TWI345465B - Proteasome inhibitors and methods of using the same - Google Patents

Description

1345465 IX. Description of the Invention: [Technical Leadership of the Invention] The present invention relates to a dihydroxyboron pit and a dihydroxyborane ester compound which can be used as a white matter degrading body inhibitor and a modulated cell. [Prior Art]

Protein degradation bodies (also known as multi-catalytic proteinases (MCP), multi-catalytic proteases, multi-catalytic protease complexes, multi-catalytic endopeptidase complexes, 20S, 26S or giant alizarin) are present in A breakdown of all eukaryotic cells - a large multi-protein complex of both cytoplasm and nucleus. It is a highly conserved cellular structure responsible for ATP-dependent proteolysis of most cellular proteins (Tanaka, ocA, es., pp. 1998, 537). The 26S protein degradation system contains a 20S core catalytic complex that is capped at each end by a 19S regulatory subunit. The cytoplasmic 20S protein degrading body contains fourteen copies of two different types of subunits, alpha and yt, which form a cylindrical structure comprising four stacked rings. The top and bottom rings each contain seven sub-units, while the inner ring contains seven yS-subunits. The more complex eukaryotic 20S egg cold white matter degradation system consists of about 15 different 20-30 kDa subunits, and its characteristics are the three main activities related to peptide acceptor. For example, protein degradants display trypsin-, chymotrypsin- and peptidyl glutamine-peptidyl-hydrolysis activities (Rivett, ocAem. /, 1993, 29/, 1 and Orlowski, 1990, 2P, 10289 ). Furthermore, protein degradants have a unique active site mechanism and are generally considered to use sulphonic acid residues as catalytic nucleophilic groups (Seemuller et al.,

Science, 1995, 268, 519). The 26S protein degradation system is capable of degrading proteins that have been labeled with 95014 1345465 by the addition of ubiquitin molecules. Typically, ubiquitin is linked to a lysine & amine-based polyubiquitinated receptor protein system in a multi-step process using ATP and E1 (ubiquitin-activated) and E2 (ubiquitin-conjugated) enzymes. It is identified by the 26S protein degradation body and is degraded. Polyubiquitin chains are generally released from complexes and recover ubiquitin (Goldberg et al., 1992, 357, 375) »

Many regulatory protein lines are receptors for ubiquitin-dependent proteolysis. Many of these protein systems act as modulators of physiological and pathophysiological cellular processes. Alterations in the activity of protein degrading organisms involve a variety of pathological conditions, including neurodegenerative diseases such as Bajin's disease, Alzheimer's disease, and occlusion/separational reperfusion injury, and aging of the central nervous system. The ubiquitin protein degrading pathway also plays a role in tumor growth. Regulatory degradation of salty 4 proteins such as quercetin, CDK2 inhibitors and tumor suppressors is important in cell cycle progression and mitosis. The species of protein decomposer is known as the tumor dust suppressor p53, which is involved in several cellular processes (see, for example, wu-6, W =

The inhibitor P53 has (4) actually caused cell gamma in several hematopoietic cell lines ((4) M., 〇_纸 1994, ;, 221). The p53 causes cell growth inhibition in cell cycle (4) and cell death due to cytoplasm. It is known that the degradation of p53 by the tumor suppressor is carried out via the ubiquitin-protein degradation pathway, and the degradation of the degradation by the degradation of the protein is a possible mode of causing cell wilting. The protein degrading body is also required to activate the inhibitory substance by degrading the transcription factor = mass I (9), and (10) war% is contaminated by the transcription of the cell-regulating inhibitor to maintain cell survival 95014 1345465 , has a role. Blockade of NF-/cB activity has been shown to make cells more susceptible to fading.

Several inhibitors of the proteolytic activity of protein degradants have been reported. See, for example, Kisselev et al., /6 Xuelan Lan#, 2001, <?, 739. The lactacysamine is a Streptomyces metabolite that specifically inhibits the proteolytic activity of protein degradation complexes (Fenteany et al., 1995, 726). This molecule is capable of inhibiting proliferation of several cell types (Fenteany et al., /Voc. iVai/. «Sd. C/SL4, 1994, 97, 3358). It has been shown that lactacysine undergoes irreversible binding to the threonine residue at the amino terminus of the protein degrading rash subunit via its bed ester moiety.

Peptide aldehydes have been reported to inhibit chymotrypsinogen activity associated with protein degradation bodies (Vinitsky et al., 1992, 37, 9421; Tsubuki et al., 5z_oc/zem. Commtm., 1993, /96). , 1195; and Rock et al., Ce//, 1994, 7<?, 761). Dipeptide-based aldehyde inhibitors (Iqbal, Μ., et al, J. Med. Chem., 1995, 2276) having an in vitro IC5 enthalpy in the KMO OnM range have also been reported. The same effective in vitro inhibitors have been reported from a series of α-ketocarbonyl groups and dihydroxyborane ester-derived dipeptides (Iqbal et al., 〇〇 M Met/· C/iem. 1 hunger, 1996 , 287, U.S. Patent Nos. 5,614,649; 5,830,870; 5,990,083; 6,096,778; 6,310,057; U.S. Patent Application Publication No. 2001/0012854 and WO 99/30707). N-terminal peptidyl dihydroxy borane esters and acid compounds have been previously reported (U.S. Patent Nos. 4,499,082 and 4,537,773; WO 91/13904; Kettner et al, J. 〇/. CAem·, 1984, 259(24), 15106) . These compounds are reported to be inhibitors of certain proteolytic enzymes. The N-terminal tri-peptide dihydroxyborane ester and the acidified 95014 1345465 compound have been shown to inhibit the growth of cancer cells (U.S. Patent 5,106,948). A broad class of N-terminal tri-peptide dihydroxyborane esters with acid compounds and analogs thereof has been shown to inhibit sylvestre (U.S. Patent 5,169,841). Various inhibitors of protein degrading peptide peptidase activity have also been reported. See, for example, Dick, et al., 1991, 30, 2725; Goldberg et al, Nature, 1992, 357, 375; Goldberg, Eur. J. Biochem., 1992, 203, 9; Orlowski, Biochemistry, 1990, 29, 10289 ; Deaf, Archs·Biochem. Biophys.,

1989, Knife 5, 1 ; Rivett et al., /· 5zo/· C/zem·, 1989, 2(54, 12215; Tanaka et al., iVew 历/., 1992, 彳, 1; Murakami et al., iVoc Mzi/· jciwi. &7'· C/&4, 1986, 53, 7588 ; Li et al., odem plus 1991, 30,9709; Goldberg, quintuple /· Βωάιετη.,\99Ί,203, 9 ·, Sl specific protease and biological control,

Cold Spring Harbor Laboratory Press (1975), pp. 429-454.

U.S. Patent Application Serial No. 08/212,909, the entire disclosure of which is incorporated herein by reference in its entirety to the entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire portion These compounds are also said to reduce the rate of degradation of p53 protein in animals. Palombella et al., WO 95/25533, report the use of peptide aldehydes by contacting animal cells with a protein dermatological function or a ubiquitin-conjugated peptide aldehyde inhibitor to reduce cellular content in animals and NF-/ cB activity. Goldberg and Rock, WO 94/17816 report the use of protein degrading inhibitors to inhibit the presentation of MHC-I antigens. Stein et al., U.S. Patent No. 5,693,617, which is incorporated herein by reference in its entirety, is incorporated herein by reference in its entirety in its entire entire entire entire entire entire entire disclosure in The 26S and 20S protein degradants are inhibited by a hydroquinone derivative, and a method for inhibiting cell proliferation using an indolone derivative is reported by Lum 95014 1345465 et al., U.S. Patent 5,834,487. In mammals, alpha-ketoguanamine compounds useful in the treatment of conditions mediated by 20S protein degrading agents are reported in Wang et al., U.S. Patent 6,075,150, France et al., WO 00/64863, report 2, Use of a 4-diamino-3-hydroxycarboxylic acid derivative as a protein degradation inhibitor. A carboxylic acid derivative as a protein degradation inhibitor is reported by Yamaguchi et al., EP 1166781. Ditzel et al., EP 0995757 report a bivalent inhibitor of protein degradation. A 2-aminomercaptomycin-derived substance that inhibits the chymotrypsinogen activity of a 20S protein degrading body in a non-covalent manner, has been approved by Garcia-Echeverria et al., (8) rg. Med. CAem.Z/batch , 2001, ", 1317 Report. Some other protein degradation inhibitors may contain boron partial groups. For example, Drexler et al., WO 00/64467 report the use of a protein degradation agent inhibitor containing four skin dihydroxyborane vinegar in a activated endothelial cell or leukemia cell having a high expression level of c-myc, optionally A method that causes cells to die. Furet et al., WO 02/096933 report 2-[[N-(2-amino-3-(heteroaryl or aryl)propenyl)amine fluorenyl]amino]alkyldihydroxyborane and ester Class, ® In warm-blooded animals, for the treatment of proliferative diseases. U.S. Patent Nos. 6,083,903, 6, 297, 217, 5, 780, 454, 6, 066, 730, 6, 297, 217, 6, 548, 668; U.S. Patent Application Publication No. 2002/0173488; and WO 96/13266, disclose dihydroxy borane esters and acid compounds, and a method for reducing the rate of protein degradation. A method of inhibiting viral replication using certain dihydroxyboranes and esters is also reported in U.S. Patent Nos. 6,465,433 and WO 01/02424. A pharmaceutically acceptable composition of a dihydroxyborane with a novel dihydroxyborane anhydride and a dihydroxyboran ester compound is reported by plamond〇n et al., U.S. Patent Application Publication No. 95014,10- 1345465 2002/0188100. In Gardner et al., ocAew. /, 2000, 447, a series of di- and tripeptide-based dihydroxy scaffolds are inhibitors of 20S and 26S protein degradants. Other Peptidyl-containing and related compounds are reported in U.S. Patent Nos. 5,250,720, 5,242,904, 5,187,157, 5,159,060, 5,106,948, 4,963,655, 4,499,082, and WO 89/09225, WO 98/17679, WO 98/22496, WO 00/66557,

WO 02/059130, WO 03/15706, WO 96/12499, WO 95/20603, WO 95/09838, WO 94/25051, WO 94/25049, WO 94/04653, WO 02/08187, EP 632026 and EP 354522 in. As evidenced by the above references, there is great interest in drugs that modulate the activity of protein degrading organisms. For example, a molecule capable of inhibiting the activity of a protein degrading body can suppress or delay the progression of cancer by interfering with the regular degradation of cell cycle proteins or tumor suppressors. Therefore, there is a current need for new and/or improved protein degradation inhibitors. [Summary of the Invention]

The present invention is directed to novel dihydroxyborane and dihydroxyborane ester compounds which can be used as protein degradation inhibitors and cell wilting modulation. "The invention also includes a multi-catalytic protease C'MCP" which inhibits certain disorders. The method includes treatment of a muscle wasting condition. In a specific embodiment, a compound of formula (I) is provided:

95014-11 wherein the component members and the preferred component members are defined below in another embodiment, the invention provides a pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable carrier Agent. In another embodiment, the invention provides a method of inhibiting the activity of a protein degrading agent comprising contacting a compound of formula (I) with the protein degrading agent. In another embodiment, the invention provides a method of treating cancer comprising administering a therapeutically effective amount of a compound of formula 1 to a mammal having or susceptible to the cancer. In another specific embodiment, the invention provides a method of treating cancer comprising administering to a mammal having or susceptible to the cancer a therapeutically effective amount of a compound of formula (I), and wherein the cancer is selected from the group consisting of Skin, prostate, colorectal, pancreas, kidney, ovary, breast, liver, tongue, lung, and smooth muscle tissue. In another embodiment, the invention provides a method of treating cancer comprising administering a therapeutically effective amount of a compound of formula (I) to a mammal having or susceptible to the cancer, and wherein the cancer is selected from the group consisting of Leukemia, lymphoma, non-Hodgkin lymphoma, myeloid cell tumor and multiple myeloma. In another embodiment, the invention provides a method of treating cancer comprising administering a therapeutically effective amount of a compound of formula (I) to a mammal having or susceptible to the cancer, and using one or more anti-tumor Or anticancer agents and / or radiation therapy. In another embodiment, the invention provides a method of inhibiting transcription factor NF_ /cB activity comprising contacting I/cB, a transcription factor inhibitor, 95014 12 1345465, with a compound of formula (i) In another specific embodiment, the invention provides a method of preparing a compound of formula (II):

(II) wherein the component members are defined herein by the formula (π-b) diol:

(II-b) Reacts with the appropriate formula (ΙΙ-a) trialkoxyborane: r17o /OR17

OR17 (Π-a) wherein the group injury members are defined herein, under the conditions and conditions suitable for the formation of the intermediate of formula (II-c):

(II-c) and the intermediate of formula (II-c), under the conditions and conditions of the formula (II) suitable for the formation of the compound of formula (II): 9514 -13 - 1345465, and the formula of the formula RiCI^MXha1, wherein the ruthenium is a metal And Xhal is a halogen atom, or ii) a reaction of the formula R1 CH2 Li. These and other features of the compounds will be presented in an expanded form as disclosed in the continued disclosure. Description of a specific embodiment of the invention

The present invention specifically provides a compound which inhibits the activity of a protein degrading body and is useful for treating a disease or condition associated with the activity of a protein degrading body. The compounds of the invention include a compound of formula (I)

Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: is a heart-alkyl group, a c2-c8 alkenyl group, a C2-C8 alkynyl group or a c3-c7 cycloalkyl group;

R2 is Η, -(CH2)a CH2 NHC(=NR4)NH-Y, _(ch2)b CH2 CONR5 R6, -(CH2)c CH2 N(R4)CONH2, -(CH2)d CH(R7)NR9 R1 〇 or -(CH2)eCH(R7)ZR8 ; a, b and c are each independently 〇, 1, 2, 3, 4, 5 or 6; d and e are each independently 〇, 1, 2, 3 or 4 R4 is an alkyl group; R5 and R6 are each independently Η, Cl-C1()alkyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or R5 and R6 together with the N atom to which they are attached A heterocarbon ring group is formed; R is Η or C! -Ci 〇 基; 95014 -14· 1345465 R is Η, Ci -C! 〇 基, 院 _s(=〇) 2 -, aryl-S (=0) 2 -, H2NS(=0)2-, -S03H or a protecting group; R9 is an anthracene, a Q-Cw alkyl group, a carbocyclic group or a heterocarbocyclic group; R10 is an anthracene, a Ci-Cw alkyl group, Carbocyclyl, heterocarbocyclyl, Cl_Cl0 alkyl _C(-0)-, C2-C1Q dilute-C(=0)-, C2-Ci 〇 fast-C(=0)-, carbocyclic group -C(=0)-, heterocarbocyclyl-c(=0)-, carbocyclylalkyl·(:(=〇)-, heterocarbon% ketone-C(-0)-, c! -C! 〇院基-S(=0)2 -, carbocyclyl-S(=0)2 -, φ heterocarbocyclyl-s(=0)2·, carbocyclyl-S(= 0) 2·, heterocarbocyclylalkyl spring-S(=〇)2-, CrCio alkyl-NHC (=0) _, carbocyclyl-NHC (=0)-, heterocarbocyclyl-NHC (=0)-, carbocyclylalkyl_NHC (=0>, heterocarbocyclylalkyl-NHC (=0)- , Q 〇院基-〇C(=0)- 'carbocyclyl _〇c(=〇)·, heterocarbocyclyl-carbonyl (=0> 'carbocyclylalkyl-〇C(=0)_ , heterocarbocyclyl-based alkyl group - 0C (=0)-, (VC!. alkyl-NH-C(=0)-NHS(=0)2-, carbocyclyl-NH-C(=0)- NHS(=0)2 -, heterocarbocyclyl _NH_C (=(7)_,

Ci oxime-S(=0)2 -NH-C(=0)-, carbocyclyl _s(=〇)2, φ heterocarbocyclyl-SpOh-NH-CK^- or amine protecting group Wherein Rio is replaced by 1, 2 or 3 R23 as φ; or R9 together with Rio and the N atoms to which they are attached form a heterocarbocyclic group, which is optionally 1, 2 or 3 R2 3 Substitution; Y is Η, _CN, -N〇2, -S(=0)2 R11 or fluorenyl protecting group; Ruler 11 is <:1-(:6 alkyl, aryl or nr12ru; R and R13 Independently Η, c! -C! 〇alkyl, carbocyclyl, heterocarbocyclyl guanamine protecting group; or R12 and R13 together with the atoms to which they are attached to form a heterocarbocyclic group; 95014 -15-" 45465 2 is Ο, S, Se or Te; Q is -B(OH)2, -B(OR14)2 or cyclic dihydroxyborane ester, wherein the cyclic di-based borax vinegar contains 2 to 20 a carbon atom, and optionally a hetero atom which may be N, S or hydrazine; R14 is H'C^-C: 4 alkyl, cycloalkyl 'cycloalkylalkyl, aryl or aralkyl; X Is RA C(=0)-, RA NHC(=0)-, RA S(=0)2 -, RA 〇C(=〇)-, RA SC(=0)- or RA;

RA is a q-CM alkyl group optionally substituted by R2G; a C2-C2G alkenyl group optionally substituted by R2G; a C2-C2Q alkynyl group optionally substituted by R2G; a carbocyclic ring optionally substituted by 1 to 5 R21 a heterocarbon ring group substituted with 1-5 R21 as appropriate; the R2Q system is selected from the group consisting of:

-CN, halo, dentate-, Ci-C4 alkyl, C2-C4 dilute, C2-C4 fast radical, -C〇2 Η, -C(=0)C〇2 Η, -C(= 0) NH2, -0(=0)11, -S(=0)NH2, -S(=0)2NH2, -OH, -SH, -ΝΗ2, -ΝΗ(alkyl), -N(alkyl) 2. -NHC(=0)NH2, -NHC(=O)R20a, -NHC(=O)OR20a, -OR20a, -SR20a, -S(=O)R20a, -S(=O)2R20a, -S (=O)2-NHR20a, -SC(=O)R20a, -C(=O)R20a, _C(=O)NHR20a, -C(=O)O-R20a, -NHS(=O)2R20a,- NHR20b, phthaliminium, -(〇-alkyl)r-OH, -(0-alkyl)r-(〇-alkyl), -〇R2Qc, -SR2Gc, -Ο-alkyl -R20c, -S-alkyl-R20c, -S(=O)-R20c, -S(=O)2-R20c, -S(=O)2-NHR20c, -sc(=o)r20c, -C (=O) R20c, -C(=O)OR20c, -C(=0)NHR2 0 c, carbocyclic group substituted by 1-5 R21 as the case may be; and 95014 -16-1345465 case is 1-5 a heterocarbyl group substituted with R21; an alkyl group, a c2-c20 alkenyl group or a c2_C2 decynyl group; wherein the alkyl, alkenyl or alkynyl group is optionally substituted by one or more halo groups, 0H, CN, q - C4 alkyl, Q-C4 alkoxy, C2-C8 alkoxyalkoxy, aryl, heteroaryl or -NHR2Gb substituted; R2()b is an amine protecting group; R20c Cycloalkyl group is optionally substituted with 1-5 of R22 carbons; or optionally substituted with 1-5 of R22 heteroaryl carbocyclyl;

R21 is selected from the group consisting of: CVCm alkyl, C2-C2 nonenyl, c2-C2 decynyl, -OR21a, -SR21a, _CN, _ group, _alkyl, -NH2, -NH(alkyl), - N(alkyl) 2, -NHC(=0)0-alkyl, -NHC(=0)alkyl, -COOH, -C(=0)0-alkyl, -C(=0)alkyl, -C(0)H, -S(=0)-hospital, -S(=0)2 _ alkyl, -S(=0)-aryl, -S(=0)2-aryl, visual a carbocyclic group substituted with 1 to 5 R22 and a heterocarbocyclic group optionally substituted with 1 to 5 R 2 2;

R21a*H, CVCm alkyl, C2-C2 nonenyl, C2-C2 decynyl, carbocyclyl or heterocarbocyclyl; R22 is selected from the group consisting of:

Cl -Cl arsenazo, C 2 -Cl 〇, C 2 -Cl decynyl, phenyl, hydryl, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino 'dialkylamine Base, carboxyl group, alkyl-〇C(=0)-, alkyl-c(=0)-, aryl-0C(=0)-, alkyl-0C(=0)NH-, aryl-0C (=0) NH-, alkyl_C(=0)NH-, alkyl-C(=0)0·, (alkyl-〇)r_alkyl, H0-(alkyl-0)r • Alkyl _, ·0 Η, -SH, -CN, -N3, -CNO ' -CNS, alkyl-S(=0)-, alkyl-S(=0)2-, 95014 -17- 1345465 H2 NS (=0)- and H2 NS(=0)2 _ ; R23 is selected from the group consisting of: CVQ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, F, Cl, Br, I, haloalkyl, - NH2, -NHR23a, -N(R23a)2, -N3, -N02, -CN, -CNO, -CNS, -C(=0)0R23a, -C(=〇)R23a, -0C(=0)R23a , -N(R2 3 a )C(=0)R2 3 a, -N(R2 3 a )C(=0)〇R2 3 a, -C(=0)N(R2 3 a )2, Urea group , -OR2 3 a' -SR2 3 a, -S(=〇)-(Ci -C6 alkyl), -S(=0)2 -(q -C6 alkyl), -S(=0)-fang a group, -S(=0)2-aryl, -S(=0)2-N(R23a)2; a carbocyclic group substituted with 1-5 R24 depending on the situation; and optionally replaced by i_5 r24 a heterocarbocyclyl; R23a is H or a Ci-Q alkyl; Alternatively, two R23a may be combined with the N atom to which they are attached to form a 5- to 7-membered heterocyclic group; and R24 is selected from the group consisting of:

Ci-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, hydrazine Carboxyl, alkyl-0C(=0)-, alkyl-c(=o)-, aryl-〇〇(=〇)-, alkyl-0C(=0)NH-, aryl-0C(= 0) NH-, alkyl-C(=0)NH-, alkyl_C(=0)〇-, (hospital-oxime)r-alkyl, H0-(alkyl-0)r-alkyl -, -0H, -SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkyl-S(=0)2-, H2NS(=0)·, and h2NS( =0) 2 -; and r is 1,2,3,4,5,6,7,8,9 or 1〇; the condition is 'when Q is ^2,2-tetradecylethanediol In the case of dihydroxyborane ester, then X is not an aralkoxycarbonyl group; 95014 •18· 1345465 with the proviso that when Q is 1,1,2,2-tetradecylethanediol dihydroxyborane ester And when R1 is a cycloalkyl group, then R2 is not -CH2CONH2; and with the proviso that when X is RAC(=0)-, RA is a C4-C15 linear alkyl group substituted by R20, and R2Q is -CN, -C02H, -C(=0)0-R2()a, -NHS(=0)2R2()a, -NHC(=0)R2()a, -NHR2()b or phthalate When the carbenium imine group; then R2 is not -(CH2)aCH2NHC(=NR4)NH-Y, where Y is Η, -CN -Ν〇2 or a guanidino protecting group.

In a further embodiment, when R2 is _(CH2)eCH(R7)ZR8, e is 0, R7 is Η, 圮 is ^7(7)alkyl, and X is RAC(=0)-, then RA is not It is an amine group, an amine group, a dialkylamine group or a ketone group. In some embodiments, R1 can be a -C4 alkyl group, and in further specific embodiments, R1 can be a propyl group, such as a 2-propyl group. In some embodiments, R2 can be -(CH2)a CH2 NHC(=NR4)NH-Y, -(CH2)bCH2CONR5R6, -(CH2)cCH2N(R4)CONH2, -(CH2)dCH(R7) NR9 R10 or -(CH2)e CH(R7)ZR8.

In some embodiments, R2 is -(CH2)aCH2NHC(=NR4)NH-Y, and a is 1, 2, 3, 4 or 5. In some embodiments, R2 is -(CH2)aCH2NHC(=NR4)NH-Y, and a is 2. In some embodiments, R2 is -CH2CH2CH2NHC(=NR4)NH-Y. In some embodiments, R2 is -(CHJdCKKR^NR9!^ 〇, and d is 0, 1, or 2. In some embodiments, R2 is -(CH2)dCH(R7)NR9R1(), and d Is 0. In some embodiments, R2 is -(CHOdCHCR^NI^R10, and R9 is 95014-19-1345465 Η. In some embodiments, R1 2 3 4 5 6 is -(CI^dCHiRqNR7! In some embodiments, R2 is -CHCRqNl^R8. In some embodiments, R2 is -CH2NH-C(=0)0CH2(C6H5). In some embodiments, R2 is -( CH2) eCH(R9)ZR10, and e is 0 ' 1 or 2.

In some embodiments, R2 is _(CH2)eCH(R9)ZR10 and e is zero. In some embodiments, R2 is _(CH2)eCH(R9)ZR10. In some embodiments, R2 is _CH(R9)ZR10. In a further embodiment, Z is zero. In a further embodiment, Q has the formula (II_a):

95014 •20- 1

X 2 . And 3 (Ha) 4 wherein D, R15a, Rl5b, Rl5c, Rl5d, p and q are as defined below in ά 5 In a further embodiment, Q is Β(0Η) 2 or cyclic dihydroxyborane 6 vinegar, Wherein the cyclic dihydroxyborane ester contains from 6 to 10 carbon atoms and contains 7 in a further embodiment 'Q is a decanediol dihydroxyborane ester. 8 In a further embodiment, 'Q is a dicyclohexyl glycol dihydroxyboron. 9 at least one cycloalkyl moiety. In a further embodiment, Q is Β(ΟΗ)2. In a further embodiment, 9 is a 1 boryl borane. ~ 3 ‘, 实实苑例 t, Q is -B(OH)2, -B(OR14)

〆 Ο -Β

Oh,

*R 15c

Rl5d

\ /〇, Y (CH2)p ό. /NH (CH2)q where: R1 4, R1 5 a, 5 b are defined.

Rl5c, Rl5d, w, W1 p and q are as follows. In a further embodiment, Q is:

W is a substituted or unsubstituted c4-c1()cycloalkyl ring. In some embodiments, X is rAc(=〇)_. In some embodiments, χ is rAnHC(=〇)_. In some embodiments, X is RAS(〇)2-. In some embodiments, RA is Ci-Cl4 alkyl substituted with _(〇-alkyl)r-〇H or _(〇-alkyl)r-(0-alkyl), wherein r is 1. 2, 3, 4 or 5. In some embodiments, RA is a C[-C14 yard based on _(〇炫)r-0H or -(0-炫95014 •21-1345465) Γ-(〇-alkyl), wherein , 2 or 3. In some specific palladium examples, 'RA contains at least one _CH2CH2〇- group. In some embodiments, 'RA is, CH2(〇CH2ai2X()eH3. In some embodiments, 'RA' is _CH2〇CH2CH2〇CH2CH2C)CH3 or -CH2 OCH2CH2 OCH3. In some embodiments, RA is aryl or heteroaryl, each optionally substituted with from 1 to 5 R21. In some embodiments, RA is cycloalkyl or heterocycloalkyl, each optionally substituted with from 1 to 5 R21. In some embodiments, #为〇1<2〇 alkyl; C2_c2 decene Or a C2-C2G alkynyl group, each optionally substituted by 112(). In some embodiments, an alkyl group; c2_c2 nonenyl; or a C2-C:2 decynyl group, each substituted by a carbocyclic or heterocarbocyclyl group, wherein the carbocyclic or heterocarbocyclyl group is optionally Replaced by 1, 2 or 3 R21. In some embodiments, an alkyl group; a C2_C2q alkenyl group; or a C2<2 decynyl group, each substituted with an aryl group, wherein the aryl group is optionally substituted with hydrazine, 2 or 3 R21. In some embodiments, an alkyl group; a C2_C2 fluorene group; or a 匸2-C2 decynyl group, each substituted with a heteroaryl group, wherein the heteroaryl group is optionally substituted with 1, 2 or 3 R21. In some embodiments, RAGCi-Qo alkyl; C2_C20 cyclized; or A-〇2 decynyl' are each substituted with a cycloalkyl group, wherein the cycloalkyl group is optionally replaced by 1, 2 or 3 R21 . In some embodiments, an alkyl group; a C2-C20 dilute group; or a 95014-22-2345465 c2-c2G alkynyl group, each substituted with a heterocycloalkyl group, wherein the heterocycloalkyl group is optionally 1, 2 or Three R21 substitutions.

In some embodiments, RAaCVQoalkyl; C2-C20 alkenyl; or C2-C20 alkynyl, each optionally substituted by R2, wherein R20 is selected from the group consisting of CN, halo, haloalkyl, -co2h, - c(=o)co2h, -C(=0)NH2, -C(=0)H, -S(0)NH2, -S(0)2NH2, -OH, -SH, -NH2, -NH (alkane Base), -N(alkyl)2, -NHC(=0)NH2, -NHC(=O)R20a, -NHC(=O)OR20a, -OR20a, -SR20a, -S(O)R20a, -S (O) 2R20a, -S(O)2-NHR20a, -SC(=O)R20a, -C(=O)R20a, -C(=O)NHR20a, -C(=O)〇-R20a, -NHS (O) 2R20a, -NHR20b, phthalimido, -(〇-alkyl), -(〇-alkyl)r-OH, -(〇-alkyl)r-(〇-alkyl ), -OR20c, -SR20c, -〇-alkyl-R20c, -S-alkyl-R20c, -S(O)-R20c, -S(O)2-R20c, -S(O)2-NHR20c, -SC(=O)R20c ' -C(=O)R20c, -C(=0)0R2 0 c and -C(=0)NHR2 0 c. In some embodiments, R2 is H and X is (O-alkyl)-(〇-alkyl)r-(C]4 alkyl)-C(=0)- or HO-(alkyl- 0)r -(Q -C! 4 alkyl)-C(=0)-.

