z.(M + H) + = 614.11 m / z. dietoksifenil)propanojska kislina diethoxyphenyl) propanoic acid (3S)-3-[({[l-(2-kloro-6- (3S) -3 - [({[1- (2-chloro-6-) 4 4 izrač.: (M+H)+ =calcd. (M + H) + =

-211211-211211

izopropoksibenzil)-4-hidroksi-5-metil-2- isopropoxybenzyl) -4-hydroxy-5-methyl-2- 558,20 m/z; 558.20 m / z; okso-1,2-dihidropiridin-3-il] oxo-1,2-dihydropyridin-3-yl] ugot.: found: amino} karbonil)amino]-3 -(3 - amino} carbonyl) amino] -3- (3 - (M+H)+ = 558,02 m/z.(M + H) + = 558.02 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-5-metil-2-okso-1,2- hydroxy-5-methyl-2-oxo-1,2- 558,20 m/z; 558.20 m / z; dihidropiridin-3-il] dihydropyridin-3-yl] ugot.: found: amino}karbonil)amino]-3-(3- amino} carbonyl) amino] -3- (3- (M+H)+ = 558,07 m/z.(M + H) + = 558.07 m / z. propoksifenil)propanojska kislina propoxyphenyl) propanoic acid (3 S)-3-(3 -butoksifenil-3 - [({[ 1 -(2-kloro-6- (3 S) -3- (3-Butoxyphenyl-3 - [({[1- (2-chloro-6-)) 4 4 izrač.: (M+H)+ =calcd. (M + H) + = etoksibenzil)-4-hidroksi-5-metil-2-okso- ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo- 572,22 m/z; 572.22 m / z; 1,2-dihidropiridin-3 -il] 1,2-dihydropyridin-3-yl] ugot.: found: amino} karbonil)amino]propanoj ska amino} carbonyl) amino] propane (M+H)+ = 572,04 m/z.(M + H) + = 572.04 m / z. kislina acid (3S)-3-[({[5-kloro-l-(2-kloro-6- (3S) -3 - [({[5-chloro-1- (2-chloro-6-) 3 3 izrač.: (M+H)+ =calcd. (M + H) + = etoksibenzil)-4-hidroksi-2-okso-1,2- ethoxybenzyl) -4-hydroxy-2-oxo-1,2- 564,13 m/z; 564.13 m / z; dihidropiridin-3 -il] dihydropyridin-3-yl] ugot.: found: amino } karbonil)amino] -3 -(3 - amino} carbonyl) amino] -3- (3 - (M+H)+ = 563,99 m/z.(M + H) + = 563.99 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3-[( {[ l-(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-1,2-dihidropiridin-3 - hydroxy-2-oxo-1,2-dihydropyridine-3 - 544,19 m/z; 544.19 m / z; il]amino}karbonil)amino]-3-(3- yl] amino} carbonyl) amino] -3- (3- ugot.: found: izopropoksifenil)propanoj ska kislina isopropoxyphenyl) propanoic acid (M+H)+ = 544,06 m/z.(M + H) + = 544.06 m / z. (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro- 1H- oxo-2,5,6,7-tetrahydro-1H- 524,16 m/z; 524.16 m / z; ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- ugot.: found: il] amino } karbonil)amino] -3 -(2,3 -dihidro- yl] amino} carbonyl) amino] -3- (2,3-dihydro- (M+H)+ = 524,03 m/z.(M + H) + = 524.03 m / z. l-benzofuran-5-il)propanojska kislina 1-Benzofuran-5-yl) propanoic acid (3 S)-3 - [({ [2-(2-kloro-6-etoksibenzil)-5 - (3S) -3 - [({[2- (2-chloro-6-ethoxybenzyl) -5 - 7 7 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-6-metil-3-okso-2,3- hydroxy-6-methyl-3-oxo-2,3- 515,19 m/z; 515.19 m / z; dihidropiridazin-4- dihydropyridazine-4- ugot.: found:

-212212-212212

il] amino} karbonil)amino] -3 -(4- yl] amino} carbonyl) amino] -3- (4- (M+H)+ = 515,05 m/z.(M + H) + = 515.05 m / z. metilfenil)propanojska kislina methylphenyl) propanoic acid (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4- (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 584,21 m/z; 584.21 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino} karbonil)amino] -3 -(3 - yl] amino} carbonyl) amino] -3- (3 - (M+H)+ = 584,10 m/z.(M + H) + = 584.10 m / z. propoksifenil)propanoj ska kislina propoxyphenyl) propanoic acid (3 S)-3-[( {[2-(2-kloro-6-etoksibenzil)-5- (3 S) -3 - [({[2- (2-chloro-6-ethoxybenzyl) -5- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-6-metil-3 -okso-2,3 - hydroxy-6-methyl-3-oxo-2,3 - 545,18 m/z; 545.18 m / z; dihidropiridazin-4- dihydropyridazine-4- ugot.: found: i 1] amino } karbonil)amino] -3 -(3 - and 1] amino} carbonyl) amino] -3- (3 - (M+H)+ = 545,05 m/z.(M + H) + = 545.05 m / z. etoksifenil)propanojska kislina ethoxyphenyl) propanoic acid (3 S)-3 - [({[2-(2-kloro-6-etoksibenzil)-5- (3 S) -3 - [({[2- (2-chloro-6-ethoxybenzyl) -5- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-6-metil-3 -okso-2,3 - hydroxy-6-methyl-3-oxo-2,3 - 559,20 m/z; 559.20 m / z; dihidropiridazin-4- dihydropyridazine-4- ugot.: found: il] amino} karbonil)amino] -3-(3- yl] amino} carbonyl) amino] -3- (3- (M+H)+ = 559,04 m/z.(M + H) + = 559.04 m / z. izopropoksifenil)propanoj ska kislina isopropoxyphenyl) propanoic acid (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 6 6 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 610,23 m/z; 610.23 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino} karbonil)amino]-3 -(3 - yl] amino} carbonyl) amino] -3- (3 - (M+H)+ = 610,14 m/z.(M + H) + = 610.14 m / z. ciklopentiloksi)fenil]propanoj ska kislina cyclopentyloxy) phenyl] propanoic acid (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 7 7 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro-lH- oxo-2,5,6,7-tetrahydro-1H- 566,21 m/z; 566.21 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino} karbonil)amino] -3 - [3 - yl] amino} carbonyl) amino] -3- [3 - (M+H)+ = 566,09 m/z.(M + H) + = 566.09 m / z. (ciklopentiloksi)fenil]propanojska kislina (cyclopentyloxy) phenyl] propanoic acid (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 526,17 m/z; 526.17 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino } karbonil)amino] -3 - yl] amino} carbonyl) amino] -3 - (M+H)+ = 526,07 m/z.(M + H) + = 526.07 m / z.

-213213 fenilpropanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3i 1] amino } karbonil)amino] -3 fenilpropanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3iljamino} karbonil)amino]-3 -(2,3-dihidro1 -benzofuran-5-il)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il]amino}karbonil)amino]-3-(l,3-dietil-2okso-2,3 -dihidro-1 H-benzimidazol-5 -il) propanoj ska kislina (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3il]amino}karbonil)amino]-3[(trifluorometil)fenil]propanojska kislina (3 S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-5-metil-2-okso-l ,2dihidropiridin-3i 1] amino } karbonil)amino] -3 - [3 (trifluorometoksi)fenil]propanojska kislina (3S)-3-{[({l-(2-kloro-6-(2metoksietoksi)benzil-4-hidroksi-2-okso2,5,6,7-tetrahidro-lH-ciklopenta[b]piridin3-il}amino)karbonil]amino}-3-(4izrač.: (M+H)+ =-213213 Phenylpropanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3i 1] amino} carbonyl) amino] -3-phenylpropanoic acid (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-ylamino} carbonyl) amino ] -3- (2,3-dihydro-1-benzofuran-5-yl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6, 7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (1,3-diethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) propanoic acid ( 3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3 [(trifluoromethyl) phenyl] propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- [3 (trifluoromethoxy) phenyl] propanoic acid (3S) -3 - {[({1- (2-chloro-6- (2methoxyethoxy) benzyl-4-hydroxy-2-oxo2,5,6,7- tetrahydro-1H-cyclopenta [b] pyridin3-yl} amino) carbonyl] am foreign} -3- (4 Calc: (M + H) + =

482.15 m/z; ugot.:482.15 m / z; found:

(M+H)+ = 482,07 m/z.(M + H) + = 482.07 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

512.16 m/z; ugot.:512.16 m / z; found:

(M+H)+ = 512,03 m/z.(M + H) + = 512.03 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

594,21 m/z; ugot.:594.21 m / z; found:

(M+H)+ = 594,05 m/z.(M + H) + = 594.05 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

568,15 m/z; ugot.:568.15 m / z; found:

(M+H)+ = 568,00 m/z.(M + H) + = 568.00 m / z.

izrač.: (M+H)+ 584,14 m/z; ugot.:Calcd. (M + H) + 584.14 m / z; found:

(M+H)+ = 584,01 m/z.(M + H) + = 584.01 m / z.

izrač.: (M-H)' 568,18 m/z; ugot.: (M-H) = 568,03 m/z.Calcd. (M-H) '568.18 m / z; found: (M-H) = 568.03 m / z.

-214214 metilfenil)propanojska kislina (3S)-3-{[({l-(2-kloro-6-(2- 4 metoksietoksi)benzil-4-hidroksi-2-okso2,5,6,7-tetrahidro-lH-ciklopenta[b]piridin3 -il} amino)karbonil] amino} -3 -(3 etoksifenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- 4 okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il}amino)karbonil]amino}-3-[3(ciklopropiloksi)fenil])propanojska kislina (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4- 4 hidroksi-5,6-dimetil-2-okso-1,2dihidropiridin- 3 -il] amino} karbonil) amino]-3-(3-etoksifenil)propanojska kislina (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4- 4 hidroksi-5,6-dimetil-2-okso-1,2dihidropiridin-3-il]amino}karbonil) amino]-3-(4-metilfenil)propanojska kislina (3S)-3-[({[l -(2-kloro-6-etoksibenzil)- 5 - 4 etil-4-hidroksi-6-metil-2-okso-1,2dihidropiridin-3il] amino} karbonil)amino]-3-(3 etoksifenil)propanojska kislina (3 S)-3 -[( {[ 1 -(2-kloro-6-etoksibenzil)- 5- 4 etil-4-hidroksi-6-metil-2-okso-1,2dihidropiridin-3il]amino}karbonil)amino]-3-(4metilfenil)propanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi- 5- 25 izrač.: (M-H)' =-214214 Methylphenyl) propanoic acid (3S) -3 - {[({1- (2-chloro-6- (2- 4 methoxyethoxy) benzyl-4-hydroxy-2-oxo2,5,6,7-tetrahydro-1H) -cyclopenta [b] pyridin3-yl} amino) carbonyl] amino} -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 4 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- [3 (cyclopropyloxy) phenyl]) propanoic acid (3 S) -3 - [({[ 1- (2-chloro-6-ethoxybenzyl) -4-4 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic (3 S) -3 - [({[1- (2-Chloro-6-ethoxybenzyl) -4-4 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl acid ) amino] -3- (4-methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5-4 ethyl-4-hydroxy-6-methyl-2- oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3 ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) - 5- 4 ethyl -4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4 methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-5 calc. (M-H) '=

598.19 m/z; ugot.: (M-H) = 598,01 m/z.598.19 m / z; found: (M-H) = 598.01 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

538,17 m/z; ugot.:538.17 m / z; found:

(M+H)+ = 538,09 m/z.(M + H) + = 538.09 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

556.19 m/z; ugot.: (M-H) = 556,02 m/z.556.19 m / z; found: (M-H) = 556.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

526,17 m/z; ugot.: (M-H) - 526,02 m/z.526.17 m / z; found: (M-H) - 526.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

570,20 m/z; ugot.: (M-H) = 570,04 m/z.570.20 m / z; found: (M-H) = 570.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

540,19 m/z; ugot.: (M-H) = 540,05 m/z.540.19 m / z; found: (M-H) = 540.05 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

-215215 metil-2-okso-1,2-dihidropiridin-3 il]amino} karbonil)amino] -3 -(2 ’ -metoksi1,1 ’-bifenil-4-il)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- 3 hidroksi-5,6-dimetil-2-okso-l,2dihidropiridin-3il] amino} karbonil)amino]-3-(3izopropoksifenil)propanoj ska kislina (3S)-3-[({ [l-(2-kloro-6-etoksibenzil)-4- 4 hidroksi-5,6-dimetil-2-okso-1,2dihidropiridin-3il] amino } karboniljamino] -3 fenilpropanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-5 - 5 etil-4-hidroksi-6-metil-2-okso-1,2dihidropiridin-3i 1] amino} karbonil)amino] -3 -(3 izopropoksifenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-5- 4 etil-4-hidroksi-6-metil-2-okso-1,2dihidropiridin-3il]amino} karbonil)amino] -3 fenilpropanojska kislina (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4- 6 hidroksi-5-metil-2-okso-1,2dihidropiridin-3iljamino} karboniljamino] -3 -(6-etoksi-2naftiljpropanojska kislina (3S)-3-[({[2-(2-klorobenzil)-6-etil-5- 22 hidroksi-3 -okso-2,3 -dihidropiridazin-4il] amino} karboniljamino] -3 -(4562,09 m/z; ugot.:-215215 Methyl-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (2 '-methoxy,1,1'-biphenyl-4-yl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-3 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3isopropoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-4 hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonylamino] -3 Phenylpropanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5-5 ethyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine-3i 1 ] amino} carbonyl) amino] -3- (3 isopropoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5-4 ethyl-4-hydroxy-6 -methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3-phenylpropanoic acid (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-6 hydroxy- 5-Methyl-2-oxo-1,2-dihydropyridine-3-ylamino} carbonylamino] -3- (6-ethoxy-2-naphthylpropanoic acid (3S) -3 - [({[2- (2-chlorobenzyl) -6-ethyl-5- 22 hydroxy-3-oxo-2,3-dihydropyridazine-4 yl] amino} carbonylamino] -3- (4562.09 m / z; found:

(M+H)+= 562,17 m/z. izrač.: (M-H) =(M + H) + = 562.17 m / z. Calcd. (MH) =

570,20 m/z; ugot.: (M-H) = 570,00 m/z.570.20 m / z; found: (M-H) = 570.00 m / z.

izrač.: (M-H) =Calcd. (M-H) =

512,16 m/z; ugot.: (M-H) = 512,01 m/z.512.16 m / z; found: (M-H) = 512.01 m / z.

izrač.: (M-H) =Calcd. (M-H) =

584,22 m/z; ugot: (M-H) = 584,03 m/z.584.22 m / z; found: (M-H) = 584.03 m / z.

izrač.: (M-H) =Calcd. (M-H) =

526,17 m/z; ugot.: (M-H) = 526,00 m/z.526.17 m / z; found: (M-H) = 526.00 m / z.

izrač.: (M-H) =Calcd. (M-H) =

592,19 m/z; ugot.: (M-H) = 592,00 m/z.592.19 m / z; found: (M-H) = 592.00 m / z.

izrač.: (M-H) =Calcd. (M-H) =

483,14 m/z; ugot.: (M-H) = 483,03 m/z.483.14 m / z; found: (M-H) = 483.03 m / z.

-216216-216216

metilfenilpropanojska kislina methylphenylpropanoic acid (3 S)-3 -[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 15 15 izrač.: (M-H)' = calcd. (M-H) '= okso-2,5,6,7-tetrahidro-1H- oxo-2,5,6,7-tetrahydro-1H- 536,20 m/z; ugot.: (M-H)' 536.20 m / z; found: (M-H) ' ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- = 535,99 m/z. = 535.99 m / z. il] amino} karbonil)amino]-3 -(3 - izobutilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5- yl] amino} carbonyl) amino] -3- (3 - isobutylphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 4 4 izrač.: (M+H)+ =calcd. (M + H) + = metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 509,16 m/z; 509.16 m / z; il]amino} karbonil)amino]-3 -(1 -metil-1H- yl] amino} carbonyl) amino] -3- (1-methyl-1H- ugot.: found: indol-6-il)propanojska kislina indol-6-yl) propanoic acid (M+H)+ = 509,05 m/z.(M + H) + = 509.05 m / z. (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- 4 4 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 550,17 m/z; ugot.: (M-H)' 550.17 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 550,01 m/z. = 550.01 m / z. il] amino} karbonil)amino] -3 -[3 - (ciklopropiloksi)fenil]propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- yl] amino} carbonyl) amino] -3- [3 - (cyclopropyloxy) phenyl] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 15 15 izrač.: (M-H)' = calcd. (M-H) '= okso-2,5,6,7-tetrahidro-lH- oxo-2,5,6,7-tetrahydro-1H- 574,17 m/z; ugot.: (M-H)' 574.17 m / z; found: (M-H) ' ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- = 574,02 m/z. = 574.02 m / z. il]amino}karbonil)amino]-3-(6-etoksi-2- naftil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4- yl] amino} carbonyl) amino] -3- (6-ethoxy-2- naphthyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 23 23 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-5-propil-1,2- hydroxy-2-oxo-5-propyl-1,2- 526,17 m/z; ugot.: (M-H)' 526.17 m / z; found: (M-H) ' dihidropiridin-3- dihydropyridine-3- = 526,04 m/z. = 526.04 m / z. il] amino } karbonil)amino] -3 - fenil]propanojska kislina (3 S)-3 -[( {[ 1 -(2-kloro-6-etoksibenzil)-4- yl] amino} carbonyl) amino] -3 - phenyl] propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 22 22 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-5-propil-1,2- hydroxy-2-oxo-5-propyl-1,2- 584,22 m/z; ugot.: (M-H)' 584.22 m / z; found: (M-H) ' dihidropiridin-3- dihydropyridine-3- - 584,09 m/z. - 584.09 m / z. il] amino } karbonil)amino]-3 -(3 - izopropoksifenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- yl] amino} carbonyl) amino] -3- (3 - isopropoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 20 20 izrač.: (M-H)' = calcd. (M-H) '=

-217217 hidroksi-2-okso-5-propil-1,2dihidropiridin-3il Jamino} karbonil)amino] -3 -(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-2-okso-5-propil-1,2dihidropiridin-3i 1] amino} karbonil)amino] -3-(3etoksifenil)propanojska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 iljamino} karbonil)amino J-3 -(4 ’ -metil1,1 ’-bifenil-4-il) propanojska kislina (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-1Hciklopenta[bJpiridin-3 ilJamino}karbonil)aminoJ-3-( 1-metil-1Hindol-5-il)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)- 5 ciklopropil-4-hidroksi-2-okso-1,2dihidropiridin-3il J amino} karbonil)amino J -3-(3izopropoksifenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)- 5ciklopropil-4-hidroksi-2-okso-1,2dihidropiridin-3ilj amino }karbonil)aminoJ-3 -(4metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-5-propoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3540,19 m/z; ugot.: (M-H) = 540,05 m/z.-217217 Hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3yl Jamino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6 -ethoxybenzyl) -4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3ethoxyphenyl) propanoic acid (3S) -3 - [({[1- (2- chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3 ylamino} carbonyl) amino J-3- (4 '-methyl1,1'-biphenyl-4-yl) propanoic acid (3 S) -3 - [ ({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 ylamino} carbonyl) amino] -3- (1-methyl-1Hindol-5-yl ) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5-cyclopropyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino J - 3- (3isopropoxyphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5cyclopropyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl amino} carbonyl) amino-3- (4methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-5-propoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3 540.19 m / z; found: (M-H) = 540.05 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

570,20 m/z; ugot.: (M-H) = 570,04 m/z.570.20 m / z; found: (M-H) = 570.04 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

530.15 m/z; ugot.: (M-H) = 530,02 m/z.530.15 m / z; found: (M-H) = 530.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

533.16 m/z; ugot.: (M-H) = 533,00 m/z.533.16 m / z; found: (M-H) = 533.00 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

582,20 m/z; ugot.: (M-H)' = 582,07 m/z.582.20 m / z; found: (M-H) '= 582.07 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

538,17 m/z; ugot.: (M-H)' = 538,06 m/z.538.17 m / z; found: (M-H) '= 538.06 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

526,17 m/z; ugot.: (M-H) = 526,05 m/z.526.17 m / z; found: (M-H) = 526.05 m / z.

-218218 il]amino} karbonil)amino] -3-(4metilfenil)propanojska kislina (3S)-3-[({[l-(2-kloro-5-metoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3i 1] amino} karbonil)amino]-3 -(4metilfenil)propanojska kislina-218218 yl] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chloro-5-methoxybenzyl) -4-hydroxy-5-methyl-2-oxo- 1,2dihydropyridine-3i 1] amino} carbonyl) amino] -3- (4methylphenyl) propanoic acid

3-[({ [ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3i 1] amino } karbonil)amino] -3 -(2naftil)propanojska kislina3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-yl] amino} carbonyl) amino] -3- (2-naphthyl) propanoic acid

3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-5-metil-2-okso-1,2dihidropiridin-3i 1] amino } karbonil)amino] -3 - [4(metilsulfonil)fenil]propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3’-etoksi1,1 ’-bifenil-4-il)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il]amino} karbonil)amino] -3 -[3 (ciklobutiloksi)fenil]propanoj ska kislina (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il]amino } karbonil)amino]-3 -(3 ciklobutiloksil)fenil)propanojska kislina izrač.: (M-H)' =3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- [4 (methylsulfonyl) phenyl ] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3'- ethoxy,1,1'-biphenyl-4-yl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-2-oxo-2,5,6,7- tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- [3 (cyclobutyloxy) phenyl] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (3-cyclobutyloxy) phenyl) propanoic acid calc .: (MH) '=

498,14 m/z; ugot.: (M-H) = 498,01 m/z.498.14 m / z; found: (M-H) = 498.01 m / z.

izrač.: (M-H)’=calcd. (M-H) '=

548,16 m/z; ugot.: (M-H)' = 548,01 m/z.548.16 m / z; found: (M-H) '= 548.01 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

576,12 m/z; ugot.: (M-H) = 576,00 m/z.576.12 m / z; found: (M-H) = 576.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

560,16 m/z; ugot.: (M-H)' = 560,04 m/z.560.16 m / z; found: (M-H) '= 560.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

564,19 m/z; ugot.: (M-H)' = 564,00 m/z.564.19 m / z; found: (M-H) '= 564.00 m / z.

izrač.: (M-H) =Calcd. (M-H) =

550,17 m/z; ugot.: (M-H) - 550,02 m/z.550.17 m / z; found: (M-H) - 550.02 m / z.

-219219 (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4hidroksi-6-metil-2-okso-1,2dihidropiridin-3i 1] amino} karbonil)amino] -3-(3izopropoksifenil)propanojska kislina-219219 (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3 - (3isopropoxyphenyl) propanoic acid

3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil2- okso-1,2-dihidropiridin-3i 1] amino } karbonil)amino]-3 -(3 -pirolidin1- ilfenil)propanojska kislina3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-pyrrolidin-1-ylphenyl) propanoic acid

3- [({[l-(2-klorobenzil)-4-hidroksi-5-metil2- okso-1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3 -(3 -piperidinl-ilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3i 1 ] amino} karbonil)amino] -3 - [(3 -(1 etilpropoksi)fenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3 il]amino}karbonil)amino]-3-(3-( 1 etilpropoksi)fenil]propanojska kislina (3S)-3-(4-kloro-3-izopropoksifenil)-3[({[ 1 -(2-kloro-6-metilbenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il] amino} karbonil)amino]propanoj ska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-1H3 izrač.: (M-H)'=3- [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-piperidinyl-phenyl) propanoic (3 S) -3 - [({[1- (2-Chloro-6-methylbenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3i 1] amino acid } carbonyl) amino] -3 - [(3- (1-ethylpropoxy) phenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5, 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (3- (1 ethylpropoxy) phenyl] propanoic acid (3S) -3- (4-chloro-3-isopropoxyphenyl) -3 [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-2oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] propanoyl (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo-2,5,6,7-tetrahydro-1H3) calcd .: (MH) '=

556,19 m/z; ugot.: (M-H) = 556,05 m/z.556.19 m / z; found: (M-H) = 556.05 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

523,17 m/z; ugot.: (M-H) = 522,99 m/z.523.17 m / z; found: (M-H) = 522.99 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

537,19 m/z; ugot.: (M-H) = 537,08 m/z.537.19 m / z; found: (M-H) = 537.08 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

580,22 m/z; ugot.: (M-H) = 580,04 m/z.580.22 m / z; found: (M-H) = 580.04 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

566,20 m/z; ugot.: (M-H) = 566,01 m/z.566.20 m / z; found: (M-H) = 566.01 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

586,15 m/z; ugot.: (M-H)' = 585,92 m/z.586.15 m / z; found: (M-H) '= 585.92 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

572,14 m/z; ugot.: (M-H)572.14 m / z; found: (M-H)

-220220 ciklopenta[b]piridin-3 il]amino}karbonil)amino]-3-(4-kloro-3izopropoksifenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2- 3 0 okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-(3’-metil1,1 ’-bifenil-4-il)propanojska kislina (3 S)-3 -[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- 3 okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il] amino } karbonil)amino] -3 -(1 -metil-1Hindol-6-il)propanojska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4- 3 hidroksi-5-metil-2-okso-l,2dihidropiridin-3il]amino}karbonil)amino]-3-( 1 -metil- 1Hindol-6-il)propanojska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5- 23 metil-2-okso-1,2-dihidropiridin-3i 1] amino } karbonil)amino] -3 -(4 ’ -metoksi1,1 ’-bifenil-4-il)propanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-5- 5 5 metil-2-okso-l,2-dihidropiridin-3i 1] amino} karbonil)amino] -3 -(2 ’ -metil1,1 ’-bifenil-4-il)propanojska kislina (3 S)-3- [( {[ 1 -(2-klorobenzil)-4-hidroksi-2- 3 okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3il]amino } karbonil)amino] -3 -(6-metoksi-2naftil)propanojska kislina (3S)-3-(4-kloro-3-etoksifenil)-3-[({[l- (2- 25 = 572,00 m/z.-220220 cyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- (4-chloro-3isopropoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-2- 3 O oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- (3'-methyl,1,1'-biphenyl-4-yl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 3 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3 - ( 1-Methyl-1Hindol-6-yl) propanoic acid (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-3 hydroxy-5-methyl-2-oxo-1, 2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (1-methyl-1H-indol-6-yl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 23 Methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4'-methoxy,1,1'-biphenyl-4-yl) propanoic acid (3 S) -3- [ ({[1- (2-chlorobenzyl) -4-hydroxy-5- 5 5 methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (2 '-methyl1,1 '-biphenyl-4-yl) propanoic acid (3S) -3- [({[1- (2-chlorobenzyl) -4-hydroxy-2- 3 oxo-2,5,6,7-t Etrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (6-methoxy-2naphthyl) propanoic acid (3S) -3- (4-chloro-3-ethoxyphenyl) -3 - [({[ 1- (2- 25 = 572.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

530.15 m/z; ugot.: (M-H) = 530,02 m/z.530.15 m / z; found: (M-H) = 530.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

533.16 m/z; ugot.: (M-H) = 532,97 m/z.533.16 m / z; found: (M-H) = 532.97 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

551,17 m/z; ugot.: (M-H) = 551,02 m/z.551.17 m / z; found: (M-H) = 551.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

560,16 m/z; ugot.: (M-H) = 560,01 m/z.560.16 m / z; found: (M-H) = 560.01 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

546,18 m/z; ugot.:546.18 m / z; found:

(M+H)+ = 546,11 m/z. izrač.: (M-H)' =(M + H) + = 546.11 m / z. Calcd. (MH) '=

560,16 m/z; ugot.: (M-H) = 560,00 m/z.560.16 m / z; found: (M-H) = 560.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

-221221 kloro-6-metilbenzil)-4-hidroksi-2-okso2,5,6,7-tetr ahidro-1 H-ciklopenta[b]piridin3 -il]amino} karbonil)amino]propanoj ska kislina (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2- 30 okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3 il]amino}karbonil)amino]-3-(4-kloro-3etoksifenil)propanojska kislina (3 S )-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4- 4 hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il]amino}karbonil)amino]-3-(3izobutilfenil)propanoj ska kislina (3 S)-3-[( {[ 1 -(2-kloro-5-etoksibenzil)-4- 4 hidroksi-5-metil-2-okso-1,2dihidropiridin-3i 1] amino } karbonil)amino] -3 -(4metilfenil)propanojska kislina-221221 chloro-6-methylbenzyl) -4-hydroxy-2-oxo2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin3-yl] amino} carbonyl) amino] propanoic acid (3S) - 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 30 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3 - (4-chloro-3ethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-4 hydroxy-2-oxo-2,5,6,7- tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (3isobutylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-5-ethoxybenzyl) -4- 4 hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid

- [( {[ 1 -(2-klorobenzil)-4-hidroksi- 5 -metil- 134- [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-134]

2- okso-1,2-dihidropiridin-3 il]amino}karbonil)amino]-3-[4(metilsulfonil)fenil]propanojska kislina (3 S)-3-[({[ 1 -(2-klorobenzil)-4-hidroksi-2- 225 okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3i 1] amino} karbonil)amino]-3 -(2,4-dikloro3- etoksifenil)propanojska kislina (3S)-3-{[({l-(2-kloro-5-(piperidin-l- 27 ilsulfonil)benzil]-4-hidroksi-5-metil-2okso- l,2-dihidropiridin-3572,14 m/z; ugot.: (M-H) = 571,94 m/z.2-Oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- [4 (methylsulfonyl) phenyl] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) - 4-hydroxy-2- 225 oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3I] amino} carbonyl) amino] -3- (2,4-dichloro3-ethoxyphenyl) propanoic acid (3S ) -3 - {[({1- (2-chloro-5- (piperidin-1- 27 ylsulfonyl) benzyl] -4-hydroxy-5-methyl-2oxo-1,2-dihydropyridine-3572,14 m / z) Found: (MH) = 571.94 m / z.

izrač.: (M-H) =Calcd. (M-H) =

558,12 m/z; ugot.: (M-H) = 557,77 m/z.558.12 m / z; found: (M-H) = 557.77 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

582,24 m/z; ugot.:582.24 m / z; found:

(M+H)+= 582,10 m/z.(M + H) + = 582.10 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

514.17 m/z;514.17 m / z;

ugot.:found:

(M+H)+= 514,08 m/z.(M + H) + = 514.08 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

534,11 m/z; ugot.:534.11 m / z; found:

(M+H)+ = 534,07 m/z. izrač.: (M+H)+ =(M + H) + = 534.07 m / z. calcd. (M + H) + =

594,09 m/z; ugot.:594.09 m / z; found:

(M+H)+ - 593,98 m/z.(M + H) + - 593.98 m / z.

izrač.: (M-H) =Calcd. (M-H) =

615.17 m/z; ugot.: (M-H) = 615,04 m/z.615.17 m / z; found: (M-H) = 615.04 m / z.

-222222-222222

il} amino)karbonil]amino} -3 -(4- yl} amino) carbonyl] amino} -3- (4- metilfenil)propanojska kislina (3S)-3-{[({l-(2-kloro-5-(pirolidin-l- methylphenyl) propanoic acid (3S) -3 - {[({1- (2-chloro-5- (pyrrolidin-1- 15 15 izrač.: (M-H)' = calcd. (M-H) '= ilsulfonil)benzil-4-hidroksi-5-metil-2- ilsulfonyl) benzyl-4-hydroxy-5-methyl-2- 601,15 m/z; ugot.: (M-H)' 601.15 m / z; found: (M-H) ' okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- = 601,03 m/z. = 601.03 m / z. il} amino)karbonil]amino} -3 -(4- metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-4- yl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 2 2 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 582,20 m/z; ugot.: (M+H) 582.20 m / z; found: (M + H) ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- = 582,10 m/z. = 582.10 m / z. il] amino }karbonil)amino]-3 - [3 - (ciklopropiloksi)fenil]propanoj ska kislina (3S)-3-{[({l-(2-kloro-6- yl] amino} carbonyl) amino] -3- [3 - (cyclopropyloxy) phenyl] propanoic acid (3S) -3 - {[({1- (2-chloro-6- 20 20 izrač.: (M-H)' = calcd. (M-H) '= (ciklopentilmetoksi)benzil]-4-hidroksi-5- (cyclopentylmethoxy) benzyl] -4-hydroxy-5- 566,20 m/z; ugot.: (M-H)‘ 566.20 m / z; found: (M-H) ' metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- = 566,09 m/z. = 566.09 m / z. il} amino)karbonil]amino } -3 -(4- metilfenil)propanojska kislina (3 S)-3 - {[({1 -(2-(benziloksi)-6- yl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid (3 S) -3 - {[({1 - (2- (benzyloxy) -6- 10 10 izrač.: (M-H)' = calcd. (M-H) '= klorobenzil]-4-hidroksi-5-metil-2-okso- chlorobenzyl] -4-hydroxy-5-methyl-2-oxo- 574,17 m/z; ugot.: (M-H)' 574.17 m / z; found: (M-H) ' 1,2-dihidropiridin-3 - 1,2-Dihydropyridine-3 - = 574,01 m/z. = 574.01 m / z. il} amino)karbonil]amino} -3 -(4- metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2- yl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 3 3 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro-lH- oxo-2,5,6,7-tetrahydro-1H- 604,16 m/z; 604.16 m / z; ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- ugot.: found: il] amino }karbonil)amino] -3 -(3 -kloro-4,5 - yl] amino} carbonyl) amino] -3- (3-chloro-4,5 - (M+H)+ = 604,02 m/z.(M + H) + = 604.02 m / z. dietoksifenil)propanoj ska kislina (3 S)-3 - [({[ 1 -(2-kloro-6-metilbenzil)-4- diethoxyphenyl) propanoic acid (3 S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- 500 500 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 652,14 m/z; 652.14 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino }karbonil)amino] -3 -(2,4-dikloro- yl] amino} carbonyl) amino] -3- (2,4-dichloro- (M+H)+= 651,98 m/z.(M + H) + = 651.98 m / z.

-223223-223223

3,5-dietoksifenil)propanojska kislina 3,5-diethoxyphenyl) propanoic acid (3 S)-3 -[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 450 450 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro- IH- oxo-2,5,6,7-tetrahydro-1H- 638,12 m/z; 638.12 m / z; ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- ugot.: found: iljamino } karbonil)amino] -3 -(2,4-dikloro- 3,5 -dietoksifenil)propanojska kislina islamino} carbonyl) amino] -3- (2,4-dichloro- 3,5-diethoxyphenyl) propanoic acid (M+H)+ = 637,97 m/z.(M + H) + = 637.97 m / z. (3 S)-3 -[( {[ 1 -(2-klorobenzil)-4-hidroksi-2- (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- 9 9 izrač.: (M+H)+ =calcd. (M + H) + = okso-2,5,6,7-tetrahidro-1 H- oxo-2,5,6,7-tetrahydro-1H- 552,19 m/z; 552.19 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino } karbonil)amino]-3 -[3 - (ciklopropilmetoksi)fenil]propanojska kislina yl] amino} carbonyl) amino] -3- [3 - (cyclopropylmethoxy) phenyl] propanoic acid (M+H)+ = 552,10 m/z.(M + H) + = 552.10 m / z. (3 S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4- (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4- 4 4 izrač.: (M+H)+ =calcd. (M + H) + = hi droksi-2-okso-2,5,6,7-tetrahidro- IH- hi droxy-2-oxo-2,5,6,7-tetrahydro-1H- 596,21 m/z; 596.21 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: il] amino } karbonil)amino] -3 -[3 - (ciklopropilmetoksi)fenil]propanojska kislina yl] amino} carbonyl) amino] -3- [3 - (cyclopropylmethoxy) phenyl] propanoic acid (M+H)+ = 596,11 m/z.(M + H) + = 596.11 m / z. (3S)-3-[({[l-(2-kloro-6-metilbenzil)-4- (3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- 10 10 izrač.: (M+H)+ =calcd. (M + H) + = hidroksi-2-okso-2,5,6,7-tetrahidro-IH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 566,20 m/z; 566.20 m / z; ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - ugot.: found: iljamino} karbonil)amino]-3 -[3 - (ciklopropilmetoksi)fenil]propanojska kislina islamino} carbonyl) amino] -3 - [3 - (cyclopropylmethoxy) phenyl] propanoic acid (M+H)+ = 566,12 m/z.(M + H) + = 566.12 m / z. (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-5- (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 13 13 izrač.: (M-H) = Calcd. (M-H) = metil-2-okso-1,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 544,16 m/z; ugot.: (M-H) 544.16 m / z; found: (M-H) il] amino } karbonil)amino] -3-(2,4dietoksipirimidin-5-il)propanojska kislina yl] amino} carbonyl) amino] -3- (2,4diethoxypyrimidin-5-yl) propanoic acid = 544,00 m/z. = 544.00 m / z. (3 S)-3-[({[1 -(2,3-dikloro-6-etoksibenzil)- (3 S) -3 - [({[1- (2,3-dichloro-6-ethoxybenzyl) - 5 5 izrač.: (M-H)' = calcd. (M-H) '= 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lH- 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 572,13 m/z; ugot.: (M-H)' 572.13 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 571,97 m/z. = 571.97 m / z.