In some embodiments, X is RAC(=0)- and RA is a C4-C16 alkyl group. In some embodiments, X is RAC(=0)- and RA is an aryl group optionally substituted with 1-3 R21. In some embodiments, X is RAC(=0)- and RA is a heterocarbocyclyl optionally substituted with 1-3 R21. In some embodiments, X is RAc(=0)-; RA is a phenyl substituted by one R21; and R2! is a phenoxy group. In some embodiments, X is RaC(=0)-, RA is a Q-C4 alkyl group substituted by R2Q and r2〇 is an aryl group substituted by a ruler 2! as appropriate; and in another 95014- 23- 1345465 In further embodiments, the aryl is substituted with at least one halo. In some embodiments, X is RAC(=〇)·; RA is a Cl-Cl4 alkyl group substituted by R2 ;; and R20 is _〇R20a4〇R20c. In some embodiments, X is RAc(=〇)· ; ra is a Ci-Cw alkyl group substituted by R20; and a 2' is a heterocarbocyclic group optionally substituted with 13 RZ1. In some embodiments, X is RAS(〇)2_ and rA is c3_Ci 6 alkyl. In some embodiments, the invention provides a compound of formula 1, wherein the stereochemistry has the formula (I_S):

(I-s) or a pharmaceutically acceptable salt form thereof. In some embodiments, the invention provides a compound of formula 1

Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein:

RlCVQ alkyl, C2-C8 alkenyl, C2-C8 alkynyl or C3-Cp_t alkyl; R2 is Η, -(CH2)aCH2NHC(=NR4)NH-Y, -(CH2)bCH2CONR5R6, -(CH2)c CH2 N(R4)CONH2, -(CH2)d CH(R7)NR9 R10 or -(CH2)eCH(R7)ZR8; 95014 -24-5 or 6; a 'b and c are each independently 〇, Xia, 2 3d and e are each independently 〇, 1, 2, 3 or 4; R4 is Η or Ci-C! 〇alkyl; heterocarbocyclyl or amine R5 and R6 are each independently Η, Cl_Cl. An alkyl group or a carbocyclic group; a heterocarbon ring group; or R5 and R6 and the atoms to which they are attached - R7 is Η *(:!-(:! 〇 alkyl;

R8 is Η, Cl-Cl. Alkyl, alkyl-s(=〇)2, aryl hydrazine, H2NS(=〇)2-, .s〇3h or protecting group; R9 is hydrazine, q-CM alkyl, carbocyclic or heterocarbon Ring group; Rl ° is Η, CA. Alkyl, carbocyclic, heterocarbocyclyl, Ci Ci. Alkyl-CH))-, carbocyclyl-C (which, heterocarbocyclyl-c(=〇)_, carbocyclic group

-c(=〇)-, heterocarbocyclic thiol fluorene), Ci Α 〇 _ _s (= 〇) 2, carbocyclic group - s (= 〇) 2, heterocarbocyclyl _s (=0)2·, carbocyclylalkyl n, heterocarbocyclylalkyl-S(=0)2_, C1-C1G alkyl-NHC(=〇)_, carbocyclyl•NHCK))-, Heterocarbocyclyl-NHcpo)·, carbocyclylalkyl, heterocarbocyclylalkyl-NHC (=0>, Cl-C1G alkyl-0C(=0)·, carbocyclic group

-〇c(=o)-, heterocarbocyclyl-_0C (=0>, carbocyclylalkyl 〇c(=〇)·, miscyl-alkylalkyl·0(:(=0)- or amine a protecting group; wherein R10 is optionally substituted by 1, 2 or 3 R23; or 妒 together with the ruler 10 and the N atoms to which they are attached form a heterocarbocyclic group; Y is -H, -CN, -N02 , -SpOhR11 or thiol protecting group; RU is cvc6 alkyl, aryl or NR12R13;

Rl2 and R13 are independently an anthracene, a q-Cw alkyl group, a carbocyclic group, a heterocarbocyclyl group or an amine 95014-25 group protecting group; or, Ri2 and R13 together with the atoms to which they are attached form a heterocarbocyclic group; Z is 〇, s, Se or Te; Q is Β(ΟΗ)2, -BCOR14)2 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxy sulfonate ester has 2 to 20 carbon atoms, and Included as a hetero atom which may be N, S or hydrazine; R14 is H'q-C: 4 alkyl, cycloalkyl 'cycloalkylalkyl, aryl or aralkyl; X is RaC (=0) )-, RaNHC(=0)-, RaS(=〇)2-, ra〇c(=〇)_, rAsc(=0)- or Ra; RA is a q-CM alkyl group optionally substituted by R2Q; a C2-C2Q alkenyl group substituted by R2Q, optionally a C2-C2Q alkynyl group substituted by R2G; a carbocyclic group substituted with 1-5 R21 as appropriate; or a heterocyclic ring substituted by 1-5 R21 as appropriate Carbocyclyl; R2G is selected from the group consisting of: -CN, iS, haloalkyl, C! -C4 alkyl, C2 - C4 alkenyl, C2 - C4 alkynyl, -C02H, -C(=0)C02H , -C(=0)NH2, -C(=0)H, -S(=0)NH2, -S(=0)2NH2, -OH, -SH, -NH2, -NH(alkyl), - N(alkyl)2, -NHC(=0)NH2, -NHC(=O)R20a, -NHC(=O)OR20a, -OR20a, -SR20a, -S(=O)R20a, -S(=O)2R20a, -S(=O)2-NHR20a, -SC(=O)R20a, -C(=O)R20a, -C (=O)NHR20a, -C(=〇)〇-R20a '-NHS(=O)2R20a, -NHR20b, o-diphenylenimine, alkyl)r, -0-alkyl group _OH,- (0-^*)r-OH, -OR20c, -SR2()c, -〇-alkyl-R2()c, -S-alkyl-R20c, -S(=0)-R2()c, -S(=O)2-R20c, 1345465 -S(=〇)2-NHR20c, -SC(=O)R20c, -c(=o)r20c, -c(=o)or20c, -C(=0 a NHR2Ge, a carbocyclic group optionally substituted with 1 to 5 R21; and a heterocarbocyclyl group optionally substituted with 1 to 5 R21; an alkyl group, a C2-C20 alkenyl group or a C2-C20 alkynyl group; The alkyl, alkenyl or alkynyl group is optionally substituted by one or more halo, alkyl, aryl, heteroaryl or -NHR2()b; &2()13 is an amine protecting group; R2( And e is a carbocyclic group substituted with 1-5 R22 as the case may be; or a heterocarbocyclic group substituted with 1 to 5 R22 as the case may be; R21 is selected from the group consisting of: 匸1-匸2〇 基, 〇2 -〇2〇 dilute base, 〇2-匚2〇 block base, 〇!1<2〇 alkoxy group, q-C20 thioalkoxy group, -OH, -CN, dentate group, haloalkyl group, -NH2 -NH(alkyl), -N(alkyl)2, -NHC(=0)0-alkyl, -NHC (=0) alkyl, -C(=0)0_alkyl, -c(=o)alkyl, -S(=0)-alkyl, -s(=o)2-alkyl, -s( =o)-aryl, -S(=0)2-aryl, carbocyclic group optionally substituted by 1 to 5 R22; and heterocarbocyclic group optionally substituted by 1 to 5 R22; R22 Selected from:

Cl -Cl Q alkyl, C 2 -Cl 〇 dilute, C 2 -Cl Q fast radical, phenyl, functional group, halogen-based, alkoxy, sulfur alkoxy, amine, acryl, diplex I Amine, carboxyl, alkyl-〇c(=o)-, alkyl-c(=o)-, aryl-oc(=o)-, alkyl-0C(=0)NH-, aryl- 0C(=0)NH-, alkyl-C(=0)NH-, alkyl-C(=0)0-, (alkyl-0)r-alkyl, H0-(alkyl-0)r -alkyl·,-0H, -SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkyl-S(=0)2 _, H2 NS(=0) - and H2 NS (=0) 2 -, 95014 • 27- R23 are selected from:

Ci-Cg, C2-Cg, such as C2, C2 - Cg, F, Cl, Br, I, haloalkyl, -NH2, -NHR23a, -N(R23a)2, -N3, -N02, - CN, -CNO, -CNS, -C(=0)0R23a, -C(=0)R23a, -〇C(=0)R23a, -N(R2 3 a )C(=0)R2 3 a,- C(=0)N(R2 3 a )2, ureido, -〇R2 3 a, -SR2 3 a' -SPCOHCVQ alkyl), -s(=0)2-aryl and -S(=0) 2-N(R23a)2; 1^233 is 11 or (:1-(:6 alkyl); or, two R23a may be combined with the N atom to which they are attached to form a 5- to 7-membered heterocyclic ring. a group of groups; and Γ is 2, 3, 4, 5, 6, 7, 8, 9 or 1〇; and the conditional condition is 'when Q is ^2,2-tetramethylethanediol dihydroxyboron In the case of an alkyl ester, 'X is not an aralkoxycarbonyl group; the condition is 'when Q is i, 2,2-tetramethylethanediol dihydroxyborane vinegar' and R1 is a cycloalkyl group, then R2 is not -CH2C〇NH2; and the condition is that when X is rac(=〇)·, rA is a C4_Ci5 linear alkyl group substituted by R2〇, and R2G is _CN, _c〇2h, _C( =〇)〇-R20a, _NHS«)2R2Qa, -NHC(=0)R2()a, -NHR20b or phthalic acid imine; then R2 is not _(;CH2)aCH2NHC(=NR4) NH_Y, Wherein γ is Η, -CN, -Ν〇2 or thiol protecting group. In some embodiments, Ri is 2·propyl; R 2 is Η, -(CH 2 ) a CH 2 NHC (=NR 4 ) NH-Y > -(CH2 )b CH2 CONR5 R6 ' -(CH2 )c CH2 N(R4 )CONH2,(CH2 )d CH(R7 )NR9 R10 or •(〇ί2)εαι(ίΐ7)ζίΐ8; q is _B(0H) 2 or decanediol dihydroxyborane ester; χ is RAC (=0)-; and RA is c4_Ci6 alkyl; optionally 丨3 R; Z1 substituted 95014 -28-1345465 aryl; or Heterocarbocyclyl β substituted by 1-3 R21 In some embodiments, the invention provides a compound of formula (I)

Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: φ is a heart--alkyl group; R2 is -(CH2)aCH2NHC(=NH)NH-Y, _(CH2)cCH2NHCONH2, _ (CH2 )d CH(R7 )NR9 R1 〇 or _(CH2 )e CH(R7 )ZR8 ; a is 1, 2, 3, 4 or 5; c is 1, 2, 3, 4 or 5; d is 0 , 1 or 2; e is Ο, 1 or 2; R7 is Η or methyl; φ R8 is Η, Ci -C! 〇 alkyl, -s(=0)2 -alkyl, -s(=0) 2 -Aryl, _s(=0)2 -ΝΗ2, -so3h or protecting group; Y is -Η, -CN, -N〇2, -S(=0)2Ru or fluorenyl protecting group; R9 is Η, Q-Cm alkyl, carbocyclyl or heterocarbocyclyl; R is H, Q-Cw alkyl, carbocyclyl, heterocarbocyclyl, Ci_Ci decyl-C(=〇)_, carbocyclyl _ c(=〇)_, heterocarbocyclyl _c(=〇), carbocyclylalkyl-c(=o)-, heterocarbocyclylalkyl_c(=0)-, Ci _Ci oxime _s(=0)2 _, carbon%-S(=0)2 -, heterocarbocyclyl-s(=0)2, carbocyclylalkyl_s(=〇)2 _, heterocarbon Ring base group -S(=0)2 -, Q morphine group, carbocyclic group 95014 •29· 1345465 -NHC(=0)-, heterocarbocyclyl-NHC(=0)_, carbocyclylene -NHC(=0)_ 'heterocarbocyclylalkyl-NHC (=0>, q G alkyl-0C(=0)-, Cyclol-00(=〇)·, heterocarbocyclyl-〇C(=〇)-, carbocyclylalkyl-〇C(=〇)-, heterocarbocyclylalkyl-〇C(=0) Or an amine protecting group; wherein Ri 〇 is optionally substituted by 1, 2 or 3 R 23 ; or R 9 together with Ri 〇 and the N atom to which they are attached form a heterocarbocyclic group; R 11 is (^-( ^alkyl, aryl or NR12Ri3;

R and R13 are independently oxime, Ci-Ci decyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or R12 and Ri3 together with the atoms to which they are attached form a heterocarbocyclic group; Z is 〇 Or s ; ^ Q is -B(OH)2, -BPR14)2 or cyclic dihydroxyborane ester, complex, T硪-formed dihydroxyborane ester contains 6 to 20 carbon atoms and contains right π芏a less than a cycloalkyl moiety; R14 is hydrazine, (VC4 alkyl or cycloalkyl;

X is RAC(=0)-, RA 腾(=〇)_, RAS(=〇)2_, RA〇c(=〇)·, RA or RA; ~)- RA is q- replaced by R2G as appropriate CM alkyl; C2-C2Q dilute group substituted by R2G; C2_C2Q alkynyl substituted by R2G as appropriate; carbocyclic group substituted by 1 - 5 R21 as appropriate. Substituted by 1-5 R21 a heterocarbocyclyl; R20 is selected from the group consisting of: -CN, halo, halo-, C, -C, 栌: a: n 〇1 q alkyl, c2-c4 alkenyl, C2_c 95014 -30. Alkynyl, -C02H, -C(=0)C02H, -C(=0)NH2, -C(=0)H, -S(=0)NH2, -S(=0)2NH2, -OH, - SH, -NH2, -NH(alkyl), -N(alkyl)2, -NHC(=0)NH2, -NHC(=O)R20a, -NHC(=O)OR20a, -OR20a, -SR20a, -S(=O)R20a, -S(=O)2R20a, -S(=O)2-NHR20a, -SC(=O)R20a, -C(=O)R20a, -C(=O)NHR20a, -C(=O)O-R20a, -NHS(=O)2R20a, -NHR20b, phthalic acid imine, -(〇-alkyl)r, 〇-alkyl-〇H, _( 0·&*)r-0H,_0R2Gc, -SR2()e,-0-alkyl-R20c, -S-alkyl-R20c, -S(=0)-R2()c, -S(= O)2-R20c, -S(=O)2-NHR20c ' -SC(=O)R20c ' -C(=O)R20c ' -C(=O)OR20c ' -C(=0)NHR2Gc, as appropriate Replaced by 1-5 R21 a carbocyclic group; and a heterocarbocyclyl group optionally substituted with 1 to 5 R21; an alkyl group, a C2-C20 alkenyl group or a C2-C2 alkynyl group; wherein the alkyl, alkenyl or alkynyl group is optionally One or more halo, alkyl, aryl, heteroaryl or -NHR2Gb substituted; R2^b is an amino protecting group; a carbocyclic group substituted with 1-5 R22 as appropriate; or optionally - 5 R22 substituted heterocarbocyclyl; R21 is selected from the group consisting of: 〇1_〇2〇 base, 〇2-〇2〇 baking base, 〇2<2〇 fast base, 〇^<2 〇院Oxy, q-C2 oxiranyloxy, -OH, -CN, halo, dentate, -NH2, -NH(alkyl), -N(alkyl)2, -NHC(=0)0 -alkyl, -NHC(=〇)alkyl, -C(=0)0-alkyl, -C(=0)alkyl, -S(=0)-alkyl, -S(=0)2 -alkyl, -s(=o)-aryl, -S(=0)2-aryl, carbocyclyl optionally substituted by 1-5 R22 and optionally substituted by 1-5 R22 Carbocyclyl; 1345465 R22 is selected from the group consisting of: CVCb alkyl, c2-c1()alkenyl, c2-c1()alkynyl, phenyl, self-group, haloalkyl, alkoxy, thioalkoxy' Amino, alkylamino, dialkylamino, carboxy, alkyl-oc(=o)-, alkyl-c(=o)-, aryl-00 (=0) -, alkyl-0C(=0)NH-, aryl-0C(=0)NH-, alkyl-C(=0)NH-, alkyl-C(=0)0-, (alkyl- 0) r-alkyl, H0-(alkyl-0)r-alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkane Base -S(=0)2 - 'H2NS(=0)- and H2NS(=0)2-;

R23 is selected from the group consisting of: CVQ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, F, Cl, Br, I, haloalkyl, -ΝΗ2, -NHR23a, -N(R23a)2, -Ν3, -Ν02 ' -CN, -CNO, -CNS, -C(=0)0R23a, -C(=0)R23a, -0C(=0)R23a, -N(R2 3 a )C(=0)R2 3 a, -C(=0)N(R2 3 a )2, urea group, -OR2 3 a, -SR2 3 a, -S(=0)2 -(q -C6 alkyl), _S(=0) 2-aryl group and -S(=0)2 -N(R2 3 a )2 ; group;

Or 'two R23a may be combined with the N atom to which they are attached to form a 5 to 7 membered heterocyclic group; and Γ is 2, 3, 4, 5, 6, 7, 8, 9 or 10 The condition is that when X is RAc(=〇)_, rA is C4_Ci 5 linear alkyl group substituted by R2〇 and R20 is _CN, -C02H, -C(=O)O-R20a, -NHS(=C〇2il2()a, -NHC(=0)R2()a, -NHR201^ phthalic acid imine; then R2 is not -(CH2)aCH2NHC(=NR4)NH- Y, wherein Y is hydrazine, _CN, -Ν02 or fluorenyl protecting group. In a further embodiment, the invention provides a compound of formula 1 95014 - 32· 1345465

Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof; wherein: is a ^-decyl group;

R2 is -(CH2)a CH2 NHC(=NH)NH-Y, _(CH2)c CH2NHCONH2 or -(CH2)dCH(R7)NR9R10; a is 1, 2 or 3; c is 1, 2 or 3 d is 0 or 1; R7 is hydrazine or methyl; R is hydrazine or Ci-Ci fluorenyl, hydrazine, alkyl or amine protecting group; Y is hydrazine, CN or N〇2;

Q is -b(oh)2, decanediol dihydroxyborane ester, dicyclohexyl-1,1'-diol dihydroxyborane or 1,2-dicyclohexyl-ethane_1,2_ The diol dihydroxyborane X is RAC(=0)-, RaNHC(=0)-, RaS(=〇)2-, rA〇c(=〇)_, rasc(=〇)· or RA; RA is Substituted by r2G (VCm alkyl; C2_C2() thin group substituted by R2G as appropriate; C2-C2Q alkynyl substituted by R20 as appropriate; carbocyclic group substituted by 1-5 R21 as appropriate; bite 95014 -33- 1345465 Heterocarbocyclyl substituted by 1-5 R21 as appropriate; R2G is selected from the group consisting of:

-CN, halo, i-alkyl-, CVQ-alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -co2h, -c(=o)co2h, -C(=0)NH2, -C(= 0) H, -S(=0)NH2, -S(=0)2NH2, -OH ' -SH, -NH2, -NH(alkyl), -N(alkyl)2, -NHC(=0) NH2, -NHC(=O)R20a, -NHC(=O)OR20a, -OR20a, -SR20a, -S(=O)R20a, -S(=O)2R20a, -S(=O)2-NHR20a, -SC(=O)R20a, -C(=O)R20a, -C(=O)NHR20a, -C(=O)O-R20a, -NHS(=0)2R2Ga, -NHR2Gb, phthalate Imino, -(〇-alkyl)r, -〇-alkyl-OH, -(0-alkyl)r-〇H, -〇R2Qc, -SR2Ge, -0·alkyl-R20c, -S -alkyl-R20c, -S(=O)-R20c, -S(=O)2-R20c, -S(=O)2-NHR20c, -SC(=O)R20c, -C(=O)R20c , -C(=O)OR20c, -C(=0)NHR2 G e, a carbocyclic group substituted with 1-5 R 2 1 as the case may be; and a heterocarbocyclic group substituted with 1-5 R 2 1 as the case may be ; hospital base, C2-C20 alkenyl or 〇2<2〇 fast base;

Wherein the alkyl, alkenyl or alkynyl group is optionally substituted by one or more halo, q-C4 alkyl, aryl, heteroaryl or -NHR20b; R2 (3bs amine protecting group; R2Qe is optionally a carbocyclic group substituted with 1 to 5 R22; or a heterocarbocyclic group optionally substituted with 1 to 5 R22; R2 1 is selected from the group consisting of:

Ci-C2 (3 alkyl, C2-C2 nonenyl, C2-C2 fluorenyl, C^-C^q alkoxy, C!-C20 thioalkoxy, -OH-CN, halo, halo Alkyl, _NH2, -NH(alkyl), -N(alkyl)2, -NHC(=0)0-alkyl, -NHC(=0)alkyl, -C(=〇)〇·95014 - 34- 1345465 alkyl, -c(=o)alkyl, -s(=o)-alkyl, -s(=o)2-alkyl, -s(=o)-aryl, -S(= 0) a 2-aryl group, a carbocyclic group optionally substituted by 1 to 5 R 2 2 and a heterocarbocyclic group optionally substituted by 1 to 5 R 2 ;

Cl oxime, C2-Ci 〇, C2-C10, benzyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl , alkyl-〇c(=o)-, alkyl-C(=0)-, aryl-0C(=0)-, alkyl-0C(=0)NH-, aryl-0C (=0 NH-, alkyl-C(=0)NH-, alkane φ-C(=0)0-, (alkyl-)r-alkyl, HO-(alkyl-)r-alkyl -, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkyl-S(=0)2 ·, H2 NS(=0)_ and H2 NS(=0)2 ·; and r is 2, 3, 4 or 5; with the proviso that when X is RAC(=〇)-, RA is a C4_Ci 5 straight bond-like base replaced by R2〇 and When R20 is -C02H, -C(=O)O-R20a, _NHSH^2K2Qa ' ·ΝΗ0:(=〇)Ι^&, or phthalic acid imine, then R2 is not -(CH2 aCH2NHC(=NR4)NH-Y, where Υ φ is Η, -CN or -Ν02. In still a further embodiment, the invention provides a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is Cl-C6 alkyl, C2_C6 alkenyl, C2_C6 Alkynyl or fluorene-cycloalkyl; R2 is -CH2NH2 or -CH2 NR9 R10; R9 is alkyl; P is hydrazine, Cl-Cl. Alkyl, carbocyclic, heterocarbocyclyl, μ. Alkyl ()* %, yl-C(-O), heterocarbocyclyl _c(=〇), carbocyclic group 95014 -35-

-C(=〇)-, heterocarbocyclylalkyl-c(=0)-, q 0 alkyl-s(=o)2 -, carbocyclyl-S(=0)2-'heterocarbon ring Base-s(=0)2-, carbocyclylalkyl-s(=o)2-, heterocarbocyclylalkyl-S(=0)2-, C! decyl-NHC (=0) -, carbocyclyl-NHC (=0) - 'heterocarbocyclyl-NHC (=0)-, carbocyclylalkyl-NHC (=0)- 'heterocarbocyclylalkyl-NHC (=0> , CVCw alkyl-0C(=0)-, carbocyclyl-〇C(=〇)_, heterocarbocyclyl _〇c(=〇)_, carbocyclylalkyl_〇c(=〇)_ , a heterocarbocyclylalkyl-OC(=0)- or an amine protecting group; wherein the Ri〇 is optionally substituted by 1, 2 or 3 R 2 3 ; or R 9 and R 10 and the N atom to which they are attached Forming a heterocarbocyclic group together; Q is -B(OH)2, -BCOR14)2 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms, and optionally contains a hetero atom which may be N, S or hydrazine; R14 is H'Ci-C4 alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; X is RAC(=0)_, RaNHC ( =0)-, RaS(=0)2·, rA〇c(=〇)_, rasc(=〇)· or RA;

RA is a Ci-Czo alkyl group which is optionally substituted by R20; a C2-C2Q alkenyl group which is optionally substituted by R2Q; a C2-C2Q alkynyl group which is optionally substituted by R2Q; a carbocyclic ring which is optionally substituted by 1 to 5 R21 a heterocarbocyclyl group substituted with 1 to 5 R 2 1 groups; R 2 () is selected from the group consisting of: -CN, a group, a functional alkyl group, a q -C 4 alkyl group, a c 2 -C 4 alkenyl group, C2 -C4 alkynyl, -C02 Η, -C(=0)C02 Η, -C(=0)NH2 ' .(:(=〇)!!, -S(=0)NH2, -S(=0 2NH2, -〇Η, -SH, -Νη2, shed (alkyl), 95014 -36-1345465 -N(alkyl)2, -NHC(=0)NH2, NHC(=0)R2()a , -NHC(=0)0R2()a, -OR20a, -SR20a, -S(=O)R20a, -S(=O)2R20a, -S(=O)2-NHR20a, -SC(=O) R20a, -C(=O)R20a, -C(=O)NHR20a, -C(=O)O-R20a, -NHS(=O)2R20a, -NHR20b, phthalic acid imine, -( 〇_alkyl)Γ,-0-alkyl-OH, -(Ο-alkyl\-011,-0112()<:,-3112()<:,-0-alkyl-R20c,- S-alkyl-R20c, -S(=O)-R20<:, -s(=o)2-r20c, -S(=O)2-NHR20c, -SC(=O)R20c, _C(=O R20c, -C(=O)OR20c, -C(=0)NHR2Gc, a carbocyclic group substituted with 1-5 R21 as appropriate; and a heterocyclic ring substituted by 1-5 R21 a cyclic group; a "seven" alkyl group, a C2-C20 alkenyl group or a C2-C20 alkynyl group; wherein the alkyl, alkenyl or alkynyl group is optionally one or more functional groups, q-Ct alkyl , aryl, heteroaryl or -NHR2Gb substituted; 1^2()15 is an amino protecting group; R2Ge is a carbocyclic group optionally substituted by 1 to 5 R22; or optionally substituted by 1 to 5 R22 Heterocarbocyclyl; R21 is selected from the group consisting of: Lu

Ci -C2 〇 pit base, C2 - C2 〇 alkenyl, C2 - C2 快 fast radical, Ci - C2 〇 alkoxy,

Ci-C2 sulfonium alkoxy, -OH-CN, halo, haloalkyl, -NH2, (throw), -N(alkyl) 2, -NHC(=0)0-alkyl, _NHC ( =0) alkyl, -C(=0)0-alkyl'-C(=0)alkyl, -S(=0)-hospital, _s(=〇)2-alkyl, -S(= 0)-^, -S(=0)2-aryl, a carbocyclic group substituted with 1-5 R2 2 and optionally a heterocarbocyclic group substituted with 1-5 R2 2; R22 Selected from:

Ci-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, phenyl, functional group, 95014 37-Ϊ345465 haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dioxane Amine, carboxyl, alkyl-〇c(=o)-, alkyl-c(=o)-, aryl-oc(=o)-, alkyl-OC(=0)NH-, aryl- 0C(=0)NH·, alkyl-C(=0)NH-, alkyl-C(=0)0-, (alkyl-〇)r-alkyl, H0-(alkyl-0)r -alkyl-,-0H, -SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkyl-S(=0)2 -, H2NS(=0)- And H2NS (=0)2-; R23 is selected from the group consisting of:

Burning base, dilute base, C2-Cg block group, F, Cl, Br, I, halogen group, -ΝΗ2, -NHR2 3 a, -N(R2 3 a )2, -Ν3, -Ν〇2, - CN, _CNO, -CNS, -C(=0)0R2 3 a, -C(=〇)R2 3 a, -〇c(=0)R2 3 a, -N(R2 3 a )C(=0) R2 3 a, -C(=0)N(R2 3 a )2, urea group, -〇R2 3 a ' _SR2 3 a ' -S(=0)2 -(Ci -C6 alkyl), -s( =0) 2 -aryl group and -S(=0)2 -N(R2 3 a )2 ; alkyl group;

Alternatively, two R23a may be combined with the N atoms to which they are attached to form a 5- to 7-membered heterocyclic group; and r is 2, 3, 4 or 5. In still a further embodiment, the invention provides a compound or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form of Formula 1, wherein: R1 is (VQ alkyl, c2-c8 alkenyl, c2 -c8 alkynyl or alkyl; Han 2 is oxime; Q is -B(OH)2, -B(OR14)2 or cyclic dihydroxyborane ester, wherein the cyclic di-based boron vinegar contains 2 to 20 carbon atoms, and as the case may be: a hetero atom which may be N, S or hydrazine;

Rl4 is H, CV (: 4 counties, ring filaments, ring-based base, aryl or aryl groups; X is RAC (=0)-, rAnhc (=0)-, RAS (=0) 2-, RA〇C(=0)-, RASC(=〇)· or RA; RA is a Cl-C2() alkyl group optionally substituted by r2〇; C2-C2Q alkenyl substituted by R2G as appropriate; a C2-C2G alkynyl group substituted by R2G; a carbocyclic group optionally substituted by 1 to 5 R22; or a heterocarbocyclic group optionally substituted by 1 to 5 R2 2; the R2Q is selected from the group consisting of: -OR20a ^ - SR20a ^ -S(=O)R20a > -S(=〇)2R2〇a. -S(=0)2-NHR2〇a . -SC(=〇)R20a, -C(=〇)R20a,- C(=〇)NHR20a, -C(=〇)〇.R2〇a, o-o-dimethylanilinium, -(〇-alkyl)r, 〇·alkyl-〇H,-(〇_烧-) - - - - - - - - - - - - - - - - - - - - - - -R20c ' -S(=O)2-NHR20c ' -SC(=〇)r2〇c λ -C(=0)R2()e, _c(=〇)〇r2〇c, <(=〇) _·, a carbocyclic group substituted by i 5 R22 as the case may be; and a heterocarbocyclic group substituted by 丨5 ft. 22 as the case may be; 尺2〇3 is Ci-C^o burning base, C2-C2〇 a dilute group or a C2-C20 alkynyl group; wherein the pendant, alkenyl or alkynyl group is as appropriate Substituted by one or more halo, q-c4 alkyl, aryl, heteroaryl or -NHR20b; R2()c is a carbocyclic group optionally substituted with 1-5 R22; or optionally 1- 5 R22 substituted heterocarbocyclyl; R22 is selected from the group consisting of: Q-Cioalkyl, C2-C10 alkenyl, C2-C10 alkynyl, phenyl, alkyl, haloalkyl, alkoxy, sulfane Oxyl, amine, alkylamino, dialkylamine 1345465, carboxy, alkyl-oc(=o)-, alkyl-c(=o)-, aryl-oc(=o)-, alkyl -OC(=0)NH·, aryl-0C(=0)NH-, alkyl-C(=0)NH-, alkyl-〇(=0)〇-, (alkyl-〇)r- Affiliation, H0-(alkyl-0)r-alkyl-, 〇Η, -SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkyl-S (=0) 2 -, H2NS (=0) - and H2NS (=0) 2; and r is 2, 3, 4, 5, 6, 7, 8, 9 or 10. In still further embodiments :

X is RAC(=0)- 'RANHC(=0)-, RAS(0)2- or RA; RA is CVCm alkyl substituted by R20 as appropriate; R20 is -(Ο-alkyl)r-〇H Or -(〇-alkyl)r-(〇-alkyl); and r is 1, 2, 3, 4 or 5. In a further embodiment, the 0-yard group is methoxy, ethoxy or propoxy. In still a further embodiment, the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is 2-propyl;

R2 is -CH2CH2CH2NHC(=NH)NH-N02, -CH2CH2CH2NHC(=0)NH2, CH(CH3)OH, -CH2CONH2, -CH2NH2 or -CH2NR9R10; R9 is H; R10 is methyl-C(=0)- , ethyl-c(=0)-, propyl-C(=0)-, butyl-c(=0)-, pentyl-C(=0)-, 2-(ethoxycarbonyl)ethyl _c(=0)_, 4·decyl-phenyl-C(=0)-, cyclopropyl_c(=0)_, 4·fluorophenyl (:(=〇)-, 4-H2NS 〇2-phenyl-C(=0)-, 4-H3CS02-stupyl-c(=0)-, 4-phenyl-phenyl-C(=0)-, 3,4-dimethoxy ·Ge-C(=0)-, 3-pyridyl-C(=0)-, 2-(radio)-bite-3-yl-C(=0)-, 6-(? Base)-p ratio bite·3·yl-C(=〇)- ' 2-(v>pyridin-4-yl>pyrazol-4-yl-C(=0)-, 2-pyrylene -c(=0)-, 2,5-dimethyl-95014 •40- 1345465 p than spyryl-C(=0)·, N-mercapto-2-?l-l-based-C(=0) -, 2-tetrahydro p is more specific than decyl-C(=0)-, 2-thiophenyl-C(=0)·, 5-iso-1^defenyl-C(=0)-, 4-( Tetras-5-yl)phenyl-C(=0)-, (5-tetrazolyl)CH2-C(=0)-, N-H3CS02-hexahydropyridyl-C(=0)-, butyl Base-〇C(=0)-, (benzyl)-0C(=0)-, (9-diylmethyl)-〇C(=0)-, pentyl-NHC(=0)-, C Base-NHC (=0)-, stupid-NHC (=0)·, 4-methyl- -NHC(=0)-, methyl-S(=0)2-, 4-fluorophenyl-S(=0)2-, 4-cyano-styl-S(=0)2-, 1-methyl-imidazol-4-yl-S(=0)2-, 2-thiophenyl-S(=0)2-, (4-methyl-phenyl)-NHC(=0)NH- 0 ® S(=0)2 - and (4-mercapto-phenyl)-S(=0)2NHC(=0)-, or, R9 and R10 together with the N atom to which they are attached form a pyrrolyl group or Pyrazolyl; Q is -B(OH)2, decanediol dihydroxyborane ester, dicyclohexyl glycol dihydroxyborane ester or 1,2·dicyclohexyl-ethane_1,2-diol Dihydroxyborane ester; X is rac(=o)-, ranhc(=o)_, RaS(=0)2- or raoc(=o)-; Φ# is CH3-, C2H5-, c3h7-, c4h9 -, C5H"-, C6H13-, C7H15-, φ C8H17-, C9H19-, C10H21-, CuHu-, C12H25-, C13H27-, gold steel alkyl-, bicycloheptanyl-, replaced by R2G (: Bu 3 alkyl; C2-1 nonenyl substituted by R20; cyclopropyl substituted by 0-3 R2 1; cyclopentyl substituted by 0-2 R2 1; substituted by 0-2 R2 1 Cyclohexyl; a styl group substituted by 0-3 R2 1; 95014 -41· 1345465 naphthyl substituted by 0-2 R21; pyridyl substituted by 0-1 R21; 0-1 R2. a substituted quinolinyl group; An imidazolyl group substituted with 0-1 R21; a tetrahydrofuranyl group substituted with 0-1 R21; a ketothiazolidinyl group substituted with 0-1 R21; a benzoxazolyl group substituted with 0-1 R21;

a thiazolyl group substituted with 0-2 R2 1; a furyl group substituted with 0-2 R21; a tetrahydropyrrole group substituted with 0-1 R21; a hexahydropyridyl group substituted with 0-1 R2 1 ; a hexahydropyrazine substituted by 0-1 R2 1; or a pyridyl group substituted by 0-1 R21; R2() is selected from the group consisting of: hydroxy-, decyloxy, ethoxy, propoxy · Butoxy-, pentyloxy-, hexyloxy-, heptyl-, octyloxy-, methoxyethoxy-, methoxyethoxyethoxy-, methyl-S -, ethyl-S-, octyl-s-, fluorenyl-C(=0)s-, (ethylammonium) fluorenyl-S-, amino-, methylamino-, diammonium -, mercapto-C(=0)-, stupid-C(=0)-, .(H3CS02)phenyl-C(=0)-, thiostyl-c(=0)-, methyl· 0(:(=0)-, ethyl-0C(=0)-, butyl-0C(=0)NH-, fluorenyl-C(=〇)NH-, methoxyethoxymethyl_ C(=0)NH-, H2NC(=0)·, methyl-NHC(=0)_, ethyl-NHC(=0)-, propyl-NHC(=0)-, phenyl-NHC〇 =0)-, H2NC(=0)NH-, H2NS(=0)2-, octyl-s(=0)2-, phenyl-s(=o)2-, nonylphenyl 95014·42 · 1345465

_S(=0)2 -, thiophenyl-S(=0)2-, cyclodecyl-, cyclohexyl-, cycloheptyl-, gold-steel alkyl-, bicycloheptyl-, cyclopentenyl -, phenyl, methoxy-phenyl-, methyl-phenyl, di-decyl-phenyl-, ethyl-phenyl-, propyl-phenyl-, butyl-phenyl-, Fluorophenyl-, di-phenyl-phenyl-, phenyl-, bromophenyl-, iodophenyl-, dimethylamino-phenyl-, cyclohexyloxy-, 2-isopropyl-5- Methyl-cyclohexyloxy-, decyl-, methoxyindenyl-, naphthyloxy-, phenoxy-, (methyl-phenyl)oxy-, (ethyl-phenyl)oxy -, (propyl-phenyl)oxy-, (butyl-phenyl)oxy, (fluorophenyl)oxy-, (oxyphenyl)oxy-, (bromophenyl)oxy- , mercapto-S-, benzyl-S-, (decyl-phenyl)methyl-S-, pyrimidinyl-S-, hexahydropyridyl-, N-methyl-hexahydrop-bite-- , n-propyl-hexa-argon p-bite-, o-phthalimido-, thiophenyl-, decyl-thiophenyl-, imidazolyl-, fluorenyl-, tetradecyl- a ketotetrahydroanthracene ratio π-group-, a fluorenyl- and a methyl-choline-yl group; and the R21 group is selected from the group consisting of:

Mercapto-, ethyl-, propyl-, butyl-, decyl-, hexyl-, heptyl-, vinyl-, propyl-, butenyl-, decyloxy-, ethoxy, Propoxy-, phenoxy-, qi-, qi-, m-, methyl-C(=0)-, butyl-0C(=0)-, butyl-0C(=0)NH- , phenyl-, methoxyphenyl-, fluorophenyl-, chlorophenyl-, > odor phenyl-, p-D-group- and acetonyl-. It is to be understood that certain features of the present invention are described in the context of the specific embodiments, and may be On the contrary, the various features of the invention are described in the context of a single embodiment for the sake of brevity, and may be provided individually or in any suitable combination of 95014 - 43 - 1345465. As used herein, the term "dihydroxyborane" refers to a compound containing a quinone moiety. In some embodiments, the dihydroxyborane compound can form an oligo-polymeric anhydride by dehydration of a dihydroxyborane moiety. For example, 'Snyder et al., /. c/iew. Soc., 1958, 80, 3611 report oligo-polymerized aryl dihydroxyborane β. Therefore, unless otherwise indicated, dihydroxyboron or contains -Β ( The chemical formula of the 2 part group is intended to cover free-form di-based deparaffinic, oligo-polymeric anhydrides including, but not limited to, dimers, trimers, tetramers, and mixtures thereof. As used herein, "dihydroxyborane anhydride" or "dihydroxyborane anhydride" means a dihydroxyborane compound of formula 1 in which two or more molecules are combined, and A portion of a group that burns one or more water molecules by burning a group of compounds. When contacted with water, the dihydroxyborane anhydride compound can be hydrated to liberate the free state dihydroxyborane compound. In some embodiments, the dihydroxyborane anhydride structure may contain two, three, four or more dihydroxyborane units and may have a cyclic or linear configuration. In some embodiments, the di- ur hydroxyborane anhydride compound is substantially present in a single-polymerized form; however, the 'di-based deuterated genus also encompasses mixtures of different polymeric di-based (tetra) anhydrides, and free-state two Hydroxyborane. Non-limiting examples of the monohydroxyborane anhydrides of the present invention include compounds of the formula (Io) and Baye, wherein G is a moiety of formula (IV) and is up to 1 〇, or 1, 2, 3 or 4. 95014 •44- 1345465

OH

G

(II) G

(IV)

In some embodiments, at least about 80% of the dihydroxyborane present in the dimeric pendant anhydride compound is present as a single oligomeric anhydride. In a further embodiment, at least about 85, about 90, about 95 or about 99% of the dihydroxybutter' present in the dihydroxyborane anhydride is present in a single oligomeric field. In some embodiments, the dihydroxyborane anhydride compound comprises substantially a single oligomeric dihydroxyborane anhydride. In still further embodiments, the dihydroxyborane anhydride compound comprises a single oligomerized dihydroxyborane anhydride. In a further embodiment, the dihydroxyborane anhydride compound contains a formula (ΙΠ) boroxine wherein t is i. The di-based Wei if compound can be prepared from its corresponding second (four) compound' by exposure to dehydrating conditions, including, for example, crystallization, 95014 -45-

丄州465 where: D is non-existent, 〇, S, NRl 6 R15n R15C ' R" d, Rl5e, Rl5f are each independently H, Ci Ci. Alkyl, qc:7 cycloalkyl, aryl or heteroaryl, wherein the Ci_Ci 〇 alkyl M C3-c10 cycloalkyl, aryl or heteroaryl, each optionally 丨, 2, 3 or 4 Tooth base, yard base, cvq decyloxy, Cl_C4^ alkoxy, hydrazine H, amine, hydrazone; amine, dialkylamine, aryl or heteroaryl; or R15a linked to RUb and The argon atoms together form a q7 〇cycloalkyl or a 3- to 10-membered heterocycloalkyl group, each optionally being 2, 3 or 4 halo, CVQ alkyl, CVC4 alkoxy, halo Oxygen, hydrazine H, amine, alkane group 'monoamine, aryl or heteroaryl substituted; or R15c and RlSd and the atoms to which they are attached, together form a C3_Ci anthracene or 3- to 10-membered heterocyclic thiol, optionally as defined, 2, 3 or 4 halo, Q-Cj alkyl, Ci-Cj alkoxy, atostanoxy, hydrazine H, amine, alkylamine Substituted with a dialkylamino, aryl or heteroaryl group; or R15b and R15c and the C atom to which they are attached and the intervening d moiety, together form an aryl, heteroaryl, C3-C1() ring Alkyl or 3- to 10-membered heterocycloalkyl, each optionally 1, 2, 3 or 4 halo, CVq alkyl, Ci -Q alkoxy, (VQ haloalkoxy, OH, amine, alkylamino, dialkylamino, 95014 • 47· 1345465 aryl or heteroaryl substituted;

Rl6 is an alkyl group; and P and q are each independently 1, 2 or 3. In some embodiments, D is absent. In some embodiments, D is NR16. In some embodiments, D is NH. In some embodiments, D is CH2.

In some embodiments, ❿ and (4) together with the attached 's' form a C3-Cl()(tetra) group or a 3• to 10• member heterocyclic base, each being 1'2. 3 or 4 dentate groups, Cl_C4 alkyl 'ci' alkoxy group, substituted with atoleoxy, 0H, an amine group, a (tetra) group, a di-, an aryl group or a heteroaryl group; and R15. The ruthenium atom to which Rbd and the other are bonded to form a cycloalkyl group or a 3- to U-membered heterocyclic group, each optionally t, 2, 3 or 4: a group, a qQ alkyl group, a Cl_C4 alkane An oxy group, a Ci_C4 dentate alkoxy group, an amine group, an amine group, an aryl group or a heteroaryl group.

In some embodiments, 111& and 111515 and the C atoms to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl group; and R& and Riw and they The attached ruthenium atoms together form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl group. In some embodiments, D is absent, and Han 14 and 1115 (: and the C atoms to which they are attached, together form an aryl group, a heteroaryl group, a C3_Ci 〇 cycloalkyl group, or a 3- to 10-membered Cycloalkyl, each optionally by, 2, 3 or 4 halo, q-C4 alkyl, -C: 4 alkoxy, q-C: 4 haloalkoxy ' 〇 H, amine, alkane Substituted with an amine, dialkylamino, aryl or heteroaryl group. 95014 • 48· 1345465 In some embodiments, D is absent, and the ruler ^ and "5. and the C atom to which they are attached, together Forming a C3_Ciq cycloalkyl group, optionally as 1, 2, 3 or 4 halo, Ci_C4 alkyl, Ci_C4 alkoxy, haloalkoxy, hydrazine H, amine, alkylamino, dialkylamino, aromatic Substituted or heteroaryl substituted. In some embodiments, D is absent and 'R1Sb and Rl5c and the C atoms to which they are attached, together form a C3-ClD cycloalkyl, optionally 1, 2, 3 or 4 halo or q-C4 alkyl substituted. In some embodiments, D is absent, and 151> and Rise and the C atom to which they are attached form a C7-CIQ bicyclic cycloalkyl, Depending on the situation, 2, 3 or 4 tooth bases or (^ - (: 4 alkyl substitution. In some embodiments, p and q are each 1. In some embodiments, at least one of 'R15a, R15b, R15c, Ri5d is not Η» /\ as defined herein Other examples of "cyclic dihydroxyborane esters" include dihydroxyborane esters having the following structure:

Wherein a substituted or unsubstituted C4-Cl0 cyclodeptyl ring or a substituted or 95014 • 49-unsubstituted stupid ring; W1 is independently substituted or unsubstituted C3- in each presence C6 cycloalkyl ring. The groups Rl5a, Rl5b, Rl5c, Rl5d Rl5e Rl5f p and q' are all as defined above. The term "alkyl" or "alkyl" as used herein is intended to mean a straight or branched saturated hydrocarbon group. Examples of the alkyl group include mercapto (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, first-butyl, Di-butyl), pentyl (eg, n-pentyl, isopentyl, neopentyl) and the like. The alkyl group can contain hydrazine to about 2 Torr, 2 to about 2 Torr, fluorene to about 1 Torr, 1 to about 8, 1 to about 6 '1 to about 4 or 1 to about 3 carbon atoms. "Alkenyl" as used herein refers to an alkyl group having one or more carbon-carbon double bonds. Examples of the alkenyl group include a vinyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a butadienyl 'pentadienyl group, a hexadienyl group and the like. As used herein, alkynyl" refers to an alkyl group having one or more carbon-carbon bonds. Examples of alkynyl groups include ethynyl, propynyl, butynyl, pentynyl and the like. As used herein, "toothed base" means an example of an alkyl group having one or more functional substituents including CF3, C2f5, coffee 2, %, cHci2, C2C15%-s, all hydrogen atoms The radix that is replaced by _ atoms can be called "All-burning bases include examples of % and Ming. The carbocyclic group used herein is saturated (meaning that it does not contain a double or a ginseng bond) or unsaturated (ie, contains one or more double or ginseng bonds). It is single or multi-ring. Examples of the carbocyclic group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclopentyl group, a U-cyclopentadienyl group, a cyclohexyl group, a n-hexyl group, a n-butyl group. , positive leaf base, gold steel base, 95014 -50-1345465 phenyl and so on. A carbocyclic group (for example, an alkyl group). In some embodiments, up to about 10 or 3 to about 7 carbon atoms. Aryl) or non-aromatic (eg, "cyclocarbocyclyl can have from 3 to about 20, 3 as used herein. "Aryl" refers to an aromatic carbocyclic group which: poly = family: class such as benzene Base, base, base: phenanthryl, hydrogen impression: formation = atom in some embodiments, 'aryl has

As used herein, "cycloalkane" is a radical non-membered carbocyclic group, including the alkyl, alkenyl and alkyne of the cyclization. The aryl group can include double or multiple rings. Examples of the cap calcining group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group heptyl group, a cyclopentyl group, a cyclohexenyl group, a cyclohexanediyl group, a cycloheptatriene group, and a positive group. Pingji, Zhengqikaji, Jinsteel base, etc. In the ring-based group, it also includes the aromatic 璟 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 々 Groups, such as cyclopentane (hydroquinone), cyclohexane (tetrahydronaphthyl), ugly, etc. In some specific examples, a cycloalkyl group can have 3, 4, 5, 6 or 7 carbon atoms which can form a ring. In some embodiments, a cycloalkyl group can have a fluorene, ... can be formed or sold. The bond of the ring.

The #carbocyclyl group used herein may be a saturated or unsaturated carbocyclic group, wherein the carbocyclic group - or a plurality of carbon atoms which may form a ring, is a hetero atom such as hydrazine, S or N. Replacement. The heterocarbocyclyl can be aromatic (e.g., "heteroaryl") or non-aromatic (e.g., "heterocyclic base"). The heterocarbocyclyl group may correspond to a hydrogenated and partially nitrided heteroaryl group. The heterocarbocyclyl can contain from about 1 to about 20, from about 2 to about 10, or from about 2 to about 7 carbon atoms in addition to at least one heteroatom, and can be attached via a carbon 95014 • 51 · ^45465 atom or a hetero atom. . Examples of heterocarbocyclyl groups include morpholinyl, thiomafrylinyl, hexahydropyridinyl, tetrahydrofuranyl, tetrahydroanthenyl, 2,3-dihydrobenzofuranyl, 1,3·benzoic Oxypyrene, benzo-1,4-dioxane, hexahydrocarbyl, tetrahydropyrrolyl, isotetrahydrocarbazolyl, isothiazolidinyl, tetrahydroindolyl, tetrahydrocarbazole A group, a pyrazolyl group, a tetrahydroimidazolyl group or the like. As used herein, "heteroaryl" is an aromatic heterocarbocyclyl group and includes monocyclic and polycyclic % aromatic hydrocarbons having up to V hetero atom ring members such as sparse, oxygen or nitrogen. . Heteroaryl groups include, but are not limited to, pyridinyl, pyrimidinyl, pyridinyl, hydrazine, tri-cultivation, furyl, quinolyl, isoindolyl, pyrenyl, imidazolyl, thiazolyl, hydrazine Base, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzopyrazole, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, fluorene , oxadiazolyl, isothiazolyl, benzothienyl, fluorenyl, sulphate, stupid and milami. In some embodiments, the heteroaryl group can have from 3 to about 2 carbon atoms which form a ring, and in the further embodiment' is from about 3 to about 12 carbon atoms which form a ring. • In some embodiments, 'heteroaryl has from 1 to about 4, from about 3 to about 1 or 2, and as used herein, "heterocyclic alkyl" refers to a non-aromatic heterocarbocyclic group, which is: , a base, an alkenyl group and an alkynyl group wherein one or more of the carbon atoms of the ring may form a hetero atom substitution of ==: or 5 atoms. Can form a ring of carbon. Heteroatoms such as S and N can be further stepped in the heterocyclic thiol moiety. For example, a carbon or heteroatom that can form a ring can carry one or two (four) $clawed moiety groups (e.g., > C = 〇, > s = (), > SK)) 2, N: In the definition of a heterocyclic thiol group, a partial group having an aromatic ring of - or a plurality of stalks (Io 295014-52·1345465 having a common bond) to a non-aromatic 'chiral heterocyclic ring is also included. For example, anthracene dimethyl anthracene, naphthalene dicarboxylic acid T-imine, memantite diterpene imine, phthalate, and a saturated heterocyclic benzo derivative, such as... With an iso (tetra) group. In some embodiments, the heterocycloalkyl has from 3 to about 2 to - ring atoms. In some embodiments, the heterocyclic matrix has 3, 4, 5, 6 or 7 atoms which form a ring. In some embodiments, the heterocyclic filaments have a ruthenium, lsiu linkage that forms a double or a sulphide.

As used herein, "dental base," or ", dentate," includes gas radicals, gas radicals, molybdenum, and moth. "Hypoxic" as used herein refers to _〇_炫基. Examples of the methoxy group include a methoxy group, an ethoxy group, a propoxy group (e.g., n-propoxy group and isopropoxy group), a third-butoxy group and the like. In some embodiments, the alkoxy group has (10), m 1 i 8 ' m i to 4 or i to 3 carbon atoms. As used herein, "pyroxyloxy," refers to 〇 〇 烧 〇 〇 〇 。. "thiooxooxy group" as used herein refers to an alkoxy group in which a ruthenium atom is replaced by a s atom. As used herein, "aryloxy" means 〇-aryl. aryloxy "Phenoaryloxy" as used herein refers to an aryloxy group in which the o atom is replaced by a s atom. As used herein, "aralkyl" refers to an alkyl moiety substituted with an aryl group. Examples of aralkyl include benzyl and naphthylmethyl. In some embodiments, 'aralkyl has 7 to 11 carbon atoms. As used herein, "amine" refers to an N-NH2 group. "alkylamino" refers to an amine group substituted with a 95014-53·1345465 alkyl group, and &quot Dialkylamino" refers to an amine group substituted with two alkyl groups. Conversely, "aminoalkyl" refers to an alkyl group substituted with an amine group. As used herein, "carbonyl" means > c = 0. As used herein, "carboxy" or "quote" refers to _c〇〇H. "Hydroxy" as used herein refers to . "巯基" as used in this document refers to _SH. • Urea base used in this article. "sulfinyl""S" as used herein. "sulfonyl" as used herein refers to >S02. As used herein, "oxy" refers to 〇. The above chemical terms can be combined to refer to a moiety containing a combination of chemical groups. 5, the terminology is read so that the recited terms are understood to be the substituents of the next term. For example, an alkenyl group substituted by a carbonyl group, which in turn is substituted with an alkyl group. The following terms can also illustrate such combinations. As used herein, a carbocyclic group refers to a group of alkyl groups substituted by a carbocyclic group. Examples of carbocyclic pure groups include "Norky" ("alkyl substituted alkyl") and "cycloalkylalkyl" (alkyl substituted by cycloalkyl). < Base•• means a dilute moiety substituted by a carbocyclic group. The carbocyclic group (IV) includes ("bases" (alkenyl substituted by aryl) and "ring-burning base" ( Baked base replaced by a ring base.) "Carbocycloalkynyl" as used herein, refers to a fast-radical moiety substituted with a carbocyclic group. Carbon "Examples of silk (10) 1 silk " ("substituted alkynyl group" and, cycloalkylalkynyl" (fast radical substituted by a cycloalkyl group). 95014 • 54-1345465 "Heterocarbocyclylalkyl" as used herein refers to an alkyl moiety substituted with a heterocarbocyclyl group. Examples of the heterocarbocycloalkyl group include "heteroarylalkyl" (alkyl substituted with heteroaryl) and "heterocycloalkylalkyl" (alkyl substituted by heterocycloalkyl). "Heterocarbocyclyl" as used herein refers to an alkenyl moiety which is substituted by a heterocarbocyclyl group. Examples of heterocarbocycloalkenyl groups include "heteroarylalkenyl,,(heteroaryl substituted by heteroaryl) and "heterocycloalkylalkenyl" (alkenyl substituted by heterocycloalkyl) . As used herein, "heterocarbocyclylalkynyl" refers to an alkynyl moiety substituted with a heterocarbocyclyl group. Examples of heterocarbocyclyl alkynyl include "heteroarylalkynyl" Heteroaryl substituted alkynyl) and "heterocycloalkynylalkyl" (alkynyl substituted by heterocycloalkyl). As used herein, the term "protecting group" means optionally attachable a chemical functional group such as a radical, an amine group, and a carboxyl group. The protecting group is usually introduced into the compound such that the functional group is inert to the chemical reaction conditions to which the compound is exposed. Any of the protecting groups can be used together with the present invention. The protecting group of the amine moiety can be referred to as an "amino protecting group, and the protecting group of the thiol moiety can be referred to as ";胍基保护基". The amine group and the thiol protecting group may have the formula aryl _s 〇 2, alkyl-S 02 ·, aryl _c (= 〇) _ ' aralkyl _c (=0) _, alkyl _c ( =〇)_, aryl-0C(=0)-, aralkyl-〇C(=〇)-, alkyl-0C(=0)-, aryl-NHC(=0)-, alkyl- NHC (=0)·etc., wherein the alkyl, aryl and aralkyl groups may be substituted or unsubstituted. Examples of the amine group and the thiol protecting group may also include a third-butoxy group (BOC), a methoxycarbonyl group (Fmoc), a benzyloxycarbonyl group (Cbz), and an o-phenylene 95014-55·1345465 carbamide. Amine. Other protecting groups include the following partial groups:

Other representative protecting groups can be found in T. W. Green and P. G. M. Wuts, et al., Protective Groups, 3rd Edition, Wiley & Sons, Inc., New York (1999), which is incorporated herein by reference in its entirety. As used herein, "substituted" means that at least one gas atom of a chemical group is replaced by a non-hydrogen moiety. Examples of substituents include F, C1, order, I, -C6, Q- C6 dilute, C! -C6, alkynyl, halo, nrerf, N3, N02, CN, CNO, CNS, C(=0)ORE, Rec, rec(=〇)〇reconre, rErpnc〇, urea The group, 〇rE, srE s〇2-alkyl group aryl group and SCVNRErf, wherein 舻 and 鲈 are each independently ugly or nucleus. Or the combination of RF and RF may be combined with the nitrogen to which they are attached to form 5 to 7 member%, such as tetrahydropyrrolyl, hexahydropyridyl, morpholinyl, hexahydropyrryl and N-oxime. Hexahydropyrrolidine. When the chemical group herein is "substituted", it may have a substitution of a high full valence bond, provided that the formed s is a ruthenium compound or a stable structure; for example, the methyl group may be 1, 2 Or a 3 solid substituent substituted, the fluorenylene group may be substituted by hydrazine or 2 substituents, and the phenyl group may be substituted by 1, 2, 3, 4 or 5 substituents, etc. 95014 -56- 1345465 is used herein. "Debonded base" means any group which may be replaced by a nucleophilic group upon nucleophilic substitution. Examples of the leaving group include a halogen group (F, Cl, Br, I), a hydroxyl group, an alkoxy group, a fluorenyl group, Thioalkoxy, trifluoromethanesulfonate, alkylsulfonyl, substituted alkylsulfonate, arylsulfonate, substituted arylsulfonate, heterocyclic sulfonate or trimethylacetate Amino acid salt. Representative examples include p-(2,4-dinitroanilino)benzenesulfonate, benzenesulfonate, methanesulfonate, p-toluenesulfonate, p-bromobenzenesulfonate, trigas基 醯 醯 k k 、 酿 酿 酿 酿 酿 酿 酿 酿 k k k k k k k k k k k k k k k k k k k k k k k k k k k k k k k k k k Stabilizing compound " or "stable structure" means a compound that is sufficiently robust to remain in the reaction mixture, is isolated to a useful purity, and is preferably capable of being formulated into an effective therapeutic agent. The present invention is directed only to a stable compound. .

The compounds described herein can be asymmetric (e.g., have one or more 4 body centers). All stereoisomers, such as p-isomers and diastereomers, are intended unless otherwise indicated. Compounds of the invention containing an asymmetrically substituted subject can be isolated in optically active or racemic form as to how to prepare an optically active form from optically active starting material f, as is known in the art, for example by A plurality of geometries in which the resolved side of the racemic mixture is stereoselectively synthesized by double bonds or the like may also be present in the compounds described herein, and all such isoforms are intended to encompass the inventive W^ isomers of the present invention. It is described and can be separated by s 1 long form. a mixture of isomers or isolated 95014 -57-1345465 In addition to the above, the compounds described herein may have an asymmetric center which will result in a superior organism for the palm isomer of the compound of formula (I) Working 14 is better than its opposite counterpart. Both configurations are considered to be part of the present invention. For example, the R2 substituent of the compound of formula (I) may be present in either the S or R configuration. An example of a preferred palm isomer configuration of the present invention is a compound of formula (I-s):

(I-s) . Not forbearance is limited to this example. When desired, separation of the racemic material can be achieved by methods known in the art. The compounds of this month may also include tautomeric forms such as thiol-dilute alcohol tautomers. The tautomeric form may be in equilibrium or may be stereoscopically blocked into one form by appropriate substitution.

The compounds of the invention may also include all isotopes of the atoms present in the intermediate or final compound. Isotopes include atoms of the same atomic order but of different mass numbers. For example, isotopes of hydrogen include strontium and barium.

The term "pharmaceutically acceptable" is used herein to refer to a substance: a composition and/or a dosage form that is within the scope of a safe and reliable medical judgment and is suitable for use in contact with human and animal tissues. No excessive, irritating, allergic reactions or other problems or complications are accompanied by a benefit/risk ratio. a pharmaceutically acceptable salt. The invention also includes the compounds 95014-58, 1345465, as used herein, and "pharmaceutically acceptable salts" as used herein, refer to derivatives of the disclosed compounds, wherein the parent compound is via the acid or moiety present. The group is converted to its salt form and is modified. Examples of pharmaceutically acceptable salts, including but not limited to basic residues such as amine mineral acids or organic acid salts: acidic residues such as carboxylic acid bases or Organic salts, etc. The pharmaceutically acceptable sleep of the present invention comprises the conventional non-toxic salts or quaternary ammonium salts of the parent compound, which are formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic sleeping systems include derivatives. From inorganic acids, the inorganic acid such as hydrochloric acid, argon bromate, sulfuric acid, aminosulfonic acid, phosphoric acid, nitric acid, etc.; and salts derived from organic acids such as acetic acid, propionic acid, succinic acid, glycolic acid , stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, hydroxamic acid, maleic acid, mercapto maleic acid, phenylacetic acid, face acid, benzoic acid, salicylic acid, Sulfamic acid, 2- Alkoxybenzoic acid, fumaric acid, toluenesulfonic acid, decanesulfonic acid, ethanedisulfonic acid, oxalic acid, isethionethane, etc. The pharmaceutically acceptable salt of the present invention may be self-contained or The parent compound of the acidic moiety is obtained by chemical synthesis. In general, such a salt may be in the form of the free acid or base form of the compound and the stoichiometric amount of the appropriate base or acid in water or It is prepared by reacting in an organic solvent or a mixture of the two. In general, a non-aqueous medium such as singular, ethyl acetate, ethanol, propanol or ethyl is preferred. A list of suitable salts can be used. See 痹#痹存学, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, and Nightmare Tour, 66, 2 (1977), each of which reveals This is also incorporated herein by reference. Hefei 95014 -59- 1345465 The present invention, including salts and solvates thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of a number of possible synthetic routes. The reaction of the compound of the invention can be carried out in a suitable solvent, which The ex situ is selected by the skilled organic synthesis artist. The temperature at which the solvent is subjected to the reaction may range from the solvent freezing temperature to the solvent boiling temperature range, and the starting material (reactant), intermediate or product may be Substantially non-reactive. The specific reaction can be carried out in a solvent or in a mixture of more than one solvent. Depending on the particular reaction step, a suitable solvent for the particular reaction step can be selected. Protection and removal protection of various chemical groups. The need for protection and removal of protection, and the choice of appropriate protection groups, can be determined by the artist. The chemistry of the protection group can be found, for example, TW Greene and RG.M. Wuts , #合合戒J: The protection of shame, 3rd edition, Wiley & Sons, New York (1999), which is incorporated by reference herein in its entirety. The reaction can be monitored according to any suitable method known in the art. Example φ such as 'product formation can be by spectroscopy, such as nuclear magnetic resonance spectroscopy (such as 1 Η or 13 C), infrared spectroscopy, spectrophotometry (such as uy-visible light) or mass spectroscopy, or by chromatography For example, high performance liquid chromatography (HPLC) or thin layer chromatography. The compounds of the present invention can be prepared according to the methods described in the art for the preparation of amine di-based sheds, esters and related compounds, for example, in U.S. Patent 4,537,773 and U.S. Patent 5,614,649, each of which is incorporated herein by reference. The full text is hereby incorporated by reference. In some embodiments, the compounds of the invention can be made by sequential coupling of three fragment components (FI, F2 and F3). 95014 • 60· 1345465 F1 fragment The synthesis of the compound of the present invention may involve a boron fragment (F1). And having the structure represented by the formula (A)

R1

The η bis-partial group may include, for example, the two (four) formula (Α) represented by the oxygen atom to which the coil is attached. In the formula, in the preparation of the stereochemistry of the carbon atom of the county, the preparation of (4) is controlled by using an asymmetric diuretic side vinegar base. For example, the decanediol esters of dihydroxyborane can aid in the preparation of stereochemically pure or substantially stereochemically pure F1 fragments. By way of example below, the /fragment can be made in the following manner in the presence of di-methane or dibromomethane via a compound of the formula (indole) which exhibits a dihydroxyl diol derived from (+)-decanediol. a borane ester) and a strong base (such as lithium diisopropylamine or lithium dicyclohexylamine, followed by the addition of a Lewis acid (such as ZnC12 to produce a compound of formula (C) wherein l is a halo), For the carbon where the boron is in the alpha position, it has a newly introduced stereocenter. 95014

(Β) •61 · 1345465

The compound of formula (c) may be in turn with an alkali metal aminide (for example lithium bis(trimethylindenyl)amine, sodium bis(trimethyldecyl)amine and potassium bis(trimethyldecyl)amine or other A nucleophile reaction that effectively converts a newly formed stereocenter (for example, by the SN2 type mechanism) and introduces an amine group (NR2) to replace a halogen group (such as a chloro group) to form a compound of formula (D) ( Wherein R can be, for example, an alkyl group, a Si(alkyl)3, an aryl group or an aryl group.

The compound of formula (D) can be further reacted with an agent capable of converting an NR2 group into nh2 or a salt thereof to form an F1 fragment which is substantially capable of coupling with another fragment via the amine. A suitable agent for converting a % group to a ^2 may be a protonic acid such as HCl, such as when r is an alkyl group (e.g., a trimethylsulfanyl group). The compound of formula (B) can also be prepared according to a two-step procedure involving the trialkoxyborane, preferably triisopropoxyborane, reacted with (ls, 2S, 3R, 5S)-(1) decanediol. And a mono-indolyl [[1S, 2S, 3R, 5S)_(+) decanediol] pentane intermediate, wherein the two alkoxy groups of the trialkoxyborane have been (1S, 2S, 3R, 5S), (7) decanediol substitution. The mixed decanediol alkoxyborane is obtained in a good yield and purity when reacted with an appropriate metal halide/organism such as Grignard reagent Ri CH2MgBr or an alkyl group via RiCI^Li. Out). The procedure for obtaining the intermediate mixed decanediol isopropoxyborane (F) and the compound of formula (B) starting from triisopropoxyborane is described in the following scheme:

Take Example A.2 of this example as an example. Therefore, the present invention is further directed to the preparation of the formula (π) compound R1.

Wherein the variable component is defined above by the following method, &) (Π-b)diol: ® H〇\ (Rl5a

P Η0^ι (Π-b) is reacted with a suitable formula (II-a) trialkoxyborane: R17〇\ /OR17 OR17 (Π-a) 95014 -63- wherein each R17 is independently a hepta-7 (7) alkane a group or a C3-C1()cycloalkyl group; under the conditions and conditions suitable for forming an intermediate of the mixed trialkoxyborane of formula (II-c):

(Π-c) and the intermediate of formula (II-c), under the conditions and conditions suitable for the formation of the compound (Π), with i) the formula I^a^MXha1 reagent, wherein ruthenium is a metal, and Xhal It is a halogen atom, or ii) a reaction of the formula R1 CH2Li. In some embodiments, the ruler is a heart-helium alkyl group. In some embodiments, R1 7 is isopropyl. In some embodiments, the formula (ΙΙ-b) diol is decane diol, guanidine, dicyclohexyl diol, 1,2-ethane diol, 1,3-propane diol, 1,2-propanediol , 2,3-butanediol, ι,ι,2,2-tetramethylethanediol, 1,2-diisopropylethanediol, 5,6-nonanediol, ι,2 - Dicyclohexylethane diol, dicyclohexyl hydrazine, diol, diethanolamine or 1,2-diphenyl-1,2-ethane diol. In some embodiments, the formula (ΙΙ-b) diol is decane difer. In some embodiments, the formula R1 CH2MXhal is a Grignard reagent. In some embodiments, the formula R1 CH2MXhai is R1 CH2MgBr. In some embodiments, R1 is isopropyl. In some embodiments, the invention provides a method of preparing a compound of the formula: 95014 - 64 - 1345465

It comprises: a) reacting (1S, 2S, 3R, 5S)-(+)-clayed alkanediol with triisopropoxyborane under suitable conditions (11_time and conditions along the intermediate) :

And b) reacting the intermediate of the formula (Π-ii) with isobutyl magnesium bromide under conditions suitable for the formation of the formula (11_〇 compound). In some embodiments, the invention provides the formula (11) VII) Compounds:

The reaction step can be carried out in any suitable solvent which is non-reactive with the reagents and the product and which allows the reagents to be combined at a reduced temperature (e.g., at a temperature which is cooler than room temperature). Suitable solvents include ethers such as dimethoxymethane, tetrahydrofuran, 1,3-dioxane, iota, dioxane, hydrazine. South 'Ji Jun, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, toluene or the first Tri-butyl methyl ether. In some embodiments, the ether solvent contains tetrahydrofuran and/or ethylene. The reaction of the methods described herein can be carried out at a suitable temperature, which can be readily determined by the skilled artisan. The reaction temperature is based on, for example, the melting point and boiling point of the reagent and the solvent of 95014-65-1345465; if the reaction is 疋六风汉应疋 thermodynamics (for example, the intense exothermic reaction may need to enter the pole at a low temperature and should be temple + 丄"埂仃" and the kinetics of the reaction (for example, high activation energy barriers may require southerly temperature). ",, θ, · total -.皿 叩疋 叩疋 姐 系 means that the temperature is higher than room temperature (about 22 C) and ''low temperature' means the temperature is lower than room temperature.

In some embodiments, the appropriate temperature is a low temperature. The reaction of a trialkoxyborane with an alcohol to prepare a mixed trialkoxyborane intermediate can be carried out, for example, at a temperature of from about -20 to about 1 (TC). In some embodiments, the trimethoxy group is alkoxy. The reaction of the borane with the diol can be carried out at about 0 C. The reaction of the mixed trialkoxyborane intermediate with the organometallic reagent Ri or the alkyllithium reagent R1 Ch2u can be, for example, from about 400 to about -20 ° C. The temperature is carried out. In some embodiments, the 'reaction of the mixed trialkoxyborane intermolecular with RlcH2Mxha丨' is carried out at about -78 ° C. The reaction of the process described herein can be carried out in air or in The reaction is carried out under an inert atmosphere. Typically, the reaction containing reagents or products which are substantially reactive to air can be carried out using air-sensitive synthetic techniques well known to the skilled artisan. B. F2 Fragment Central segment of the compound of the invention It can be represented by fragment F2, which is coupled to the F1 fragment by peptide bond formation to form an F2-F1 intermediate. The method of coupling a compound via a peptide bond or a urethane bond is known in the art and is described. For example, 焱··分,合竑,至钞第一卷, by Gross et al., University Press, 1979, examples of β-type F2 fragments are provided in formula (E) (pg is an amine protecting group, R2 is defined herein). In addition, the amino group of the amino acid The use of Boc or other amine protecting groups is known in the art as taught in U.S. Patent No. 95014-66-1345465.