-224224-224224

il] amino } karbonil)amino]-3-(4- yl] amino} carbonyl) amino] -3- (4- metilfenil)propanojska kislina (3 S)-3 -[3 -(ciklopropilmetoksi)fenil] -3 - methylphenyl) propanoic acid (3 S) -3- [3- (cyclopropylmethoxy) phenyl] -3 - 7 7 izrač.: (M-H)‘ = calcd. (M-H) '= [({[ 1 -(2,3-dikloro-6-etoksibenzil)-4- [({[1- (2,3-dichloro-6-ethoxybenzyl) -4- 628,16 m/z; ugot.: (M-H)' 628.16 m / z; found: (M-H) ' hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- = 627,98 m/z. = 627.98 m / z. ciklopenta[b]piridin-3- il] amino }karbonil)amino]propanoj ska kislina (3 S)-3-[( {[ 1 -(2,3-dikloro-6-etoksibenzil)- cyclopenta [b] pyridine-3- yl] amino} carbonyl) amino] propane acid (3 S) -3 - [({[1- (2,3-dichloro-6-ethoxybenzyl) - 3 3 izrač.: (M-H)‘ = calcd. (M-H) '= 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lH- 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 602,15 m/z; ugot.: (M-H)' 602.15 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 601,99 m/z. = 601.99 m / z. il] amino }karbonil)amino] -3 -(3 - etoksifenil)propanojska kislina (3 S)-3 - [({[ 1 -(2,3 -dikloro-6-etoksibenzil)- yl] amino} carbonyl) amino] -3- (3 - ethoxyphenyl) propanoic acid (3S) -3 - [({[1- (2,3-dichloro-6-ethoxybenzyl) - 5 5 izrač.: (M-H)' = calcd. (M-H) '= 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lH- 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 616,16 m/z; ugot.: (M-H)' 616.16 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 616,01 m/z. = 616.01 m / z. il] amino } karbonil)amino] -3-(3- izopropoksifenil)propanojska kislina (3 S)-3 -({[[ 1 -(2-klorobenzil)-4-metoksi-2- yl] amino} carbonyl) amino] -3- (3- isopropoxyphenyl) propanoic acid (3 S) -3 - ({[[1- (2-chlorobenzyl) -4-methoxy-2- 2000 2000 izrač.: (M-H)' = calcd. (M-H) '= okso-1,2-dihidropiridin-3- oxo-1,2-dihydropyridine-3- 482,14 m/z; ugot.: (M-H)‘ 482.14 m / z; found: (M-H) ' il](metil)amino]-karbonil} amino)-3-(4- yl] (methyl) amino] carbonyl} amino) -3- (4- = 482,07 m/z. = 482.07 m / z. metilfenil)propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-5- methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- 15 15 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-l,2-dihidropiridin-3- methyl-2-oxo-1,2-dihydropyridine-3- 560,16 m/z; ugot.: (M-H)' 560.16 m / z; found: (M-H) ' il]amino}karbonil)amino]-3 -(2 ’ -metoksi- yl] amino} carbonyl) amino] -3- (2 '-methoxy- = 559,98 m/z. = 559.98 m / z. 1,1 ’-bifenil-3-il)propanojska kislina 3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-5-metil- 1,1'-biphenyl-3-yl) propanoic acid 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl- 20 20 izrač.: (M-H)' = calcd. (M-H) '= 2-okso-1,2-dihidropiridin-3 - 2-oxo-1,2-dihydropyridine-3 - 458,13 m/z; ugot: (M-H)' 458.13 m / z; found: (M-H) ' il]amino}karbonil)amino]-3-(5-metil-2- yl] amino} carbonyl) amino] -3- (5-methyl-2- = 457,99 m/z. = 457.99 m / z. furil)propanojska kislina 3 -[({[ 1 -(2-kloro-6-metilbenzil)-4-hidroksi- furyl) propanoic acid 3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy- 43 43 izrač.: (M+H)+ =calcd. (M + H) + =

-225225-225225

5-metil-2-okso-1,2-dihidropiridin-3 il] amino} karbonil)amino] -3 - [4metilsulfonil)fenil]propanojska kislina (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il]amino}karboniI)amino]-3-(2furil)propanojska kislina5-Methyl-2-oxo-1,2-dihydropyridin-3 yl] amino} carbonyl) amino] -3- [4methylsulfonyl) phenyl] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) ) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (2-furyl) propanoic acid

3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil2- okso-1,2-dihidropiridin-3il]amino}karbonil)amino]-3-(2furil)propanojska kislina3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (2-furyl) propanoic acid

3- [({[l-(2-klorobenzil)-4-hidroksi-2-okso2,5,6,7-tetrahidro-lH-ciklopenta[b]piridin3-il]amino}karbonil)amino]-3-(4trifluorometil)fenil]propanoj ska kislina (3 S)-3-[({[1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro- 1Hciklopenta[b]piridin-3 il]amino} karbonil)amino] -3-(3metilfenil)propanojska kislina (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il] amino} karbonil)amino] -3 - [3 (trifluorometil)fenil]propanojska kislina (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il] amino} karbonil)amino] -3 -(3,5 dimetilfenil)propanojska kislina3- [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- ( 4trifluoromethyl) phenyl] propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl) ] amino} carbonyl) amino] -3- (3methylphenyl) propanoic acid (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2oxo-2,5,6,7-tetrahydro- 1Hcyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] -3- [3 (trifluoromethyl) phenyl] propanoic acid (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 2oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl] amino} carbonyl) amino] -3- (3,5 dimethylphenyl) propanoic acid

548,13 m/z; ugot.:548.13 m / z; found:

(M+H)+ = 548,07 m/z.(M + H) + = 548.07 m / z.

izrač.: (M-H) =Calcd. (M-H) =

470,11 m/z; ugot.: (M-H) = 469,96 m/z.470.11 m / z; found: (M-H) = 469.96 m / z.

izrač.: (M-H) =Calcd. (M-H) =

444,10 m/z; ugot.: (M-H) - 443,91 m/z.444.10 m / z; found: (M-H) - 443.91 m / z.

izrač.: (M-H) =Calcd. (M-H) =

548,12 m/z; ugot.: (M-H) = 548,00 m/z.548.12 m / z; found: (M-H) = 548.00 m / z.

izrač.: (M-H) =Calcd. (M-H) =

494,15 m/z; ugot.: (M-H) = 494,02 m/z.494.15 m / z; found: (M-H) = 494.02 m / z.

izrač.: (M-H) =Calcd. (M-H) =

548,12 m/z; ugot.: (M-H) = 547,99 m/z.548.12 m / z; found: (M-H) = 547.99 m / z.

izrač.: (M-H) =Calcd. (M-H) =

508,16 m/z; ugot.: (M-H) = 508,02 m/z.508.16 m / z; found: (M-H) = 508.02 m / z.

-226226-226226

(3S)-[3,5-bis(trifluorometil)fenil]-3-[({[l- (2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7- tetrahidro-lH-ciklopenta[b]piridin-3i 1 ] amino } karbonil)amino] -propanoj ska kislina (3S) - [3,5-bis (trifluoromethyl) phenyl] -3 - [({[1 - (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7- tetrahydro-1H-cyclopenta [b] pyridine-3i 1] amino} carbonyl) amino] -propionic acid 130 130 izrač.: (M-H)' = 615,11 m/z; ugot.: (M-H)' = 615,99 m/z. calcd. (M-H) '= 615.11 m / z; found: (M-H) ' = 615.99 m / z. (3S)-3-{[({l-(2-kloro-5- (trifluorometil)benzil]-4-hidroksi-5-metil- 2-okso-1,2-dihidropiridin-3- il} amino)karbonil]amino} -3 -(4- metilfenil)propanojska kislina (3S) -3 - {[({1- (2-chloro-5- (trifluoromethyl) benzyl] -4-hydroxy-5-methyl- 2-oxo-1,2-dihydropyridine-3- yl} amino) carbonyl] amino} -3- (4- methylphenyl) propanoic acid 6 6 izrač.: (M-H)' = 536,12 m/z; ugot.: (M-H)' = 535,99 m/z. calcd. (M-H) '= 536.12 m / z; found: (M-H) ' = 535.99 m / z. (3 S)-3 - [({[ 1 -(2-kloro-5-fluorobenzil)-4- hidroksi-5-metil-2-okso-1,2- dihidropiridin-3- il] amino } karbonil)amino] -3 -(4- metilfenil)propanojska kislina (3 S) -3 - [({[1- (2-chloro-5-fluorobenzyl) -4- hydroxy-5-methyl-2-oxo-1,2- dihydropyridine-3- yl] amino} carbonyl) amino] -3- (4- methylphenyl) propanoic acid 5 5 izrač.: (M-H)' = 486,12 m/z; ugot.: (M-H)' = 485,97 m/z. calcd. (M-H) '= 486.12 m / z; found: (M-H) ' = 485.97 m / z. (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-5- metil-2-okso-1,2-dihidropiridin-3- il]amino}karbonil)amino]-3-[3- (dietilamino)fenil]propanojska kislina (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5- methyl-2-oxo-1,2-dihydropyridine-3- yl] amino} carbonyl) amino] -3- [3- (diethylamino) phenyl] propanoic acid 2 2 izrač.: (M-H)' = 525,19 m/z; ugot.: (M-H)' = 525,00 m/z. calcd. (M-H) '= 525.19 m / z; found: (M-H) ' = 525.00 m / z. 3-(l,l’-bifenil-4-il)-3-[({[l-(2- klorobenzil)-4-hidroksi-2-okso-2,5,6,7- tetrahidro-1 H-ciklopenta[b]piridin-3 il] amino } karbonil)amino]propanoj ska kislina 3- (l, l'-biphenyl-4-yl) -3 - [({[l- (2- chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7- tetrahydro-1H-cyclopenta [b] pyridin-3 yl] amino} carbonyl) amino] propane acid 30 30 izrač.: (M-H)' = 556,16 m/z; ugot.: (M-H)' = 555,99 m/z. calcd. (M-H) '= 556.16 m / z; found: (M-H) ' = 555.99 m / z. (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2- okso-2,5,6,7-tetrahidro- 1H- ciklopenta[b]piridin-3- il] amino} karbonil)amino] -3-(2,3 -dihidro- lH-inden-5-il)propanojska kislina (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2- oxo-2,5,6,7-tetrahydro-1H- cyclopenta [b] pyridine-3- yl] amino} carbonyl) amino] -3- (2,3-dihydro- 1H-inden-5-yl) propanoic acid 8 8 izrač.: (M+H)+ = 522,17 m/z; ugot.: (M+H)+ = 522,03 m/z.Calcd .: (M + H) + = 522.17 m / z; found: (M + H) + = 522.03 m / z. (3S)-3-[({[l-(2-kloro-6-metilbenzil)-4- hidroksi-2-okso-2,5,6,7-tetrahidro-lH- (3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 10 10 izrač.: (M+H)+ = 536,19 m/z;calcd (M + H) + = 536.19 m / z;

-227227-227227

ciklopenta[b]piridin-3 - il] amino } karbonil)amino]-3 -(2,3 -dihidro- lH-inden-5-il)propanojska kislina cyclopenta [b] pyridine-3 - yl] amino} carbonyl) amino] -3- (2,3-dihydro- 1H-inden-5-yl) propanoic acid ugot.: (M+H)+ = 536,08 m/z.found: (M + H) + = 536.08 m / z. N-{l-[(2-klorofenil)metil]-4-hidroksi-5- metil-2-okso-1,2-dihidro-3 -piridinil} -N’ - [(lS)-l-(4-metilfenil)-2-(lH-l,2,3,4- tetrazol- 5 -i 1) eti 1] sečnina N- {1 - [(2-chlorophenyl) methyl] -4-hydroxy-5- methyl-2-oxo-1,2-dihydro-3-pyridinyl} -N '- [(1S) -1- (4-methylphenyl) -2- (1H-1,2,3,4- tetrazol-5-yl) ethy 1] urea 6000 6000 izrač.: (M+H)+ = 494,17 m/z; ugot.: (M+H)+ = 494,01 m/z.Calcd .: (M + H) + = 494.17 m / z; found: (M + H) + = 494.01 m / z. (3S)-3-[l,l’-bifenil]-3-il-3-{[({l-[(2- klorofenil)metil]-4-hidroksi-2-okso- 2,5,6,7-tetrahidro-1 H-ciklopenta[b]piridin- 3 -il} amino)karbonil] amino }propanoj ska kislina (3S) -3- [l, l'-biphenyl] -3-yl-3 - {[({l - [(2- chlorophenyl) methyl] -4-hydroxy-2-oxo- 2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridine- 3-yl} amino) carbonyl] amino} propane acid 17 17 izrač.: (M-H)' = 556,16 m/z; ugot.: (M-H)' = 556,01 m/z. calcd. (M-H) '= 556.16 m / z; found: (M-H) ' = 556.01 m / z. (3 S)-3 - {[({1 -(2-klorofenil)metil]-4- hidroksi-2-okso-2,5,6,7-tetrahidro-lH- ciklopenta[b]piridin-3- il} amino)karbonil] amino } -3 - {4- [trifluorometil)oksi]propanojska kislina (3 S) -3 - {[({1- (2-chlorophenyl) methyl] -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- cyclopenta [b] pyridine-3- yl} amino) carbonyl] amino} -3- {4- [trifluoromethyl) oxy] propanoic acid 13 13 izrač.: (M-H)' = 564,11 m/z; ugot.: (M-H) = 564,01 m/z. calcd. (M-H) '= 564.11 m / z; found: (M-H) = 564.01 m / z. (3 S)-3 - {[({1 -(2-klorofenil)metil]-4- hidroksi-2-okso-2,5,6,7-tetrahidro-lH- ciklopenta[b]piridin-3 - il}amino)karbonil]amino}-3-{4- [difluorometil)oksi] fenil} propanoj ska kislina (3 S) -3 - {[({1- (2-chlorophenyl) methyl] -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- cyclopenta [b] pyridine-3 - yl} amino) carbonyl] amino} -3- {4- [difluoromethyl) oxy] phenyl} propane acid 13 13 izrač.: (M-H)' = 546,12 m/z; ugot.: (M-H)' = 545,97 m/z. calcd. (M-H) '= 546.12 m / z; found: (M-H) ' = 545.97 m / z. (3 S)-3-{[({1 -(2-klorofenil)metil]-4- hidroksi-2-okso-2,5,6,7-tetrahidro-lH- ciklopenta[b]piridin-3 - il} amino)karbonil]amino} -3 - {3 - [(trifluorometil)oksi] fenil} propanoj ska kislina (3 S) -3 - {[({1- (2-chlorophenyl) methyl] -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- cyclopenta [b] pyridine-3 - yl} amino) carbonyl] amino} -3- {3 - [(Trifluoromethyl) oxy] phenyl} propane acid 10 10 izrač.: (M-H)' = 564,11 m/z; ugot.: (M-H)' = 563,98 m/z. calcd. (M-H) '= 564.11 m / z; found: (M-H) ' = 563.98 m / z. (3 S)-3- {[({1 -(2-klorofenil)metil]-4- hidroksi-2-okso-2,5,6,7-tetrahidro-lH- (3 S) -3- {[({1- (2-chlorophenyl) methyl] -4- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 5 5 izrač.: (M-H)' = 546,12 m/z; ugot.: (M-H)' calcd. (M-H) '= 546.12 m / z; found: (M-H) '

-228228 ciklopenta[b]piridin-3il} amino)karbonil]amino } -3 - {3 [(difluorometil)oksi] fenil }propanoj ska kislina (3 S)-3- {[({1 -(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil]amino }-3- {3-[( 1,1,2,2tetrafluoroetil)oksi] fenil} propanoj ska kislina (3 S)-3- {[({1 -(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil]amino } -3 - [3,5 -dimetil4-(metiloksi)fenil]propanojska kislina (3S)-3-{[({l-(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil]amino } -3 -(1 -etil-1Hindol-5-il)propanojska kislina (3 S)-3 - {[({1 -(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino } -3 -(3,5difluorofenil)propanojska kislina (3 S)-3- {[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - [3 -fluoro-4(metiloksi)fenil]propanojska kislina (3 S)-3-{[({1 -[(2-klorofenil)metil]-4= 546,01 m/z.-228228 Cyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- {3 [(difluoromethyl) oxy] phenyl} propanoic acid (3 S) -3- {[({1- (2-chlorophenyl) methyl] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- {3 - [(1,1,2,2tetrafluoroethyl) oxy ] phenyl} propanoic acid (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 yl} amino) carbonyl] amino} -3- [3,5-dimethyl4- (methyloxy) phenyl] propanoic acid (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-2-oxo -2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- (1-ethyl-1H-indol-5-yl) propanoic acid (3 S) -3 - {[ ({1- (2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- (3,5-difluorophenyl) propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino carbonyl] amino} -3- [3-fluoro-4 (methyloxy) phenyl] propanoic acid at (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4 = 546.01 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

596,12 m/z; ugot.: (M-H) = 596,02 m/z.596.12 m / z; found: (M-H) = 596.02 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

538,17 m/z; ugot.: (M-H) = 538,04 m/z.538.17 m / z; found: (M-H) = 538.04 m / z.

izrač.: (M+H)+=calcd. (M + H) + =

549,19 m/z; ugot.:549.19 m / z; found:

(M+H)+ = 549,02 m/z.(M + H) + = 549.02 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

516,11 m/z; ugot.: (M-H) = 516,01 m/z.516.11 m / z; found: (M-H) = 516.01 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

528,13 m/z; ugot.: (M-H) = 528,00 m/z.528.13 m / z; found: (M-H) = 528.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

-229229 hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino} -3 -(4propilfenil)propanojska kislina (3 S)-3-{[({l-[(2-kloro-6-metilfenil)metil]- 20-229229 hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- (4propylphenyl) propanoic acid (3 S) -3 - {[( {1 - [(2-chloro-6-methylphenyl) methyl] - 20

4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il} amino)karbonil] amino } -3 -(4propilfenil)propanojska kislina (3 S)-3-{[({l-[(2-klorofenil)metil]-4- 267 hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(2metilfenil)propanojska kislina (3S)-3-{[({ l-[(2-klorofenil)metil]-4- 25 hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il}amino)karbonil]amino}-3-(4ciklopropilfenil)propanojska kislina (3S)-3-{[({ 1-[(2-kloro fenil)metil]-4- 22 hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(3kinolinil)propanojska kislina (3S)-3-{[({ l-[(2-klorofenil)metil]-4- 22 hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil]amino } -3 -(3 kinolinil)propanojska kislina4-Hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- (4propylphenyl) propanoic acid (3 S) -3 - {[( {1 - [(2-chlorophenyl) methyl] -4- 267 hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2methylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-25 hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino } -3- (4cyclopropylphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chloro-phenyl) methyl] -4-22-hydroxy-5-methyl-2-oxo-1,2-dihydro- 3pyridinyl} amino) carbonyl] amino} -3- (3quinolinyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-22 hydroxy-2-oxo-2,5. 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- (3 quinolinyl) propanoic acid

-({[(1 - {[2-kloro-6-(etiloksi)fenil]metil} - 8- ({[(1 - {[2-chloro-6- (ethyloxy) phenyl] methyl} - 8

4-hidroksi-5-metil-2-okso-l,2-dihidro-3piridinil)amino]karbonil} amino)-3 -(2furanil)propanojska kislina4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl) amino] carbonyl} amino) -3- (2-furanyl) propanoic acid

522,18 m/z; ugot.: (M-H)' = 522,04 m/z.522.18 m / z; found: (M-H) '= 522.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

536,20 m/z; ugot.: (M-H) = 536,06 m/z.536.20 m / z; found: (M-H) = 536.06 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

468.13 m/z; ugot.: (M-H)' = 468,00 m/z.468.13 m / z; found: (M-H) '= 468.00 m / z.

izrač.: (M+H)+ =calcd. (M + H) + =

522,18 m/z; ugot.:522.18 m / z; found:

(M+H)+ = 522,04 m/z.(M + H) + = 522.04 m / z.

izrač.: (M-H) =Calcd. (M-H) =

505.13 m/z; ugot.: (M-H)' = 504,98 m/z.505.13 m / z; found: (M-H) '= 504.98 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

531.14 m/z; ugot.: (M-H)' = 530,99 m/z.531.14 m / z; found: (M-H) '= 530.99 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

488,12 m/z; ugot.: (M-H) = 487,98 m/z.488.12 m / z; found: (M-H) = 487.98 m / z.