Pg/

OH (Ε)

The compound of the formula (Ε), which is an amino acid or an amino acid derivative, is commercially available or can be produced by a conventional method. For example, azlactone can generally be prepared by Hofftnan rearrangement (Hoffinan's reaction) using, for example, aspartate, wherein the indole amine of the aspartate side chain is converted to an amine (which can then be protected). . φ The method of Hofftnan rearrangement, such as for amino acids, is known in the art and is also provided in the examples below. Further, azlactone can be prepared as disclosed in Zhang et al., */. Og. ae/n., 1997, (52, 6918-6920. Boc-cyano arginine derivatives can be used by Wagenaar et al. , Org. CAern·, 1993, 5 <?, 4331-4338. The synthesis of the F2 fragment, wherein R2 is -CH2 CH2 CH2 NHC(=NR4)NH-Y, -CH2CONR5R6, -CH2NHCONR5R6, -CH2NR9R10 Or -CH(R7)ZR8 is further disclosed herein. The F2 fragment can be obtained from commercial sources or by methods known to those skilled in the art. _ C. F3 Fragment Another fragment (F3) can be borrowed in any of a variety of ways. , for example, by a nucleophilic substitution or addition reaction, coupled to an F2 fragment of the F2-F1 intermediate, wherein, for example, F2 contains a nucleophilic group (eg, an amine) and F3 contains an electrophilic group (eg, CO, S02) And the like, and optionally, a leaving group (for example, a halogen group, a hydroxyl group, an alkoxy group, an alkylsulfonyl group, an arylsulfonyl group, etc.). Examples of the F3 fragment may have the formula RxCOXL, RxS02XL, RxNCO or RxHCO (for example, Rx can be RA, RB or Rc as defined herein, and XL can be a leaving group. RxCOXL (for example, when 95014-67·1345465 # is 011) Coupling to the F2-F1 intermediate can be carried out according to standard procedures for peptide bond formation to prepare compounds having the formula F3-F2_F1, wherein the F3 and F2 fragments are coupled via a guanamine linkage. In other embodiments, F3 is F2 can be coupled by a mercapto-amine chain, which is prepared by reacting rxs〇2X1 with an F2-F1 intermediate, wherein the amine moiety on the F2_F1 intermediate is substituted for RxS〇 The xl of 2XL is decoupled from the group. In addition, the reaction of the amine moiety of the RxNCC^F2 Fi intermediate can cause the urea chain to bind (7) cis), while the amine moiety of the RxHCO and F2-F1 intermediates The reaction of the group, followed by reduction of the imine moiety formed, forms an amine chain. Other coupling methods are known in the art and are also suitable. The F3 fragment can be obtained from commercial sources or by methods known in the art. Certain compounds of the invention, wherein R2 is _(CH2)dCH(R7)NR9Rl, can be made in the following manner to remove Ri. An amine protecting group to form its corresponding deprotecting compound, wherein R1. Why? The deprotected compound can be reacted with a reagent having the formula R10aXL where R10a has the same meaning as R1〇 except for 'and is separated from a radical such as a dentate or a sulfonic acid derivative: · or, R As used in relation to X-, it means, for example, a reactive alkyl group, a carbocyclic iso(tetra)ester' or a leuco' carbocyclic group, a heterocarbocyclic aryl-based sulphuric acid vinegar. For example, the compound of Example D.26 can be prepared by the removal protection of the oxygen group of Example di66, obtaining Example Di7, which can subsequently be thiolated. 95014 -68 · 1345465 A nitrogen attached to a nitrogen serine group (eg, a compound of formula i wherein R2 is -CH2NR9R10, and R9 is deuterium, and R1 (^_C(=〇)〇CH2(C6H5). Oxygen The removal of the carbonyl group can be carried out via treatment with a reducing agent such as a hydrogenating reagent. In some embodiments, the hydrogenating agent contains H2, which is optionally used in the presence of a metal catalyst (e.g., Pd/C 10%). The hydrogenation can be carried out further in the presence of a protonic acid such as HCl and in a suitable hydrogenation solvent containing, for example, an alcohol and/or an ether solvent. In some embodiments, hydrogen

The solvating solvent contains an ether such as 1,4_dioxan. In a further embodiment, the hydrogenation solvent contains an alcohol, such as methanol. In a further embodiment, the hydrogenation solvent contains a mixture of an alcohol and an ether. An example of the preparation of a nitrogen serine compound according to this method is provided, for example, in Example D17. The reaction parameters, including temperature, pressure, atmosphere, etc., are readily determined by the skilled artisan, and the progress of the reaction can be monitored by routine methods, including, for example, NMR. Accordingly, the present invention provides a process for the preparation of a compound of formula (I):

(I) wherein: Q C6, K2-C6 alkenyl, C2_C6 alkynyl or (cyclo)alkyl; R2 is _CH2NH2; Q is b(or)2 or % dihydroxyborane, of which The bismuth dihydroxyborane vinegar contains 2 to 20 carbon atoms, and optionally, a hetero atom which may be N, s 95014 • 69· 1345465 or hydrazine; R is a -C4 pit group, a cyclosyl group, a cycloalkyl, aryl or aryl group; X is RAC(=0)-; RA is a Ci-CM alkyl group optionally substituted by R2Q; a C2-C2() alkenyl group optionally substituted by R2G; a C2-C2G alkynyl group substituted by R2G, optionally a carbocyclic group substituted with 1 to 5 R21 groups; or a heterocarbocyclic group optionally substituted with 1 to 5 R2 1;

The R2 Q series is selected from the group consisting of:

-CN, halo, haloalkyl-, (VC4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -C02H, -C(=0)CO2H, -C(=0)NH2, -C( =0) H, -S(=0)NH2, -S(=0)2NH2, -OH, -SH, -NH2, -NH(alkyl), -N(alkyl)2, -NHC(=0 NH2, -NHC(=0)R2()a, -NHC(=O)OR20a, -OR20a, -SR20a, -S(=O)R20a, -S(=O)2R20a, -S(=O) 2-NHR20a, -SC(=O)R20a, -C(=O)R20a, -C(=O)NHR20a, -C(=O)O-R20a, -NHS(=O)2R20a, -NHR20b, neighbor Benzene imino group, -(0-alkyl)r, _〇.alkyl_〇H, _(0-alkyl)r-0H, _OR20c, -SR20c, _0-alkyl-R20. -S-alkyl-R20c ' -S(=0)-R2()c, -S(=O)2-R20c, -S(=O)2-NHR20c, -SC(=O)R20c, -C (=O)R20c, -C(=O)OR20c ' -C(=0)NHR2Gc, a carbocyclic group optionally substituted by 1 to 5 R21; and a heterocarbocyclic ring optionally substituted by 1 to 5 R21 RMagq-Czo alkyl, C2-C20 alkenyl or C2-C20 alkynyl; wherein the alkyl, alkenyl or alkynyl group is optionally substituted by one or more halo, alkyl, aryl, heteroaryl Or -NHR2Gb substituted; 95014 • 70· 1345465 1^2()1} is an amino protecting group; R20c is a carbocyclic group optionally substituted with 1-5 R22; or 1-5 R22 substituted heterocarbocyclyl; R21 is selected from the group consisting of:

Ci-C^oalkyl, C2-C2 nonenyl, C2-C2 decynyl, C^-Ch alkoxy,

Ci-C2 sulfonium oxy-oxyl group, -OH-CN, _ group, _ alkyl group, -ΝΗ2, · ΝΉ (hyun; base) '-Ν(alkyl) 2, -NHC(=0)〇-alkyl , _NHC (=0) yard, -C(=0)0-alkyl, -c(=o)alkyl, -S(=0)-alkyl, -S(=0)2-alkyl, -S(=0)- φ aryl, -S(=0)2-aryl, carbocyclic group optionally substituted by 1 to 5 R22 and heterocarbocyclic group optionally substituted by 1 to 5 R22 R22 is selected from the group consisting of: Q-Ci oxime, C2-Cl 〇, C2 -Cl 〇, phenyl, halo, haloalkyl, alkoxy, sulfinyl, amine, Alkylamino, dialkylamino, carboxyl, alkyl-〇c(=o)-, alkyl-c(=o)-, aryl-0C(=0)-, alkyl-0C(=0) NH-, aryl-0C(=0)NH-, alkyl-C(=0)NH-, alkyl-C(=0)0-, (alkyl-0)r-alkyl, HO-( Burning base-0)r-alkyl-, -OH, _-SH, -CN, -N3, -CNO, -CNS, alkyl-S(=0)-, alkyl-S(=0)2 , H2 NS(=0)- and H2 NS(=0)2 -; and r is 2, 3, 4 or 5; which includes: time and conditions suitable for forming a compound of formula (I) wherein R2 is -CH2NH2 Let the compound of formula (1) wherein hydrazine is - 0121^-0(=0)0(:112((:6115), with appropriate hydrogenation The reaction is carried out under the condition that the hydrogenating agent is selective for the oxycarbonyl group of R2. 95014 - 71 - 1345465 In some embodiments, the hydrogenating agent is hydrazine, at pd/c 1% and i 4 dioxo In the presence of HCl in the earthworms, the dipredomylborane vinegar/dihydroxyborane converts a compound of the invention containing a dihydroxyborane ester such as a decanediol ester, which can be hydrolyzed by any suitable means to prepare a corresponding a dihydroxyborane (-B(OH)2) derivative. The hydrolysis conditions may include contacting the dihydroxyboran ester with an excess of acid such as a protic acid, for example. Conversely, the dihydroxyborane may be via an acid compound (_B) (〇H) 2) Contact with an alcohol such as a diol, for a sufficient time to be esterified to produce its corresponding ester. The esterification reaction can be catalyzed by acid or catalysis. The invention will be described in more detail by way of specific examples. The following examples are presented for illustrative purposes and are not intended to limit the invention in any way. Those skilled in the art will readily appreciate a variety of non-critical parameters which may be modified or modified to produce substantially the same results. Embodiments] Example A.1 (1拗-1-[(338,48,68,731〇-hexa-argon-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxole-2-yl] Steps for the synthesis of 3-methylbutylamine hydrochloride 1. 2-(2-Methylpropyl)-(3〇^,48,63,7〇1 ft)-hexahydro-3(1,5, 5-trimethyl-4,6-Yin Xuan> base-1,3,2-stupid and two-in-one

a mixture of (d)·decanediol (23.9 g '0.140 mol) and 2-mercaptopropyldihydroxyboron 9514-72·1345465 alkane (15 g, 0.147 mol) in diethyl ether (300 ml) Stir at room temperature for 24 hours. The mixture was dried over anhydrous sodium sulfate and purified by column chromatography (yield: 230-400 mesh) to elute with hexane:ethyl acetate 9 〇 : 1 。 mixture. The product was obtained as a clear oil (32.6 g, 94% yield). 1H NMR (DMSO-d6): 4.28 (1H, dd, J = 8.8 Hz, 2.0); 2.30 (1H, m); 2.18 (lH,m); 1.96 (lH,t,J=5.3); 1.86 (lH , m); 1.78 (1H, combination, J=6.8); 1.68 (1H, m), 1.30 (3H, s), 1.25 (3H, s) » 1.01 (1H, d) > 0.9 (6H, d, J=6.6) *. 0.81 (3H, s); 0.69 (2H, m). Step 2: 2-[(lS)-l-carbyl-3-methylbutyl]-(3aS,4S,6S, 7aR)-:^^-3a,5,5-l methyl-4,6-methylalkyl-1,3,2-benzodioxine

By adding 10.0 M butyllithium solution (25.4 mL, 0.254 mol) in hexane to diisopropylamine (35.7 mL, 0.254 mol) in anhydrous tetrahydrofuran (60 mL) _5 (in solution under TC, prepare lithium diisopropylamine solution 'and raise the temperature to -30 ° C. Transfer this solution via cannula to step 2-(2-methylpropyl)- (3 into 43 winds 7 &amp; feet) - six argon _3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzinc oxonium (50 g, 0.212 Mohr) and CH2C12 (50 ml '0.848 mol) in a solution of anhydrous tetrahydroanthracene (South) (7 ml) while maintaining the temperature below -70 ° C. Then, add anhydrous zinc vapor in 1.0 Μ solution in dimethyl ether (039 ml, 0.339 mol), over a period of 3 Torr, while maintaining the internal temperature below -7 ° C. The reaction mixture was stirred at _78t: 3 small 95014 -73 - 1345465 leaves and then allowed to warm to the warmth. After removing the solvent by rotary evaporation, the residue was partitioned between petroleum ether (1000 ml) and 10% aqueous ammonium sulfate (8 liters). The aqueous layer was further extracted with petroleum ether (3 mL). The combined organic phases were dried over anhydrous sodium sulfate and concentrated. The product was obtained as a brown oil (59.0 g, 98% yield) containing about 9% Mo/Mole starting material (1H-NMR) and used in the next step without further purification. </ RTI> <RTIgt; (lH5m); 1.84-1.55 (5H, m); 1.34 (3H, s); 1.26 (3H, s); 1.09 (1H, J = 10.1); 0.9 (3H, d, J = 6.8) ; 0.87 (3H , d, J=6.4) ; 0.82 (3H, s). Step 3: N,N-bis(trimethyldecyl)·(10) small [(3aS 4S,6S 7aR)hexahydro_3a 5,5· three Methyl-4,6-nonylalkyl-1,3,2-benzodioxanthene]methylbutylamine

Add a solution of bis(trimethyldecyl)amine in tetrahydrofuran (189 ml '0.189 mol) to the crude 2-[(ls)-l-carbyl-3-methyl group of step 2 Butyl]-(333,43 thief 7&amp;!〇-hexahydrogen also 5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxanil (59.0 g, 91% purity, 0.189 mol) in a solution of tetrahydrofuran (580 liters) over 30 minutes while cooling at _78. The reaction mixture was slowly warmed to room temperature overnight. The solvent was removed, and the residue was dissolved in anhydrous hexane (800 mL). The suspension of the formed suspension of 95014-74-1345465 was stirred at room temperature for 2 hours, then on the Shishizao cake. The solid was removed by filtration, and the celite cake was washed with anhydrous hexanes (3×100 mL). The product was used in the next step without further purification. 1H NMR (DMSO-d6): 4.33 (1H, dd, J = 1.5 Hz, 8.6); 2.58 (1H, m); 2.29 (1H, m); 2.18 (lH ,m); 1.95 (lH,t,J=5.9); 1.85 (l H,m); 1.9-1.55 (3H,m); 1.31 (3H, s) ; 1.24 (3H, s) ; 1.17 (1H, m) ; 1.01 (1H, d, 1=10.6) ; 0.85 (3H, d, J=6.6), 0.83 (3H, d, J=6.6); 0.80 (3H, s) ; 〇.〇8 (18H, s). ^ ^ 4 : (lR)-l-[(3aS,4S ,6S,7aR)~ M -3a,5,5~=if ^ ψ ^ -1,3,2-stupid and bismuth boron oxindole-2·yl]-3-methylbutylamine hydrochloride

Crude N,N-bis(trimethyldecyl)-(lR)-i-[(3as,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4, in step 3 6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutylamine (79 g, 0.193 mol) in dioxane (1 mL) In a solution of the mixture of diethyl ether (2 mL), a 4N solution of hydrogen chloride in dioxane (193 ml '0.772 mol) was added, simultaneously with hydrazine. (: Cooling down) Then, the mixture was stirred at room temperature for 4 hours, and concentrated. The residue was dissolved in anhydrous hexanes (500 ml), and a 2M solution of hydrogenated hydrogen in diethyl ether (48 ml '0.096) was added. The mixture was stirred at TC for 1 hour and then concentrated. The residue was dissolved in anhydrous hexane and the resulting suspension was stirred overnight at room temperature. Drying under vacuum gave 38.1 95 014 - 75 - 1345465 g (yield: 66%). The second fraction of product (4.13 g, 7% yield) was obtained from the mother liquor. 1H NMR (DMSO-d6): 7.85 (3H , br) ; 4.45 (1H, dd, J=9.2 Hz); 2.78 (1H, m); 2.34 (lH,m); 2.21 (lH,m); 2.01 (1H, t, J=5.3) ; 1.89 ( lH,m); 1.82-1.65 (2H, m) ; 1.49 (1H, m) ; 1.38 (3H, s) ; 1.27 (3H, s) ; U2 (1H, d, J= 1.12); 0.87 (6H, d, J=6.6) ; 0.83 (3H, s). Example A.2

2-(2-methylpropyl)-(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzoic Alternative synthesis of bismuth and boron

Step 1: 2-(1-Methylethoxy)-(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3, 2- stupid and dioxon

In a solution of (IS, 2S, 3R, 5S)-(+)-calinediol (50.0 g, 0.293 mol) in anhydrous tetrahydrofuran (350 ml), triisopropoxide was added slowly. At the same time, it was stirred at 0 ° C under nitrogen. After 2 hours, the solvent was removed by rotary evaporation. The oily residue was redissolved in hexanes (150 mL) and filtered to remove a very small white solid. The filtrate was concentrated by rotary evaporation to give the product as a white oil (62.6 g, 90% yield). 1H NMR (DMSO-d6): 4.31-4.20 (2H, m); 2.34-2.16 (2H, m); 1.96 (1H,

t, J = 5.5); 1.90-1.85 (lH, m); 1.74-1.67 (lH, m); 1.32 (3H, s); U1 (1H d, J = 7.6); 1.25 (3H, s); (3H,d,J=6_l); 1.13 (3H,d,J=6.1);〇,81(3H,s) / 2-(2- f S ^ S)-(3aS,4S,6S, 7aR) -^ M -3ar5,5~=: F S-4 6-f alkyl-1,3,2-benzodioxine 圜95014 •76- 1345465 2M of isobutylmagnesium bromide in ether The solution (1315 ml, 〇263 mol) was added dropwise to the 2(1 methylethoxy)-(3&amp;3,43,63,7&amp;11) obtained in step i over 1 hour. Hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanil (62.6 g, 〇·263 mol) in anhydrous tetrahydrofuran (The solution in phantom liters) was stirred at -78 ° C under nitrogen. Then, the mixed φ was warmed to room temperature, and then transferred to a mixture of 2N sulfuric acid (150 ml) and diisopropyl ether (250 ml). After stirring for 1 hr, a solution of 1% (: 1 solution (100 mL) was added and the layers were separated. The organic phase was washed with brine (1 mL), dried over sodium sulfate, and concentrated. Purification by column chromatography (chrome), eluting with 5% diethyl ether in hexanes to give the product as a clear oil (38.45 g, 62% yield). Example B.1 Aminomethyl 1 1,1-dimethyl Ethyl ester, N-[(lS)-l-[[[(lR)-i_[(3aS 4S 6S 7aR)_A Lu hydrogen_3a,5,5-dimethylmethylalkyl}»3,2· Benzodioxanoxane _2_yl]-3-methylbutyl]amino group] benzyl]-4,[[imino(desineamino)methyl]amino]butyl] _

Method A : HOAt/HATU 95014 -77- 1345465

In a solution of BocNH(N02)ArgOH (15.7 g, 49.3 mmol) in anhydrous DMF (100 mL), HATU (0-(7-nitrobenzotriazole-l-yl)-l-hexafluorophosphate ,l,3,3-tetramethylguanidine; 18.7 g, 49.3 mmol; and HOAt (l-hydroxy-7-nitrobenzotriazole; 6.71 g, 49·3 mmol) to cool the mixture to Hey. 〇, and added N-mercapto porphyrin (13.6 ml, 0.123 mol). After 10 minutes, add (1 ft)-1-[(333,43,68,7 wang 11)-hexahydro-33,5,5-trimethyl-4,6-methyl-alkyl- 1,3,2- benzodioxanthene-2-yl]-3-methylbutylamine hydrochloride (12.4 g, 4 U mmol). The cooling bath was removed and the mixture was stirred at room temperature for 45 hours. The mixture was diluted with ethyl acetate (8 mL), 2% citric acid solution (2 X 150 mL), 2% NaHC03 solution (2 X 150 mL) and 2% NaCl solution

(2 x 150 ml) wash. The aqueous phase was further extracted with ethyl acetate (15 mL). The combined organic phases were dried over sodium sulfate and concentrated. The resulting oily residue was redissolved in ethyl acetate (5 mL) and washed with cold water (2 mL). The aqueous phase was further extracted with ethyl acetate (5 mL). The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in diethyl ether (100 mL). A white solid (43.4 g) was collected by filtration and purified by column chromatography to &lt;RTI ID=0.0&gt;&gt; The product-containing fractions were concentrated, the residue was dissolved in diethyl ether (100 ml), and the resulting solution was slowly added to hexane (6 mL)

The white solids (15.2 g, 66% yield) were collected by filtration. Method B: IBCF was added to a suspension of BocNH(N〇2)ArgOH (5.82 g, 18.2 mmol) in anhydrous dichloromethane (1 〇〇 liter) to add N-mercapto rifaline (2.0 ml) , 18.2 95014 -78- 1345465

Millions of ears). The mixture was cooled to -15 ° C, followed by the addition of isobutyl chlorohydrazide (2.37 mL, 18.2 mmol). The mixture was stirred at -15 ° C for 1 , minutes, and then '(R)_i_[(3aS, 4S, 6S, 7aRy^ hydrogen-3a, 5, 5-three) as obtained in Example A.1 was added. Methyl-4,6-methylalkyl-1,3,2-benzodioxanthene bromide-2-yl]_3_methylbutylamine hydrochloride (5_0 g, 16.6 mmol) Additional N-indolyl-fufen" strain (2.0 ml '18_2 mmol) was added. The reaction mixture was stirred at -15 for 1.5 hours, then allowed to warm to room temperature and taken in ethyl acetate (150) The organic phase was washed with a saturated NaHC03 solution, dried over anhydrous sodium sulfate and concentrated, and then evaporated. Purification by crystallization from ethyl acetate afforded three portions of the product as a product which was satisfactorily pure (5.03 g, 54% yield).

^NMRCDMSO-dg): 8.80 (1H, br); 8.50 (1H, br), 7.87 (2H, br); 7.01 (1H,d,J=7_9), 4.07 (lH,dd,J=7.9); (lH,m); 3.12(2H,m); 2.55 (1H, m); 2.2(lH,m); 2.01 (lH,m); 1.83 (1H, t, J=5.1) ; 1.78 (lH,m ); 1.74-1.44 (7H, m); 1.38 (9H, s); 1.33 (1H, d, J = 10.3); 1.24 (5H, s); 1.22 (3H, s); 0.84 (6H, d, J =6.6) ; 0.81 (3H, s). Example B.2 1,1-dimethylethylamine methyl, N_[(lS,2R)-l-[[[(lR)-H(3aS, 4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxanthene-2-yl l-3-methyl Butyl]amino]carbonyl]-2-hydroxypropyl]- 95014 •79- 1345465

Boc-L-threonine (870 mg, 3.97 mmol, 12 equivalents) was dissolved in dry DMF (30 mL). In this solution, add (tetrafluoroluban yttrium, yttrium, lanthanum, yttrium-tellurium-9 fluorenyl-0- (stupid and vomiting small base; wo mg, 3.97 millimolar, 1.2 equivalent), and make the mixture Cool down at 〇_rc. Then, add NMM (0.9 ml, 8.27 mmol, 2.5 equivalents) and the example nine (111) small [(3aS, 4S, 6S, 7aR)-hexahydro-3\5,5 -trimethyl-4,6-nonylalkyl-i,3,2-benzodioxanthene-2-yl]-3-methylbutylamine hydrochloride (1 mg, 3.3 m Moore, 1 eq.) The mixture was stirred at room temperature for 16 hours, then extracted with ethyl acetate (1 mL) and washed with the following solutions: citric acid 2% (5 mL), sodium bicarbonate 2 % (50 ml), NaCl 2% (50 ml). The organic solution was dried <RTI ID=0.0></RTI> <RTI ID=0.0>

</ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; (lH,m); (lH,m); 2.51 (lH,m); 2.19 (lH,m); 2.01 (lH,m); 1.83 (lH,t,J=5.9), 1.78 (lH,m) 1.68 (lH,m); 1.62 (1H, m); 1.39 (9H, s); 1.34 (1H, d, J=10.0); 1.24(3H, s); 1.22 (3H, s); 1.06 (3H , d, J=6.4) ; 0.85 (6H, d, J=6.4) ; 0.80 (3H, s). Example B.3 Other intermediate compounds 95014 -80- 1345465 The intermediates reported below start with the appropriate intermediates And made according to any of the procedures described in Examples B.1 and B.2. (2S)-2-[(l,l-dimethylethoxycarbonyl)amino]_5•ureidopentaamine, N__卜卜[(36^,45风7(111)-hexahydro-3 (1,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxole shed 2-_2]-3-methylbutyl]

lHNMR (DMSO-d6): 8.85 (1H, br); 7.01 (1H, d, J = 8.0 Hz); 5.9 (1H, t, J = 5.7); 5.36 (2H, br); 4.03 (2H, m) 2.93 (2H,m); 2.19 (lH,m); 2.0 (1H, m); 1.83 (lH,t,J=5.3); 1.78 (lH,m); 1.68 (lH,m); 1.62 (lH , m); 1.52 (2H, m); 1.38 (9H, s); 1.33 (1H, d, J = 9.9); 1.24 (3H, s); 1.22 (2H, s); 0.86 (3H, d, J =6.6) ; 0.84 (3H, d, J=6.6) ; 0.80 (3H, s). (2S)-3-(Aminocarbonyl)-2-[(U-dimethylethoxycarbonyl)amino] Propylamine, % [(lR)-l-[(3aS,4S,6S,7aR)-^ Μ, -3α,5,5-^. f S -4,6- ψ -1,3,2- Μ- #二氧硼伍园-2-yl]-3-methylbutyl]

1H NMR (DMSO-d6): 8.74 (lH, br); 7.28 (1H, br); 6.95 (2H, m); 4.36 (1Η, 95014 •81 · 1345465 m); 4.07 (lH,m); 2.55 ( lH,m); 2.38 (2H,m); 2.2 (lH,m); 2.02 (2H,m); 1.84 (lH,t,J=5.5); (lH,m); 1.79 (lH,m); 1.68 (lH,m); 1.63 (lH,m); 1.38(9H,s); 1.33 (lH,d,J=10); 1.24 (3H,s); 1.22 (2H,s); 0.85 (3H, d, J = 6.4); 0.83 (3H, d, J = 6.4); 0.81 (3H, s).

Mf S Ψ S m ,N-[(lS,2R)-l-[[[(1R,6S,7aR)-^ M -3a, 5,5-trimethyl- 4,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]

Melting point 57-60 ° C. 1H NMR (DMSO-d6): 8.66 (1H, s); 7.40-7.29 (5H, m); 7.09 (1H, d, J = 8.75); 5.06 (2H, s); 4.90 (1H, J=5.68); 4.11-3.99 (2H, m); 3.91-3.77 (1H, m); 2.58-2.53 (1H, m); 2.26-2.14 (1H, m); 2.07-1.97 (1H, s); 1.84 (lH, t, J = 5.52); 1.81-1.75 (1H, m); 1.73-1.58 (2H, m); 1.33 (2H, d, J = 10.1); 1.27-1.20 (7H, m 1.06 (3H, t, J=6.27); 0.91-0.79 (9H, m). Example B.4 (2S)-2-[(l,l-Dimethylethoxycarbonyl)amino]-3 -[(4-methylbenzimidino)amino]propanamine, N-[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4--4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl

95014 •82- 1345465

(2S)-2-[(l,1-Dimethylethoxycarbonyl)amino]-3·[(4-methyl-carboxamyl)amino]-propionic acid (650) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; _5. (:, cooled in an ice bath, and added ΝΜΜ (0.55 ml, 5 mmol, 2.5 eq.) and the example Α.1 (lR)-l-[(3aS,4S,6S,7aR)4 hydrogen-3a ,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutylamine hydrochloride (500 mg, 1.65 Milliol, 1 eq.). The mixture was stirred overnight, poured over water (200 mL) EtOAc, and ethyl acetate (100 mL). The organic layer was washed with the following solution: citric acid 2% (20 ml), carbonic acid Sodium hydrogenate 2% (20 ml), NaCl 2% (20 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated to give 740 mg of glassy solid (quant.

1H NMR (DMSO-d6) 8.76 (1H, br); 8.28 (1H, t, J = 5.31 Hz); 7.71 (2H, d, J = 7.9); 7.26 (2H, d, J = 7.9); 6.97 (1H , d, J = 8.0); 4.27 (lH, m); 4.07 (lH, dd, J = 8.2, 1.5); 3.48 (2H, m), 2.58 (lH, m); 2.35 (3H, s); 2.19 (lH,m); 2.02 (lH,m); 1.83 (lH,t,J=4.9); 1.78 (lH,m); 1.62 (2H,m); 1.35 (12H,m); 1.24 (3H, s ; 1.23 (3H, s) ; 0.82 (3H, d) ; 0.80 (3H, d) ; 0.78 (3H, s). Example B.5 2-S-[(l,1-dimethylethoxycarbonyl) Amino]-3-(hexylamino)-propanamide, N-[(1S)-1 -[[(111)-1-[(325,48,68,7311)-hexahydro-3&amp ;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanoxa-2-yl]-3-mercaptobutyl]amino]carbonyl] 95014 - 83· 1345465

2-S-[(l,l-Dimercaptoethoxycarbonyl)amino]-3·(hexylamino)propionic acid (300 mg '1 mmol, 12 equivalents) of Example G.7, Dissolve in anhydrous DMF (25 mL) under nitrogen and add xbju (318 mg, 1 mmol). The mixture was cooled in 冰_5 and cooled in an ice bath and added

(0.27 ml '2_47 mM, 2.47 eq.) and Example Α.1 (lR)-l-[(3aS,4S, 63,7&amp;11)-hexahydro-315,5-trimethyl-4, 6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutylamine hydrochloride (250 mg, 0.82 mmol, 1 eq.). The mixture was stirred for 3 hours, poured into water (5 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with the following solution: citric acid 2% (5 mL), sodium bicarbonate 2% (50 mL), and NaCl 2% (50 mL). The organic solution was dehydrated and dried with anhydrous sodium sulfate, filtered, and evaporated to yield 450 mg of a glassy solid. The yield is quantified. Analytical data: 1H NMR (DMSO-d6).: 8.71 (1H, br d, J = 2.6 Hz); 7.73 (1H, br t, J = 5.9 Hz); 6.81 (1H, d, J = 8.2); 4.10 ( 2H,m); 3.24 (2H,m); 2.56 (lH,m); 2.19 (lH,m); 2.03 (3H, m); 1.83 (lH,t,J=5.5); 1.78 (lH,m) 1.64 (2H, m); 1.47 (2H, m); 1.36 (9H, s); 1.4-1.15 (9H, m); 1.24 (3H, s); 1.21 (3H); 0.83 (9H, m); 0.79 (3H, s). Example B.6 95014 -84- 1345465 2-S-[(l,l-Dimethylethoxycarbonyl)amino]-3-(4-fluorosulfonylamino) Propylamine, N-[(1S)-1-[丨(111)-1-[(338,48,68,731〇-hexahydro-33,5,5-trimethyl-4,6-methylalkyl) -1,3,2-benzodioxan-2-yl-1-yl-3-yl]amino]amino]

2-S-[(l,1-Dimethylethoxycarbonyl)amino]-3-(4-fluorosulfonylamino)propanoic acid of Example G.8 (1.39 g, 3.83 m) Moor, 1.2 eq.) was dissolved in dry DMF (20 mL) EtOAc (EtOAc) The mixture was cooled in an ice bath at 〇-5 ° C, and NMM (1 mL, 9.57 mmol, 3 eq.) was added with &lt;RTI ID=0.0&gt;&gt; )-six-rat-3a,5,5-dimercapto-4,6-methylalkyl-1,3,2-benzodioxanthene-2_yl]-3-mercaptobutylamine hydrochloride (0.96 g, 3.19 mmol, 1 equivalent). The mixture was stirred for 2 hours, poured into water (200 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with the following solutions: citric acid 2% (50 ml), sodium sulphate 2% (50 ml) The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated with diethyl ether. The yield was 77%. Analytical data: ^NMR (DMSO-d6). δη: 8.54 (1Η, d, J=2.9 Hz); 7.91 (2H, m); 7.75 (1H, t, J=5.9); 7.50 (2H, t, J = 8.8); 6.83 (1H, d, J=8.4); 4.19 (1H, br d, J=8.2); 95014 -85- 1345465 4.14(lH,m); 3.01 (2H,m); 2.69 (lH, m); 2.25 (lH, m); 2.09 (lH, m); 1.90 (lH, t, J = 5.7); 1.85 (lH, m); 1.8-1.6 (2H, m); 1.5-1.2 (5H, m); 1.43 (9H, s); 1.29 (6H, s); 0.89 (6H, d, J=6.4) ; 0.86 (3H, s). Example B.7 2-S-[(l,l-two Methyl ethoxycarbonyl)amino]-3-(3,4-dimethoxyphenylacetamido)propanamine, N-[(lS)-l-[[(lR)-l-[ (3aS, 4S, 6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan bismuth_2_yl]-3 -methylbutyl]amino]carbonyl]

2-S-[(l,1-Dimethylethoxycarbonyl)amino]3-(3,4-dimethoxyphenylacetamido)-propionic acid (0.73) of Example G.9 </ RTI> </ RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; The mixture was cooled in an ice bath at 〇-5 °C and NMM (0.52 mL, 4.7 mmol, 2.5 eq.) was added as in Example A.1 (1 ft)-1-[(333,43,68, 7311)-Hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxosin-2-yl]-3-methylbutylamine salt Acid salt (〇·47 g, 1.6 mmol, 1 equivalent). The mixture was stirred for 2 hours, poured into water (2 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with the following solution: citric acid 2% (50 ml), sodium bicarbonate 2% (50 ml), and NaCl 2% (50 ml). 95014 -86· 1345465 The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated with diethyl ether to give EtOAc (EtOAc). Beads. The yield was 30%. Analytical data: TLC tannin (solvent ethyl acetate 100%, R.f. = 0.50) ^NMRCDMSO-dg).

Δκ : 8.69 (1Η, d, J=2.6 Hz); 7.90 (1H, t, J=5.7); 6.85 (2H, m); 6.74 (1H, dd, J=1.5, 8.1); 6.85 (3H,m 4.12 (2H, m); 3.73 (3H, s); 3.72 (3H, s); 3.34 (2H, s); 3.31 (2H, m); 2.58 (lH, m); 2.20 (1H, m) 2.03 (lH,m); 1.85 (1H, t, J=5.3) ; 1.79 (lH,m); 1.66 (2H,m); 1.38 (9H,s); 1.40-1.15 (3H, m); (3H, s); 1.23 (3H, s); 0.83 (6H, d, J=6.6); 0.81 (3H, s). Example Β·8 2-S-[(l, 1-dimethylethoxy) Carbonyl)amino 1-3-(3-phenylureido)propanamine, N-[(1S)-H[(1R)-1-丨( know 8,48,68,7玨11)-hexahydro -3~5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]

2- 2-S-[(l,l-Dimethylethoxycarbonyl)amino]-3-(3-phenylureido)propionic acid of Example G.10 (0.41 g '1.26 mmol, 1.2 equivalents) , dissolved in anhydrous DMF (20 mL) under nitrogen, and TBTU (0.40 g, 1.26 mmol, 1.2 eq.). The mixture was cooled in an ice bath at 0-5 ° C, and hydrazine (0.346 mL ' 3.15 mM, 2.5 eq.) and (1R)-l-[(3aS,4S,6S,7aR) of Example A.1 were added. )- 95014 •87· 1345465 Hexanitro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methyl Butylamine hydrochloride (0.31 g, i mmol, i equivalent). The mixture was stirred for 2 hours and poured into water (2 mL) and extracted with ethyl acetate (1 mL). The organic layer was washed with the following solution: citric acid 2% (50 ml), sodium bicarbonate 2% (50 liters), and NaCl 2% (50 ml). The organic solution was dried <RTI ID=0.0></RTI> <RTI ID=0.0> Yield 96.6% » Analytical data: TLC oxime (solvent ethyl acetate 丨〇〇%, Rf =0 47), melting point 128-130 〇C. 1H NMR (DMSO-d6). 5H: 8.79 (lH,d,J =2.7 Hz); 8.69 (lH,s); 7.38 (2H,d,J=7.9); 7.22 (2H,t, J-8.1)' 7.00 (lH,d,J=8.1)' 6.90 (lH,t , J=7.3); 6.16 (lH,t,J=5.7); 4.12 (2H, m) ; 3.45 (1H, m) ; 3.17 (1H, m) ; 2.60 (1H5 m) ; 2.21 (1H, m) 2.04 (lH,m); 1.85 (lH,t,J=5'3); 1.79 (lH,m); 1.66 (2H,m); 1.38 (9H,s); 1.40-1.15 (3H, m) 1.26 (3H, s) ; 1.23 (3H, s) ; 0.84 (6H, d, J=6.6) ; 0.81 (3H, s). Example B.9 Synthesis of other compounds according to Example B.4-B.8 The procedure for the following compounds can be carried out by substituting (1R)-l-[(3aS,4S,6S,7aR)-/,虱-3a,5,5-dimethyl-4,6-methyl for the example α·1 The base-1,3,2- benzodioxanthene-2-yl]-3-methylbutylamine hydrochloride is reacted with an intermediate of the examples G.11, G.12 and G.13. . 95014 -88- 1345465 B.9.1 2-S-[(l,l-Didecylethoxycarbonyl)amino]-3-(acetamido-)propanamine, N-[(1S)-1 -[[(1R)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine Bora-2-yl]-3-methylbutyl]amino]carbonyl]·B.9.2 2-S-[(l,1-dimethylethoxycarbonyl)amino]-3 -(9 - benzyloxymethylaminomethyl)ethyl]-propanamide, N-[(lS)-l-[[(lR)-l-[(3aS,4S,6S, 7aR)-hexanitro) -3a,5,5-dimethyl-4,6-methylalkyl-1,3,2-benzoquinonedioxoindol-2-yl]-31methylbutyl]amino]amino] · B.9.3 2-S-[(l,l-Dimethylethoxycarbonyl)amino]-2-[(pentylureido)ethyl]-N-[(lS)-l-[[[ (lR)-l -[(3&amp;5,43,68,7&amp;11)-hexahydro-3&amp;,5,5-trimethyl-4,6-methyl-in-1,3,2-benzene And dioxin shed 圜-2-yl]-3-mercaptobutyl]amino] ruthenium] - / Yan. B.9.4 2-S-[(l,1-Dimethylethoxycarbonyl)amino]-2-(decanesulfonylamino)ethyl]-N·[(lS)-l-[[[ (lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan圜-2-yl]-3-methylbutyl]amino]carbonyl]- o=s=o 1 B.9.5 2-S-[(l,1-dimethylethoxycarbonyl)amino]- 2-[(ethoxycarbonylamber)-decylamine]ethyl]-N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexaquinone -3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino] sulfhydryl] - —' 0 B.9.6 2-S-[(l,l-Dimethylethoxycarbonyl)amino]-3-(yloxyaminocarbamoyl)ethyl]-propanamide, N-[ (lS)-l-[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trif-yl-4,6-nonanyl-1,3, 2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]amino]] 95014 -89- 1345465

2-S-[(l,l-dimethylethoxycarbonyl)amino]-3 -[2-(1Η-pyrazole)ethyl]-N-[(1S)-1-[[[(1R) )-1 -[(3aS,aS,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methyl-indenyl-1,3,2-indigo-dioxaboron- 2-yl-]-3-methylbutyl]amino]indenyl]

Example B.10 1,1-dimethylhexylamine methyl N,N-[(1S,2R)-1-丨[[(lR)-l-[(3aS,4S,6S,7aR)-six Hydrogen-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxanthene-2-yl]-l-methylbutyl]amino]carbonyl] -methyl

This compound has been derived from (111)-1-[(333,43,63,7&amp;11)-hexahydro-33,5,5-trimethyl-4,6-nonanyl-1, 3,2-benzodioxanil-2-yl]-3-mercaptobutylamine hydrochloride and commercially available N-(l,l-dimethylethoxycarbonyl)glycine Prepared according to the procedure of Example B.1 Method B. 1H-NMR (DMS0-d6): 8.84 (1H, s); 7.08 (1H, t5 J = 5.93 Hz); 4.06 (lH, d5J = 7.48 Hz); 3.67 (2H, t, J = 5.32 Hz); -2.48 (1H, m) ; 2.24-2.16 (1H, m); 2.06-1.96 (1H, m) ; 1.84 (1H, t, J=5.50 Hz) ; 1.82-1.76 (1H, m) ; 1.74-1.58 (2H, m); 1.39 (10H, bs); 1.23 (9H, d, J = 8.18 Hz); 0.87-0.83 (6H, m); 0.82 (3H, bs). Example C.1 (2S)-2-Amino-5-indenylamino (decylamino)methyl]amino] amylamine, Mu [(111)-1-[(3aS, 4S, 6S,7aR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan 95014 •90- 1345465 棚伍园-2-基】-3 -methylbutyl]; hydrochloride

A 4N solution of gasified hydrazine in an oxanthrene (15 ml) was added to the 1,5-i-didecylethylamine of the amino acid of Example B.1, N_[(1S) small [[[(1R) )_H(3aS,4S,6S 7aR)· · Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl] 3-methylbutyl]amino]]yl]-4-[[imino(nitroamino)methyl]amino]butyl]-(4.04 g '7.06 mmol) in dioxane In a solution of a mixture of guanidine (4 ml) and diethyl ether (7 ml), while cooling under 〇〇c. The reaction mixture was allowed to warm to room temperature and stirred for additional 4 hours. The solvent was removed by rotary evaporation. The residue was taken up in diethyl ether (50 mL) and the mixture was stirred at room temperature for three days. The solid formed was collected by filtration to obtain 3-18 g of pure product (yield: 90%). Reference

Method B: 1,1-dimethylethylamine of the amino acid of Example B.1, 沁叽幻+(10)(8)小[(3aS,4S,6S,7aR)-hexahydro-3\5,5-trimethyl Base-4,6-oxime-i,3,2- benzodioxolan-2-yl]-3-methylbutyl]-amino]-yl]-4-[[亚Amino (nitroamino)-methyl]-amino]butyl]- (3 g, 5.3 mmol), dissolved in sputum (4 mM), and at 0 ° C under nitrogen. A solution of approximately 10% HCl in Et20 (20 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for additional 5 hours. The solvent was dissolved in EtOAc EtOAc (EtOAc: EtOAc (EtOAc) (EtOAc) DMSO-d6): 8.56 (2H, br); 8.22 (3H, br); 7.97 (2H, br); 4.28 (lH, dd, J = 8.6 Hz, 2.01); 3.77 (lH, m); 3.04 (lH , m); 2.28 (1H, m); 2.11 (2H, m), 1.92 (lH, t, J = 5.5); 1.83 (lH, m); 1.79-1.59 (4H, m); 1.59-1.37 (3H , m) ; 1.31 (4H, s) ; 1.24 (3H, s) ; 1.19 (1H, d, J = 10.4); 0.88 (3H, d, J = 6.0); 0.86 (3H, d, J = 6.0) ; 0.81 (3H, s). Example C.2

Dihydroxyborane, [(lR)-l-[[(2S)-2-amino-5-[[imino(nitroamino)methyl 1 amide]-1-ketopentyl] Amino]-3-methylbutyl], hydrochloride

1,1-dimethylethylamine of the amino acid of Example B.1, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)- Hydrogen-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] -4-[[imino(nitroamino)indolyl]amino]butyl]-(3.11 g, 5.48 mmol), carefully dissolved in 20 ml of HC1 under nitrogen and (TC) 37%; warm the mixture to room temperature and stir overnight. Wash the reaction mixture with EtzO until the decanediol is completely removed; concentrate the aqueous solution to dryness and dry in vacuo to give 1.82克(4.93 mmol, yield 90%) of the title compound, mp s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s (m, 1H); 1.71 (m, 2H); 1.70-1.48 (m, 3H); 1.49-1.23 (m, 2H); 0.89 (d, J = 5.8 Hz, 3H); 0.88 (d, J=5.8 Hz, 3H). Example C.3 Synthesis of Other Intermediates The intermediates reported below were prepared from the appropriate intermediates and prepared according to any of the procedures described in Example Cl: (2S,3R)-2-Amino -3-hydroxyl Butylamine, N.[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2 -benzobenzodiazepine-2 -yl]-3-methylbutyl]-, hydrochloride

^NMRCDMSO-^): 8.62 (1H, cU = 5.0 Hz); 8.17 (3H, d, J = 3.5); 4.28 (lH, dd, J = 8.8, 1.8); 3.78 (lH, m); 3.52 (lH , m); 3.00 (lH, m); 2.28 (lH, m); 2.10 (lH, m); 1.92 (1H, t, J = 5.7); 1.84 (lH, m); 1.75-1.62 (2H, m 1.43 (lH,m); 1.31 (3H,s); 1.25 (3H,s); 1.22 (1H, d, J=10.6); 1.14 (3H, d, J=6.2) ; 0.88 (3H, d , J=6.4) ; 0.86 (3H, d, J=6.4) ; 0.81 (3H, s). (2S)-2-m S -5-m S Λ Si m ,N-[(lR)-l- [(3aS,4S,6S,7aR)-^ M -3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]- 3-methylbutyl]; hydrochloride 95014 • 93- 1345465

1H NMR (DMSO-d6) 8.51 (iH d J = 5 1 Hz); 817 (3H &gt;br); 6.1 (lH, br); 4.27 (1H, dd, J = 8.6 Hz, 1.8); 3 73 (m, m 2 99 (m,m) ; 2 94 (2H,t); 2.27 (lH,m); 2.10 (lH,m); 1.92 (1H, t, J=5.5) ; 1.82 (lH,m); 1.75-1.15

(9H, m) ; 1.30 (3H, s) ; 1.23 (3H, m) ; 0.87 (3H, d, J=6.0) ; 0.85 (3H, d, J=6.0) ; 0.80 (3H, s). 2S)-2-m S -3-^ f Si s. mm , N-[(lR)-l-[(3aS,4S,6S,7aR)~ ^ M -3a,5,5-trimethyl- 4,6-methylalkyl_1&gt;3 2_benzodioxanthene-2-yl]-3-mercaptobutyl]; hydrochloride

Palm

1H-NMR (DMSO-d6): 8.46-8.41 (1H, m); 8.06 (3H, bs); 7.67 (1H, s); 7.26 (1H, s); 4.30-4.25 (1H, m); 4.08- 4.02 (1H, m); 2.96 (1H, m); 2.60-2.52 (lH, m); 2.36-2.24 (1H, m); 2.20-2.10 (1H, m) ; 1.95 (1H, t, J=5.5 ; 1.88-1.83 (lH,m); 1.75-1.60 (2H,m); 1.46-1.36 (1H, m); 1.32 (3H,s); 1.30-1.18 (6H, m) ; 0.86 (6H, t , J=6.7) ; 0.82 (3H, s). 2-^ S ύ ^ M -3a,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan圜-2-yl] small methyl butyl 95014 • 94· 1345465 base j; hydrochloride

</ RTI> <RTIgt; 2.36-2.24 (lH,m); 2.20-2.10 (lH,m); 1.95 (1H, t, J=5.38 Hz); 1.85 (1H, s) ; 1.75-1.60 (2H, m) ; 1.50-1.38 ( 1H, m); 1.35-1.30 (3H, m); 1.28-1.25 (4H, m); 1.24-1.17 (1H, m); 0.86 (6H, t, J=5.94 Hz); 0.84 (3H, s) Example C.4 (2S)-2-Amino-3-[(4-methylbenzhydryl)]propanamine, N-[(lR)-l-[(3aS,4S, 6S) ,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl] -,Hydrochloride

(2S)-2-[(l,l-Dimercaptoethoxy)amino]-3_[(4·methylbenzyl keto)-amino]-propanamide, of Example B.4, Team [(1 ft)-1-[(3,43,63,7&amp;11)-hexahydro-3屯5,5-trimethyl-4,6-nonyl-1,3,2- stupid And dioxonium bromide_2_yl]_3_methylbutyl]_ (740 mg, 1.65 mmol, 1 equivalent), dissolved in hydrazine, 4 • dioxane (2 〇 ml). To this solution, 4 N HCi (5 ml, 19.8 mmol, 12 eq.) in 1,4-dioxane was added and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure of 95014 • 95 to 1345465 to give 800 mg of a glassy solid (quantitative yield). 1H NMR (DMSO-d6) 8.63 (1H, d, J = 5.5 Hz); 8.38 (1H, t, J = 8.4 Hz); 8.34 (3H, br); 7.80 (2H, t, J = 8.2); 7.28 ( 2H, d, J=8.2 Hz); 4.15 (1H, dd, J=8.8, 1.8); 4.02(lH,br); 3.66 (lH,m); 3.55 (lH,m); 2.99 (1H, m) 2.35 (3H, s); 2.19 (lH, m); 2.06 (1H, m); 1.86 (1H, t, J=5.7); 1.80 (lH,m); 1.64 (2H,m); 1.41 (lH , m); 1.33-1.19 (2H, m); 1.27 (3H, s); 1.21 (3H, s); 1.16 (lH, d, J = 10.6); 0.82 (3H, d); 0.80 (3H, d 0.78 (3H, s). Example C.5 2_S-Amino-3-(hexylamino)-propanamine, N-[(lS)-l-[[(lR)-l-[( 3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3- Methylbutyl]amino]carbonyl], hydrochloride

Example B.5 2-S-[(l,1-dimethylethoxycarbonyl)amino]-3(hexylamino) propylamine,yi[(15)-1-[[ (111)-1-[(3&amp;3,43,63,73 ft)-hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-stuppy Boron bromide-2-yl]-3-methylbutyl]amino]amino] (450 mg, 0.8 mmol, 1 equivalent), dissolved in l,4-dioxane (15 ml) in. To this solution, 4NHC1 (2.45 ml, 0.98 mmol) was added to 1,4-dioxane, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure to give 400 mg of a glassy solid. The yield is quantified. Analytical data: iHNMUpMSOO. δΗ 8.54 (1Η, d, J=5.3 Hz); 8.18 (3H, br); 7.74 (1H, t, J=5.7); 4.29 (1H, dd, 95014 • 96· 1345465 J=1.8 , 8.8); 3.83 (1H, m); 3.40 (2H, m); 3.00 (1H, m); 2.29 (1H, m); 2.11 (lH, m); 2.08 (2H, t, J=7.5); 1.93 (1H, t, J=5.5); 1.84 (lH,m); 1.75-1.15 (llH,m); 1.32 (3H,s); 1.24 (3H,s); 0.86 (3H, d, J=6.6 0.84 (3HS d, J=6.6); 0.81 (3H, s). Example C.6 2-S-Amino-3-(4-fluorosulfonylamino)propanamine, N-[ (1S)-1-丨丨(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl_1,3,2 _Benzo-dioxaboron-2-yl]-3-methylbutyl]amino]carbonyl], hydrochloride

2-S-[(l,1-Dimethylethoxycarbonyl)amino]-3-(4-fluorosulfonylamino)propanamine in Example B.6, 汴[(13) -1-[[(1 ft)-1-[(3&amp;8,43,68,7&amp;11)-hexahydro-315,5·tridecyl-4,6-decyl-1,3, 2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] (0.7 g ' 1.14 mmol, 1 equivalent), soluble in 1,4-dioxane (20 ml). To this solution was added 4NHC1 (3.4 mL) &lt;RTIgt;&lt;/RTI&gt; The solvent was removed under reduced pressure to give 440 mg of white solid. Yield 71% » Analytical data: ^NMR (DMSO-d6). δ Η: 8_54 (lH, d, J = 5.5 Hz); 8.26 (3H, br); 7.89 (3H, m); 7.48 (3H, t, J= 8.8); 4.26 (lH, dd, J=l.3, 8.6); 3.84 (lH,m); 3_06(2H,m); 2.97 (lH,m); 95014 •97· 1345465 2.25 (lH, m); 2.03 (lH,m); 1.83 (2H,m); 1.64 (2H,m); 1.42 (lH,m); 1.35-1.15 (3H,m); 1.28(3H,s); 1.22(3H , s); U1 (1H, d, J = 10.8); 0.85 (6H, m); 0.80 (3H, s). Example C.7 2-8-Amino-3-(3,4-dimethoxy Phenylaminoindolylamine,]\-[(18)-1-[[(lR)-l-[(3aS,4S,6S,7aR)·hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl 1amino]carbonyl hydrazine, hydrochloride

2_S-[(1,1-Dimercaptoethoxycarbonyl)amino]w·dimethoxyphenylacetamido)-propanamine, N-[(lS)- in Example B.7 L-[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimercapto-4,6-methylalkyl-1,3,2-benzoyl Boron bromide]-3-methylbutyl]amino]carbonyl] (0.3 g, 0.47 mmol, 1 eq.) was dissolved in m. To this solution, 4 N HCl (1.43 ml ' 5.71 mmol, 12 eq.) of hydrazine, 4 - dioxane was added, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure, diethyl ether was evaporated, and evaporated, The yield was 85%. Analytical data: 1H NMR (DMSO-d6). (?η. 8.57 (lH, br); 8.12 (3H, br); 7.91 (lH,t,J=5.7 Hz); 6.86 (2H,m); 95014 -98 - 1345465 6.76 (lH, dd, J=l.8, 8.2); 4.26 (1H, br d, J=7.3); 3.82 (lH, m); 3.72 (3H, s); 3.71 (3H, s); 3.36 (2H, s) ; 3.34 (2H, m) ; 2.99 (1H, m) ; 2.26 (1H, m); 2.10 (lH,m); 1.92 (lH,t, J=5.3) ; 1.83 (lH, m); 1.67 (2H, m); 1.45-1.15 (3H, m); 1.31 (3H, s); 1.23 (3H, s); 0.86 (3H, d, J = 6.6); 0.84 (3H, d, J = 6.6); 0.80 (3H, s). Example C.8 2-S-Amino-3-(3-phenyl-yl)-propanamide,]&gt;[-[(18)-1 -[[(111)-1-[([8,48,683])-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan Park-2_yl]-3_methylbutyl]amino]carbonyl], hydrochloride

δ Let 2-S-[(l,1-dimethylethoxyxo)aminophenylureido)propanamine in the example Β8, team [(13)-1-[[(111)- 1-[(333,43,68,7 design)-hexahydro-3\5,5-trimethyl_-4,6-decyl-1,3,2- benzodioxan 2_yl]·3_mercaptobutyl]amino]carbonyl] (0.58 g of '0_1 mmol, 1 equivalent) was dissolved in ι, 4-dioxane (25 ml). To this solution, 4 N HCl (3 mL, 12.1 mmol) &lt;RTI ID=0.0&gt;&gt; The solvent was removed under reduced pressure, and the mixture was evaporated and evaporated to give the desired product. The yield is 100%. Analytical data: ^NMR (DMSO-d6). 95014 -99- 1345465: 8.82 (1H, s); 8.59 (1H, d, J = 5.7 Hz); 8.18 (3H, br) ; 7.40 (2H, d, J = 7.9); 7.22 (2H, t, J=8.1); 6.90 (1H, t, J=7.3); 6.31 (1H, t, J=5.7); 4.26 (1H, dd, J=1.5, 8.6); 3.89 (lH,m); 3.48 (1H, m) ; 3.36 (lH,m); 3.01 (lH,m); 2.24 (lH5m); 2.10 (lH,m); 1.92 (1H, t, J=5.3) ; 1.82 (lH,m); 1.67 (2H, m); 1.50-1.15 (3H, m) ; 1.31 (3H, s); 1.21 (3H, s) ; 0.85 (3H, d, J=6.6); 0.84 (3H, d, J=6.6) ; 0.79 (3H, s). Example C.9 Synthesis of other compounds

The following compounds can be prepared starting from the intermediate of Example B.9 according to the procedure of Example C.4-C.8.

C.9.1 2-S-Amino-3-(ethylammonium)-propanamide, N-[(lS)-l-[[(lR)-l-[(3aS,4S,6S,7aR) -^^ -3\5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-indole-2-yl]-3-methylbutyl]amino] a few bases], HCl salt. C.9.2 2-S-amino-3-(9-ylmethyloxyaminecarbamyl)-propanamine, N-[(lS)-l-[[( lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxon- 2-yl]-3-methylbutyl]amino]carbonyl], HCl salt. C.9.3 2-S-amino-3-(pentylureido)-propanol, N-[(lS) -l-[[(lR)-l-[(3aS54S,6S,7aR)-^ II -3\5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine侧 园-2-yl]-3-methylbutyl]amino] carbonyl], HCl salt. C.9.4 2-S-amino-3-(曱 醯 醯 ))-propionamide, N-[(lS)-l-[[(lR)-l-[(3aS,4S,6S,7aR)-AlL -3a,5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxanthene-2-yl]-3-methylbutyl]amino] carbonyl], HCl salt.

95014 -100- 1345465

C.9.5 2-S-Amino-3-[(ethoxyxyl)-bristamine]ethyl]-)·propanamine, N-[(lS)-l-[[(lR) )-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxime -yl]-3-methylbutyl]amino]carbonyl], HCl salt. C.9.6 2-S-amino-3-(benzyloxyaminecarbamyl)-propanamide, N-[( 1S)-1-[[(1R)小[(3aS,4S,6S,7aRX Hydrogen-3〇Trimethyl-4,6-methylalkyl-1,3,2-benzodioxon-5圜-2 -yl]-3-methylbutyl]amino]carbonyl], HCl salt. CIH \Η ^ d C.9.7 3·[2-(1Η-pyrazole)ethyl]-N-[(1S)- 1-[[[(1R)-1-[(3&amp;3,,6,7&amp;&quot;)-hexahydro-3,5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxanthene-2-yl-]-3-methylbutyl]amino]amino]], HCl salt. CIH Example Dl decylamine,]\-[(18)-1- [[[(1,3,48,68,7))-hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine伍园_2-yl]-3-methylbutyl]aminol-l-yl]-4-[[imino(nitroamino)methyl]amino]butyl]-

HATU (1.84 g, 4.83 mmol) and HOAt (0.66 g, 4.83 mmol) were added to a solution of decanoic acid (0.84 g, 4.83 mmol) in anhydrous DMF (30 mL). After stirring at room temperature for 15 minutes, the mixture was cooled at 〇 ° C, and N-decyl-formoline (1.33 mL, 12.1 mmol) was added. After a further 20 minutes, add (2S)-2.Amino-5-[[imino(indolyl)methyl]amino]amylamine, 1^-[(111)- 1-[(eg 3,43,63,73 ft)-hexahydro-3&amp;,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxine 2-yl]-3-methylbutyl]-hydrochloride (2.2 g, 4.03 95014 -101 · 1345465 mmol). The mixture was allowed to warm to room temperature and stirred for 5 hours, then diluted with ethyl acetate (150 mL), 2% EtOAc (2 X 1 mL), 2% NaHC03 (2 X 100 mL) Wash with 2% NaCl solution (2 X 100 ml). The organic phase was dried over sodium sulfate and concentrated. The residue was purified by column chromatography eluting with a mixture of 80/20 to 100/0 AcOEt / n-hexane. The resulting solid was triturated with diethyl ether, filtered and dried in vacuo to give &lt

Melting point 89-94 ° C Elemental analysis calculated: C 59.99% Η 9.26% Ν 13.54% ® Measured value C 59.47% Η 9.51% Ν 13.42% ^ NMRPMSO-dg): 8.82 (1H, d, J = 2.7 Hz); 8.53(lH,br); 7.99 (1H, d, J=8.05); 7.88(2H,br); 4.33 (lH,m); 4.08 (1H, dd,J=1.6, 8.6) ; 3.14 (2H, m 2.56 (lH,m); 2.20 (lH,m); 2.11 (2H,m); 2.01 (lH,m); 1.84 (lH,t, J=5.7); 1.79 (lH,m); 1.74- 1.58 (3H, m) ; 1.57-1.39 (5H, m) ; 1.32 (lH,d, J=9.9) ; 1.24 (19H, m) ; 0.85 (9H, m) ; 0.80 (3H, s). (2S)-2-Amino-5-[[imino(triosylamino)indolyl]amino]--pivalylamine, team [(111)-1-[(333,48, 63&gt;11)-Hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Other compounds, prepared essentially according to the above experimental procedures, starting with the hydrochloride salt and the appropriate carboxylic acid are reported in Table D-1. 95014 • 102· 1345465 Table D-l Example No. Structure Chemical name 舆 Analytical data D.1.1

Chemical name: 荅-2-carboxyguanamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S, 6民7311)-hexahydro-33,5,5-three Methyl 4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]*4-[[imino] Hydrazinyl)indenyl]amino]butyl] Analytical data: 1H-NMR (DMSO-d6): 8.97 (1H, d, J = 2.8 Hz); 8.71 (1H, d, J = 8.0 Hz); 8.54 (1H, br); 8.50 (1H, s); 8.1-7.9 (4H, m); 7.85 (2H, br); 7.6 (2H, m); 4.63 (1H, m); 4.09 (1H, m) 3.20 (2H, m); 2.61 (1H, m); 2.20 (1H, m); 2.01 (1H, m); 1.9-1.2 (11H, m); 1.23 (3H, s); 1.21 (3H, s ); 0.85 (6H, d, J=6.6); 0.79 (3H, s)._

D.1.2 D.1.3 95014

For palm chemical name: 2-pyridinium carboxamide. N-KlSW-aKlRH-maSjS/SJaR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2 -benzoxaoxaborin-2-yl]-3-mercaptobutyl]amino]carbonyl]*4-[[imino(nitroamino)indolyl]amino]butyl]- Analytical data: 1H-NMR (DMSO-d6): 9.18 (1H, d, J = 1.3 Hz); 8.89 (1H, d, J = 2.4); 8.8-8.65 (3H, m): 8.5 (2H, br) ; .9 (1H, m); 4.15 (1H, m); -1.2 (11H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H, 2 d, J-6.6); 0.79 (3H, s).

r^Y

For palmity 103- Chemical name: 3-(1,3-diketo-1,3-dihydro-isoindol-2-yl)-propanamine, meaning [(13)-1-[[[ (111) Small [(3&amp;3,43,63&gt;11)-hexahydro-3\5,5-trimethyl 4,6-nonylalkyl-1,3,2-benzodioxine 2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: lH-NMR (DMSO- D6): 8.79 (1H, br); 8.51 (1H, br); 8.44 (1H, d, J = 7.8 Hz); 8.2-7.6 (2H, br); 7.85 (4H, m); 4.30 (1H, m ); 4.08 1H, dd, J= 1.8, 8.6); 3.78 (2H, t, J-6.3); 3.11 (2H, m); 2.59 (3H, m); 2.20 (1H, m); 2.01 (1H, m); 1.9-1.2 (11H, m); 1.23 (3H, s); 1.22 (3H, s); 0.84 (6H, d, J=6.6); 0.80 (3H, s)._

1345465

D.1.4 1 Pair of palm 'human HLO' Chemical name: 4-butylbenzamide, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR )-hexa-argon-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino Carbonyl hydrazine-[[imino(indolyl)methyl]amino]butyl] Analytical data: 1H-NMR (DMSO-d6): 8.93 (1H, d, J = 2.9 Hz); 8.51 ( 1H, br); 8.24 (1H, d, J = 7.8); 8.2-7.6 (2H, br); 7.86 (2H, d, J=8.2); 7.29 (2H, d, J=8.2); 4.56 (1H , m); 4.07 1H, dd, J= 1.8, 8.6); 3.16 (2H, m); 2.63 (2H, t, J=7.7); 2.57 (1H, dt, J= 2.5, 7.1); 2.20 (1H , m); 2.01 (1H, m); 1.9-1.2 (15H, m); 1.23 (3H, s); 1.22 (3H, s); 0.90 (3H, d, J=7.3); 0.84 (6H, d , J=6.6); 0.80 (3H, s). D.1.5 AO^^NH | H to 0 Chemical Name: 3-[(l,1-Dimethylethoxy)carbonylamino]benzamide , 1^-[(13)-1-[[[(111)-1-[(333,43,63,7))-hexahydro-3a,5,5-trimethyl*4,6-methane Base-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] winter [[imino(nitroamino)methyl]amino group ]butyl]-analytical data: 1H-NMR (DMSO-d6): 9.48 (1H, s); 8.88 (1H, d, J=2.8 Hz); 8.51 (1H, br); 8.42 (1H, d, J= 8.0); 7.6-8.4 (2H, br): 7.97 (1H, s); 7.55 (1H, Dd, J=7.8, 1.1); 7.47(1H, d, J=7.8); 7.34 (1H, t, J=7.8); 4.55 (1H, m); 4.09 (1H, dd, J= 1.8, 8.6) 3.17 (2H, m); 2.60 (1H, dt, J= 2.9, 8.4); 2.20 (1H, m); 2,02 (1H,m); 1.9-1,2 (11H, m); 1.48 ( 9H, s); 1.23 (3H, s); 1.21 (3H, s); 0.85 (6H, d, J=6.6); 0.80 (3H, s). D.1.6 1 Pair of palmity. 1 χ Njh h A 0 Chemical name: 2-(2-decyloxyethoxy)acetamidine, N-[(1S)-1-[[[(1R)-l-[(3aS,4S,6S ,7aR)-hexa-argon-3a,5,5-trimethyl A6-decyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino [carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl analysis data: 1H-NMR (DMSO-d6): 8.74 (1H, d, J = 2.8 Hz); 8.51 (1H, br); 8.2-7.4 (2H, br); 7.69 (1H, d, J = 8.6); 4.39 (1H, m); 4.12 (1H, dd, J = 1.8, 8.6); 3.91 (2H, s); 3.57 (2H, m); 3.46 (2H, t, J=4.6); 3.26 (3H, s); 3.13 (2H, m); 2.63 (1H, m); 2.21 (1H, m); 2.03 (1H, m); 1.9-1.2 (11H, m); 1.24 (3H, s); 1.21 (3H, s); 0.85 (3H, d, J=6.6); 0.83 (3H, d, J= 6.6) ; 0.80 (3H, s).