-230230-230230

(3 S)-3 - [2,4-bis(etiloksi)- 5 -pirimidinil]-3 - (3S) -3- [2,4-bis (ethyloxy) -5-pyrimidinyl] -3 - 15 15 izrač.: (M-H)' = calcd. (M-H) '= {[({l-(2-klorofenil)metil]-4-hidroksi-2- {[({1- (2-chlorophenyl) methyl] -4-hydroxy-2- 570,18 m/z; ugot.: (M-H)' 570.18 m / z; found: (M-H) ' okso-2,5,6,7-tetrahidro-lH- oxo-2,5,6,7-tetrahydro-1H- = 570,14 m/z. = 570.14 m / z. ciklopenta[b]piridin-3- il} amino)karbonil]amino }propanoj ska kislina (3 S)-3 - {[({1 -(2-kloro-6-metilfenil)metil]- cyclopenta [b] pyridine-3- yl} amino) carbonyl] amino} propane acid (3 S) -3 - {[({1- (2-chloro-6-methylphenyl) methyl] - 19 19 izrač.: (M+H)+ =calcd. (M + H) + = 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lH- 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 536,20 m/z; 536.20 m / z; ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- ugot.: found: il}amino)karbonil]amino)-3-(4- yl} amino) carbonyl] amino) -3- (4- (M+H)+ = 536,07.(M + H) + = 536.07. ciklopropilfenil)propanojska kislina (3R)-3 - {[({1 -(2-klorofenil)metil] -4- cyclopropylphenyl) propanoic acid (3R) -3 - {[({1- (2-chlorophenyl) methyl] -4- 15 15 izrač.: (M-H)‘ = calcd. (M-H) '= hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 418,12 m/z; ugot.: (M-H)‘ 418.12 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 418,00 m/z. = 418.00 m / z. il} amino)karbonil] amino } butanoj ska kislina yl} amino) carbonyl] amino} butane acid (3 S )-3 - {[({1 -(2-klorofenil)metil]-4- (3 S) -3 - {[({1- (2-chlorophenyl) methyl] -4- 8 8 izrač.: (M-H) = Calcd. (M-H) = hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 508,16 m/z; ugot.: (M-H) 508.16 m / z; found: (M-H) ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 508,06 m/z. = 508.06 m / z. il} amino)karbonil] amino} 3 -(4- etilfenil)propanojska kislina (3 S)-3- {[({1 -(2-klorofenil)metil]-4- yl} amino) carbonyl] amino} 3- (4- ethylphenyl) propanoic acid (3 S) -3- {[({1- (2-chlorophenyl) methyl] -4- 17 17 izrač.: (M-H) = Calcd. (M-H) = hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 522,17 m/z; ugot.: (M-H) 522.17 m / z; found: (M-H) ciklopenta[b]piridin-3- cyclopenta [b] pyridine-3- = 522,06 m/z. = 522.06 m / z. il} amino)karbonil] amino}3-[4-(1- metiletil)fenil]propanojska kislina (3 S)-3-{ [({l-(2-klorofenil)metil]-4- yl} amino) carbonyl] amino} 3- [4- (1- methylethyl) phenyl] propanoic acid (3 S) -3- {[({1- (2-chlorophenyl) methyl] -4- 30 30 izrač.: (M-H) = Calcd. (M-H) = hidroksi-5-metil-2-okso-1,2-dihidro-3- hydroxy-5-methyl-2-oxo-1,2-dihydro-3- 482,14 m/z; ugot.: (M-H) 482.14 m / z; found: (M-H) piridinil} amino)karbonil] amino} -3 -(4- pyridinyl} amino) carbonyl] amino} -3- (4- = 482,00 m/z. = 482.00 m / z. etilfenil)propanojska kislina (3 S)-3-{ [({1 -(2-klorofenil)metil]-4- ethylphenyl) propanoic acid (3 S) -3- {[({1- (2-chlorophenyl) methyl] -4- 175 175 izrač.: (M-H) = Calcd. (M-H) =

-231231 hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3-(4-( 1 metiletil)fenil]propanojska kislina (3 S)-3 - {[({1 -(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(4(ciklopropiloksi)fenil]propanojska kislina (3S)-3-{[({l-(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(4propilfenil)propanojska kislina 3 - {[({1 -(2-klorofenil)metil]-4-hidroksi-5metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino }-3-(4ciklopropilfenil)propanoj ska kislina (3S)-3-{[({l-(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino } -3-(2,3 dihidro- lH-inden-5-il)propanojska kislina (3 S)-3 - {[({1 -(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil]amino } -3 -(9-etil-9Hkarbazol-3-il)propanojska kislina (3 S)-3- {[({1 -(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(9-etil9H-karbazol-3-il)propanoj ska kislina (3S)-3-{[({l-(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 496,16 m/z; ugot.: (M-H)' = 496,01 m/z.-231231 hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4- (1-methylethyl) phenyl] propanoic acid (3 S) -3 - {[( {1- (2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4 (cyclopropyloxy) phenyl] propanoic acid (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-propylphenyl) propanoic acid 3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-5methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4cyclopropylphenyl) propanoic acid (3S ) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2,3-dihydro) - 1H-inden-5-yl) propanoic acid (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [ b] pyridin-3 yl} amino) carbonyl] amino} -3- (9-ethyl-9Hcarbazol-3-yl) propanoic acid (3 S) -3 - {[({1- (2-chlorophenyl) methyl] - 4hydroxy-5-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) k arbonyl] amino} -3- (9-ethyl-9H-carbazol-3-yl) propanoic acid (3S) -3 - {[({1- (2-chloro-6-methylphenyl) methyl] 4-hydroxy-2- oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 496.16 m / z; found: (M-H) '= 496.01 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

510.14 m/z; ugot.: (M-H)' = 510,00 m/z.510.14 m / z; found: (M-H) '= 510.00 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

496,16 m/z; ugot.: (M-H)' = 495,99 m/z.496.16 m / z; found: (M-H) '= 495.99 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

494.15 m/z; ugot.: (M-H)' = 494,01 m/z.494.15 m / z; found: (M-H) '= 494.01 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

494,15 m/z; ugot.: (M-H)' = 494,02 m/z.494.15 m / z; found: (M-H) '= 494.02 m / z.

izrač.: (M-H) =Calcd. (M-H) =

597,19 m/z; ugot.: (M-H)' = 597,01 m/z.597.19 m / z; found: (M-H) '= 597.01 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

571.17 m/z; ugot.: (M-H) = 570,99 m/z.571.17 m / z; found: (M-H) = 570.99 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

547.17 m/z; ugot.: (M-H) = 547,04 m/z.547.17 m / z; found: (M-H) = 547.04 m / z.

-232232 il} amino)karbonil]amino } -3 -(1 -metil-1Hindol-5-il)propanojska kislina (3 S)-3 - {[({1 -(2-kloro-6-metilfenil)metil] 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino} -3 - {3 [(difluorometil)oksi] fenil }propanoj ska kislina (3S)-3-{[({l -(2-klorofenil)metil]-4hidroksi-5 -metil-2-okso-1,2-dihidro-3 piridinil} amino)karbonil] amino} -3 - [2(etiloksi)[l, 1 ’-bifenil]-4-il]propanojska kislina (3S)-3-{[({l-(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - [2(etiloksi)[ 1, l’-bifenil]-4-il]propanojska kislina (3 S)-3 - {[({1 -(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(2 ’ metil] 1,1 ’-bifenil]-3-il)propanojska kislina (3 S)-3 - {[({1 -(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(3 ’ metil[l,l’-bifenil]-3-il)propanojska kislina (3 S)-3 -({[(1 - {[2-kloro-6-tetrahidro-1 (2H)piridinilfenil]metil} -4-hidroksi-5 -metil-2okso-l,2-dihidro-3piridinil)amino]karbonil}amino)-3-(43 izrač.: (M-H)' =-232232 yl} amino) carbonyl] amino} -3- (1-methyl-1H-indol-5-yl) propanoic acid (3S) -3 - {[({1- (2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3 - {3 [(difluoromethyl) oxy] phenyl} propanoic acid (3S ) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- [2 (ethyloxy) ) [1,1'-biphenyl] -4-yl] propanoic acid (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7- tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3- [2 (ethyloxy) [1,1'-biphenyl] -4-yl] propanoic acid (3 S) -3 - {[( {1- (2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2 'methyl] 1,1'-biphenyl] (3-yl) propanoic acid (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3 - (3 'methyl [1,1'-biphenyl] -3-yl) propanoic acid (3 S) -3 - ({[(1 - {[2-chloro-6-tetra hydro-1 (2H) pyridinylphenyl] methyl} -4-hydroxy-5-methyl-2oxo-1,2-dihydro-3-pyridinyl) amino] carbonyl} amino) -3- (43 calc .: (M-H) '=

560,14 m/z; ugot.: (M-H)' - 560,03 m/z.560.14 m / z; found: (M-H) '- 560.03 m / z.

izrač.: (M-H) =Calcd. (M-H) =

574,17 m/z; ugot.: (M-H)' = 574,00 m/z.574.17 m / z; found: (M-H) '= 574.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

600,19 m/z; ugot.: (M-H) = 600,01 m/z.600.19 m / z; found: (M-H) = 600.01 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

544,16 m/z; ugot.: (M-H)' = 544,04 m/z.544.16 m / z; found: (M-H) '= 544.04 m / z.

izrač.: (M-H)'=calcd. (M-H) '=

544,16 m/z; ugot.: (M-H)' = 544,00 m/z.544.16 m / z; found: (M-H) '= 544.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

551,21 m/z; ugot.: (M-H)' = 551,06 m/z.551.21 m / z; found: (M-H) '= 551.06 m / z.

-233233-233233

metilfenil)propanojska kislina methylphenyl) propanoic acid (3 S)-3- {[({1 -[(2-klorofenil)metil]-4- (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4- 23 23 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-5-metil-2-okso-l,2-dihidro-3- hydroxy-5-methyl-2-oxo-1,2-dihydro-3- 544,16 m/z; ugot.: (M-H)' 544.16 m / z; found: (M-H) ' piridinil} amino)karbonil]amino }-3-(4 ’ - pyridinyl} amino) carbonyl] amino} -3- (4 '- = 543,99 m/z. = 543.99 m / z. metil[ 1,1’ -bifeni 1]-3 -il)propanoj ska kislina (3 S)-3-{[({1 -[(2-klorofenil)metil]-4- methyl [1,1 '-biphenes 1] -3-yl) propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- 3 3 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 551,21 m/z; ugot.: (M-H)' 551.21 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 551,05 m/z. = 551.05 m / z. il}amino)karbonil]amino}-3-[3- (dietilamino)fenil]propanoj ska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-4- yl} amino) carbonyl] amino} -3- [3- (diethylamino) phenyl] propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- 20 20 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-5-metil-2-okso-1,2-dihidro-3- hydroxy-5-methyl-2-oxo-1,2-dihydro-3- 504,11 m/z; ugot.: (M-H)' 504.11 m / z; found: (M-H) ' piridinil} amino)karbonil]amino }-3-[3- pyridinyl} amino) carbonyl] amino} -3- [3- = 503,96 m/z. = 503.96 m / z. (difluorometil)fenil]propanoj ska kislina (3 S)-3- {[({1 -[(2-klorofenil)metil]-4- (difluoromethyl) phenyl] propanoic acid (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4- 16 16 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-2,5,6,7-tetrahidro-1H- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 498,12 m/z; ugot.: (M-H)' 498.12 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 498,02 m/z. = 498.02 m / z. il} amino)karbonil] amino } -3 -(3 - fluorofenil)propanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4- yl} amino) carbonyl] amino} -3- (3 - fluorophenyl) propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- 9 9 izrač.: (M-H)' = calcd. (M-H) '= hidroksi-2-okso-2,5,6,7-tetrahidro-lH- hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 498,12 m/z; ugot.: (M-H)' 498.12 m / z; found: (M-H) ' ciklopenta[b]piridin-3 - cyclopenta [b] pyridine-3 - = 498,01 m/z. = 498.01 m / z. il} amino)karbonil]amino} -3 -(4- fluorofenil)propanojska kislina N-{l-[(2-klorofenil)metil]-4-hidroksi-5- yl} amino) carbonyl] amino} -3- (4- fluorophenyl) propanoic acid N- {1 - [(2-chlorophenyl) methyl] -4-hydroxy-5- >10000 > 10000 izrač.: (M-H)' = calcd. (M-H) '= metil-2-okso-1,2-dihidro-3 -piridinil} -N’ - methyl-2-oxo-1,2-dihydro-3-pyridinyl} -N '- 464,12 m/z; ugot.: (M-H)' 464.12 m / z; found: (M-H) ' [(R)-fenil( IH-1,2,3,4-tetrazol-5- [(R) -phenyl (1H-1,2,3,4-tetrazole-5- = 464,01 m/z. = 464.01 m / z. il)metil] sečnina (3S)-3-{[({ 1 -[(2-kloro-6-metilfenil)metil] - il) methyl] urea (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] - 4 4 izrač.: (M-H) = Calcd. (M-H) = 4-hidroksi-5-metil-2-okso-1,2-dihidro-3- 4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3- 521,16 m/z; ugot.: (M-H)' 521.16 m / z; found: (M-H) ' piridinil} amino)karbonil] amino} -3 -(1 - pyridinyl} amino) carbonyl] amino} -3- (1- = 521,00 m/z. = 521.00 m / z.

-234234 metil- lH-indol-5-il)propanojska kislina (3 S)-3 - {[({1 -[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il} amino)karbonil] amino} -3 -[3 (dietilamino)fenil]propanoj ska kislina (3 S)-3 - {[({1 - [(2-kloro-6-metilfenil)metil] 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino} - 3 -(3 metilfenil)propanojska kislina (3 S)-3 - {[({1 -[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 fenilpropanojska kislina (3 S)-3-{[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 -(3 hidroksifenil)propanojska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil}amino)karbonil]amino}-3-(3hidroksifenil)propanoj ska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil]amino }-3 -(3 ’ ,5 ’ dimetil[ 1, l’-bifenil]-3-il)propanojska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-410 izrač.: (M-H)' =-234234 Methyl-1H-indol-5-yl) propanoic acid (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5 , 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3- [3 (diethylamino) phenyl] propanoic acid (3 S) -3 - {[({1 - [( 2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- (3 methylphenyl) propanoic (3 S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine- 3 yl} amino) carbonyl] amino} -3 phenylpropanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro -1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- (3-hydroxyphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-5- methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3-hydroxyphenyl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] - 4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3 ', 5 'Dimethyl [1, l'-biphenyl] -3-yl) propanoic acid (3S) -3 - {[({l - [(2-chlorophenyl) methyl] -410 calc .: (M-H)' =

565,14 m/z; ugot.: (M-H)' - 565,04 m/z.565.14 m / z; found: (M-H) '- 565.04 m / z.

izrač.: (M-H)‘ =calcd. (M-H) '=

508,16 m/z; ugot.: (M-H)' = 508,03 m/z.508.16 m / z; found: (M-H) '= 508.03 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

494,15 m/z; ugot.: (M-H) = 494,09 m/z.494.15 m / z; found: (M-H) = 494.09 m / z.

izrač.: (M-H)‘ =calcd. (M-H) '=

496,13 m/z; ugot.: (M-H)' = 495,99 m/z.496.13 m / z; found: (M-H) '= 495.99 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

470,11 m/z; ugot.: (M-H) = 469,98 m/z.470.11 m / z; found: (M-H) = 469.98 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

558,18 m/z; ugot.: (M-H) = 558,00 m/z.558.18 m / z; found: (M-H) = 558.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

-235235 hidroks i - 5 -metil-2-okso-1,2-dihidro-3 piridinil} amino)karbonil] amino} -3 fenilpropanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil] -4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il}amino)karbonil]amino}-3-{3(metilsulfonil)amino] fenil }propanoj ska kislina (3 S)-3- {[({1 -[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino }-3-{3 [(metilsulfonil)amino] fenil }propanoj ska kislina (3 S)-3 - {[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3il} amino)karbonil] amino } -3 - [3 (difluorometil)fenil]propanoj ska kislina (2S,3S)-3-{[({l-[(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -2-metil3- (4-metilfenil)propanojska kislina (3 S)-3- {[({1 -[(2-kloro-6-metilfenil)metil]4- hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino }-3-(4etilfenil)propanojska kislina (3 S)-3- {[({1 -[(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-lH455.12 m/z; ugot.: (M-H) - 454,00 m/z.-235235 hydroxy and -5-methyl-2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3 phenylpropanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) ) methyl] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- {3 (methylsulfonyl) amino] phenyl} propanoic acid ( 3 S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- {3 [(methylsulfonyl) amino] phenyl} propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo- 2,5,6,7-Tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3- [3 (difluoromethyl) phenyl] propanoic acid (2S, 3S) -3 - {[({l - [(2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -2-methyl3- (4-methylphenyl) propanoic acid (3 S) -3- {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl ] amino} -3- (4-ethylphenyl) propanoic acid (3 S) -3- {[({1 - [ (2-chlorophenyl) methyl] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1H455.12 m / z; Found: (M-H) - 454.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

573.12 m/z; ugot.: (M-H) = 572,98 m/z.573.12 m / z; found: (M-H) = 572.98 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

587,14 m/z; ugot.: (M-H) = 586,98 m/z.587.14 m / z; found: (M-H) = 586.98 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

530,13 m/z; ugot.: (M-H)' = 530,03 m/z.530.13 m / z; found: (M-H) '= 530.03 m / z.

1500 izrač.: (M-H)'=1500 Calc .: (M-H) '=

482,15 m/z; ugot.: (M-H)' = 481,99 m/z.482.15 m / z; found: (M-H) '= 481.99 m / z.

izrač.; (M-H)' =calcd .; (M-H) '=

522,18 m/z; ugot.: (M-H)' = 522,04 m/z.522.18 m / z; found: (M-H) '= 522.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

550,17 m/z; ugot.: (M-H)550.17 m / z; found: (M-H)

-236236 ciklopenta[b]piridin-3il} amino)karbonil]amino } 3 -(2,2-dimetil2,3 -dihidro-1 -benzofuran-5-il)propanojska kislina (3 S)-3- {[({1 -[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - [3 - fluoro-4(metiloksi)fenil]propanoj ska kislina (3 S )-3 - {[({1 -[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3il} amino)karbonil] amino} -3 - {3 [(trifluorometil)oksi]fenil}propanojska kislina (3 S)-3 - {[({1 - [(2-klorofenil)metil] -4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - {3 [metil(metilsulfonil)amino]fenil}propanoj ska kislina (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - { 3 [metil(metilsulfonil)amino]fenil}propanoj ska kislina (3 S)-3- {[({l-[(2-klorofenil)metil]-4hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - {3 = 550,05 m/z.-236236 cyclopenta [b] pyridin-3yl} amino) carbonyl] amino} 3- (2,2-dimethyl2,3-dihydro-1-benzofuran-5-yl) propanoic acid (3 S) -3 - {[({ 1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3 - [3 - fluoro-4 (methyloxy) phenyl] propanoic acid (3 S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5 , 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3yl} amino) carbonyl] amino} -3 - {3 [(trifluoromethyl) oxy] phenyl} propanoic acid (3 S) -3 - {[({1 - [ (2-chlorophenyl) methyl] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3 - {3 [methyl (methylsulfonyl) amino ] phenyl} propanoic acid (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [ b] pyridin-3 yl} amino) carbonyl] amino} -3- {3 [methyl (methylsulfonyl) amino] phenyl} propanoic acid (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl ] -4hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino ) carbonyl] amino} -3 - {3 = 550.05 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

542,15 m/z; ugot.: (M-H)' = 542,00 m/z.542.15 m / z; found: (M-H) '= 542.00 m / z.

izrač.: (M-H)’ 578,13 m/z; ugot.: (M-H) = 578,02 m/z.Calcd .: (M-H) '578.13 m / z; found: (M-H) = 578.02 m / z.

1,6 izrač.: (M-H)'=1.6 calc .: (M-H) '=

587,14 m/z; ugot.: (M-H) = 586,99 m/z.587.14 m / z; found: (M-H) = 586.99 m / z.

1,3 izrač.: (M-H)'=1.3 Calc .: (M-H) '=

601,15 m/z; ugot.: (M-H) = 601,00 m/z.601.15 m / z; found: (M-H) = 601.00 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

601,15 m/z; ugot.: (M-H) = 601,00 m/z.601.15 m / z; found: (M-H) = 601.00 m / z.

-237237 [etil(metilsulfonil)amino] fenil }propanoj sk a kislina (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil] amino } -3 - {3 [etil(metilsulfonil)amino] fenil} propanoj sk a kislina (3 S)-3- {[({1 -[(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 -(2 ’ fluoro[ 1,1 ’-bifenil]-3-il)propanojska kislina (3S)-3-{[({l-[(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino }-3-[2 ’ trifluorometil)[l, 1 ’-bifenil]-3-il] propanojska kislina (3 S)-3 - {[({1 -[(2-klorofenil)metil]-4hidroksi-5-metil-2-okso-1,2-dihidro-3piridinil} amino)karbonil] amino} -3 - [2fluorofenil)propanojska kislina (3 S)-3 - {[({1 - [(2-kloro-6-metilfenil)metil] 4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3 il}amino)karbonil]amino}-3-( 1 H-indol-5il)propanojska kislina (3 S)-3 - {[({ 1 -[(2-kloro-6-metilfenil)metil] 4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 il} amino)karbonil] amino} -3 -(3,51 izrač.: (M-H)' =-237237 [ethyl (methylsulfonyl) amino] phenyl} propanoic acid (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2.5 , 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3- {3 [ethyl (methylsulfonyl) amino] phenyl} propanoic acid (3 S) -3 - {[( {1 - [(2-chlorophenyl) methyl] -4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (2 'fluoro [1,1' -biphenyl) ] -3-yl) propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4hydroxy-5-methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl ] amino} -3- [2 'trifluoromethyl) [1,1'-biphenyl] -3-yl] propanoic acid (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4hydroxy- 5-Methyl-2-oxo-1,2-dihydro-3pyridinyl} amino) carbonyl] amino} -3- [2fluorophenyl) propanoic acid (3S) -3 - {[({1 - [(2-chloro-6 -methylphenyl) methyl] 4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3- (1H-indol-5yl) propanoic acid (3 S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] 4-hydroxy-2-oxo-2,5 , 6,7-tetrahydro-1Hcyclopenta [b] pyridin-3 yl} amino) carbonyl] amino} -3- (3.51 calc .: (M-H) '=

615,17 m/z; ugot.: (M-H) = 615,04 m/z.615.17 m / z; found: (M-H) = 615.04 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

548,14 m/z; ugot.: (M-H) = 547,96 m/z.548.14 m / z; found: (M-H) = 547.96 m / z.

157 izrač.: (M-H)'=157 Calc .: (M-H) '=

598,14 m/z; ugot.: (M-H) = 597,97 m/z.598.14 m / z; found: (M-H) = 597.97 m / z.

izrač.: (M-H)' =calcd. (M-H) '=

472,11 m/z; ugot.: (M-H) = 471,98 m/z.472.11 m / z; found: (M-H) = 471.98 m / z.

izrač.: (M-H) =Calcd. (M-H) =

533,16 m/z; ugot.: (M-H) = 533,01 m/z.533.16 m / z; found: (M-H) = 533.01 m / z.

izrač.: (M-H) =Calcd. (M-H) =

530,13 m/z; ugot.: (M-H) = 530,00 m/z.530.13 m / z; found: (M-H) = 530.00 m / z.

-238238 difluorofenil)propanojska kislina-238238 Difluorophenyl) propanoic acid

SEZNAM SEKVENC (1) OMISSIS (2) Informacija za SEQ ID NO: 1:LIST OF SEQUENCES (1) OMISSIS (2) Information for SEQ ID NO: 1:

(i) Sekvenčne karakteristike (A) Dolžina: 26 amino kislin (B) Tip: amino kislina (C) Verižnost: enojna (D) Topologija: linearna (ii) Tip molekule: protein (xi) Opis sekvence: SEQ ID NO:1:(i) Sequential characteristics (A) Length: 26 amino acids (B) Type: amino acid (C) Chain: single (D) Topology: linear (ii) Molecule type: protein (xi) Sequence description: SEQ ID NO: 1 :

Cys Asp Glu Leu Pro Gin Leu Val Thr Leu Pro His Pro Asn Leu His 15 10 15Cys Asp Glu Leu Pro Gin Leu Val Thr Leu Pro His Pro Asn Leu His 15 10 15

Gly Pro Glu Ile Leu Asp Val Pro Ser Thr 20 25Gly Pro Glu Ile Leu Asp Val Pro Ser Thr 20 25

Vse tukaj citirane reference so semkaj vključene kot referenca.All references cited herein are hereby incorporated by reference.

Predloženi izum je prikazan s predhodnim opisom in primeri. Predhodni opis je namenjen kot neomejevalni prikaz, ker bodo strokovnjakom postale očitne mnoge variacije glede nanje. Mišljeno je, da so vse take variacije v obsegu in smislu priloženih zahtevkov zajete s tem.The present invention is illustrated by the foregoing description and examples. The foregoing description is intended as a non-limiting indication because many variations will become apparent to those skilled in the art. It is intended that all such variations are covered by the scope and meaning of the appended claims.

Spremembe se lahko naredijo pri sestavi, izvajanju in pripravi postopka v smisluChanges can be made to the composition, implementation and preparation of the process in terms of

-239239 predloženega izuma, ki je tukaj opisan, ne da bi se oddaljili od koncepta in obsega izuma, kot je definiran v naslednjih zahtevkih.-239239 of the present invention described herein without departing from the concept and scope of the invention as defined in the following claims.

Claims (31)