95014 104- 1345465

D.1.7 H 〇^ pair of palm chemical name: 2-[2·(2-methoxyethoxy)ethoxy]ethylamine, N-[(lS)-H[[(lR)-l -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl group&gt; 3-MethylbutylJ-amino]carbonyl]imino(nitroamino)methyl]amino]butyl analysis data: 1H-NMR (DMSO-d6): 8.74 (1H, d, J=2.8 Hz); 8.52 (1H, br); 8.2-7.6 (2H, br); 7.69 (1H, d, J== 8.6); 4.40 (1H, m); 4.11 (1H, dd, J= 1.8, 8.6) 3.91 (2H, s); 3.6-3.4 (8H, m); 3.23 (3H, s); 3.13 (2H, m); 2.63 (1H, m); 2.20 (1H, m); 2.02 (1H, m ); 1.9-1.2 (11H, m); 1.24 (3H, s); 1.21 (3H, s); 0.84 (3H, d, J=6.6); 0.83 (3H, d, J= 6.6); 0.79 (3H , s). D.1.8 1 Pair of palmar Η L 〇 々〇 Chemical name: (E)-3-(ethoxycarbonyl) acrylamide, N-[(1S)-1-[[[(1R) -l-[(3aS,4S,6S,7aR)-Hexahydro-3a,5,5-trimethyl 4,6-decyl-1,3,2- benzodioxan-2- Methyl 3-methylbutyl]amino]carbonyl M-[[imino(nitroamino)methyl]amino]butyl] Analytical data: 1H-NMR (DMSO-d6): 8.78 ( 1H, d, J=8.6 Hz); 8.77 (1H, s); 8.55 (1H, br); 8.3-7.6 (2H, br); 7.12 (1H, d, J=15.5); 6.58 (1H, d, J=15,5); 4,45 (1H, m 4.19 (2H, q, J=7.1); 4.12 (1H, dd, J=1.8, 8.6); 3.15 (2H, m); 2.63 (1H, dt, J=3.3, 8.6); 2.21 (1H, m); 2.04 (1H, m); 1.9-1.2 (11H, m); 1.25 (3H, s); 1.24 (3H, t, J=6.9); 1.23 (3H, s); 0.85 (3H, d, J=6.6); 0*83 (3H, d, J= 6.6); 0.80 (3H, s). D.1.9, Ν^^ΝΗ Η Λ ο ~ο Chemical name: 2-hexafluoropyridin-1-yl -Acetamine. N-IXlSVl-QGRO-l-WaSjSjSJaR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxon- 2-yl]-3-mercaptobutyl]amino]carbonyl H-[[imino(indolyl)methyl]amino]butyl] Analytical data: 1H-NMR (DMSO-d6): 8.79 (1H, d, J=1.8 Hz); 8.53 (1H, br); 8.3-7.5 (2H, br); 7.79 (1H, br); 4.37 (1H, m); 4.12 (1H, dd, J= 1.8, 8.6); 3.13 (2H, m); 2.87 (2H, br); 2.62 (1H, m); 2.36 (4H, m); 2.20 (1H, m); 2.03 (1H, m); 1.9-1.2 (17H, m); 1.24 (3H, s); 1.21 (3H, s); 0.83 (6H, d, J = 6.6); 0.79 (3H, s).

95014 -105- 1345465

D.1.10 Chemical Name:

4-(1-methyl·hexahydropyridine 4·yl)·butanamine, 1^-[(13)-1-[[[(1))-1-[(3&amp;3,43,6min 7〇11)-hexa-argon-3\5,5-trimethyl·4,6-methylalkyl-1,3,2·benzodioxan-2-yl]-3-methylbutyl Amino]carbonyl]&gt;4-[[imino(nitroamino)methyl]amino]butyl]analytical data: 1H-NMR (DMS0-d6): 8.82 (1H, d, J= 2.7 Hz); 8.51 (1H, br); 8.01 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 6.94 (1H, t, J=5.8): 4.33 (1H, m); 4.07 (1H, dd, J= 1.8, 8.6); 3.13 (2H, m); 2.78 (2H, br); 2.68 (3H, br s); 2.55 (1H, m); 2.19 (1H, m); 2.10 (2H, t, J=7.5); 2.00 (1H, m); 1.85-U (22H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H, 2 d, J=6.6 ); 0.79 (3H, s)._ Chemical Name:

2-Ethylamino-acetamide, 1^-[(13)-1-[[[(111)-1-[(3 and 3,45,63,7〇11)-hexahydro-3a, 5,5-tridecyl·4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonylindole-[[ Imino (nitroamino)methyl]amino]butyl] Analytical data: 1H-NMR (DMSO-d6): 8.67 (1H, d, J = 2.7 Hz); 8.51 (1H, br); 8.14 (1H, t, J=5.7); 8.08 (1H, d, 8.0 Hz); 83-7.5 (2H, br); 4.34 (1H, m); 4.09 (1H, dd, J= 1.8, 8.6); 3.68 (2H, m); 3.13 (2H, m); 2.56 (1H, m); 2.20 (1H, m); 2.01 (1H, m); 1.84 (3H, s); 1.85-1.2 (11H, m); 1.24 (3H, s); 1.21 (3H, s); 0.83 (6H, d, J=6.6); 0.79 (3H, s). The compounds reported in Table D-1A are in accordance with the procedure of Example D1 above. And using (2S)-2-amino-5-[[imino(nitroamino)indolyl]amino]pentanylamine of Example C.1, N-[(lR)-l-[( 3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3- Methyl butyl]-hydrochloride is prepared as a starting material with a suitable carboxylic acid. 106- 95014 1345465

Table D-1A

Example No. Structure Chemical Name 舆 Analytical Data D.1.2 Λ" Chemical Name: 6- oxasulfonyl hexamethyleneamine, &gt; 1-[(18)-1-[[[(1 ft)-1· [( 3〇8,45,63,7))-H-argon-33,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl] -3-decylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.83 ( 1H, d, J = 2.8 Hz); 8.51 (1H, br); 7.97 (1H, d, J = 7.8 Hz); 8.2-7.6 (2H, br); 7.77 (2H, m); 7.65-7.5 (4H , m); 4.31 (1H, m); 4.05 (1H, dd, J= 1.8, 8.6); 3.12 (2H, m); 2.69 (2H, q, J=7.0); 2.54 (1H, m); 2.20 (1H, m); 2.05 (2H, t, J=7.5); 2.01 (1H, m); 1.85-1.1 (21H, m); 1.22 (3H, s); 1.21 (3H, s); 0.82 (6H , d, J=6.6); 0.79 (3H, s). D.1.3 ^ fi r 0^0 Chemical name: 8-(ethanesulfonylamino)octylamine ^-[(13)-1- [[[(111)-1-[(3&amp;3,48,aluminum,7〇11)-hexahydro-3&amp;5,5-trimethyl*4,6-methylalkyl-1,3,2- Stupid and dioxoboron-2-yl]-3-methylbutyl]amino]carbonyl H-[[imino(indolyl)methyl]amino]butyl analysis data: 1H- NMR (DMSO-d6): 8.81 (1H, br s); 8.51 (1H, br); 7.98 (1H, d, J = 7.8 Hz); 8.3-7.5 (2H, br); 6.93 (1H, t, J=5.7): 4.32 (1H, m); 4.06 (1H, dd, J-1.8, 8.6); 3.13 (2H, m); 2.95 (2H, q, J=7.3); 2.87 (2H, q, J=6.7); 2.55 (1H, m); 2.19 ( 1H, m); 2.10 (2H, t, J=7,0); 2.00 (1H, m); 1.85-U (17H, m); 1.23 (3H, s); 1.21 (3H, s); 1.16 ( 3H, t, J= 7.3); 0.83 (6H, d, J=6.6); 0.79 (3H, s). D.1.4 κ human r 〇-*N^o Chemical name: 6-(ethanesulfonyl) Amino) hexylamine, N-[(1S)-1-[[[(1R)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4 ,6-decyl-l,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[iminoamine (nitroamine) Analytical data: lH-NMR (DMSO-d6): 8.83 (1H, d, J = 2.7 Hz); 8.51 (1H, br); 8.00 (1H, d, J= 8.0 Hz); 8.3-7.5 (2H, br); 6.94 (1H, t, J=5.8): 4.32 (1H, m); 4.06 (1H, dd, J= 1.8, 8.6); 3.13 (2H, m) 2.95 (2H, q, J=7.3); 2.87 (2H, q, 1=6.1); 2.55 (1H, m); 2.19 (1H, m); 2.10 (2H, t, J=7.5); 2.00 ( 1H, m); 1.85-U (17H, m); 1.24 (3H, s); L21 (3H, s); 1.16 (3H, t, J= 7.5); 0.83 (6H, d, J=6.6 ); 0.79 (3H, s).

Example D.2 10-(1,3-Diketo-1,3-dihydro-iso-threo-2-yl)-decylamine,]\-[(18)-1-[[[(111 )-1- 95014 • 107- 1345465 [(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl]4,6-methylidyl_ι,3,2-stupid Dioxo oxo-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(desylamino)methyl]amino 1 butyl]-:

10-(1,3-Diketo-ι, 3-dihydro-isoindolizin-2-yl)-decanoic acid (353 mg, 1.11 mmol) prepared according to Example G.1 in anhydrous N-mercapto whallow (122 μl, U1 mmol) was added to the solution in dioxane (1 mL). The mixture was allowed to cool to -15 ° C ' then 'n-butylic acid isobutyl ester (144 μl, 1.11 mmol) was added slowly. After 15 minutes, the (2S)-2-amino-5-[[imino(decylamino)indolyl]amine]pentanylamine of Example C.1 was added: ^-[(111)- 1-[(3&amp;3,43,65,7〇11)-hexahydro-3a,5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxole圜_2_yl]-3-methylbutyl]-hydrochloride (508 mg, 1.01 mmol) with other N-methylmorpholine (122 μl ' 1.11 mmol). The reaction mixture was stirred at 45 to 1 Torr for 4 hours. then concentrated to a small volume and partitioned between ethyl acetate (20 mL) and water (10 mL). The aqueous phase was further extracted with ethyl acetate (10 mL). The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in ethyl acetate (3 ml), and the solution was applied dropwise to hexane (120 ml), and stirred at room temperature. The solid was collected by decantation and dried under vacuum (730 mg, 94%). 1H NMR (DMSO-d6): 8.81 (1H, d, J = 2.7 Hz); 8.52 (1H, br); 7.98 (1H, d, 95014 -108 - 1345465 J = 8.05); 7.88 (2H, br); (4H, m); 4.34 (lH, m); 4.06 (1H, dd, J = 7.1); 3.56 (2H, t, J = 7.14); 3.14 (2H, m); 2.55 (lH, m); (lH,m); 2.10 (2H, t, J=7.14); 2.0(lH,m); 1.82 (1H, t, J=5.7) ; 1.78 (lH,m); 1.73-1.35 (10H,m) 1.31 (lH,d,J=9.9); 1.24(19H,m); 0.84 (9H,m); 0.79 (3H, s). Other compounds prepared essentially according to the above experimental procedure are reported in Table D- 2 in. Table D2

Example No. D.2.1 Structure Chemical Name 舆 Analysis Data

Chemical name: 4-(methoxycarbonyl)butanamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexa-argon-3a,5, 5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[亚Amino (decylamino)methyl]amino]butyl] Analytical data:

D.2.2 1H-NMR (DMSO-d6): 8.79 (1H, d, J = 2.7 Hz); 8.51 (1H, br); 8.04 (1H, d, J = 7.9 Hz); 8.3-7.5 (2H, br 4.31 (1H, m); 4.07 (1H, dd, J=1.8, 8.6); 3.57 (3H, s); 3.13 (2H, m); 2.55 (1H, m); 2.28 (2H, t, J = 7.7); 2.20 (1H, m); 2.28 (2H, t, J = 7.5); 2.01 (1H, m); 1.85-1.2 (13H, m); 1.23 (3H, s); 1.21 (3H, s ); 0.83 (6H, d, J=6.6); 0.79 (3H, s)._ Chemical Name:

4-(1-butyl-hexahydropyridin-4-yl)-butanamine, team [(13)-1-[[[(1))-1-[(3 mad 3,43,63,7 a) hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amine ]]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: 1H-NMR (DMSO-d6): 8.78 (1H, d, J = 2.7 Hz) 8.51 (1H, br); 7.97 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 4.32 (1H, m); 4.07 (1H, dd, J= 1.8, 8.6); 3.13 (2H, m); 2.78 (2H, br d, J=11.2); 2.55 (1H, m); 2.19 (3H, m); 2.09 (2H, t, J=7.5); 2.00 (1H, m); 1.85-1.0 (26H, m); 1.23 (3H, s); 1.21 (3H, s); 0.85 (3H, t, J=7.9); 0.83 (6H, 2 d, J=6.6); 0.79 (3H, s).

109- 95014 1345465

D.2.3

According to the above, the chemical name is reported in Example D.2: 2· Butoxyethylamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)4t3a ,5,54f*&gt;4,6-Methyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]Erythryl]·4·[ [Imino][,]amino]methyl]amino]butyl] Analytical data: lH-NMR (DMS0-d6): 8.74 (1H, d, J = 2.8 Hz); 8.51 (1H, br); 8.3-7.5 (2H, br); 7.61 (1H, d, J= 8.0); 4.39 (1H, m); 4.12 (1H, br d, J= 8.2); 3.85 (2H, s); 3.42 (2H, t, J=6.4); 3.13 (2H, m); 2.64 (1H, m); 2.20 (1H, m); 2.03 (1H, m); 1.95-1.2 (15H, m); 1.24 (3H, s) 1.21 (3H, s); 0.87 (3H, _t, J=7.3); 0.83 (6H, d, J= 6.6); 0.79 (3H, s). Other compounds made by the procedure' are reported in Table D-2A. The compound of Example D.2.6 is from the 2-aminoacetamide of Example D.14, small [(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6- Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]-amino]carbonyl]-4-[[iminoamino(nitroamino) A The base]-amino]-butyl] is prepared starting from the hydrochloride. The compounds of Examples D.2.7 and D.2.8 were prepared from the 2-aminoacetamide of Example C.3, team [(18,21〇-1-[[[(111)小[(3&amp;8,48 , 63, 7 set) - hexahydro-3 〇 tridecyl-4,6-decyl-1,3,2-benzodioxanthene-2-yl]-1-decyl butyl] Hydrochloride. The compounds of Examples 2·9 and 2.10 were prepared from the example (C.3) of (2S)-2-amino-5-ureido-amylamine, 沁[(111)-1-[(3 3,43,68,7311)-hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3 -methylbutyl]; hydrochloride. 95014 110- 1345465

Table D-2A

Example No. Structure Chemical name 舆 Analytical data D.2.4 Person. _ 、, r 0-~〇 Chemical name: 12-[(1,1-Bisthylethoxy)carbonylamino]dodecane decylamine, Mu [(18)-1-[[[(11 〇-1-[(3,43,63,7〇11)-hexa-argon-3a,5,5-trimethyl*4,6-methyl-peptidyl-1,3,2- benzodioxan -2--2-yl]-3-methylbutyl]amino]carbonyl] sorb [[imino(nitroamino)methyl]amino]butyl]-analytical data: lKNMR (DMSO-d6) 8.81 (1H, d, J=2.4); 8.52 (1H, br); 7.98 (1H, d, J=8.05); 7.85 (2H, v. br); 6.73 (1H, t, J=5.3); 4.33 (1H, m); 4.07 (1H, d, J=8.4); 3.14 (2H, m); 2.88 (2H, q, J=6.6); 2.56 (1H, m); 2.19 (1H, m); (2H, t, J=7.1); 2.01 (1H, m); 1.83 (1H, t, J=5.7); 1.78 (1H, m); 1.73-1.41 (8H, m); 1.36 (9H, s) 1.33-1.15 (25H, m); 0.84 (6H, d, J=6.5); 0.80 f3H, s). D.2.5 . For palm lift Η 1. 0』々0 Chemical name: 4·(曱Oxycarbonyl)heptinamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR&gt; hexahydro-3a,5,5-trimethyl*4, 6-Methyl-1,3,2- benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl hydrazine [imido (nitroamino)methyl]amine Analytical data: 1H-NMR (DMSO- D6): 8.80 (1H, br s); 8.51 (1H, br); 7.98 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 4.32 (1H, m); 4.06 (1H, Br d, J= 8.4); 3.12 (2H, m); 2.55 (1H, m); 2.26 (2H, t, J= 7.3); 2.18 (1H, m); 2.09 (2H, t, J= 7.1) 2.01 (1H, m); 1.85-1.2 (19H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H, d, J=6.6); 0.79 (3H, s). D .2.6 I to palm. ^又Μ Ι· 〇-~. Chemical name: 2-[2-(2-decyloxyethoxy)acetamido]acetamide, N-[(lS)-l-[[[(lR)-l-[(3aS,4S ,6S,7aR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoboron-2-yl]-3-methylbutyl [Amino]carbonyl] Winter [[imino(nitroamino)methyl]amino]butyl] butyl analysis data: lH-NMR (DMSO-d6): 8.71-8.68 (1H, m); 8.53 ( 1H, m); 8.15 (1H, d, J=8.1); 8.10-7.60 (3H, m); 4.40-4.33 (1H, m); 4.13^.08 (1H, m); 3.92 (2H, s) ; 3.82-3.78 (2H, m); 3.64-3.58 (2H, m); 3.52-3.46 (2H, m); 3.27 (3H, s); 2.62-2.56 (1H, m); 2.26-2.16 (1H, (m); 1.32-1.26 (4H, m); 1.25 (3H, s); 1.22 (3H, s); 0.86-0.83 (6H, m); 0.81 (3H, s). 1345465

D.2.7 Pair of palm ft Chemical name: X decylamine, N-[l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl 4,6-Methyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]methyl] Analytical data: lH-NMR( DMSO-d6): 8.85 (1H, s); 8.11 (1H, t, J=5.9); 4.07-4.03 (1H, m); 3.83-3.78 (2H, d, J=6.4); 2.24-2.16 (1H m); 2.11 (2H, t, J=7.40); 2.05-1.95 (1H, m); 1.84 (Ih, t, J=5.6); 1.81-1.75 (1H, m); 1.74-1.60 (2H, m); 1.54-1.45 (2H, m); 1.35-1.30 (1H, d, J = 10.1); 1.28^1.20 (21H, m); 0.90-0.84 (9H, m); 0.81 (3H, s). D.2.8 «The palm X X. The name of the school: 2-[2-(2-methoxyethoxy)ethoxy]acetamidine, N-[l-[[[(lR)-l-[( 3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxan-2-yl]-3 -Methylbutyl]amino]carbonyl]indenyl] Analytical data: lH-NMR (DMSO-d6): 8.81 (1H, m); 7.97 (1H, t, J=6.0); 4.09-4.04 (1H, m); 3.93 (2H, s); 3.85 (2H, d, J=6.0); 3.64-3.57 (2H, m); 3.57-3.50 (4H, m); 3.45-3.40 (2H, m); 3.23 ( 3H, s); 2.58-2.52 (1H, m); 2.24-2.15 (1H, m); 2.05-1.97 (1H, m); 1.83 (1H, t, J=5.6); 1.80-1.76 (1H, m); 1.72-1.58 (2H, m); 1.31 (1H, d, J=10.1); 1.28 -1.25 (2H, m); 1.23 (3H, s); 1.21 (3H, s); 0.86-0.82 (6H, m); 0.80 (3H, s). D.2.9 〇^N^^NH2 , confrontation X Chemical Name: Indoleamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl -4,6-decyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-5-ureidopentyl]-D .2.10 0 V? Η 2 嘢 palmity &lt; Chemical name: 4-butylbenzamide N-[(lS)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR )-hexa-argon-3a,5,5-tridecyl·4,6-nonyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amine Alkyl]carbonyl]-5-ureidopentyl]·

Example D.3 11-Cyanoundecylamine, N-[(1S)-1-[[丨(111)-1-[(338,48,68,7311)-hexahydro-33,5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxolybdenyl-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[亚Amino (decylamino)methyl]amino]butyl]- 95014 -112- 1345465

PS-carbodiimide (N-cyclohexylcarbodiimide _NL propoxymethylpolystyrene, 769 mg, 1 mmol, loading U1 mmol/g) with H〇At (1 ·•Hydroxy-7-azabenzotriazole, 115 mg, 0.8.5 mM) added to u•cyanoundecanoic acid (115 mg, 0.54 mmol) in dioxane g)CM) (9 ml) in solution. After stirring for 10 minutes, (2S)-2-amino-5-[[imino(decylamino)methyl]amino]amylamine, N-[(lR)-i-, of Example C-1 was added. [(3aS, 4S, 6S, 7aR) - hexahydro-3a,5,5-trimethyl-4,6-anthracene-1,3,2-stupidyl boron oxide _2-yl] -3-Methylbutyl]-, hydrochloride (251 mg, 0. 50 mmol) and DIPEA (0.128 mL '0.75 mmol). The suspension was shaken overnight at room temperature, then PS-carbodiimide was filtered off and washed several times with DCM (4×6 mL).

The organic phase was passed through a VARIAN CHEM ELUT cartridge for liquid-liquid extraction, pre-conditioned with saturated aqueous NaHC03, and finally washed with DCM (15 mL). The solvent was evaporated, and the crude material was purified (jjjjjjjjj NMR (CDC13): 7.53 (s, br, 2H); 7.36 (d, br, J = 4.7 Hz, 1H); 6.88 (d, J = 8.2 Hz, 1H); 4.46 (m, lH); 4.15 (dd , J=8.5, 1.9 Hz, 1H); 3.19 (m, 2H); 2.93 (m, 1H); 2.23 (t, J=7.2 Hz, 2H); 2.21 (m, 1H); 2.09 (t, J= (7.5, 2H) (m, 4H); 1.26 (s, 3H); 1.24-1.12 (m, 16H); 0.80 (d, 95014 • 113- 1345465 J=6.6, 3H); 0.79 (d, J=6.6, 3H); 0.73 (s, 3H). LC-MS 659.7, MH+. ESI POS ; AQA ; spray 4 kV / demister: 20 V / probe 250 C. Basically other compounds prepared according to the above experimental procedure are reported in In Table D-3. Table D-3

Example No. Structure Chemical Name 舆 Analytical Data D.3.1 〇-~〇 Chemical Name: 癸醯 cavity, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR) -hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino] Carbonyl]-4-[[imino(decylamino)indolyl]amino]butyl] Analytical data: MS : MH+ 621.5 D.3.2 1 at 1^ V, 'N*^SNH Η I. o -^o Chemical name: 荇-1-carboxyguanamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5, 5-tridecyl·4,6-methylalkyl-l,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[亚Amino (hulkamino)methyl]amino]butyl] Analytical data: MS : MH+ 621.4 D.3.3 I Pair of palmitic chemical name: 2-phenylacetamide, N-[(1S)- 1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzoyl Oxyboron-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 585.3 D.3.4 Lipping chemical name: 1-phenylcyclopentane carboxamide "-[(lSVH^lig-l-paSeSjSJaR)-hexahydro- 3^5,5-trimethyl&gt;4,6- 0_々0 decyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amine [carbonyl]][[imino(desineamino)methyl]amino]butyl] Analytical data: MS : MH+ 639.4 114- 95014 1345465

D.3.5 | The name of the palm o-^o Chemical name: (2R)-2-phenylbutylamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S) ,7aR)-hexahydro-3a)5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxan-2-yl]-3-methylbutyl] Amino]carbonyl]ice[[imino(desineamino)methyl]amino]butyl] Analytical data: MS : MH+ 613.4 D.3.6 I vs. tt κ human ΪΤ Chemical Name: (2S)- 2-p-butyrylamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)4lL-3a,5,5Jf&amp;*4,6-methane Base-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]4-[[imino(nitroamino)indenyl]amine Analytical data: MS: MH+ 613.4 D.3.7 littivity - nA Chemical name: dodecyl decylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS, 4S,6S, 7aR)-hexa-argon-3a,5,5-trimethyl-4,6-nonyl-1,3,2-benzophenoxynonan-2-yl]-3-A Benzyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 649.5 D.3.8 κ ro' Chemical name: Xin 醯Amine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-decane Base-1,3,2-benzoic Bora-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 593.4 D.3.9 For zero sex Η 1. 0~. Chemical name: acetamidine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4 ,6-methylalkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4·[[imino group (nitroamino group) Methyl]amino]butyl] Analytical data: MS : MH+ 509.3 D.3.10 , 4: H I. o' Chemical name: 4-(1,1-dimethylethyl)cyclohexanecarboxamide , team [(13)-1-[[[(1 ft)-1-[(3&amp;3,45,63,7311)-hexahydro-33,5,5-trimethyl-4,6-methane Base-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino)methyl] Amino]butyl] Analytical data: MS : MH+ 633.5

95014 115- 1345465

D.3.11 To zero H group chemical name: trans 4-pentylcyclohexane carboxamide, 1^-[(18)-1-[[[(111)-1-[(3&amp;3, 45,68,7〇11)-hexa-argon-33,5,5-trimethylsulfonium 6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutene Amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 647.5 D.3.12 | For palm ΒΛο Chemical name: 4- Phenylbutyramine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethylhydrazine 6-oxime Alkyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[iminoamino(nitroamino)] fluorenyl Amino]butyl] Analytical data: MS : MH+ 613.4 D.3.13 o A Na?? Chemical name: 2-(3-methoxyphenyl)acetamide, N-[(1S)-1 -[[[(1R)-1-[(3&amp;3,45,63,7〇11)-hexahydro-3&amp;,5,5-trimethyl-4,6-decyl-1,3 ,2-benzodioxanoxa-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl Analytical data: MS : MH+ 615.3 D.3.14 HU 〇-~〇 Chemical name: 4-(1,1-didecylethyl)benzamide, 沁[(18 )-1-[[[(111)-1-[(335,43,65,7311)-hexahydro-3〇-trimethyl] 4,6-methylalkyl-1,3,2-benzodiox Bora-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 627.5 D.3.15 1 Pairs of palms - 〇-~〇 Chemical name: decylamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)- Hydrogen-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl] -4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 607.4 D.3.16 Η Ι· 〇-% Chemical name: (RS)-2-cyclopentyl Benzoamine, N-[(1S)-1-[[[(1R)-1-[(3&amp;3,45,68,7311)-hexa-argon-33,5,5-trimethyl-4 ,6-Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) )methyl]amino]butyl] Analytical data: MS : MH+ 633.5 95014 116- 1345465

D.3.17 D.3.18 D.3.19 D.3.20 D.3.21 D.3.22 95014

«The palm of the hand

〇ΝΗ 〇人Ο Chemical name: 喽-phen-2-carboxamide, N-[(1S)-1-[[[(1R)-1-[(3,5,45,63,731〇-hexa-argon-33 ,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]·4- [[Iminoamino]methyl]amino]butyl] Analytical data: MS : MH+ 577.2 Chemical name: 2,3-Difluoro benzoate, N-[(1S)-1- [[[(1R)-1-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxine Born-2-yl]-3-methylbutyl]amino]carbonyl H-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 607.3 The palm of the palm to the palm of the chemical name: 2-(2-iodophenyl)acetamidamine, N-[(1S)-1-[[[(1R)-1-. [(3aS,4S,6S ,7aR)-AlL-3a,5,5if&amp;-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino] Carbonyl]·4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 711.3 Chemical name: Cyclohexane carboxamide, N-[(1S)-1 -[[[(1R)-1-[(333,48,65,7])-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzo Dioxon -yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)indolyl]amino]butyl]analytical data: MS : MH+ 577.3

ΝΗ A Pair of palm chemical name: 2-(4-bromophenyl)acetamidine, N-[( 1S)-1 -[[[(1R)-1 -[(333,43,63&gt;!1) -hexahydro-3-7,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl ]-4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 663.2

0·々0 117- Chemical name: Benzylamine, N-[(1S)-1-[[[(1R)-1-[(333,45,63,7pressure 11)-hexahydro-315, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[亚Amino (nitroamino) fluorenyl]amino]butyl] Analytical data: MS : MH+ 571.3 1345465

D.3.23 D.3.24 D.3.25 D.3.26 D.3.27 D.3.28 95014

I-to-palm HL _ 〆, sputum chemical name: 2-methylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS, 48,68,7 a) hexahydro-33,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino ]carbonyl&gt;4-[[imino(desineamino)indolyl]amino]butyl]analytical data: MS : MH+ 585.3 Chemical name: 4-bromobenzamide, N-[(1S )-1-[[[(1R)-1-[(3玨3,43,68,7311)-hexahydro-33,5,5-trimethyl 4,6-methylalkyl-1,3,2 -benzodioxaboron-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl] analysis Data: MS : MH+ 649.3

«掌性〇·'〇

CT々0 for palm chemical name: (2S)-2-phenylpropanamide, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)- Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl ]·4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 599.3 Chemical name: (E)-2-methyl-3-phenyl-acrylofluorene Amine, team [(18)-1-[[[(1,1,1,1,1,3,6,7,7)-hexahydro-33,5,5-trimethyl*4,6-methane -1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]*4-[[imino(()amino) thiol] Amino] butyl] Analytical data: MS : MH+ 611.4 οα,

For zero-118-chemical name: 2-[(indol-2-yl)oxy]acetamide, team [(13)-1-[[[(1)-1-[(335,48,63, 7311)-Hexahydro-33,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzoindoleboron-2-yl]-3-mercaptobutyl]amine Alkyl]carbonyl]-4-[[imino(decylamino)indolyl]amino]butyl] Analytical data: MS : MH+ 651.4 Chemical name: 2,2-dimercaptobutylamine, N- [(1S)-1-[[[(1R)-1-[(338,45,6民7311)-hexahydro-33,5,5-trimethyl*4,6-nonanyl-1, 3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino] butyl Analysis data: MS : MH+ 565.4 1345465

D.3.29 D.3.30 D.3.31 D.3.32 D.3.33 D.3.34 95014

〇-々〇

Zeroness

119- Chemical name: 2-(2-Phenylphenyl)acetamidine, N-[(1S)-1-[[[(1R)-1-[(335,45,63,7111)-hexa-argon- 33,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl]·4 -[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 619.3 Chemical name: 5-methylsulfon-2-carboxycarboxamide, N-[(1S) -1-[[[(1R)-1-[(338,45,6民731〇-hexahydro-33,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzene) And dioxonium-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(desineamino)methyl]amino]butyl] Analytical data: MS : MH+ 591.3 Chemical name: cis-3-(2-indolyl)propenylamine, 1^-[(15)-1-[[[(11〇-1-[(3&amp;3,43) ,63,7311)-Hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxaninoin-2-yl]-3-mercaptobutyl Amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 627.4 Chemical name: (2-methylphenyloxy)B Indoleamine, N-[(1S)-1-[[[(1R)-1-[(338,48,68,7311)-hexahydro-33,5,5-trimethyl-4,6-methane Base-1,3,2-benzodioxan-2-yl]-3- Benzyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 615.4 Chemical Name: 2-(2,5-II Methyl phenyl) acetamidine, team [(13)-1-[[[(111)-1-[(333,43,63,7])-hexahydro-33,5,5-tridecyl) *4,6-Methyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl H-[[imino group] ) mercapto]amino]butyl] Analytical data: MS : MH+ 613.4 Chemical name: trans-3-(2-bromophenyl)propenylamine, :^[(13)-1-[[[(111 )-1-[(3&amp;8,45,68,7311)-hexahydro-3〇trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl] -3-methylbutyl]amino]]-based H-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 675.3

1345465

D.3.35 s. Human chemical name: 4-isopropylbenzamide, N-[(1S)-1-[[[(1R)-1-[(333,43,68,7〇11)-hexa-argon-3〇 Triamyl*4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino group (decylamino) fluorenyl]amino]butyl] Analytical data: MS : MH+ 613.4 D.3.36 〇Λ, human NH HA〇 Chemical name: 4 gas 4-methylphenyl) butyl hydrazine, hydrazine [ (15)-1-[[[(111)-1-[[335,43,65,7])-hexahydro-3〇trimethylhydrazine 6-methylalkyl-1,3,2-benzodioxine硎 圜-2-yl]-3-methylbutyl]amino]carbonyl M-[[imino(indolyl)f-yl]amino]butyl] Analytical data: MS : MH+ 627.4 D .3.37 I Η 1. 〇-~0 Chemical name: 2-(2-mercaptothio)acetamide, N-[( 1S)-1-[[[( 1R)-1 -[(3 ug 8 ,43,65,7311)-Hexahydro-33,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxoboron-2-yl]-3-indenyl Butyl]amino]carbonyl]·4-[[imino(decylamino)methyl]amino]butyl] Analytical data: MS : MH+ 667.3 D.3.38 | For palmar Η 1, 〇- ~0 Chemical name: 5-methylhexylamine, 1^-[(15)-1-[[[(1!〇-1-[(3aS,4S,6S,7aR)-hexahydro-3a 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[ [Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 579.4 D.3.39 | For zero, N^^NH Η I. 〇-', 〇Chemical name: 3 -cephen-2-yl-propionamide, N-[(1S)-1-[[[(1R)-1-[(3&amp;5,43,65,7玨11)-hexa-ar-33, 5,5-trimethyl-4,6-nonyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]_4_[[ Imino (nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 605.4 D.3.40 1 Pair tt Si human r 〇-% Chemical name: 2,4-dimethyl Oxazol-5-carboxyguanamine, team [(15)-1-[[[(1,1,1,1,1,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,3 ,6-Methyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) ) methyl]amino]butyl] Analytical data: MS : MH+ 606.4 95014 120- 1345465