Patentni zahtevki kjer Y pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR1, C(R2)(R3), NR5, CH, O in S;Claims wherein Y at each occurrence is independently selected from the group consisting of C (O), N, CR 1 , C (R 2 ) (R 3 ), NR 5 , CH, O and S; q je celo število od 3 do 10;q is an integer from 3 to 10; A izberemo iz skupine, ki obstoji iz O, S, C(R16)(R17) in NR6;A is selected from the group consisting of O, S, C (R 16 ) (R 17 ) and NR 6 ; E izberemo iz skupine, ki obstoji iz CH2, O, S in NR7;E is selected from the group consisting of CH 2 , O, S and NR 7 ; J izberemo iz skupine, ki obstoji iz O, S in NR8;J is selected from the group consisting of O, S and NR 8 ; T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število od 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b , where b is an integer from 0 to 3; M izberemo iz skupine, ki obstoji iz C(R9)(R10) in (CH2)U, kjer je u celo število od 0 do 3;M is selected from the group consisting of C (R 9 ) (R 10 ) and (CH 2 ) U , where u is an integer from 0 to 3; L izberemo iz skupine, ki obstoji iz O, NR1 *, S in (CH2)n, kjer je n celo število 0 ali 1; X izberemo iz skupine, ki obstoji iz CO2B, PO3H2;L is selected from the group consisting of O, NR 1 *, S and (CH 2 ) n , where n is an integer 0 or 1; X is selected from the group consisting of CO 2 B, PO 3 H 2 ; SO3H, SO2NH2, SO2NHCOR12, OPO3H2, C(O)NHC(O)R13,SO 3 H, SO 2 NH 2 , SO 2 NHCOR 12 , OPO 3 H 2 , C (O) NHC (O) R 13 , C(O)NHSO2R14, hidroksila, tetrazolila in vodika;C (O) NHSO 2 R 14 , hydroxyl, tetrazolyl and hydrogen; W izberemo iz skupine, ki obstoji iz C, CR15 in N; inW is selected from the group consisting of C, CR 15 and N; and B, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 in R17 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so: vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(Cr C3 alkilna), -NHC(O)N(C,-C3 alkil)C(O)-NH(CrC3 alkilna), -NHC(O)NH(Cr C6alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)-NH-(CrC3)alkilna, C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna,B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 at each occurrence is independently selected from the group consisting of: hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC ( O) N (C, -C 3 alkyl) C (O) -NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C-C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, -C (O) -NH- (C r C 3 ) alkyl, C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, -241241 cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-241241 cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) groups; kjer so B, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 in R17 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali ki odtegne elektrone; kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč;where B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; wherein when L is NR 11 , R 4 and R 11 together may form a ring; in kjer, kadar je M C(R9)(R10), lahko R9 in R10 skupaj tvorita obroč;and where, when MC (R 9 ) (R 10 ), R 9 and R 10 together can form a ring; in kjer, kadar je A NR6 in vsaj en Y CR1, lahko R1 in R6 skupaj tvorita obroč;and wherein when A is NR 6 and at least one Y CR 1 , R 1 and R 6 together may form a ring; ali njihova farmacevtsko sprejemljiva sol;or a pharmaceutically acceptable salt thereof; pod pogojem, da kadar je A C(R16)(R17), E ni NR7.provided that when AC (R 16 ) (R 17 ), E is not NR 7 . 2. Spojina po zahtevku 1, označena s tem, dajeCompound according to claim 1, characterized in that ANR6 ANR 6 ENR7;ENR 7 ; JO;JO; M C(R9)(R10);MC (R 9 ) (R 10 ); q 4 ali 5;q 4 or 5; T (CH2)b, kjerjebO;T (CH 2 ) b , where jeO; Lje(CH2)n, kjer jen 0;L is (CH 2 ) n where je is 0; XjeCO2B;X is CO 2 B; W je C ali CR15;W is C or CR 15 ; R4 izberemo iz skupine, ki obstoji iz arila, alkilarila, aralkila, heterociklila, alkilheterociklila in heterociklilalkila; terR 4 is selected from the group consisting of aryl, alkylaryl, aralkyl, heterocyclyl, alkylheterocyclyl and heterocyclylalkyl; ter R6, R7, R9, R10 in R15 neodvisno izberemo iz skupine, ki obstoji iz vodika in nižjega alkila.R 6 , R 7 , R 9 , R 10 and R 15 are independently selected from the group consisting of hydrogen and lower alkyl. 3. Spojina po zahtevku 1, označena s tem, daje derivat le-te, izbran iz skupine, ki obstoji iz estrov, karbamatov, aminalov, amidov, optičnih izomerov in predzdravil.Compound according to claim 1, characterized in that the derivative thereof is selected from the group consisting of esters, carbamates, amines, amides, optical isomers and prodrugs. -242242-242242 4. Spojina s strukturo kjer Y pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR1, C(R2)(R3), NR5, CH, O in S; q je celo število od 3 do 7;A compound having a structure wherein Y at each occurrence is independently selected from the group consisting of C (O), N, CR 1 , C (R 2 ) (R 3 ), NR 5 , CH, O and S; q is an integer from 3 to 7; T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b, where b is an integer from 0 to 3; L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1; W izberemo iz skupine, ki obstoji iz C, CR15 in N; inL is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1; W is selected from the group consisting of C, CR 15 and N; and B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 in R15 neodvisno izberemo iz skupine, v kateri so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(Cr C3 alkilna), -NHC(O)N(C,-C3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(Cr C6alkilna), -NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH(CrC3 alkilna), C(O)N(CrC3 alkilna)2,B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 15 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, - N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (O) N (C, -C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (Ci-C 3) amino, -C (O) O- (C 1 -C 3 ) alkyl, -C (O) NH (C r C 3 alkyl), C (O) N (C r C 3 alkyl) 2 , -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, heteroaryl, diaryl, diaryl , aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; kjer so B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 in R15 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč; in kjer R9 in R10 skupaj lahko tvorita obroč;wherein B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 15 are unsubstituted or substituted by at least one electron or electron withdrawing group ; wherein when L is NR 11 , R 4 and R 11 together may form a ring; and wherein R 9 and R 10 together may form a ring; -243243 in kjer, kadar je vsaj en Y CR1, lahko R1 in R6 skupaj tvorita obroč;-243243 and where, when at least one Y is CR 1 , R 1 and R 6 together may form a ring; ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof. 5. Spojina po zahtevku 4, označena s tem, daje q 4 ali 5;A compound according to claim 4 wherein q is 4 or 5; W C ali CR15;WC or CR 15 ; T (CH2)b, kjer je b 0;T (CH 2 ) b , where b is 0; L je (CH2)„, kadar je n 0;L is (CH 2 ) 'when n is 0; R4 izberemo iz skupine, ki obstoji iz arila, alkilarila, aralkila, heterociklila, alkilheterociklila in heterociklilalkila; terR 4 is selected from the group consisting of aryl, alkylaryl, aralkyl, heterocyclyl, alkylheterocyclyl and heterocyclylalkyl; ter R6, R7, R9, R10 in R15 neodvisno izberemo iz skupine, ki obstoji iz vodika in nižjega alkila.R 6 , R 7 , R 9 , R 10 and R 15 are independently selected from the group consisting of hydrogen and lower alkyl. 6. Spojina po zahtevku 4, označena s tem, da je derivat le-te, izbran iz skupine, ki obstoji iz estrov, karbamatov, aminalov, amidov, optičnih izomerov in predzdravil.Compound according to claim 4, characterized in that the derivative thereof is selected from the group consisting of esters, carbamates, amines, amides, optical isomers and prodrugs. 7. Spojina s strukturo kjer Y pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR1, C(R2)(R3), NR5, CH, O in S; q je celo število od 2 do 5;A compound of structure wherein Y at each occurrence is independently selected from the group consisting of C (O), N, CR 1 , C (R 2 ) (R 3 ), NR 5 , CH, O and S; q is an integer from 2 to 5; T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b , where b is an integer from 0 to 3; L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1; -244244-244244 R5, R6, R7, R11 in R18 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina; inR 5 , R 6 , R 7 , R 11 and R 18 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl , alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, aralkyl (O) NH (benzyl) group; and B, R1, R2, R3, R4, R8 9 in R10 neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(C1C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(C,-C3alkilna), -NHC(O)NH(Cr C6alkilna), -NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH-(CrC3 alkilna), -C(O)N(Ci-C3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;B, R 1 , R 2 , R 3 , R 4 , R 8 9 and R 10 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3, -CO 2 H, -SH, -CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C 1 C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C, -C 3 alkyl), -NHC (O) NH (C r C 6 alkyl) ), -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (Ci-C 3) amino, -C (O) O (Ci-C 3) alkyl, -C (O) NH- (C r C 3 alkyl), -C (O) N (Ci-C 3 alkyl) 2, -CH = NOH, -PO 3 H 2, -OPO 3 H 2, haloalkyl, alkoxyalkoxy , karboksaldehidna, carboxamide, cycloalkyl, cycloalkenyl, -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C-C 3 alki lna), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; kjer so B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 in R18 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč; in kjer lahko R9 in R10 skupaj tvorita obroč;wherein B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 18 are unsubstituted or substituted by at least one electron or electron withdrawing group ; wherein when L is NR 11 , R 4 and R 11 together may form a ring; and wherein R 9 and R 10 together may form a ring; in kjer, kadar je vsaj en Y CR1, lahko R1 in R6 skupaj tvorita obroč;and where, when at least one Y is CR 1 , R 1 and R 6 may together form a ring; ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof. 8. Spojina po zahtevku 7, označena s tem, da R18 izberemo iz skupine, ki obstoji iz vodika, alkila, arila, aralkila, cikloalkila, alkilheterociklila, heterociklilalkila in heterociklila;A compound according to claim 7, wherein R 18 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, cycloalkyl, alkylheterocyclyl, heterocyclylalkyl and heterocyclyl; -245245-245245 T (CH2)b, kjer je b 0;T (CH 2 ) b , where b is 0; L je (CH2)n, kjer je n 0;L is (CH 2 ) n , where n is 0; Y izberemo iz skupine, ki obstoji iz CR1 in C(R2)(R3), ter je q 2 ali 3.Y is selected from the group consisting of CR 1 and C (R 2 ) (R 3 ) and q is 2 or 3. 9. Spojina po zahtevku 7, označena s tem, da je derivat le-te, izbran iz skupine, ki obstoji iz estrov, karbamatov, aminalov, amidov, optičnih izomerov in predzdravil.A compound according to claim 7, characterized in that the derivative thereof is selected from the group consisting of esters, carbamates, amines, amides, optical isomers and prodrugs. 10. Spojina po zahtevku 7, označena s tem, da izberemo iz skupine, ki obstoji iz kjer R19, R20, R21 in R28 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -OH,A compound according to claim 7, characterized in that it is selected from the group consisting of wherein R 19 , R 20 , R 21 and R 28 are independently selected at each occurrence from a group consisting of the following, such as halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -OH, -CO2H, -SH, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(C]-C3 alkil)-C(O)(Ci-C3 alkilna),-CO 2 H, -SH, -CN, -NO 2 , -NH 2 , alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N (C 1 -C 3 alkyl) -C (O) (C 1 -C 3 alkyl), -NHC(O)N(CrC3 alkil)C(O)NH(Cl-C3alkilna), -NHC(O)NH(CrC6alkilna), -NHSO2(C!-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(CrC3 alkilna),NHC (O) N (C r C 3 alkyl) C (O) NH (C l -C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C! -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, -C (O) NH- (C r C 3 alkyl), C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi,C (O) N (C 1 -C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, -246246 karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-246246 carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkyl, cycloalkyl, aryl, aryl, biaryl, thioaryl, diarylamino, heterocyclic, alkyl, aralkyl, aralkyl ), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; R18 izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna)skupina;R 18 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkyloxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl , aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C (O) NH (benzyl) groups; R22 izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(Ci-C3 alkil)-C(O)(CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(Ci-C6 alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna,R 22 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH, -CN , -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (Ci-C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C3alkilna), NHC (O) NH (Ci-C 6 alkyl), -NHSO 2 (C-C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (Ci-C 3) amino, -C (O) O- (Ci-C 3) alkyl, -C(O)NH-(CrC3 alkilna), -C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2,-C (O) NH- (C r C 3 alkyl), -C (O) N (C, -C 3 alkyl) 2, -CH = NOH, -PO 3 H 2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in-OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclylalkyl, alkylaryl, alkylaryl, alkylaryl; -SO 2 - (C 1 -C 3 alkyl), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzilna) skupina;-C (O) NH (benzyl) group; c je celo število od 0 do 2;c is an integer from 0 to 2; d je celo število od 0 do 3;d is an integer from 0 to 3; e je celo število od 0 do 4; in je i je celo število od 0 do 2.e is an integer from 0 to 4; and i is an integer from 0 to 2. -247247-247247 1 K1 K 11. Spojina po zahtevku 7, označena s tem, da je R aralkil; R4 je aril;A compound according to claim 7, wherein R is aralkyl; R 4 is aryl; Tje (CH2)b, kjerjebO;Where (CH 2 ) b , where isO; L je (CH2)n, kjer je n 0; in soL is (CH 2 ) n , where n is 0; and they are B, R6, R7, R9 in R10 vsak neodvisno vodik.B, R 6 , R 7 , R 9 and R 10 are each independently hydrogen. 12. Spojina s strukturo kjer T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število od 0 do 3;A compound of the structure wherein T is selected from the group consisting of C (O) and (CH 2 ) b, wherein b is an integer from 0 to 3; L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1; g je celo število 0 do 7; ing is an integer from 0 to 7; and B, R4, R9, R10 in R23 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna,B, R 4 , R 9 , R 10 and R 23 are independently selected at each occurrence from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl , -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(Ci-C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6 alkilna), -NHSO2(C!-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(Cj-C3)alkilna, -C(O)NH-(Cr C3 alkilna), -C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna,-CF 3, -CO 2 H, -SH, -CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C -C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 ( C! -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3) amino, -C (O) O- (Cl-C 3) alkyl, -C (O) NH- (C r C 3 alkyl), -C (O) N (C, -C 3 alkyl) 2, -CH = NOH, -PO 3 H 2, -OPO 3 H 2, haloalkyl, alkoxyalkoxy, karboksaldehidna, carboxamide , cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, -248248 tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna,-248248 Thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(CrC3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; in-SO 2 - (C r C 3 alkyl), -SO 3 - (C-C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; and R , R , R in R vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldlehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina;R, R, R and R are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, carboxamide, carboxamide. cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carboxyalkyl, benzyloxyalkyl, carbamylalkyl, carbamylalkyl, carbamylalkyl, carbamylalkyl, carbamylalkyl group; kjer so B, R4, R6, R7, R9, R10, R11, R18 in R23 nesubstituirani ali substituirani vsaj z eno skupino, ki daje elektrone ali ki odtegne elektrone;wherein B, R 4 , R 6 , R 7 , R 9 , R 10 , R 11 , R 18 and R 23 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; kjer, kadar je L NR11, lahko R4 in R11 skupaj tvorita obroč;wherein when L is NR 11 , R 4 and R 11 together may form a ring; in kjer R9 in R10 skupaj lahko tvorita obroč;and wherein R 9 and R 10 together may form a ring; ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof. 13. Spojina po zahtevku 12, označena s tem, daje derivat le-te, izbran iz skupine, ki obstoji iz estrov, karbamatov, aminalov, amidov, optičnih izomerov in predzdravil.Compound according to claim 12, characterized in that the derivative thereof is selected from the group consisting of esters, carbamates, amines, amides, optical isomers and prodrugs. 14. Spojina s strukturo kjer je h celo število od 0 do 5;A compound of structure wherein h is an integer from 0 to 5; -249249-249249 B, R9, R10, R24 in R25 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna,B, R 9 , R 10 , R 24 and R 25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkyloxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2,-CF 3 , -CO 2 H, -SH, -CN, -NO 2 , -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi,-NH 2 , -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C,-C3 alkil)-C(O)(CrC3 alkilna),-N (C, -C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6 alkilna), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(C!-C3)amino, -C(O)O-(Ci-C3)alkilna,-NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C 1 -C 3 alkyl) , -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, -C(O)NH-(CrC3 alkilna), -C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2,-C (O) NH- (C r C 3 alkyl), -C (O) N (C, -C 3 alkyl) 2, -CH = NOH, -PO 3 H 2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna,-OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclylalkyl, alkylaryl, alkylaryl, alkylaryl; -SO2-(CrC3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-SO 2 - (C r C 3 alkyl), -SO 3 - (C-C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; R pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, hidroksilna, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)C(O)(CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna),R at each occurrence is independently selected from the group consisting of the following, such as halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -CO 2 H, -SH , -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) C (O) (C r C 3 alkyl), -NHC (O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC(O)NH(CrC6 alkilna), -NHSO2(CrC3 alkilna), -NHSO2(arilna), -N(CrC3 alkil)SO2(C1-C3 alkilna), N-(C,-C3alkil)SO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(CrC3)amino, -C(O)O-(Cr C3)alkilna, -C(O)NH-(CrC3 alkilna), -C(O)N(CrC3 alkilna)2, -CH=NOH,-NHC (O) NH (C r C 6 alkyl), -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), -N (C r C 3 alkyl) SO 2 (C 1 -C 3 alkyl) ), N- (C 1 -C 3 alkyl) SO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C r C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, -C ( O) NH- (C r C 3 alkyl), -C (O) N (C r C 3 alkyl) 2, -CH = NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna,-PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(CrC3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-SO 2 - (C r C 3 alkyl), -SO 3 - (C-C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; -250250-250250 R , R in R vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina; inR, R and R are each independently selected from the group consisting of the following, such as alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxalkylide, carboxamide cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl; and R izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, -CF3, alkoksikarbonilna, heterocikloilna, karboksi, -C(O)O-(CrC3 alkilna), -C(O)NH-(C,-C3)alkilna, C(O)N(C,-C3alkilna)2, -PO3H2, haloalkilna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, biarilna, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), sulfonamido, ariloksialkilna in -C(O)NH(benzilna) skupina;R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, -CF 3 , alkoxycarbonyl, heterocycloyl, carboxy, -C (O) O- (C r C 3 alkyl), -C (O) NH- (C, -C 3 ) alkyl, C (O) N (C, -C 3 alkyl) 2 , -PO 3 H 2 , haloalkyl, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl , aroyl, biaryl, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C r C 3 alkyl), sulfonamido, aryloxyalkyl and -C (O) NH (benzyl) group; kjer so B, R6, R7, R9, R10, R18, R24, R25, R26 in R27 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali ki odtegne elektrone; kjer lahko R18 in R24 skupaj tvorita obroč;wherein B, R 6 , R 7 , R 9 , R 10 , R 18 , R 24 , R 25 , R 26 and R 27 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; wherein R 18 and R 24 may together form a ring; R24 in R25 lahko skupaj tvorita obroč;R 24 and R 25 may together form a ring; R in R lahko skupaj tvorita obroč;R and R together may form a ring; in kjer R9 in R10 lahko skupaj tvorita obroč;and wherein R 9 and R 10 together may form a ring; ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof. 15. Spojina po zahtevku 14, označena s tem, da so B, R6, R7, R9, R10, R24, R25 in R26 vsak neodvisno vodik in je R18 substituiran ali nesubstituiran aralkil.A compound according to claim 14, characterized in that B, R 6 , R 7 , R 9 , R 10 , R 24 , R 25 and R 26 are each independently hydrogen and R 18 is substituted or unsubstituted aralkyl. 16. Spojina po zahtevku 14, označena s tem, daje derivat le-te, izbran iz skupine, ki obstoji iz estrov, karbamatov, aminalov, amidov, optičnih izomerov in predzdravil.A compound according to claim 14, wherein the derivative thereof is selected from the group consisting of esters, carbamates, amines, amides, optical isomers and prodrugs. 17. Spojina s strukturo17. Compound with structure -251251 kjer Z pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz C(O), N, CR30, C(R3’)(R32), NR33, CH, O in S; z je celo število od 3 do 6; kje celo število od 0 do 5;-251251 wherein Z at each occurrence is independently selected from the group consisting of C (O), N, CR 30 , C (R 3 ') (R 32 ), NR 33 , CH, O and S; z is an integer from 3 to 6; where is an integer from 0 to 5; T izberemo iz skupine, ki obstoji iz C(O) in (CH2)b, kjer je b celo število od 0 do 3;T is selected from the group consisting of C (O) and (CH 2 ) b , where b is an integer from 0 to 3; L izberemo iz skupine, ki obstoji iz O, NR11, S in (CH2)n, kjer je n celo število 0 ali 1; R6, R7, R11, R18 in R33 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina;L is selected from the group consisting of O, NR 11, S, and (CH 2) n, where n is an integer 0 or 1; R 6 , R 7 , R 11 , R 18 and R 33 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl , alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, aralkyl (O) NH (benzyl) group; B, R4, R9, R10, R30, R31 in R32 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -CO2H, -SH, OH, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O) (CrC3 alkilna), -NHC(O)N(Ci-C3 alkil)C(O)NH(Ci-C3 alkilna), -NHC(O)NH(CrC6 alkilna), -NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH-(Cr C3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna,B, R 4 , R 9 , R 10 , R 30 , R 31 and R 32 are independently selected at each occurrence from the group consisting of the following, such as hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3, -CO 2 H, -SH, -OH, -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) - C (O) (C r C 3 alkyl), -NHC (O) N (C 1 -C 3 alkyl) C (O) NH (C 1 -C 3 alkyl), -NHC (O) NH (C r C 6 alkyl) ), -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (Ci-C 3) amino, -C (O) O- (Ci-C 3) alkyl, -C (O) NH- (Ci-C 3) alkyl, -C (O) N (C r C 3 alkyl) 2, -CH = NOH, -PO 3 H 2, -OPO 3 H 2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, -252252 diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; in R pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -C02H, -SH, -CN, -NO2, -NH2, -OH, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O) (Cr C3 alkilna), -NHC(0)N(CrC3 alkil)C(O)NH(CrC3 alkilna), -NHC(0)NH(CrC6 alkilna), -NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH-(Ci-C3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=N0H, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(CrC3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-252252 diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C-C 3 alkyl), -SO 3 - (C r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; and R at each occurrence are independently selected from the group consisting of the following, such as halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -C0 2 H, -SH, -CN, -NO 2, -NH 2, -OH, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC (0) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (0) NH (C r C 6 alkyl), -NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl ), alkoxyalkyl, alkylamino, alkenylamino, di (Ci-C 3) amino, -C (O) O- (Ci-C 3) alkyl, -C (O) NH- (Ci-C 3) alkyl, -C ( O) N (C r C 3 alkyl) 2 , -CH = NO, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy , arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO 2 - (C r C 3 alkyl), -SO 3 - (Ci- C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; kjer so B, R4, R5, R6, R7, R9, R10, R11, R18 19 20, R29, R30, R31, R32 in R33 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; kjer, kadar je L NR11, R4 in R11 skupaj lahko tvorita obroč; in kjer R9 in R10 skupaj lahko tvorita obroč;wherein B, R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 , R 18 19 20 , R 29 , R 30 , R 31 , R 32 and R 33 are unsubstituted or substituted by at least one a group that gives electrons or withdraws electrons; wherein when L is NR 11 , R 4 and R 11 together may form a ring; and wherein R 9 and R 10 together may form a ring; ali njihova farmacevtsko sprejemljiva sol.or a pharmaceutically acceptable salt thereof. 18. Spojina po zahtevku 17, označena s tem, da je derivat le-te, izbran iz skupine, ki obstoji iz estrov, karbamatov, aminalov, amidov, optičnih izomerov in predzdravil.18. A compound according to claim 17 wherein the derivative thereof is selected from the group consisting of esters, carbamates, amines, amides, optical isomers and prodrugs. 19. Spojina po zahtevku 17, označena s tem, daje z 3 ali 4.A compound according to claim 17, characterized in that it is 3 or 4. 