D.3.42 D.3.43 D.3.44 D.3.45 D.3.46 95014 Chemical name: Furan-3-carboxyguanamine, N-[(is)-i-[[[(iR)-i-[(333,48 ,68,73 ft)-hexa-argon-3〇trimethyl 4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino ]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 561.3_ Chemical name:

For palmar (2R)-2-phenylpropionamide, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5 ,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl hydrazine-[[imine (Nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 599.4 Chemical name: 2-cycloheptylacetamide, N-[(1S)-1-[[[(1R) -1-[(335,43,63,7〇11)-hexahydro-315,5-trimethyl) &quot;4,6-methylalkyl-1,3,2-benzodioxime -yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 605.4 Chemical name: 1 -nonylcyclopropanecarboxamide, 1^-[(18)-1-[[[(111)-1-[(3 ugly 3,43,63,7311)-hexahydro-3-7,5-5- Trimethyl*4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imine (nitroamino)methyl]amino]butyl] Analytical data:

Palm

121 - MS : MH+ 549.3 Chemical Name: 1-Mercapto-cyclohexane Carboxamide, N-[(1S)-1-[[3(1R)-1-[(3&amp;8,48,63,7311 )-Hexahydro-315,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl] 4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 591.3 Chemical name: 2-[(lS,2R&gt;5S)-2-isopropyl- 5-methylcyclohexyl]oxyacetamidine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-six atmosphere-3a,5,5 -trimethyl 4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imine (Nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 663.3

1345465

D.3.47. A... 〇-~〇 Chemical name: (E)-2-butene decylamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)- Argon-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] 4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 535.6 D.3.48 〇Λ H &lt;A Chemical name: 3-methyl T^®, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4,6-methylalkyl-1, 3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino] Analytical data: MS: MH+ 551.3 D.3.49 I for palm, human NH H. Chemical name: 3-phenylpropanamide, N,[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino (Nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 599.3 D.3.50 p-Benzene, ΧΤΎ々夕如Η Τ 0 is 0 Chemical name: 4-(4-曱-oxyphenyl )-Butylamine, team [(13)-1-[[[(111)-1-[(333,43,68,7311)-hexahydro-33,5,5-tridecyl-4,6 -Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl H-[[imino(nitroamino)methyl] Amino] butyl] Analytical data: MS : MH+ 643.4 D.3.51 1 Pair of palm NjlH 〇-^〇 Chemical name: Umbrene-3-carboxyguanamine, N-[(1S)-1-[[[ 1R)-1-[(3 Wang 8,43,63&gt;11)-hexahydro-315,5-trimethyl 4,6-nonanyl-1,3,2- benzodioxane- 2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 577.2 D.3.52 . _ _, Ν^^ΝΗ Η 1. 〇~ Chemical name: 2-ceto-3-yl-acetamide, 1^-[(13)-1-[[[(1 -1--1-[(333) ,43,65,7311)-hexahydro-33,5,5-trimethyl hydrazine 6-methylalkyl-1,3,2-benzodioxaninoin-2-yl]-3-mercaptobutyl Amino]carbonyl] winter [[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 591.4

95014 122· 1345465

D.3.53 f A T sHr^x Η. too. Chemical Name: (E)-penta-2,4-dienylamine.N-KlSVHfKlRH-WaWSJaR)-Hexahydro-3a,5,5-trimethyl·4,6-methylalkyl-1,3, 2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 547.3 D.3.54 S human r ο is ο Chemical name: 2-(4-isopropylphenoxy)acetamidine, N-[(1S)-1-[[[(1 -1-[(3&amp;5,4 people 63,7 said)-hexa-argon-33,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxine 2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)f-yl]amino]butyl] Analytical data: MS : MH+ 643.4 D. 3.55 to zero-sex Si human 1τ 〇-% Chemical name: 2-(4-ethylphenoxy)acetamidine, N-[(1S)-1-[[[(1R)-1-[(3冴3,43,63,7〇11)-hexahydro-33,5,5-trimethyl&gt;4,6-decyl-1,3,2-benzodioxazole-2-yl ]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)indenyl]amino]butyl] Analytical data: MS : MH+ 629.4 D.3.56 Into the chemical name: (E)-2-methylhex-2-enoic acid decylamine, N-[(1S)-1-[[[(1R)-1-[(3&amp;3,43,63, 7311)- Hydrogen-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl ]·4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 577.2 D.3.57 1 嘢 zero tt H. Human chemical name: 3-(3-A Phenyl phenyl) acrylamide, bucket [(18)-1-[[[(111)-1-[(3&amp;3,43,65,7&amp;))-hexahydro-3 〇 trimethyl-4 ,6-Methyl-1,3,2-benzobisindolino-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) Methyl]amino]butyl] Analytical data: MS : MH+ 611.4 D.3.58 H L1 O' ^0 Chemical name: 2-Cronopylidene-1-ylethylamine, team [(13)-1-[ [[(111)-1-[(338,45,65,7311)-hexahydro-33,5,5-trimethyl]4,6-nonylalkyl-1,3,2-benzoic Oxyboron-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 643.3 95014 123 · 1345465

D.3.59 D.3.60 D.3.61 D.3.62 D.3.63 D.3.64 95014

124- Chemical name: (RS)-2-cyclopent-2-enylamine, N-KlSVHtKlRJ-i-^aSjSjSJaR)-hexahydro-3a,5,5-trimethyl&gt;4,6-曱alkyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[iminoamino(nitroamino) A Amino]butyl] Analytical data: MS : MH+ 575.3 Chemical name: 4-diethylaminobenzamide, N-[(1S)-1-[[[(1R)-1-[(3aS ,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methyl Benzyl]amino]carbonyl]*4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 642.4 Chemical name: (RS)-2-methyl Butylamine. N-KlSVH^lig-l-paSAS/SJaR)-Hexahydro-3a,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxine - 2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino(indolyl)methyl]amino]butyl] Analytical data: MS : MH+ 551.3_ Chemical name : 3-(4-methylphenyl)propenylamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5 ,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4 -[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 611.4_ Chemical name: hexyl-2,4-dienoate, N-[(1S) -1-[[[(1R)-1-[(333,43,6民7311)-hexahydro-33,5,5-trimethyl-4,6-decyl-1,3,2- Benzodioxaboron-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data : MS : MH+ 561.5 Chemical name: 4-pyrrol-1-yl-codantamine, N-[(1S)-1-[[[(1R)-1-[(335,4艮63,73 ft) -hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino] Carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 636.3 1345465

D.3.65 I-to-zero HK 〇_~〇 Chemical name: (E)-3-»cephen-3-yl-propenylamine, N-[( 1S)-1 -[[[(1R)-l -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4,6-decyl-1,3,2-benzodioxan-2-yl] -3-f-butyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 603.3 D.3.66 〇Λ Human r Chemical name: hept-2-enylamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-three Mercapto 4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino] · Aminomethyl)methyl]amino]butyl] Analytical data: MS : MH+ 577.3 D.3.67 For palmity KA Chemical name: 2-(3,4-Dimethylphenoxy)acetamide, team [(15)-1-[[[(111)-1-[(333,43,63,7&amp;11)-hexahydro-3〇trimethyl*4,6-methylalkyl-1,3,2 -benzobenzodiazepine-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino]methyl]amino]butyl] analysis Data: MS: MH+ 629.3 D.3.68 Hydrazine, — Λη 〇-~〇 Chemical Name: 癸-9-eneamine, team [(18)-1-[[[(11〇-1-[(3aS) , 4 S,6S,7aR)-hexa-argon-3a,5,5-trimercapto-4,6-methylalkyl-1,3,2- benzopyridinium bromide-2-yl]-3-methyl Butyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 619.3 D.3.69 1 Pairs of palms χ, Η I 8. Chemical name: (E)-undec-2-enoic acid decylamine, N-[(1S)-1-[[[(1R)-1-[(333,45,65,731〇-hexahydro-33 ,5,5-trimethyl}4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl H-[[ Imino (nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 633.4 D.3.70 I 0 V. H |. 〇-~0 Chemical name: (E)-癸-3- Hydrazine amide, N-[(1S)-1-[[[(1R)-1-[(335,48,63,7311)-hexa-argon-33,5,5-tridecyl-4,6 -decyl-1,3,2-benzobis-boron-2-oxyl-2-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino)] Methyl]amino]butyl] Analytical data: MS : MH+ 619.4

95014 125· 1345465

D.3.71 D.3.72 D.3.73 D.3.74 D.3.75 D.3.76 95014

On the palm tt

O',. ^ For palm chemical name: 2,2-dimethyl-3-(2-mercaptopropenyl)-cyclopropanecarboxylamine, N-[( 1S)-1 -[[[(1R)-1 - [(333,45,68,7&amp; ruler)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl-2-yl ]-3-methylbutyl]amino]carbonyl hydrazine [imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 616.9 Chemical name: 2-methylcyclohexane Carboxylamidine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-tridecyl 4,6-methane 1,2-3,2-benzodioxan, B-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl] Amino]butyl] Analytical data: MS : MH+ 591.4 Chemical name: 5-cyclohexylpentalamine, N-[(1S)-1-[[[(1R&gt;1-[(3 ug3,45,68) ,7 also)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl Amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 633.5

〇* *〇

〇-~〇 掌 化学 chemical name: 3-methoxycyclohexane carboxamide, N-[(1S)-1-[[[(1R)-1-[(3&amp;5,48,68, 7&amp;11)-Hexahydro-33,5,5-trimethyl-4,6-nonyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl Amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 607.3 Chemical name: (3R)-3,7-dimethyl Base-oct-6-enoic acid amide, team [(13)-1-[[[(111)-1-[(3&amp;5,43,63,7311)-hexa-argon-33,5,5- Trimethyl-4,6-methylalkyl-1,3,2- benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino (Nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 619.4

For palmity 126- Chemical name: 3-[(4-Methyl)thio]propanamine, N-[(1S)-1-[[[(1R)-l-[(3aS,4S,6S ,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl] Amino]carbonyl]-4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 659.3 1345465

D.3.77 D.3.78 D.3.79 D.3.81 D.3.82 95014

Palm

Correct? Sex Chemical Name: (3S)-3,7-Dimethyl-oct-6-enoic acid decylamine, N-[(1S)-1-[[[(111)-1-[(3〇8,48 ,63,7〇11)-hexahydro-33,5,5-trimethylsulfonium 6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl Amino]carbonyl]*4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 619.4 Chemical name: (RS&gt; 4-ethyl octylamine A-KlSi-HtKlig-l-^aSjS/SJaR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-one 3-methylbutyl]amino]carbonyl]·4·[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 621.4 Chemical name: 5- Fluoro-2-methoxy alumine, N-[(1S)-1-[[[(111)-1-[(333,48,63,7311)-hexahydro-3,5, 5-tridecyl·4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]4-[[imine (Nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 619.2 Chemical name: 2-(4-bromophenoxy)-acetamide, hydrazine [(18)-1- [[[(111)-1-[[335,43,68,7311)-hexa-argon-33,5,5-trimercapto-4,6-methylalkyl-1,3,2-benzodioxine Boron-2-yl]-3-methylbutyl Amino]carbonyl&gt;4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 679.6_ Chemical name: 2-( 1 -methyl-1H- Indole-3-yl)acetamide, 1^-[(18)-1-[[[(111)-1-[(333,48,63,7311)-hexahydro-315,5-triterpene *4,6-Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino] Amino) thiol]amino]butyl] Analytical data: MS : MH+ 638.3 Chemical name:

Hexaar-2,5-methylalkyl acenaphthene-3 &amp; (111)- amide, N-[(1S)-1 -[[3(1R)-1 -[(3 aS,4S,6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl] Amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 615.2 127- 1345465

D.3.83 D.3.84 D.3.85 D.3.86 D.3.87 D.3.88 95014

Vr Chemical name: Bicyclo[2.2.1]heptane-2-carboxyguanamine, bucket [(13)-1-[[[(111)-1-[(3氓43,68,7〇11)- Hexahydro-33,5,5-trimethylsulfonium 6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl H-[ [Imino] (decylamino)methyl]amino]butyl] Analytical data: MS : MH+ 589.2 Chemical name: (RS)-2-(4-Phenylphenyl)propanamide, N-[( 1S)-1 -[[[(1R)-1-[(3&amp;3,43,63&gt;11)-hexahydro-33,5,5-trimethyl]4,6-methylalkyl-1, 3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(desylamino)methyl]amino] butyl Analytical data: MS : MH+ 633.6 NH〇\ For palmity versus palm chemical name: (2S)-2-methylbutyramine, N-[( 1S)-1 -[[[(1R)-1 -[(3&5,48,63,7311)-hexahydro-33,5,5-trimethyl&quot;4,6-methylalkyl-1,3,2-benzodioxazole -yl]-3-methylbutyl]amino]carbonyl PK[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 551.8

For palm chemical name: (4RS)-1-[(1,1-:decylethoxy)alkyl]-hexahydropyridine-4-carboxyguanamine N-[(1S)-1-[[[ (1R) small [(3aS, 4S, 6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxon-5 -yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 678.4

〇* *〇\又ΝΗ Chemical Name: (RS)-4-methyloctylamine, N-[(1S)-1-[[[(1R)-1-[(335,48,65,7〇 11)-Hexahydro-33,5,5-trimethyl]&gt;4,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 607.3

Pair of palmity 128- Chemical name: 2-Fluoro-5-methyl carbamide, [[13]-1-[[[(111)-1-[(335,45,65,7311)- Hexafluoro-33,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino] Carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 603.2 1345465

D.3.89 D.3.90 D.3.91 D.3.92 D.3.93 D.3.94 95014

For the chemical name of the club: 2·(bicyclo[2.2.1]hept-2-yl)acetamidamine, Mu [(15)-1-[[[(lR)-l-[(3aS,4S,6S ,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl] Amino]carbonyl]ice[[imino(indolyl)methyl]amino]butyl] Analytical data: MS : MH+ 603.8

Palm

〇· 0' Chemical name: cyclopropane carboxamide. N-KlSi-l-QGIO-l-paS/SjSJaR)-hexahydro-3a,5,5-trimethyl-4,6-decyl-1 ,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino] Butyl] Analytical data: MS : MH+ 535.3 Chemical name: 4-ethoxybenzamide, N-[(1S&gt;1-[[[(1R)-1-[(3aS,4S,6S,7aR) -hexahydro-3a,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl ]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 615.2

Money palmity vs. palmity %:

129- Chemical name: (E)-3-(4-bromophenyl)propenylamine, 乂[(13)-1-[[[(111)-1-[(3 ug 3,43,68,7&amp ;11)-hexahydro-33,5,5-trimercapto-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl]-4-[[imino(decylamino)methyl]amino]butyl] Analytical data: MS : MH+ 675.1 Chemical name: (2S)-2-(6-methoxy荇-2-yl)-propanamine, N-[(1S)-1-[[[(111)-1-[(3 mad 5,43,63,7〇11)-hexahydro-33, 5,5-trimethylstilbene-4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[ [Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 679.3 Chemical name: 3-fluoro*4-methoxybenzamide, N-[(1S) -1-[[[(1R)-1-[(333,43,63,7))-hexahydro-33,5,5-tridecyl*4,6-decyl-1,3,2 - stupid and dioxonium oxa-2-yl]-3-methylbutyl]amino]carbonyl H-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 619.5

1345465

D.3.95 D.3.96 D.3.97 D.3.98 D.3.99 D.3.101 95014

«掌" «The name of the chemical: 4-fluoro-3--3-benzylbenzamide, N-[(1S)-1-[[[(1R)-1-[(3&amp;5,43,65 ,7311)-Hexahydro-3〇-trimethyl*4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino ]carbonyl H-[[imino(indolyl)methyl]amino]butyl] Analytical data: MS : MH+ 603.2 Chemical name: 壬-2-enoic acid amide, N-[(1S)- 1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3\5,5-trimethyl) 6-methylalkyl-1,3,2-benzodiox Boron-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 605.3

〇-々〇

〇-^〇 Chemical name: (E)-3 -(荇-2-yl) acrylamide, N-[( 1S)-1 -[[[(1R)-1 -[(3 mad8,43, 63,7311)-Hexahydro-3&amp;,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-methyl Butyl]amino]carbonyl]-4-[[imino(decylamino)methyl]amino]butyl] Analytical data: MS : MH+ 647.3

The palm chemical name: porphyrin-2-carboxyguanamine, 1^-[(13)-1-[[[(111)-1-[(333,43,65&gt;11)-hexahydro) -33,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl] -4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 622.3 Chemical name: 1-(4-methoxyphenyl)-cyclopropanecarboxamide, N-[(1S)-1-[[[(1))-1-[(333,45,68,7&amp;11)-hexa-argon-33,5,5-trimethyl-4,6-methane Base-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl] Amino]butyl] Analytical data: MS : MH+ 641.4

For palmity 130- Chemical name: 3-butenylamine, [[13]-1-[[[(111)-1-[(335,45,65,7〇11)-hexa-ar-33, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[ [Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 535.0 1345465

D.3.102. Λ柳Si人Γ 〇 〇 〇 chemical name: tetradecane ffi amine, N-[(1S)-1-[[[(1R)-1-[(335,45,65,7))-hexa-argon- 33,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl H-[[ Imino (decylamino)methyl]amino]butyl] Analytical data: MS : MH+ 677.3 D.3.103 1 For Ttt , N^^NH Η Ι · 〇-~0 Chemical name: 3-(1Η -&quot;ί丨哚-3-yl)-propanamine, N-[(1S)-1-[[[(1R)· 1-[(335,45,65,7311)-hexahydro-3〇 Trimethyl &quot;4,6-methylalkyl-1,3,2- benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]*4-[[imine (Nitroamino)methyl]amino]butyl] Analytical data: MS: MH+ 638.2 D.3'104 fttit. Hey. Chemical name: 4-phenoxybutylideamine, N-[(1S)-1-[[[(1R)-1-[(3&amp;5,43,68,7311)-hexa-argon-33,5, 5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[ Amino (nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 628.9 D.3.105 ΐ性'人Η.. 0-^0 Chemical name: 5-keto-5-benzene Ketopentaamine, team [(13)-1-[[[(111)-1-[(335,43,65,731〇-hexa-argon-315,5-trimethyl 4,6-methyl-1-) , 3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)indenyl]amino] Butyl] Analytical data: MS : MH+ 641.1 D.3.106 1 Pair of palmity \ανη Η Ι· ο-^ο Chemical name: (2RS)-1-((1,1-didecylethoxy)carbonyl) - hexahydropyridine-2-carboxyguanamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-three Methyl 4,6-methylalkyl-1,3,2-benzobis-boron-2-yl]-3-methylbutyl]amino]carbonyl]·4·[[imino] Nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 678.2 D.3.107 . , for zero sex 'human HA Chemical name: Pyridine-2-carboxyguanamine, N -[(1S)-1-[[[(1R)-1-[(335,45,65,7311)-hexa-argon-3〇trimethyl-4,6-methylalkyl-1,3,2- Benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data : MS : MH+ 572.1

95014 131 · 1345465 D.3.108 °\jC^ Η I. 〇-% Chemical name: Pyridine-3-carboxamide, N-[(1S)-1-[[[(1R)-1-[(3aS, 4S,6S,7aR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-indenyl Butyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 572.1 D.3.109

Chemical name: pyridine*4-carboxyguanamine, N-[(1S)-1-[[[(1R)-1-[(335,43,63,7冱))-hexa-argon-3〇trimethyl 4,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino group (nitroamine) Analytical data of methyl)amino]butyl] butyl: MS: MH+ 572.5 D.3.110

〇 *〇

Chemical Name: (2S)-1-((1,1-Dimercaptoethoxy)carbonyl)-hexahydropyridine-2-carboxyguanamine, N-[(1S)-1-[[[(1R) -1-[(3&amp;3,43,63,7)-hexa-argon-3&amp;,5,5-trimercapto-4,6-methylalkyl-1,3,2-benzodioxan Obvious-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 678.1

D.3.111 I to zero

Chemical Name: (2R)-1-((1,1-Dimethylethoxy)carbonyl)-hexahydropyridine-2-carboxyguanamine, N-[(1S)-1-[[[(1R) -1-[(338,48,65,7&amp;11)-hexa-argon-33,5,5-trimethylidene*4,6-methylalkyl-1,3,2-benzodioxime- 2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : MH+ 678.2 D.3.112

«The palm chemical name: 3,3-dimercapto-butylamine, team [(18)-1-[[[(111)-1-[(3aS,4S,6S,7aR)-hexa-argon-3a ,5,5-tridecyl·4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4- [[Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 565.0

D.3.113 aNr^r'

For palm chemical name: 4-[(phenylamino)carbonyl]butanamine, team [(15)-1-[[[(111)-l-[(3aS,4S,6S,7aR)dlL- 3a,5,5-X〒&amp;&quot;4,6-decyl-alkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl ]-4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : MH+ 656.2 95014 -132- 1345465 D.3.114 I 掌 tt 〇-~〇 Chemical name: 2,2-Dimethylpentamidine, N-[(1S)-1-[[[(1R)-1-[(3〇8,43,63,7))-hexa-argon-33,5, 5-trimethylphenyl 4,6-methylalkyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imine Analytical data: MS : MH+ 579.2 D.3.115 I «掌 tt 〇-~〇 Chemical name: 5-cephen-2-yl-pentamidine, Team [(15)-1-[[[(111)-1-[(333,48,68,7311)-hexahydro-315,5-trimethyl] 1,6-methyl-1-, 3, 2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 633.2 D.3.116 | For palmity 彳丫 0 s T 0-^0 Chemical name: (3RS)-1-((1,1-dimethylethoxy)carbonyl ))-hexahydropyridine-3-carboxamide, N-[(1S)-1-[[[(1R)-1_[(3aS,4S,6S,7aR)-hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino (Nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 678.0 D.3.117 j For palmity 0- \a„ Η I. Chemical name: 8-phenyl-octylamine, N -[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-tridecyl-4,6-methylalkyl-1, 3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl Analytical data: MS : MH+ 669.1 D.3.118 | For palmity, Ν^&gt;ΙΗ HU 〇-~0 Chemical name: 3-[[(1,1-dimethylethoxy)carbonyl]amino group ]propionamide, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4,6 -Methyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl][[iminoamino(nitroamino)indolyl] Amino]butyl] Analytical data: MS : MH+ 638.2 D.3.119 For ftt S human r VIII Chemical name: Tridecyl decylamine, N-[(1S)-1-[[[(1R)-1-[[ ( 3aS, 4S, 6S, 7aR)-hexa-argon-3a,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxan-2-yl]-3 -Methylbutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 663.3 95014 133- 1345465

D.3.120 1 财掌性 0 \JC^ 〇-% Chemical name: ^ δ£^, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR) -AlL-3a,5,5SfS4,6-nonylalkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]*4-[ [Iminoamino(nitroamino)indenyl]amino]butyl] Analytical data: MS: MH+ 566.1 D.3.121. Λ _ s τ ο'^^ο Chemical name: amylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexahydro-3a, 5,5-trimethyl·4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl] bucket[[亚Amino (decylamino)methyl]amino]butyl] Analytical data: MS : MH+ 551.2 D.3.122 For palmity ^ Si Human r 〇-~〇 Chemical name: [[[(9H-第-9 -yl)methoxy]arginyl]amino]butanamine, N-[(1S)-1 -[[[(1R)-1 -[(338,43,63,7311)-hexahydro-3a , 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-fylbutyl]amino]carbonyl H-[[ Imino (nitroamino)methyl]amino]butyl] Analytical data: MS : MH+ 775.3 D.3.123 . . . , N, N^^NH Η Ι · Chemical name: 2-(diamine Ethylamine, &gt; 1-[(13)-1-[[[(111)-1-[(335,43,65,7311)-hexahydro-33,5,5-trimethyl &quot ; 4,6-decyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl H-[[imino group (nitroamine) Analytical data: MS: MH+ 552.5 D.3.124 I vs. tt Ό El Γ 〇-~〇, chemical name: 5-(4-fluoro stupid Ethyl pentaamine, team [(13)-1-[[[(111)-1-[(335,43,65,7311)-hexahydro-33,5,5-trimethyl-4, 6-Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino)] Methyl]amino]butyl] Analytical data: MS : MH+ 645.2 D.3.125 1 Pair of oxime NhXT 0 々0 Chemical name: 8-keto-8-phenyloctylamine. NK^-HtlXlRH-KiJaSAS /SJaR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxon-2-yl]-3-methylbutyl] Amino]carbonyl H-[[imino(indolyl)indolyl]amino]butyl] Analytical data: MS : MH+ 683.1 95014 134- 1345465

D.3.126. A _ 〇-(〇chemical name: 4-(嚷-phen-2-yl)butanamine. N-KlSi-HtKlRO-l-tOaSdSjSJaR)-hexahydro-3a,5,5-trimethyl*4,6 - Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)- Amino]butyl] Analytical data: MS : MH+ 619.0 D.3.127 | For palm tt mr 〇-~〇 Chemical name: 5_keto _5_(喽 _2_2_yl) pentamidine, N- [(1S)-1-[[[(111)-1-[(3 and 3,43,68&gt;11)-hexa-argon-3〇trimethyl·4,6-methylalkyl-1,3,2 - stupid and bismuth boron oxazol-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] analysis Data: MS: MH+ 647.1 D.3.128 Pairs of palmity °_wHd \Λη H 〇Λ Chemical name: 2-(3-indolyl) acetamidine, :N-[(1S)-1-[[[(1R) )-1-[(338,45,65,7311)-hexahydro-33,5,5-trimethyl]4,6-methylalkyl-1,3,2-benzodioxine- 2-yl]-3-mercaptobutyl]amino]carbonyl M-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 619.1 D. 3.129 For palmity O 八 '0 Chemical name: undecyl decylamine N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7 aR)-hexa-argon-3a,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl] Amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 635.2 D.3.130 . For palm κλγ 0々0 chemistry Name: 4-heptyl azelaamine, team [(15)-1-[[[(111)-1-[(333,43,65,7))-hexahydro-33,5,5-three Methyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino] Aminomethyl)methyl]amino]butyl] Analytical data: MS : [MH]+ 669.6 D.3.131 ο Α摩 0TM LKAr 〇-% Chemical name: 6-phenylhexylamine, 1^-[ (15)-1-[[[(111)-1-[(338,45,68,7311)-hexahydro-33,5,5-tridecyl-4,6-methylalkyl-1,3, 2-Bist and bis-boron-boron-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 641.5

95014 135· 1345465

D.3.132 D.3.133 D.3.134 D.3.135 D.3.136 D.3.137 95014

Chemical name: 5-phenylpentamidine, N-[(1S)-1-[[[(1R)-1-[(3&amp;5,45,65,7〇11)-hexa-argon-33,5 ,5-trimethyl&quot;4,6-methylalkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]*4-[ [Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 627.5 Chemical name: 10-hydroxyfurfuralamine, N-[(1S)-1-[[ [(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- benzodioxan -2--2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: __MS : [MH] + 637.7 Chemical name: 5-keto-5-(4-phenylhexa-pyridin-1-yl) amidine, N-[( 1S)-1 -[[[(1R)-1 -[( 3aS,4S,6S,7aR)-Hexahydro-3a,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-yl Benzyl]amino]carbonyl H-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : [MH]+ 725.4 Chemical name: 2-(1Η-tetrazole -5-yl) acetamidine, N-[(1S)-1-[[[(1R)-1-[(33,43,63,7菹11)-hexahydro-33,5,5-three Mercapto-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl Amino]carbonyl]4-[[imino(nitroamino)indolyl]amino]butyl]analytical data: MS : [MH]+ 577.0_Chemical name:

2-(tetrazol-1-yl)acetamidine, N-[(1S)-H[[(1R)-1-[(3&amp;5,43,65,7311)-hexahydro-33,5, 5-trimethyl-4,6-methylalkyl-1,3,2- benzodioxoindol-2-yl]-3-methylbutyl]amino]carbonyl]4-[[imine Analytical data: MS: [MH]+ 576.9_Chemical name: 2-(pyrimidin-2-ylthio)acetamide, hydration [(13) -1-[[[(111)-1-[(333,43,63,7&amp;11)-hexahydro-315,5-tridecyl*4,6-methylalkyl-1,3,2-benzene And dioxonium-2-yl]-3-mercaptobutyl]amino]carbonyl H-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 618.9

136- 1345465

D.3.138 D.3.139 D.3.140 D.3.141 D.3.142 D.3.143 95014

Confrontation

137- Chemical name: 3-Methylthiopropionamide, team [(18)-1-[[[(1 尺)-1-[[,,,,,,,,,,,,,,,,,,,,, 5-trimethylphenyl*4,6-methylalkyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[亚Amino (nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 569.4 Chemical name: 3-(indol-2-ylthio)-propyl^@,N-[( 1S)-1-[[[(1R)-1-[(3&amp;5,48,65,7311)-hexahydro-33,5,5-trimethyl*4,6-methylalkyl-1,3 ,2-benzodioxanoxa-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl Analytical data: MS : [MH]+ 681.5 Chemical name: 2_[(phenylmethyl)thio]acetamide, N-[(1S)-1-[[[(1R)-1-[(3) 3,45,63,7&amp;11)-hexahydro-33,5,5-trimethyl 4,6-methylalkyl-1,3,2- benzodioxan-2-yl]- 3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 631.5 Chemical name: 6- Ketoheptanoin, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4, 6-Methyl-1,3,2-benzodioxon-2-yl]-3-A Butyl]amino]carbonyl]-4-[[imino(m-amino)indolyl]amino]butyl] Analytical data: MS : [MH]+ 593.5 Chemical name: 4-(4-曱Alkylsulfonylphenyl&gt; 4-ketobutylamine, N-[(1S)-1 -[[[(1R)-1 -[(3wang3,43,63,7&amp;11)-six Hydrogen-3a, 5,5-trimethyl-4,6-anthracene:yl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino] Carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 705.0_ Chemical name: (2S)-1-Ethyltetrahydrol Pyrrole-2-carboxyguanamine, N-[( 1S)-1 -[[[(1,1,1,1,1,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,6,5,6 4,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamine (nitroamine) Methyl]amino]butyl] Analytical data: MS : [MH]+ 605.9

1345465

D.3.144 D.3.145 D.3.146

«掌性

〇-~o D.3.148

Chemical Name: 3-Hydroxy-2,2-dimethylpropanamide, N-[(1S)-1-[[[(1R)- 1-[(3aS,4S,6S,7aR)-hexa-argon- 3a,5,5-trimethyl·4,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]· 4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : [MH]+ 566.9 Chemical name: 2-ethylthioethionamide, N-[( 1S )-1 -[[[(1R)-1 -[(333,45,65,7311)-hexa-argon-33,5,5-trimethyl&quot; 4,6-methylalkyl-1,3,2 -benzobenzodiazepine-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] analysis Data: MS: [MH]+ 569.8 Chemical name: 3-ureidopropionamide, N-[(1S)-1-[[3(1R)-1-[(3玨3,43,65,7 )-Hexahydro-3\5,5-trimethyl&quot;4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amine Analytical data: MS: [MH]+ 581.5_Chemical name: 3-methoxypropionamide, N-[( 1S)-1 -[[[(1R)-1 -[(338,48,65,731〇-hexa-argon-33,5,5-trimethyl*4,6-methylalkyl-1,3 , 2-benzodioxanthene-2-yl]-3-methylbutyl]amino] H-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : [MH]+ 552.9 Chemical name: 2-Methylthioacetamide, team [(18) -1-[[[(1,1,6,6,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- stupid And dioxonium oxa-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl] analytical data: MS : [MH]+ 555.6 Chemical name: 3 imidazole-4-carboxyguanamine, &gt; 1-[(13)-1-[[[(111)-1-[(338,43,68,7311) -hexa-argon-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino] Carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : [MH]+ 561.0

95014 138- 1345465

D.3.150 D.3.151 D.3.152 D.3.153 D.3.154 D.3.155 95014

For palm chemical name: 7-keto-octylamine, N-[(1S)-1-[[[(1R)-1-[(338,43,63,7&amp;11)-hexa-argon-3 〇Trimethyl*4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imine Base (decylamino)methyl]armendyl]butyl] Analytical data: MS : [MH]+ 607.1 Chemical name: (Ε)-3-(imidazole 4-yl) acrylamide, team [(13) -1-[[[(111)-1-[(333,45,65,7311)-hexahydro-33,5,5-trimethyl*4,6-decyl-1,3,2- Benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(indolyl)methyl]amino]butyl] Analytical data : MS : [MH]+ 587.4

Vi Chemical name: (RS)-tetrahydrofuran-3-carboxamide, N-[(1S)-1-[[[(1R)-l-[(3aS,4S,6S,7aR)-hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[ [Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 565.3

〇- ΝΗ 〇-4〇 on palm to palm H-139 - Chemical name: (Ε)-3-(2-methoxyphenyl) acrylamide, team [(15)-1-[[[ (11〇-1-[(335,43,63,7311)-hexahydro-33,5,5-trimethyl·4,6-methylalkyl-1,3,2-benzodioxine 2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 627.7 Chemical name: 2-ethoxyacetamide, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-AlL-3a,5,5- STl_&quot;4,61 alkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino](nitro Amino)methyl]amino]butyl] Analytical data: MS : [MH]+ 553.0 Chemical name: 3-furan-2-yl-propanamide, &gt; 1-[(13)-1-[[ [(111)-1-[(3 Wang 3,43,63,7311)-hexahydro-3-7,5-trimercapto-4,6-nonylalkyl-1,3,2-benzophenan Oxyboron-indole-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(wall-based amino)methyl]amino]butyl] Analytical data: MS : [MH]+ 589.5