20. Spojina s strukturo20. Compound with structure -253253 kjer R24 in R25 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -SH, -OH,-253253 wherein R 24 and R 25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF 3 , -SH , -OH, -CO2H, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(C,-C3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(CrC3alkilna), -NHC(O)NH(CrC6 alkilna),-CO 2 H, -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C, -C 3 alkyl), -NHC ( O) N (C r C 3 alkyl) C (O) NH (C r C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO2(Ci-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(C,C3)amino, -C(O)O-(C,-C3)alkilna, -C(O)NH-(C,-C3)alkilna,-NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C, C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, - C (O) NH- (C 1 -C 3 ) alkyl, -C(O)N(C,-C3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; in R18 in R24 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina;-C (O) N (C, -C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl , aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C-C 3 alkyl), -SO 3 - (C r C 3 alkyl) , sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) groups; and R 18 and R 24 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyloxy, carboxaldehyde, carboxalkyl , cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, benzyloxyalkyl, aryloxyalkyl group ; -254254 kjer so R18, R24, R25 in R34 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone;-254254 wherein R 18 , R 24 , R 25 and R 34 are unsubstituted or substituted by at least one electron-giving or electron-withdrawing group; in kjer lahko R24 in R25 skupaj tvorita obroč; s pridržkom, da kadar R24 in R25 skupaj tvorita obroč, nastali obroč ni benzen.and wherein R 24 and R 25 may together form a ring; with the proviso that when R 24 and R 25 together form a ring, the resulting ring is not benzene. 21. Spojina po zahtevku 20, označena s tem, daje R34 vodik;21. The compound of claim 20, wherein R 34 is hydrogen; 18 24 2518 24 25 R je aralkil; ter R in R vsakega neodvisno izberemo iz skupine, ki obstoji iz vodika, nižjega alkila ter nižjega alkila, kjer R24 in R25 lahko skupaj tvorita obroč.R is aralkyl; and R and R are each independently selected from the group consisting of hydrogen, lower alkyl and lower alkyl, where R 24 and R 25 may together form a ring. 22. Spojina po zahtevku 20, označena s tem, da ima strukturo kjer R24 in R25 vsakokrat neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so vodik, halogenska, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -CF3, -SH, -OH,Compound according to claim 20, characterized in that it has a structure wherein R 24 and R 25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy , hydroxyalkyl, aliphatic acyl, -CF 3 , -SH, -OH, -CO2H, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(C,-C3 alkil)-C(O)(CrC3 alkilna), -NHC(O)N(CrC3 alkil)C(O)NH(C,-C3alkilna), -NHC(O)NH(CrC6 alkilna),-CO 2 H, -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C, -C 3 alkyl) -C (O) (C r C 3 alkyl), -NHC ( O) N (C r C 3 alkyl) C (O) NH (C, -C 3 alkyl), -NHC (O) NH (C r C 6 alkyl), -NHSO2(C!-C3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(Ci-C3)amino, -C(O)O-(Ci-C3)alkilna, -C(O)NH-(CrC3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(CrC3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina;-NHSO 2 (C 1 -C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C 1 -C 3 ) alkyl, - C (O) NH- (C r C 3 ) alkyl, -C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, karboksaldehidna, carboxamide, cycloalkyl, cycloalkenyl, -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C-C 3 alkyl ), -SO 3 - (C r C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; -255255-255255 R34 izberemo iz skupine, ki obstoji iz naslednjih, kot so alkilna, alkenilna, alkinilna, hidroksialkilna, alifatska acilna, alkinilamino, alkoksikarbonilna, heterocikloilna, -CH=NOH, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, karbamatna, ariloksialkilna skupina, vodik in -C(O)NH(benzilna) skupina; inR 34 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH = NOH, haloalkyl, alkoxyalkyloxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl , aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C (O) NH (benzyl) groups; and R35 pri vsakem pojavljanju neodvisno izberemo iz skupine, ki obstoji iz naslednjih, kot so halogenska, hidroksilna, alkilna, alkenilna, alkinilna, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkilna, alifatska acilna, -Cf3, -CO2H, -SH, -CN, -NO2, -NH2, alkinilamino, alkoksikarbonilna, heterocikloilna, karboksi, -N(CrC3 alkil)-C(O)(C,-C3 alkilna), -NHC(O)N(Ci-C3 alkiljCCOjNHCCj-Csalkilna), -NHC(O)NH(CrC6 alkilna),R 35 at each occurrence is independently selected from the group consisting of the following, such as halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -Cf 3 , -CO 2 H, - SH, -CN, -NO 2, -NH 2, alkynylamino, alkoxycarbonyl, heterocikloilna, carboxy, -N (C r C 3 alkyl) -C (O) (C, -C 3 alkyl), -NHC (O) N (Ci-C 3 alkiljCCOjNHCCj-Csalkilna), NHC (O) NH (C r C 6 alkyl), -NHSO2(CrC3 alkilna), -NHSO2(arilna), alkoksialkilna, alkilamino, alkenilamino, di(C1-C3)amino, -C(O)O-(CrC3)alkilna, -C(O)NH-(CrC3)alkilna, -C(O)N(CrC3 alkilna)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkilna, alkoksialkoksi, karboksaldehidna, karboksamidna, cikloalkilna, cikloalkenilna, cikloalkinilna, cikloalkilalkilna, arilna, aroilna, ariloksi, arilamino, biarilna, tioarilna, diarilamino, heterociklilna, alkilarilna, aralkenilna, aralkilna, alkilheterociklilna, heterociklilalkilna, sulfonilna, -SO2-(Ci-C3 alkilna), -SO3-(Ci-C3 alkilna), sulfonamido, karbamatna, ariloksialkilna in -C(O)NH(benzilna) skupina; kjer so R24, R25, R34 in R35 nesubstituirani ali substituirani z vsaj eno skupino, ki daje elektrone ali odtegne elektrone; in je m celo število od 0 do 5.-NHSO 2 (C r C 3 alkyl), -NHSO 2 (aryl), alkoxyalkyl, alkylamino, alkenylamino, di (C 1 -C 3 ) amino, -C (O) O- (C r C 3 ) alkyl, - C (O) NH- (C r C 3 ) alkyl, -C (O) N (C r C 3 alkyl) 2 , -CH = NOH, -PO 3 H 2 , -OPO 3 H 2 , haloalkyl, alkoxyalkoxy, karboksaldehidna, carboxamide, cycloalkyl, cycloalkenyl, -cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkilheterociklilna, heterocyclylalkyl, sulfonyl, -SO 2 - (C-C 3 alkyl ), -SO 3 - (C 1 -C 3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C (O) NH (benzyl) group; wherein R 24 , R 25 , R 34 and R 35 are unsubstituted or substituted by at least one electron-donating or electron-withdrawing group; and m is an integer from 0 to 5. 23. Spojina po zahtevku 22, označena s tem, daje R34 vodik;A compound according to claim 22, wherein R 34 is hydrogen; m je celo število 1 do 3 in R35 pri vsakem pojavljanju izberemo iz skupine, ki obstoji iz vodika, alkila, halogena, alkoksi, haloalkila, sulfonila, -OH in -CN.m is an integer from 1 to 3 and R 35 at each occurrence is selected from the group consisting of hydrogen, alkyl, halogen, alkoxy, haloalkyl, sulfonyl, -OH and -CN. 24. Spojina po zahtevku 20, izbrana iz skupine, k obstoji iz naslednjih, kot so:A compound of claim 20 selected from the group consisting of the following, such as: 5-(2-klorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, -256256-256256 5-(2-klorobenzil)-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-benzil-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5-benzyl-6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-benzil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5-benzyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,5-dimetilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,5-dimethylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,4-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,4-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5 -(2-metoksibenzil)-3,5 -dihidro[ 1,3] oksazolo[4,5 -c]piridin-2,4-dion,5- (2-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,5-difluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,5-difluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[2-kloro-5-(metiltio)benzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2-chloro-5- (methylthio) benzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(4-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-5-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-5-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[3,5-bis(trifluorometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3,5-bis (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(4-terc.butilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-tert-butylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(3-klorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(4-klorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[3-(trifluorometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-bromobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-bromobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(3,4-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3,4-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(4-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[4-(trifluorometil)benzil]-3,5-dihidro[ 1,3]oksazolo[4,5-c]piridin-2,4-dion,5- [4- (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5 -(3 -metilbenzil)-benzil]-3,5 -dihidro[ 1,3] oksazolo[4,5-c]piridin-2,4-dion,5- (3-methylbenzyl) -benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5 -(piridin-2-ilmetil)-3,5 -dihidro[ 1,3] oksazolo[4,5 -c]piridin-2,4-dion,5- (pyridin-2-ylmethyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,4-difluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,4-difluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,6-difluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-difluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[3-(trifluorometoksi)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (trifluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[4-(trifluorometoksi)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [4- (trifluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[2-(trifluorometil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (trifluoromethyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, -257257-257257 5-(3-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,3-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,3-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(3,5-dimetilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3,5-dimethylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-7-pentil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-pentyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,4-diklorobenzil)-7-metil-3,5-dihidro[ 1,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,4-dichlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-7-etil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-ethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 7-butil-5-(2-klorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-butyl-5- (2-chlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[2-kloro-5-(trifluorometil)benzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- [2-chloro-5- (trifluoromethyl) benzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2,6-diklorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dichlorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-5-fluorobenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-5-fluorobenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-metilbenzil)-7-metil-3,5-dihidro[ 1,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-methylbenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(4-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b][l,3]oksazolo[5,4-d]piridin2,4(3H)-dion,5- (2-chlorobenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4-d] pyridine 2,4 (3H) -dione, 7-metil-5-[4-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,7-methyl-5- [4- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(4-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 4- [(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H)-il)metil]N,N-dimetilbenzensulfonamid,4- [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H) -yl) methyl] N, N-dimethylbenzenesulfonamide, 5 -(mezitilmetil)-3,5 -dihidro[ 1,3] oksazolo[4,5-c]piridin-2,4-dion,5 - (mesitylmethyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5- (2-klorobenzil)-3,5,6,7,8,9-heksahidro[l,3]oksazolo[4,5-c]kinolin-2,4-dion, 5-(2-klorobenzil)-7-etil-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion, 5-[2-(metiltio)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -3,5,6,7,8,9-hexahydro [1,3] oxazolo [4,5-c] quinoline-2,4-dione, 5- (2-chlorobenzyl) - 7-ethyl-6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5- [2- (methylthio) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 2-[(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H)-il)metil]N,N-dimetilbenzensulfonamid,2 - [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H) -yl) methyl] N, N-dimethylbenzenesulfonamide, 5-(2,6-dimetoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dimethoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[2-(trifluorometoksi)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (trifluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)6,7-dimetil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) 6,7-dimethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[2-kloro-5-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2582585- [2-chloro-5- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-258258 2,4-dion,2,4-dione, 5-(4-kloro-2-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chloro-2-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-5,6,7,8,9,10-heksahidro-2H-ciklohepta[b][l,3]oksazolo[5,4-d]piridin-2,4(3H)-dion,5- (2-chlorobenzyl) -5,6,7,8,9,10-hexahydro-2H-cyclohepta [b] [1,3] oxazolo [5,4-d] pyridine-2,4 (3H) - dion, 5-[2-difluorometoksi)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2-difluoromethoxy) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 7-metil-5-[((lR)-l-feniletil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-methyl-5 - [((1R) -1-phenylethyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(4-klorobenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (4-chlorobenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[2-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,6-dimetilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dimethylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 3-kloro-2-[(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin5(4H)-il)metil]benzonitril,3-chloro-2 - [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin5 (4H) -yl) methyl] benzonitrile, 5-(2-kloro-6-metilbenzil)-6,7-dimetil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-methylbenzyl) -6,7-dimethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 2-[(2,4-diokso-2,3-dihidro[l,3]oksazolo[4,5-c]piridin-5(4H)-il)metil]benzonitril,2 - [(2,4-dioxo-2,3-dihydro [1,3] oxazolo [4,5-c] pyridin-5 (4H) -yl) methyl] benzonitrile, 5-(2-kloro-6-metoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-methoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-[3-(metiltio)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (methylthio) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-klorobenzil)-7-ciklopropil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chlorobenzyl) -7-cyclopropyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(3-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3-chlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,6-diklorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2,6-dichlorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 7-metil-5-(4-metilbenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,7-methyl-5- (4-methylbenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(3,5-dimetoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (3,5-dimethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,6-difluorobenzil)-7-metil-3,5-dihidro[ 1,3] oksazolo[4,5 -c]piridin-2,4-dion,5- (2,6-difluorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-[3-(metilsulfonil)benzil]-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [3- (methylsulfonyl) benzyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-etoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-etoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-fluoro-6-metoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-fluoro-6-methoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-6-metoksibenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-methoxybenzyl) -7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(5-kloro-2-fluorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2592595- (5-chloro-2-fluorobenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-259259 2,4-dion,2,4-dione, 5-(2-klorobenzil)-7-izopropil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chlorobenzyl) -7-isopropyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(5-fluoro-2-metilbenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (5-fluoro-2-methylbenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 7-metil-5-[( 1 S)- 1-feniletil]- 3,5-dihidro[ 1,3]oksazolo[4,5-c]piridin2,4-dion,7-methyl-5 - [(1 S) -1-phenylethyl] -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-5-izopropoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-5-isopropoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(5-acetil-2-metoksibenzil)-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion, 5-(2-klorobenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-d]piridazin-2,4-dion, 5-[2-fluoro-6-(trifluorometil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5 -c]piridin-2,4-dion,5- (5-acetyl-2-methoxybenzyl) -3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5- (2-chlorobenzyl) -7-methyl- 3,5-dihydro [1,3] oxazolo [4,5-d] pyridazine-2,4-dione, 5- [2-fluoro-6- (trifluoromethyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-metilbenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b] [ 1,3]oksazolo[5,4-d]piridin-2,4(3H)-dion,5- (2-chloro-6-methylbenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4-d] pyridine-2,4 (3H) - dion, 5‘(2-kloro-6-etoksibenzil)-7-etil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5 '(2-chloro-6-ethoxybenzyl) -7-ethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2-kloro-6-propoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-propoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-6-izobutoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-isobutoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-6-etoksibenzil)-5,6,7,8-tetrahidro-2H-ciklopenta[b][l,3]oksazolo[5,4-d]piridin-2,4(3H)-dion,5- (2-chloro-6-ethoxybenzyl) -5,6,7,8-tetrahydro-2H-cyclopenta [b] [1,3] oxazolo [5,4-d] pyridine-2,4 (3H) - dion, 5-(2-kloro-6-izopropoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-isopropoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-[2-kloro-6-(2,2,2-trifluoroetoksi)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion,5- [2-chloro-6- (2,2,2-trifluoroethoxy) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione , 5-(2-kloro-6-etoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-d]piridazin2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-d] pyridazine 2,4-dione, 5-[2-kloro-6-(2-metoksietoksi)benzil]-5,6,7,8-tetrahidro2H-ciklopenta[b][l,3]oksazolo-[5,4-d]piridin-2,4(3H)-dion,5- [2-chloro-6- (2-methoxyethoxy) benzyl] -5,6,7,8-tetrahydro2H-cyclopenta [b] [1,3] oxazolo- [5,4-d] pyridine-2,4 (3H) -dione, 5-[2-kloro-6-etoksibenzil]-6,7-dimetil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2602605- [2-chloro-6-ethoxybenzyl] -6,7-dimethyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-260260 2,4-dion,2,4-dione, 5 - [2-kloro-6-etoksibenzil] -7-etil-6-metil-3,5 -dihidro[ 1,3] oksazolo[4,5 -c]piridin2,4-dion,5- [2-chloro-6-ethoxybenzyl] -7-ethyl-6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-klorobenzil)-7-etil-3,5-dihidro[ 1,3]oksazolo[4,5-d]piridazin-2,4-dion, 5-(2-kloro-6-etoksibenzil)-7-propil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chlorobenzyl) -7-ethyl-3,5-dihydro [1,3] oxazolo [4,5-d] pyridazine-2,4-dione, 5- (2-chloro-6-ethoxybenzyl) - 7-propyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-6-etoksibenzil)-7-ciklopropil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-ethoxybenzyl) -7-cyclopropyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-5-propoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-5-propoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-5-metoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-5-methoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-6-etoksibenzil)-6-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2,4-dion,5- (2-chloro-6-ethoxybenzyl) -6-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-(2-kloro-5-etoksibenzil)-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2.4- dion,5- (2-chloro-5-ethoxybenzyl) -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione, 5-[2-kloro-5-(piperidin-l-ilsulfonil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c]piridin-2,4-dion,5- [2-chloro-5- (piperidin-1-ylsulfonyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione, 5-[2-kloro-5-(pirolidin-l-ilsulfonil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c]piridin-2,4-dion,5- [2-chloro-5- (pyrrolidin-1-ylsulfonyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione, 5-[2-kloro-6-(ciklopentilmetoksi)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5c]piridin-2,4-dion,5- [2-chloro-6- (cyclopentylmethoxy) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5c] pyridine-2,4-dione, 5-[2-benziloksi)-6-klorobenzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4dion,5- [2-benzyloxy) -6-chlorobenzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione, 5-(2,3-dikloro-6-etoksibenzil)-5,6,7,8-tetrahidro2H-ciklopenta[b][ 1,3]oksazolo-[5,4-d]piridin-2,4(3H)-dion,5- (2,3-Dichloro-6-ethoxybenzyl) -5,6,7,8-tetrahydro2H-cyclopenta [b] [1,3] oxazolo- [5,4-d] pyridine-2,4 (3H) -dion, 5-[2-kloro-5-(trifluorometil)benzil]-7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin-2,4-dion in5- [2-chloro-5- (trifluoromethyl) benzyl] -7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine-2,4-dione and 5-(2-kloro-5-fluorobenzil)- 7-metil-3,5-dihidro[l,3]oksazolo[4,5-c]piridin2.4- dion.5- (2-Chloro-5-fluorobenzyl) - 7-methyl-3,5-dihydro [1,3] oxazolo [4,5-c] pyridine 2,4-dione. -261261-261261 25. Spojina, označena s tem, dajo izberemo iz skupine, ki obstoji iz naslednjih, kot so: (3 S)-3 - [({[2-metil-4-(2-metilpropil)-6-okso-1 -(fenilmetil)-1,6-dihidro5-pirimidinil]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3-( 1,3-benzodioksol-5-il)-3-[( {[2-okso-1 -(fenilmetil)-4-propil-1,2-dihidro-3 pirimidinil]amino}karbonil)amino]propanojska kislina, (3 S)-3-{[({1 -[(2-klorofenil)metil]-4-etil-2-okso-1,2-dihidro3- piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil]-2-okso-4-propil-1,2-dihidro3 -p iridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4-metil-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({6-metil-2-okso-1 -(fenilmetil)-4-[(fenilmetil)oksi]-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-2,4-dimetil-6-okso-l,6-dihidro5-pirimidinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - {[({4-amino-1 - [(2-klorofenil)metil]-6-metil-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4-metil-2-okso-1,2-dihidro3-piridini 1} amino)karbonil]amino } -3 -(4-metiloksi)fenil]propanoj ska kislina, (3 S)-3-{ [({1 -[(2-klorofenil)metil]-4-metil-2-okso-1,2-dihidro3-piridini 1} amino)karbonil]amino} -3 -(3,4-dimetilfenil)propanoj ska kislina, (3 S)-3 - {[({4-amino-l-[(2-klorofenil)metil]-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil] -4-hidroksi-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 -[(2-klorofenil)metil] -4-( 1,4-oksazinan-4-il)-2-okso-1,2-dihidro3-piridinil]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-[({ [ l-[(2-klorofenil)metil]-2-okso-4-(propilamino)-1,2-dihidro3-piridiniI]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-{[({l-[(2-bromofenil)metil]-4-metil-2-okso-l,2-dihidro3- piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina,25. A compound selected from the group consisting of: (3 S) -3 - [({[2-methyl-4- (2-methylpropyl) -6-oxo-1 - (phenylmethyl) -1,6-dihydro5-pyrimidinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3- (1,3-benzodioxol-5-yl) -3- [({[2-oxo-1- (phenylmethyl) -4-propyl-1,2-dihydro-3-pyrimidinyl] amino} carbonyl) amino] propanoic acid, (3 S) -3 - {[({1 - [ (2-chlorophenyl) methyl] -4-ethyl-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - { [({1 - [(2-chlorophenyl) methyl] -2-oxo-4-propyl-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[({6-methyl-2-oxo-1- (phenylmethyl) -4 - [(phenylmethyl) oxy] -1,2-dihydro3-pyridinyl} amino) carbonyl] amino } -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2,4-dimethyl-6-oxo -1,6-Dihydro-5-pyrimidinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] -6-methyl-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[({1 - [ (2-chlorophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methyloxy) phenyl] propanoic acid, (3 S) - 3 - {[({1 - [(2-chlorophenyl) methyl] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3,4-dimethylphenyl) propanoic acid, (3S) -3 - {[({4-amino-1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3 - (4-methylphenyl) propanoic acid, (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl ] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- (1,4-oxazinan-4-yl) - 2-Oxo-1,2-dihydro3-pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1 - [(2-chlorophenyl) methyl] - 2-oxo- 4- (propylamino) -1,2-dihydro-3-pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1 - [(2-bromophenyl) methyl) ] -4-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, -262262 (3 S)-3 - {[({1 - [(2-klorofenil)metil] -4-hidroksi-2-okso-1,2-dihidro3 - piridinil} amino)karbonil]amino } -3 -[3 -metil-4-(metiloksi)fenil]propanoj ska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-2-okso-4-fenil-l,2-dihidro3 -piridinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-[(2-{[2-(metiloksi)etil]oksi}etil)oksi]-2-okso-l,2dihidro-3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3- {[({1 -[(2-klorofenil)metil]-4-hidroksi-6-metil-2-okso-1,2-dihidro3-piridinil} amino)karbonil] amino} -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - {[({1 -[(2-klorofenil)metil]-4- [(1,1 -dimetiletil)amino] -2-okso-1,2-dihidro- 3 piridinil} amino)karbonil]amino} -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3- {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-fenilpropanojska kislina, (3 S)-3- {[({1 -[(2-klorofenil)metil]-4-[4-metiltetrahidro-1 (2H)-pirazinil]-2okso-1,2-dihidro-3-piridinil} amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 - |(2-klorofenil)metil]-4-hidroksi-2-okso-1,2dihidro-3-piridinil}amino)karbonil]amino}-3-(4-metiloksi)fenil]propanojska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-l,2dihidro-3-piridinil}amino)karbonil]amino}-3-(3,5-dimetilfenil)propanojska kislina, (3 S)-3 - {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-1,2dihidro-3 -piridinil} amino)karbonil]amino} -3-(3 -metilfenil)propanoj ska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4-hidroksi-2-okso-1,2dihidro-3-piridinil}amino)karbonil]amino}-3-[3-(metiloksi)fenil]propanojska kislina, (3S)-3-[3,5-bis(metiloksi)fenil]-3-{[({l-(2-klorofenil)metil]-4-hidroksi-2okso-1,2-dihidro-3 -piridinil} amino)karbonil]amino }propanojska kislina, (3 S)-3 - {[({1 -(2-klorofenil)metil] -4-hidroksi-2-okso-1,2-dihidro3-kinolinil} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3- {[({1 -(2-klorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-[3-(trifluorometil)fenil]propanojska kislina, (3S)-3-{[({l-(2-klorofenil)metil]-4-({etil[(etilamino)karbonil]amino}-262262 (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3 - [ 3-methyl-4- (methyloxy) phenyl] propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -2-oxo-4-phenyl-1,2-dihydro3 - pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4 - [(2 - {[2 - (methyloxy) ethyl] oxy} ethyl) oxy] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3- { [({1 - [(2-chlorophenyl) methyl] -4-hydroxy-6-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid acid, (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4 - [(1,1-dimethylethyl) amino] -2-oxo-1,2-dihydro-3 pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1, 2-dihydro3-pyridinyl} amino) carbonyl] amino} -3-phenylpropanoic acid, (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4- [4-methyltetrahydro-1 (2H ) -pyrazinyl] -2ok co-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[({1- | (2-chlorophenyl) methyl] -4-Hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methyloxy) phenyl] propanoic acid, (3S) -3 - {[({1 - [( 2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3,5-dimethylphenyl) propanoic acid, (3 S) -3 - { [({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (3-methylphenyl) propanoic acid, (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- [3- (methyloxy) ) phenyl] propanoic acid, (3S) -3- [3,5-bis (methyloxy) phenyl] -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2- dihydro-3-pyridinyl} amino) carbonyl] amino} propanoic acid, (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro3- quinolinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy i-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- [3- (trifluoromethyl) phenyl] propanoic acid, (3S) -3 - {[({1- (2-chlorophenyl) ) methyl] -4 - ({ethyl [(ethylamino) carbonyl] amino} -263263 karbonil)amino]-2-okso-l,2-dihidro-3-piridinil}amino)karbonil]amino}-3-(4metilfenil)propanojska kislina, (3 S)-3 - {[({4-( 1 -azetanil)-1 - [(2-klorofenil)metil]-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino} -3 -(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -[(2-klorofenil)metil]-4-( {2- [(2{[2-(metiloksi)etil] oksi} eti l)oks i] etil} oksi)-2-okso-1,2-dihidro-3 piridinil]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-{[({l-(2-flurofenil)metil]-4-hidroksi-2-okso-l,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 - {[({1 -(2-kloro-6-fluorofenil)metil]-4-hidroksi-2-okso-1,2-dihidro3 -piridinil} amino)karbonil]amino} -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3-{ [({1 -(2-klorofenil)metil]-5-metil-2-okso-1,2-dihidro3-piridinil}amino)karbonil]amino}-3-(4-metilfenil)propanojska kislina, (3 S)-3 -(1,3 -benzodioksol-5-il)-3 -((((2-okso-1 -((4-(trifluorometil)fenil)metil)l,2-dihidro-3-piridinil)amino)karbonil)amino)propanojska kislina, (3 S)-3 -((((1 -((2-klorofenil)metil)-2-okso-1,2-dihidro3-piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina, (3 S)-3 -((((1 -((2-fluorofenil)metil)-2-okso-1,2-dihidro3-piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanojska kislina, (3 S)-3-(((( 1 -((2-bromofenil)metil)-2-okso-1,2-dihidro3 -piridinil)amino)karbonil)amino)-3 -(4-metilfenil)propanoj ska kislina, (3 S)-3-(((( 1 -((2,4-diklorofenil)metil)-2-okso-1,2-dihidro3-piridinil)amino)karbonil)amino)-3-(4-metilfenil)propanoj ska kislina, (3 S)-3-(((( 1 -((2-kloro-6-fluorofenil)metil)-2-okso-1,2-dihidro3 -piridinil)amino)karbonil)amino)-3 -(4-metilfenil)propanoj ska kislina, (3 S)-3-(((( 1 -((2-klorofenil)metil)-4-hidroksi-2-okso-1,2-dihidro3-piridinil)amino)karbonil)amino)-3-(4-trifluorometil)oksi)fenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metoksibenzil)-2-okso-l,2-dihidropiridin3- il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina,-263263 carbonyl) amino] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4methylphenyl) propanoic acid, (3 S) -3 - {[({4- ( 1-Azetanyl) -1 - [(2-chlorophenyl) methyl] -2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) - 3 - [({[1 - [(2-chlorophenyl) methyl] -4- ({2- [(2 {[2- (methyloxy) ethyl] oxy} ethyl) oxy and] ethyl} oxy) -2- oxo-1,2-dihydro-3 pyridinyl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1- (2-fluorophenyl) methyl] -4- hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[({1- (2-chloro-6 -fluorophenyl) methyl] -4-hydroxy-2-oxo-1,2-dihydro3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - {[( {1- (2-chlorophenyl) methyl] -5-methyl-2-oxo-1,2-dihydro-3-pyridinyl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3 S) -3 - (1,3-benzodioxol-5-yl) -3 - (((((2-oxo-1 - ((4- (trifluoromethyl) phenyl) methyl) 1,2-dihydro-3-pyridinyl) amino) carbonyl) amine o) propanoic acid, (3 S) -3 - (((((1 - ((2-chlorophenyl) methyl) -2-oxo-1,2-dihydro 3-pyridinyl) amino) carbonyl) amino) -3- (4 -methylphenyl) propanoic acid, (3 S) -3 - (((((1 - ((2-fluorophenyl) methyl) -2-oxo-1,2-dihydro3-pyridinyl) amino) carbonyl) amino) -3- ( 4-methylphenyl) propanoic acid, (3 S) -3 - (((((1 - ((2-bromophenyl) methyl) -2-oxo-1,2-dihydro3-pyridinyl) amino) carbonyl) amino) -3 - (4-methylphenyl) propanoic acid, (3 S) -3 - (((((1 - ((2,4-dichlorophenyl) methyl) -2-oxo-1,2-dihydro3-pyridinyl) amino) carbonyl) amino ) -3- (4-methylphenyl) propanoic acid, (3 S) -3 - ((((1 - ((2-chloro-6-fluorophenyl) methyl) -2-oxo-1,2-dihydro3-pyridinyl) ) amino) carbonyl) amino) -3- (4-methylphenyl) propanoic acid, (3S) -3 - ((((1 - ((2-chlorophenyl) methyl) -4-hydroxy-2-oxo-1 , 2-dihydro3-pyridinyl) amino) carbonyl) amino) -3- (4-trifluoromethyl) oxy) phenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-methoxybenzyl) - 2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, 4- {[3-[({[(lS)-2-karboksi-l-(4-metilfenil)etil]amino}karbonil)amino]1 -(2-klorobenzil-2-okso-1,2 - dihidrop iridin-4 - i 1] amino} benzoj ska kislina,4- {[3 - [({[(1S) -2-carboxy-1- (4-methylphenyl) ethyl] amino} carbonyl) amino] 1- (2-chlorobenzyl-2-oxo-1,2-dihydropyridine -4 - and 1] amino} benzoic acid, -264264 (3S)-3-{[({l-(2-klorobenzil)-4-[(2,2-dimetilpropanoil)amino]-2-okso-l,2dihidropiridin-3 -il} amino)karbonil] amino } -3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - [({[4- {[(terc.butilamino)karbonilamino]amino} -1 -(2-klorobenzil)-2-okso-1,2dihidropiridin-3 -il] amino } karbonil)amino]-3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - [({[ 1 -(2-cianobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(2,3-dihidro-1,4-benzodioksin-6-il)propanojska kislina, (3 S)-3 -[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(7-metoksi-1,3-benzodioksol-5-il)propanojska kislina, (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3 - il] amino} karbonil)amino] -3 -(3 -etoksi-4-metoksifenil)propanoj ska kislina, (3S)-3-[({ [l-(2-klorobenzil)-4-hidroksi-2-okso- 1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3,4-dimetoksifenil)propanojska kislina, (3 S)-3 - [({[ 1 -(4-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 -[( {[ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-5 -metil-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2,6-difluorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S )-3 - [( {[ 1 -(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3,5-dimetoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-metoksi-4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-265265-264264 (3S) -3 - {[({1- (2-chlorobenzyl) -4 - [(2,2-dimethylpropanoyl) amino] -2-oxo-1,2-dihydropyridin-3-yl} amino) carbonyl] amino } -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[4- {[(tert-butylamino) carbonylamino] amino} -1- (2-chlorobenzyl) -2-oxo- 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-cyanobenzyl) -4-hydroxy-2 -oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy] -2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (2,3-dihydro-1,4-benzodioxin-6-yl) propanoic acid, (3 S) -3 - [ ({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (7-methoxy-1,3-benzodioxol-5-yl ) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3 -Ethoxy-4-methoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine3-i 1] amino} carbonyl) amino] -3- (3,4-dimethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (4-chlorobenzyl) -4-hydroxy-2-oxo-1, 2-Dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy- 2-Oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-5-methyl-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1 - (2 , 6-difluorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[ 1- (2-Chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,5-dimethoxyphenyl) propanoic acid, (3 S ) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid , (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} k arbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (3-methoxy-4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1, 2-Dihydropyridine-265265 3-il]amino}karbonil)amino]-3-(3,5-dimetoksi-4-metilfenil)propanojska kislina, (3S)-3-[({ [1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3 -il] amino} karbonil)amino]-3 -(3,4-dimetilfenil)propanoj ska kislina, (3 S)-3 - [({[ 1 -(2-klorobenziI)-5-etil-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-{[({l-(2-kloro-5-(trifluorometil)benzil]-4-hidroksi-2-okso1.2- dihidropiridin-3-il}amino)karbonil]amino}3-(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metoksibenzil)-4-hidroksi-2-okso-l,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metilbenzil)-4-hidroksi-5-metil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2,6-dimetoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3-[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-propoksifenil)propanojska kislina, (3 S )-3 - [( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-5-propil-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-5,6-dimetil-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-5 -propil-1,2-dihidropiridin3-il] amino} karbonil)amino]-3 -(3,4-dietoksifenil)propanoj ska kislina, (3S)-3-(3-butoksifenil)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso1.2- dihidropiridin-3-il] amino }karbonil)amino]propanoj ska kislina, (3 S)-3 - {[({1 - [2-kloro-5 -(metilsulfonil)benzil]-4-hidroksi-2-okso1.2- dihidropiridin-3 -il} amino)karbonil]amino} -3 -(4-metilfenil)propanoj ska kislina, (3S)-3-[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3 -il] amino } karbonil)amino]-3 - [3 -(2-metoksietoksi)fenil]propanoj ska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin-2662663-yl] amino} carbonyl) amino] -3- (3,5-dimethoxy-4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2 -oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (3,4-dimethylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) - 5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - {[({1- ( 2-chloro-5- (trifluoromethyl) benzyl] -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl} amino) carbonyl] amino} 3- (4-methylphenyl) propanoic acid, (3S) -3- [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-methylphenyl) propanoic acid, ( 3S) -3 - [({[1- (2-chloro-6-methylbenzyl) -4-hydroxy-5-methyl-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridine- 3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2,6-dimethoxybenzyl) -4-hydroxy-2-ox o-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy- 2-Oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (3-propoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3 S) -3 - [({[1 - (2 -chlorobenzyl) -4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid acid, (3S) -3- (3-butoxyphenyl) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] propanoic acid, (3S) -3 - {[({1- [2-chloro-5- (methylsulfonyl) benzyl] -4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl} amino) carbonyl] amino} -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2 -oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- [3- (2-methoxyethoxy) phenyl] propanoic acid, (3 S) -3 - [({[1- (2- chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridine-266266 3-il]amino}karbonil)amino]-3-(3,4-dipropoksifenil)propanojska kislina, (3 S)-3-[( {[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-[3-(difluorometoksi)fenil]propanojska kislina, (3 S)-3-[({ [ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso- 1,2-dihidropiridin3-il]amino}karbonil)amino]-3-[3,4-(dietoksifenil)propanojska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metilbenzil)-4-hidroksi-5,6-dimetil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3 S)-3-[( {[ 1 -(2-kloro-6-cianobenzil)-4-hidroksi-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, 3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karboniljamino]-3-(2-naftil)propanojska kislina, (3 S)-3-[({ [1 -(2-klorobenzil)-4-hidroksi-5,6-dimetil-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metoksibenzil)-4-hidroksi-5-metil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(3,4-dietoksifenil)propanojska kislina, (3 S )-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3 -il] amino} karboniljamino] -3-(3 -izopropoksifeniljpropanojska kislina, (3S)-3-[({[(2-klorobenzil)4-hidroksi-5-metil-2-okso-l,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-metilbenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3S)-3-[({[l -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3-[({ [ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso1.2- dihidropiridin-3 -il] amino} karboniljamino] -3 -(3 -izopropoksifeniljpropanoj ska kislina,3-yl] amino} carbonyl) amino] -3- (3,4-dipropoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo- 1,2-Dihydropyridin-3-yl] amino} carbonyl) amino] -3- [3- (difluoromethoxy) phenyl] propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy] -5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- [3,4- (diethoxyphenyl) propanoic acid, (3S) -3 - [({[l- ( 2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3S) -3 - [( {[1- (2-Chloro-6-methylbenzyl) -4-hydroxy-5,6-dimethyl-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4- diethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-cyanobenzyl) -4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, 3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonylamino] -3- (2 -naphthyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyric acid) din3-yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-methoxybenzyl) -4-hydroxy-5 -methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3,4-diethoxyphenyl) propanoic acid, (3 S) -3 - [({[1- [2- chlorobenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin3-yl] amino} carbonylamino] -3- (3-isopropoxyphenylpropanoic acid, (3S) -3 - [({[(2-chlorobenzyl) 4-hydroxy] -5-methyl-2-oxo-1,2-dihydropyridin3-yl] amino} carbonyl) amino] -3- (4-methoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro) -6-methylbenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydrol-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid , (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3 -Ethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo 1,2-dihydropyridin-3-yl] amino } carbonylamino] -3- (3-isopropoxyphenylpropanoic acid, -267267 (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-1Hciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3-[({ [ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-( 1 -metil-1 H-indol-5-il)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(2,3-dihidro-1 -benzofuran-5il)propanojska kislina, (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso2,5,6,7-tetrahidro-lH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3,5dietoksifenil)propanoj ska kislina, (3 S)-3 - [({[5-kloro-1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3-propoksifenil)propanojska kislina, (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-fenilpropanojska kislina, (3S)-3-[({l-[(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(l,3-dietil-2-okso-2,3-dihidro1 H-benzimidazol-5 -il)propanoj ska kislina, (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5 -metil-2-okso1.2- dihidropiridin-3 -il] amino} karbonil)amino] - 3 - [3 (trifluorometoksi)fenil]propanoj ska kislina, (3 S)-3 - [({[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5,6-dimetil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3 S)-3 -[({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro-268268-267267 (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridine-3 -yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl -2-Oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (1-methyl-1H-indol-5-yl) propanoic acid, (3S) -3 - [({[1 - (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (2,3-dihydro-1-benzofuran -5yl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo2,5,6,7-tetrahydro-1H-cyclopenta [b ] pyridin-3-yl] amino} carbonyl) amino] -3- (3,5diethoxyphenyl) propanoic acid, (3S) -3 - [({[5-chloro-1- (2-chloro-6-ethoxybenzyl)] ) -4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3S) -3 - [({[1- (2- chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3S) -3 - [({[ 1- (2-Chloro-6-ethoxy) sibenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3-propoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino } carbonyl) amino] -3-phenylpropanoic acid, (3S) -3 - [({1 - [(2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydrolH-cyclopenta] [b ] pyridin-3-yl] amino} carbonyl) amino] -3- (1,3-diethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- [3 (trifluoromethoxy) ) phenyl] propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5,6-dimethyl-2-oxo] 1,2-dihydropyridine-3- yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5, 6,7-tetrahydro-268268 1 H-c iklopenta[b] piridin- 3 - i 1] amino} karbonil)amino]-3 -(1 -metil-1 H-indol- 5 il)propanojska kislina, (3 S)-3 -[({[ 1 -(2-kloro-6-etoksibenzil)-5-ciklopropil-4-hidroksi-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(3-izopropoksifenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-5-ciklopropil-4-hidroksi-2-okso1.2- dihidropiridin-3 -il]amino } karbonil)amino]-3 -(4-metilfenil)propanoj ska kislina, (3 S)-3 - [( {[ 1 -(2-kloro-5 -metoksibenzil)-4-hidroksi-5-metil-2-okso1,2-dihidropiridin-3 -il] amino} karbonil)amino] -3-(4-metilfenil)propanojska kislina, (3 S)-3-[({ [ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-6-metil-2-okso1.2- dihidropiridin-3 -il] amino} karbonil)amino]-3 -(3 -izopropoksifenil)propanoj ska kislina, (3 S)-3 - [( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso1.2- dihidropiridin-3-il]amino}karbonil)amino]-3-(l-metil-lH-indol-6-il)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il]amino} karbonil)amino] -3 - [3 (ciklopropiloksi)fenil]propanoj ska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-[3(ciklopropilmetoksi)fenil]propanoj ska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il]amino} karbonil)amino] -3 -[3 (ciklopropilmetoksi)fenil]propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il] amino} karbonil)amino]-3 -(3,5 -dimetilfenil)propanoj ska kislina, (3S)-3-{[({l-(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [(difluorometil)oksi]fenil}propanojska kislina, (3S)-3-{[({l-(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-2692691 Hc of cyclopent [b] pyridin-3 - and 1] amino} carbonyl) amino] -3- (1-methyl-1H-indol-5 yl) propanoic acid, (3 S) -3 - [({[1 - (2-chloro-6-ethoxybenzyl) -5-cyclopropyl-4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3S ) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -5-cyclopropyl-4-hydroxy-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3 - ( 4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-5-methoxybenzyl) -4-hydroxy-5-methyl-2-oxo 1,2,2-dihydropyridin-3-yl] ] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-6-methyl-2] -oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (3-isopropoxyphenyl) propanoic acid, (3 S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) ) -4-hydroxy-5-methyl-2-oxo 1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- (1-methyl-1H-indol-6-yl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro] 1H-cyclopene this [b] pyridin-3-yl] amino} carbonyl) amino] -3- [3 (cyclopropyloxy) phenyl] propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4- hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- [3 (cyclopropylmethoxy) phenyl] propanoic acid, (3S) - 3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl] amino} carbonyl ) amino] -3 - [3 (cyclopropylmethoxy) phenyl] propanoic acid, (3 S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7 -H-cyclopenta-tetrahydro [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3,5-dimethylphenyl) propanoic acid, (3S) -3 - {[({1- (2-chlorophenyl) ) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3 - {3 [(difluoromethyl) oxy] phenyl} propanoic acid, (3S) -3 - {[({1- (2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-269269 1 H-ciklopenta [b]pir idin-3 -i 1} amino)karbonil]amino} -3 - {3 - [(1,1,2,2tetrafluoroetil)oksi]fenil}propanojska kislina, (3 S)-3 - {[({1 - [(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 -(1 -etil-1 H-indol-5 -il) propanojska kislina in (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonilj amino} -3 - [3 (dietilamino)fenil]propanojska kislina in njihove farmacevtsko sprejemljive soli.1 H-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3 - {3 - [(1,1,2,2tetrafluoroethyl) oxy] phenyl} propanoic acid, (3 S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino } -3- (1-ethyl-1H-indol-5-yl) propanoic acid and (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo- 2,5,6,7-Tetrahydro-1H-cyclopenta [b] pyridin-3-yl} amino) carbonyl amino} -3- [3 (diethylamino) phenyl] propanoic acid and their pharmaceutically acceptable salts. 26. (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina in njene farmacevtsko sprejemljive soli.26. (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- ( 4-methylphenyl) propanoic acid and its pharmaceutically acceptable salts. 27. (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina in njene farmacevtsko sprejemljive soli.27. (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid and its pharmaceutically acceptable salts. 28. (3S)-3-[({[ 1 -(2-klorobenzil)-4-hidroksi-5-metil-2-okso-1,2-dihidropiridin3-il]amino}karbonil)amino]-3-(3-dietilamino)fenil]propanojska kislina in njene farmacevtsko sprejemljive soli.28. (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl) amino] -3- ( 3-Diethylamino) phenyl] propanoic acid and its pharmaceutically acceptable salts. 29. Spojina, označena s tem, daje izberemo iz skupine, ki obstoji iz naslednjih, kot so: (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(4-metilfenil)propanojska kislina, (3S)-3-[({[l-(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso-l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(3-etoksifenil)propanojska kislina, (3 S)-3 - [({[ 1 -(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3-il]amino}karbonil)amino]-3-(3izopropoksifenil)propanoj ska kislina,29. A compound selected from the group consisting of: (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl -2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (4-methylphenyl) propanoic acid, (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) ) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino] -3- (3-ethoxyphenyl) propanoic acid, (3 S) -3 - [({[ 1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7-tetrahydroH-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3isopropoxyphenyl) propane acid, -270270 (3 S)-3-[( {[ 1 -(2-kloro-6-etoksibenzil)-4-hidroksi-5-metil-2-okso- l,2-dihidropiridin-3il]amino}karbonil)amino]-3-(6-metoksi-2-naftil)propanojska kislina, (3S)-3-[({[l-(2-klorobenzil)-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3-il]amino} karbonil)amino] -3 -(3 -metilfenil)propanoj ska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3-il}amino)karbonil]amino}-3-(l-metil-lH-indol-5il)propanojska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro-lHciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [(metilsulfonil)amino]fenil}propanojska kislina, (3 S)-3- {[({1 -[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [(metil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidrolH-ciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [metil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-klorofenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil] amino} -3 - {3 [etil(metilsulfonil)amino] fenil }propanoj ska kislina,-270270 (3S) -3 - [({[1- (2-chloro-6-ethoxybenzyl) -4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3yl] amino} carbonyl) amino ] -3- (6-methoxy-2-naphthyl) propanoic acid, (3S) -3 - [({[1- (2-chlorobenzyl) -4-hydroxy-2-oxo-2,5,6,7- H-cyclopenta [b] pyridin-3-yl] amino} carbonyl) amino] -3- (3-methylphenyl) propanoic acid tetrahydro, (3S) -3 - {[({1 - [(2-chloro-6 -methylphenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- (1-methyl-1H- indole-5yl) propanoic acid, (3S) -3 - {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b ] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [(methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) ) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Hcyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [(methylsulfonyl) amino] phenyl) } propanoic acid, (3 S) -3- {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro1 H-cyclopenta [b] pyridine -3-yl} amino) carbonyl] amino} -3 - {3 [(methyl (methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] -4-hydroxy-2-oxo -2,5,6,7-TetrahydrolH-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [methyl (methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3- {[({1 - [(2-chlorophenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [ethyl (methylsulfonyl) amino] phenyl} propanoic acid, -271271 (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil]amino} -3- {3 [etil(metilsulfonil)amino]fenil}propanojska kislina, (3S)-3-{[({l-[(2-kloro-6-metilfenil)metil]-4-hidroksi-2-okso-2,5,6,7-tetrahidro1 H-ciklopenta[b]piridin-3 -il} amino)karbonil]amino} -3 -(1 H-indol-5 -il)propanoj ska kislina, in njihove farmacevtsko sprejemljive soli.-271271 (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- {3 [ethyl (methylsulfonyl) amino] phenyl} propanoic acid, (3S) -3 - {[({1 - [(2-chloro-6-methylphenyl) ) methyl] -4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [b] pyridin-3-yl} amino) carbonyl] amino} -3- (1H-indole-5 - il) propanoic acid, and pharmaceutically acceptable salts thereof. 30. Farmacevtski sestavek, označen s tem, da obsega spojino po zahtevku 1 v farmacevtsko sprejemljivem nosilcu.A pharmaceutical composition comprising the compound of claim 1 in a pharmaceutically acceptable carrier. 31. Uporaba spojine po zahtevku 1 za pripravo zdravila za selektivno inhibiranje α4βι integrinske vezave pri sesalcu.Use of a compound according to claim 1 for the preparation of a medicament for selectively inhibiting α 4 βι integrin binding in a mammal.
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