1345465

D.3.156 HA Chemical name: 3-(phenylsulfonyl)propanamine, 1^-[(13)-1-[[[(111)-1-[(3aS,4S,6S,7aR)-^ H-3a,5,5-X f ^-4,6- f alkyl-1,3,2·benzodioxol-2-yl]-3-mercaptobutyl]amino]carbonyl ] 4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS: [MH]+ 663.0 D.3.157 〇Λ HU. -~. Chemical Name: 4-Aminesulfonylbutyramine, N-[(1S)-1-[[[(1R)-1-[(335,45,63,7311)-hexahydro-33,5,5 -trimethyl&quot;4,6-methylalkyl-1,3,2-benzobisindole boron-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[亚Amino (nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 615.8 D.3.158 For palmity Vk 0 into s々X^x S human r Chemical name: (4S) -2-keto-1,3-p-pyrazolidine-4-carboxyguanamine, team [(18)-1-[[[(111)-1-[(333,48,65,7〇11) -hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino] Carbonyl H-[[imino(indenylamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 595.8 D.3.159 Formic acid Cl l H Chemical name: (2R)- 1-Ethyltetrahydropyrrole-2-carboxamide, 1^-[(13)-1-[[[(111)-1-[(3&amp;5,43,65,7311)-hexahydro- 33,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4- [[Iminoamino(decylamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 605.9 D.3.160 For palm stagnation κ τ 〇~〇 Chemical name: 3-[(B醯Amino) thiol]-propanamine, hydrazine [(15)-1-[[[(111)-1-[(338,43,63,7311)-hexahydro-345,5-trimethyl &gt;4,6-Methyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino](颂Aminomethyl)methyl]amino]butyl] Analytical data: MS : [MH]+ 626.0 D.3.161 1 ° Kkn¥^knh Η 1. 〇·% Chemical name: 6-(ethenylthio Hexamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6 -Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl H-[[imino(nitroamino)indenyl] Amino]butyl] Analytical data: MS : [MH]+ 638.9 95014 140- 1345465

D.3.162 | 搿 palm sex 'human H 1* o-^o chemical name: (°cephen-2-sulfonyl) acetamamine. N-KlSW-UKlRhl-^aSjS/SJaR)-hexahydro-3a ,5,5-trimethyl·4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]*4- [[Iminoamino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 655.0 D.3.163 • fittt H 〇Λ Chemical name: 4-(ethylamidino) Indoleamine, N-[( 1S)-1 -[[[(1R)-1 -[(335,45,68,7311)-hexa-argon-33,5,5-trimethyl 4,6-decane Base-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl H-[[imino(nitroamino)methyl]amino group ] Butyl] Analytical data: MS : [MH]+ 593.7 D.3.164 For palmity 〇-% Chemical name: (2Ζ)-3-(Alanylcarbonyl)-2-propenylamine, team [(15)- 1-[[[(爪)-1-[(3,43,63,7])-hexahydro-3,7,5-trimethyl&gt; 4,6-methylalkyl-1,3,2- Benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data : MS : [MH]+ 606.1 D.3.165 Pair of palms - Chemical name: 3-(octylsulfonyl)propanamine.N-KISH-QU ig-l-KSaSjSjSJaR)-hexahydro-3a,5,5-trimethyl-4,6·methylalkyl-1,3,2-benzodioxan-2-yl]-3-methyl Butyl]amino]carbonyl]_4_[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 699.29 D.3.166 1 Pair tt - Chemical name: 3-(octylthio)propanamide, N-[(1S)-1-[[[(1R)-1-[(335,43,65,7311)-hexahydro-3-7,5-5- Trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imine (Nitroamino)indolyl]amino]butyl] Analytical data: MS : [MH]+ 667.35 D.3.167 , . 聿 、, human HH chemical name: 2,2-dimercapto oxime Amine, N-[(1S)-1-[[[(1R)-1-[(335,48,68,7〇11)-hexahydro-3&amp;,5,5-trimethyl]&quot; 6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino)曱]]amino]butyl] Analytical data: MS : [MH]+ 593.65

95014 141 - 1345465

D.3.168 D.3.169

D.3.170

D.3.173

Chemical name: 6-hydroxyhexylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl 4·6·Methyl-1,3,2-benzodioxan B-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[imino] Aminomethyl)methyl]amino]butyl] Analytical data: MS : [MH]+ 581.16 Chemical name: '~ Hexaar-3a,5,5-trimethylidene 6-decyl-1,3 , 2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl Analytical data: MS: [MH]+ 565.60 Chemical name: 5-ketohexylamine, N-[(1S)-1-[[[(1R)-1-[(3&amp;8,43,63, 7)) hexahydro-33,5,5-trimethyl&gt; 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl Amino]carbonyl]·4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : [MH]+ 579.17 Chemical name: benzopyrimidine-6-carboxylate Indoleamine, N-[(1S)-1-[[[(1R)-1-[(3&amp;8,48,63,7〇11)-hexa-argon-3〇tridecyl 4,6-methylalkyl) -1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(hulkylamino)indolyl]amine Analytical data: MS: [MH]+ 628.70 Chemical name: 3-(octyloxy)propanamide, team [(13)-1-[[[(1,5,5,45,63,7玨11)-hexa-argon- 33,5,5-trimethyl&gt;4,6-methylalkyl-1,3,2- benzodioxan B-2-yl]-3-mercaptobutyl]amino]carbonyl]- 4-[[imino(nitroamino)methyl]amino]butyl]analytical data: MS : [MH]+ 651.33_Chemical name: 2-(2-keto-tetrahydropyrrole-1- Ethylamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a, 5,5-trimethyl-4 ,6-decyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl] winter [[imino (nitroamino) Methyl]amino]butyl]analytical data: MS : [MH]+ 592.75 95014 142- 1345465

D.3.174 1 Witt Chemical name: stupid f decylamine, N-[(1S,2R)-1-[[[(1R)-1-[(3&amp;8,45,65,7〇11)-hexahydro) -33,5,5-trimethyl&gt;4,6-methylalkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl] -2-hydroxypropyl] Analytical data: MS : [MH]+471.47 D.3.175 Valuable. ~. ^ Chemical name: 2-[2-(2-decyloxyethoxy)ethoxy]acetamidine, N-[(lS,2R)-l-[[[(lR)-l-[(3aS ,4S,6S,7aR)-hexahydro-3a, 5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-yl Benzyl]amino]carbonyl]-2-hydroxypropyl] Analytical data: MS : [MH]+ 527.12 D3.176 1 to zero tt Chemical name: 4-phenylbutymidine, N-[(1S, 2R)-1-[[[(1R)-1-[(335,45,68,7&amp;11)-hexahydro-33,5,5-tridecyl*4,6-decyl-1, 3,2-benzodioxan-oxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl] Analytical data: MS : [MH]+ 513.10 D.3.177 1 Ft palm chemical name: (4_methylphenoxy)acetamide, N-KISJRO-l-TOlig-i-tPaSASjSJaR)-hexahydro-3a,5,5-trimethyl*4,6-methane Base-1,3,2-benzodioxanol-2-yl]-3-mercaptobutyl]amino]carbonyl]-2.hydroxypropyl] Analytical data: MS : [MH]+ 515.57 D.3.178 For zero-sex chemical name: hexylamine, team [(15,211)-1-[[[(111)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5- Analysis of tridecyl-4,6-methylalkyl-1,3,2-benzodioxol-5-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl] data : MS : [MH]+ 465.40 D.3.179 1 Pair of palm chemical name: 4-butyl stupid amine. N-KlSJIQ-l-UKlRH-^aSJSjSJaR)-hexa-argon-3a,5,5-trin 4-,6-Methyl-1,3,2-benzodioxol-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl] Analytical data: MS : [MH]+ 527.16 D.3.180 I For palm chemical name: 荇-2-carboxyguanamine, hexahydro-3a,5,5-trimethyl-4,6-decyl-1,3, 2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl] Analytical data: MS : [MH]+ 521.14 95014 •143- 1345465

D.3.181 D.3.182

Chemical name: hexylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl] 4,6-Methyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·4· [[imino group (nitroamine) Methyl]amino]butyl] Analytical data: MS : [MH]+ 565.33 Chemical name: 2-(4-toluene fluorenyl) acetamidine, N-[(1S)-1-[[[ (1R)-1-[(3玨5,43,68,7〇11)-hexa-argon-3-7,5-trisyl 4,6-methylalkyl-1,3,2-indigodiox Bora-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : [ MH]+ 663.30 D.3.183 D.3.184 D.3.185 Pair of palms

Chemical name: Heptasamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl*4 ,6-methylalkyl-1,3,2- benzodioxan, H-2-yl]-3-methylbutyl]amino]amino]-4-[[iminoalkyl(decylamine) Methyl]amino]butyl] Analytical data: MS : [MH]+ 579.34 Chemical name: 11-(Aminoguanidino) undecylamine, pity [(13)-1-[[[ 111) small [(333,48,63,7311)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxon-indole-2- ]]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data:

MS : [MH]+ 678.44_ Chemical name: 2-(cyclosulfonyl)acetamide. N-KlSJ-l-aKlig-l-paSySjSJaR)-hexahydro-3a,5,5-trimethylhydrazine 6-曱alkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) A Amino]butyl] Analytical data: MS : [MH]+ 649.28

Other compounds prepared according to the above example D.3 are reported in Table D-3A 0 95014 144-1345465

Table D-3A

Example No. Structure Chemical name 舆 Analytical data D.3.186 I Si human r 〇. Chemical name: 9-cyanoguanamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-three Methyl 4,6-nonylalkyl-1,3,2- benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl PK[imido (nitroamine) Methyl]amino]butyl] Analytical data: MS : MH+ 632.5 D.3.187 Pair tt, - B Chemical name: 11-IL-based undecyl decylamine, N-[(1S)-1- [[[(1R)-l-[(3aS,4S,6S,7aR)·hexaar-3a,5,5-trimethyl•4,6-methylalkyl-1,3,2-benzodioxine Born-but-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS; MH+ 659.7; 1H-NMR (CDC13): 7.53 (s, br, 2H); 7.36 (d, br, J = 4.7 Hz, 1H); 6.88 (d, J = 8.2 Hz, 1H); 4.46 (m, 1H) 4.15 (dd, J=8.5, 1.9 Hz, 1H); 3.19 (m, 2H); 2.93 (m, 1H); 2.23 (t, J=7.2 Hz, 2H); 2.21 (m, 1H); 2.09 ( t, J=7.5, 2H); 2.04 (m, 1H); 1.88 (t, J=5.4 Hz, 1H); 1.77 (m, 1H); 1.69 (in, 1H); 1.64-1.43 (m, 9H) 1.40-1.26 (m, 4H); 1.26 (s, 3H); 1.24-1.12 (m, 16H); 0.80 (d, J=6.6, 3H); 0.79 (d, J= 6.6, 3H); 0.73 ( s, 3H). D.3.188 1掌性ΛTM Η ΪΓ 〇_*% Chemical name: 6-(acetamido) hexamethyleneamine, N-[(1S)-1-[[[(1R)-l-[(3aS,4S,6S ,7aR)-hexahydro-3a,5,5-trimercapto•4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl] Amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS : [MH]+ 622.3 D.3.189 , for zero sex ^ T m human chemistry Name: 12-(1,3-Diketo-1,3-dihydro-isoindol-2-yl)-dodecanedecylamine, N-[(1S)-1-[[[(1R) -1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxazole ]]-3-mercaptobutyl]amino]carbonyl H-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS : [MH]+ 794.42

95014 145- 1345465 D.3.190 Intrusion. Chemical name: 3-[4-(2-propyl)phenyl]propanamine, N-KlSH-^KlRH-KhSjS/SJaR)-hexahydro-3a,5,5-trimethyl·4,6- Methyl-alkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]·4-[[iminoamino(nitroamino)] fluorenyl Amino] butyl] Analytical data: MS : [M]H+ 641.5 D.3.191 \ΑΓ 0 is 0 Chemical name: 3-[4-(ethyl)phenyl]propanol, N-[( 1 S&gt ; 1 -[[[(1R,6S,7aR)-hexahydro-3a,5,5·trimethyl 4,6-nonyl-1,3,2-benzene And dioxonium-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)indenyl]amino]butyl] Analytical data: MS: [M]H+ 627.7 D.3.192 to zero.- Η 1. Chemical name: 6-hydroxyhexylamine, team [(13)-1-[[[(1 ft)-1-[(333, 43,65,7311)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methyl Butyl]amino]carbonyl]-4-[[imino(indolyl)methyl]amino]butyl] Analytical data: MS : [M]H+ 581.5

Example D.4 Naphthalene-2-sulfonamide, N-[(1S) 丨[[(1R)-1-丨(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4-,6-methylalkyl-1,3,2-benzodioxan-2-yl-1-ylbutyl]amino]carbonyl]-4_[[imino] Amino)methyl]amino]butyl]-

(2S)-2-Amino-5-[[imino(nitroamino)methyl]-amino]-pentamidine, N-[(lR)-l-[ (3aS, 4S, 6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3 -methylbutyl]-, hydrochloride (70 mg, 95014-146- 1345465

TEA (0.04 ml, 0.31 mmol) and gasified naphthalene-2 sulfonate (35 丨 mg, 〇16 mmol) were added to the solution in DCM (4 mL) at room temperature. . After stirring overnight, a second portion of TEA (0.04 mL, 0.31 mmol) and &lt;RTI ID=0.0&gt;&gt; Then, the reaction mixture was washed with a saturated aqueous solution of K.sub.2CO.sub.3, and the separated organic phase was concentrated to dryness. The crude reaction was purified on a SPE_SI </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> NMR (CDC13): 8.42 (s, br, 1H); 7.96 (dd, J=7.5, 2.2 Hz , 1H); 7.95 (d, J= 8.5 Hz, 1H); 7.89 (d, br, J=7.9 Hz, 1H); 7.81 (dd, J=8.8, 1.9 Hz, 1H); 7.68-7.57 (m, 2H) ; 7.23 (s, br, 2H) ; 6.23 (s, br, 1H) ; 6.03 (d, J=8.5 Hz, 1H); 4.19 (dd, J=9.1, 2.2 Hz, 1H) ; 3.92 (s , br, 1H); 3.31 (m, 2H); 2.97 (m, 1H); 2.26 (m, 1H); 2.12 (m, 1H); 1.93 (t, J=5.7 Hz, 1H); 1.90-1.68 ( m, 6H); 1.30 (s, 3H); 1.28 (m, 1H) ; 1.25 (s, 3H) ; 1.06 (m, 4H) ; 0.79 (s, 3H); 0.58 (d, J=9.4 Hz, 3H ); 0.56 (d5 J=9.4 Hz, 3H).

LC-MS 657.3, MH+, ESI POS; AQA; spray 4 kV / demister: 20 V / probe 250 C. Other compounds prepared essentially according to the above experimental procedure are reported in Table D-4. Table D-4 Example No. Structure Chemical Name and Analytical Data D.4.1 | For the palm of the hand 0 Chemical name: 荇-1- 醢 醢, N-[(lS)-l-[[[(lR)-l -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5·trisyl-4,6-decyl-1,3,2- benzodioxan-2-yl 】]-3-methylbutyl]amino]carbonyl H-[[imino(nitroamino)methyl]amino]butyl] Analytical data: MS: MH+ 657.3 95014 -147· 1345465

D.4.2

Chemical name: 荇-2-amine decylamine, N-[( 1 S)-l -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5- Trimethyl*4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonylindole-[[imino] Analytical data: MS: MH+ 657.3; 1H-NMR (CDCB): 8.42 (s, br, 1H); 7.96 (dd, J=7.5, 2.2 Hz, 1H) ; 7.95 (d, J=8.5 Hz, 1H); 7.89 (d, br, J=7.9 Hz, 1H); 7.81 (dd, J=8.8, 1.9 Hz, 1H); 7.68-7.57 (m, 2H); 7.23 (s br, 2H); 6.23 (s br, 1H); 6.03 (d, J=8.5 Hz, 1H); 4.19 (dd, J=9.1, 2.2 Hz, 1H); 3.92 (s, br, 1H) ;3 (m, 1H); 2.26 (m, 1H); 2.12 (m, 1H); 1.93 (t, J=5.7 Hz, 1H); 1.30 (s, 3H); 1.28 (m, 1H); 1.25 (s, 3H); 1.06 (m, 4H); 0.79 (s, 3H); 0.58 (d, J = 9.4 Hz, 3H); 0.56 (d , J=9.4 Hz, 3H)·_ Chemical name: decane-1-sulfonamide, N-[(1S)-1-[[[(1R)-1-[(333,43,63,73 ft) )-hexahydro-33,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino] Carbonyl H-[[imino(indolyl)indolyl]amino]butyl] Analytical data: MS: MH+671.4

D.4.4 D.4.5

Chemical Name: Octanesulfonamide, N-[( 1S)-1-[[[(1R)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl -4,6-decyl-1,3,2- benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino](颂Amino) thiol]amino]butyl] Analytical data: MS: MH+ 643.4 Chemical name: Benzene sulfonamide, N-[(lS)-l-[[[(lR)-l-[(3aS, 4S,6S,7aR)-six IL-3a,5,5-trimethyl 4,6-nonylalkyl-1,3,2-benzodioxan-2-yl]-3-methyl Butyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] Analytical data:

D.4.6

D.4.7

MS: MH+ 607.3_ Chemical name: 4-butoxybenzenesulfonamide, team [(13)-1-[[[(111)-1-[(3aS,4S,6S,7aR)-hexahydro-3a ,5,5-trimethylidene*4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4- [[Iminoamino(nitroamino)indolyl]amino]butyl] Analytical data: MS: ΓΜ+Η1+ 679.5_ Chemical name: 4-butyl- sulfonamide, team [(15)-1 -[[[(1,1拗-1-[(338,48,65,7311)-hexahydro-33,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzophenan Oxyboron-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)indolyl]amino]butyl] Analytical data: MS: [M1H+ 663.5 95014 -148- 1345465 D.4.8, Liuliuhualiu Chemical Name: V-produced 4-pentyl-stupylamine, 乂[(18)-1-[[[(111)-1-[( 3&amp;5,48,65,7311)-Hexahydro-3〇trimethyl*4,6-methylalkyl-1,3,2- benzodioxan-2-yl]-3-methyl Butyl]amino]carbonyl]·4-[[imino(decylamino)methyl]amino]butyl] Analytical data: MS: ΓΜ1Η+ 677.3 Example D.4.9 荇-2-sulfonamide ,N-[(lS,2RH-[[[(lR)-l-[(3aS,4S,6S,7aR)_hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1 , 3 , 2-benzodioxan, benzyl-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]

Gasified benzene-2-sulfonate (144 mg, 0.637 mmol) was added to the (2S)-amino-(3R)-hydroxy-butyric acid decylamine of Example C.3, N-[(lS)- L-[[[(lR)-l-[(3aS,4S,6S, 7aR)-hexanitro-3a,5,5-dimethyl-4,6-methylalkyl-1,3,2-benzene弁二氧棚伍圜-2_yl]-3-methylbutyl]amino]-carbonyl], hydrochloride and NMM (0.175 ml, 1.59 mmol) in anhydrous dichloromethane, while Stir at 〇 ° C under nitrogen. After 6 hours, the mixture was allowed to warm to room temperature and stirred overnight. A 10% NaHCO03 solution (10 ml) was added and the layers were separated. The aqueous phase was further extracted with di-methane (5 mL). The organic phase was washed with a 20% NaH2P04 solution, dried over sodium sulfate and concentrated. The residue was purified by column chromatography (gluent, 25 g) eluting with a mixture of 1:1 (v/v) hexane and ethyl acetate. The product was obtained as a white glassy solid (219 mg, 74% yield) but still containing some decane diol. A sample (160 mg) of this product was obtained from mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj Melting point 147-149 ° C. lHNMR (DMSO-d6): 8.40 (1H, s); 8.28-8.22 (1H, m); 8.11 (lH, d, J = 7.7); 8.05 (1H, d, J = 8.7) ; 8.01 (1H, d , J=7.8); 7.81 (1H, dd, J=8.7, 1.7); 7.75 (1H, s br.); 7.72-7.61 (2H, m); 4.84 (1H, s br.) ; 4.03 (1H, Dd, J=8.5, 1.7) ; 3.82-3.72 (2H, m); 2.41-2.33 (1H, m) ; 2.20-2.10 (1H, m) ; 2.02-1.93 (lH,m); 1.82-1.72 (2H , m); 1.58-1.50 (1H, m) ; 1.36-1.24 (1H, m) ; 1.20 (3H, s) ; 1.18 (3H, s) ; 0.99 (3H, J=6.1) ; 0.94-0.82 (2H , m) ; 0.77 (3H, s); 0.63 (3H,d,J=7.1) ; 0.61 (3H,d, J=7.1) » Example D.5 (2S)-4-[[imino] Amino)methyl-1-amino]_2-[(2-teaylmethyl)-amino]-pentamidine, 1^[(111)-1_[(338,48,68,7 resistance 11) -hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-oxadioxan-2-yl]-3-methylbutyl]

(2S)-2-Amino-5-[[imino(adenylamino)indolyl]amino] amylamine, [[1 ft]-1-[(3&amp) ;3,43,63,7311)-hexahydro-3〇trimethyl-4,6-decyl-1,3,2-benzobisanthracene-2-yl]-3-methyl A solution of butyl]-, hydrochloride (88 mg, 0.175 mmol) in MeOH (4 mL). Add 2-indolaldehyde (45 mg, 0.28 mmol) to NaCNBH3 (18 mg '0.28 mmol) at room temperature in a solution of the free base in Me0H (4 mL); add AcOH until the solution The PH value is 4-5. The reaction mixture was stirred overnight, then EtOAc EtOAc (EtOAc)EtOAc. The crude reaction was purified by EtOAc (EtOAc:EtOAc:EtOAc:

NMR (CDC13 + D2 Ο): 7.81 (m, 3H); 7.71 (s, br, 1H); 7.52-7.38 (m, 3H); 4.66 (s, br, 1H); 4.27 (dd, J = 8.8, 1.9 Hz, 1H); 3.91 and 3.83 (at 4 211); 3.39-3.11 (m, 3H); 2.30 (m, lH); 2.13 (m, 1H); 1.98-1.45 (m, 8H); 1.45 (m , 2H); 1.38 (s, 3H); 1.23 (s, 3H); 1.22 (m, lH); 0.91 (d, J = 6.3 Hz, 6H); 0.81 (s, 3H). LC-MS 607.1, MH+ ESI POS ; AQA ; Spray 4 kV / Defoamer: 20 V / Probe 250 C. Other compounds prepared essentially according to the above experimental procedure are reported in Table D-5. Table D-5 Example No. D.5.1 Structure Chemical Name and Analytical Data

Chemical Name: (2S)-4-[[Imino(decylamino)methyl]amino]-2-[(2-chalymethyl)-amino]-pentamidine, N-[ (lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxine -2-yl]-3-methylbutyl] Analytical data: D.5.2

For palmar MS: MH+ 607.1; 1H-NMR (CDC13+D20): 7.81 (m, 3H); 7.71 (s, br, 1H); 7.52-7.38 (m, 3H); 4.66 (s, br, 1H% 4.27 (dd, J=8.8, 1.9 Hz, lli); 3.91 and 3.83 (ABq, 2H); 3.39-3.11 (m, 3H); 2.30 (m, 1H); 2.13 (m, 1H); 1.98-1.45 ( m, 8H); 1.45 (m, 2H); 1.38 (s, 3H); 1.23 (s, 3H); 1.22 (m, 1H); 0.91 (d, J = 6.3 Hz, 6H); 0.81 (s, 3H) ).___ Chemical name: (2S)-4-[[imino(decylamino)indolyl]amino]-2-[(l-teaylmethyl)-amino]-pentamidine, N-[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimercapto-4,6-nonylalkyl-1,3,2-benzoic Oxyborax--2-yl]-3-mercaptobutyl] Analytical data: MS: MH+ 607.2 95014 -151 - Γ345465 D.5.3

Chemical name: (2S&gt;4-[[imino(nitroamino)methyl]amino]-2-[undecylamino]-pentylamine, N-[(lR)-l-[ (3aS, 4S, 6S, 7aR)-hexa-argon-3a,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3- Mercaptobutyl]

Analytical data: __MS: MH+ 621.2 Chemical name: (2SM-[[imino(indolyl)indolyl]amino]-2-[(indolylmethyl)amino]-pentamidine, N- [(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4,6-methyl-l-yl-1,3,2-benzodioxanthene Group-2-yl]-3-mercaptobutyl] Analytical data: MS: MH+ 557.2 Example D.6

]\-[(18)-1-[[[(111)-1-[(338,48,68,7311)-hexahydro-315,5-trimethyl-4,6-methylalkyl-1, 3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino] -N'-(l-fluorenyl)urea

(2S)-2-Amino-5-[[imino(nitroamino)methyl]amino]-pentanylamine, for example C.1, :^-[(11〇-1-[ (3&amp;3,48,63,7311)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl] To a solution of -3-methylbutyl]-, hydrochloride (50 mg, 0.10 mmol) in CH3CN (4 mL), TEA (0.014 mL, 0.10 mmol) -1-Isocyanate (0.014 ml, 0.10 mmol). The reaction mixture was stirred for 4 hr then concentrated to dryness. The residue dissolved in DCM was washed with EtOAc. The title compound was obtained as a white powder (yield: 94 95 014 - 152 - 1345465 %).

NMR (CDC13): 8.08 (s, br, 1H); 7.98 (m, 1H); 7.79 (m, 2H); 7.57 (d, J = 8.2 Hz, 1H); 7.51-7.35 (m, 4H); 7.36 (d, J=7.5 Hz, 1H); 7.17 (s, br, 1H); 6.67 (d, br, J=6.6 Hz, 1H); 4.49 (m, 1H); 4.20 (dd, J=8.5, 1.9 Hz, 1H); 3.39 (m, 1H); 3.20 (m, lH); 3.04 (m, lH); 2.26 (m, 1H); 2.08 (m, 2H); 1.93 (t, J=5.6Hz, 1H 1.89-1.55 (m, 7H); 1.39 (m, lH); 1.32 (s, 3H); 1.31 (m, 1H); 1.21 (s, 3H); 1.20 (m, 1H); 0.85 (d, J=6.0 Hz, 6H); 0.79 (s, 3H). LC-MS 636.3, MH+. ESI POS ; AQA ; spray 4 kV / demister: 20 V / probe 250 C. Basically according to the above experimental procedure Other compounds made are reported in Table D-6. Table D-6 Example Structure No. Chemical Name and Analytical Data

Chemical name: N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-methane Base-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino (decylamino) fluorenyl] Analytical data of amino]T-based]-N'-(2-chaly)urea: D.6.2

MS: MH+ 636.4_ Chemical name: N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl) 4,6-Methyl-l,3,2-benzodioxan, Sl-2-yl]-3-methylbutyl]amino]carbonyl]·4-[[imino group (nitroamine) Analytical data of methyl]amino]butyl]-indole-phenylurea: D.6.3

MS: MH+ 586.3_ Chemical name: N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-AlL-3a,5,5-tridecyl-4 ,6-Methyl-1,3,2- benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) )methyl]amino]butyl]-Ν'-heptylurea Analytical data: MS: MH+ 608.4 95014 -153 - 1345465

D.6.4 • Pair tt H 〇A0 Chemical name: 1^-[(15)-1-[[[(1,1,1,1,1,1,3,6 Trimethyl sulfonium 6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-fylbutyl]amino]carbonyl hydrazine [imido (reactylamino) A Analytical data: MS: MH+ 636.3; 1H-NMR (CDCO): 8.08 (s, br, 1H); 7.98 (m, 1H); 7.79 (m, 2H); 7.57 (d, J=8.2 Hz, 1H); 7.51-7.35 (m, 4H); 7.36 (d, J=7.5 Hz, 1H); 7.17 (s, br, 1H); 6.67 (d, br, J=6.6 Hz, 1H); 4.49 (m, 1H); 4.20 (dd, J=8.5, 1.9 Hz, 1H); 3.39 (m, 1H); 3.20 (m, 1H); 3.04 ( m, 1H); 2.26 (m, 1H); 2.08 (m, 2H); 1.93 (t, J=5.6 Hz, 1H); 1.89-1.55 (m, 7H); 1.39 (m, 1H); 1.32 (s , 3H); 1.31 (m, 1H); 1.21 (s, 3H); 1.20 (m, 1H); 0.85 (d, J=6.0 Hz, 6H); 0.79 (s, 3H). D.6.5 \\ 〇-~. Chemical Name: Chemical [(18)-1-[[[(111)-1-[(3&amp;3,43,65,7311)-hexa-argon-33,5,5-tri-A 4,6-Methyl-l,3,2-benzodioxan,-2-yl]-3-fylbutyl]amino]carbonyl]-4-[[imino] Amino)methyl]amino]butyl]-indole-undecylurea Analytical data: MS: MH+ 664.4 D.6.6 I Finance name: N-[( 1 S,2R)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-Alt -33,5, 5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-2-hydroxypropyl ]-Ν'-undecylurea Analytical data: MS: ΓΜΗ1+ 564.40 D.6.7 1 pair of properties \Λη 0*^0 Chemical name: Mu [(18)-1-[[[(111)-1-[ (3 Wang 3,43,63,7 pressure 11)-hexahydro-33,5,5-trimethyl·4,6-nonanyl-1,3,2-benzodioxine -yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(decylamino)methyl]amino]butyl]-oxime-[5-(ethoxycarbonyl) Analyzed data of amyl]urea: MS: ΓΜΗ1+ 652.40 D.6.8 8 X 0 \〇Chemical name: N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR )-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxan-2-yl]-3-methylbutyl]amino ]carbonyl H-[[imino(indolyl)methyl]amino]butyl]-N'-(4-butylphenyl)urea Analytical data: MS: ΓΜ1Η+ 642.5 D.6.9 -jyYx ^^ κ Λ Chemical Name: N-[(lS)-l-[[[(1R,6S,7aR)-hexahydro-3a,5,5-trimethyl-4 ,6-methylalkyl-l,3,2 - stupid and dioxoboro-al-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]- Analytical data of N'-(4-heptyloxy 1 strepyl)urea: MS: ΓΜ1Η+ 700.7 95014 -154- 1345465 Example D.7 Dihydroxy shed Hyun [(lR)-l-[[(2S)-5- [[imino(]-aminomethyl)methyl]amino]_2_[[(E)-3_(Mos-2-yl)prop-2-enyl]amino]pyridylpentyl]amine Base]_3·methylbutyl]_

For PS-HOBT (1-hydroxybenzotriazole_6_sulfonylaminomethylpolystyrene, 277 mg, 0·31 mmol, loading U2 mmol/g) in DCM (6 mL) In a suspension with DMF (0.6 ml), add 3_荇冬基_acrylic acid (91.2 mg '0.46 mmol), DIC (diisopropylcarbodiimide, 〇22 ml '1_40 mmol) And DIPEA (0.05 ml, 0.19 mmol). The suspension was shaken at room temperature for 3 hours. Then, the resin was filtered under nitrogen, and

Wash several times with DMF (3 X 5 mL), DCM (3 X 5 mL), DMF (3 X 5 mL) and THF (3 X 5 mL). The sufficiently dried resin was suspended in DCM (6 mL) and DMF (0.6 mL), and [(lR)-l-[[(2S)-2-amino-5-[[ Imino (alkylamino)methyl]amino] ketopentyl]amino]_3_methylbutyl]-dihydroxyborate hydrochloride (50 mg, 0.14 mmol) with DIPEA (0.06 mL, 0.20 mmol) * The reaction mixture was shaken at room temperature overnight. The resin was filtered off and washed with DMF (10 mL) and DCM (2 mL) and concentrated to dryness. The crude compound was purified by EtOAc (EtOAc) (EtOAc) NMR (DMSO+D2 Ο, 343K): 8.06 (s, 1H); 7.95 (d, J=9.0 Hz, 1H); 7.94 (m, 95014 •155·1345465 2H); 7.72 (d, 1H); 7.61 ( d, J=14.9 Hz, 1H); 7.55 (d, J=9.0 Hz, 1H); 7.55 (m, 2H); 6.89 (d, J=14.9 Hz, 1H); 4.40 (m, 1H); 3.30- 3.10 (m, 3H); 1.82 (m, 1H); 1.73-1.53 (m, 4H); 1.50-1.32 (m, 2H); 0.87 (d, J=6.1 Hz, 3H); 0.86 (d, J= 6.1 Hz, 3H). LC-MS 495.0, [M-18]H+. ESI POS ; AQA ; spray 5kV / demister: 15V / probe 250 C. Other compounds basically made according to the above experimental procedure The report is reported in Table D-7.

Table D-7 Example No. Structure Chemical Name and Analytical Data D.7.1 For palm chemical name: η y Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Amino group) 0 0 -S. W methyl]amino]-2-[[(2E)-3-(2-methoxyphenyl)-1-copperylpropan-2- \nonenyl]amine ]]-1-ketopentyl]amino]-3-methylbutyl] Η I· O'^^O Analytical data: MS: MH+ 475.0 D.7.2 For palm chemical name: f^\ 1 hy f&quot; Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[((E)-2- Methyl-3-phenylpropenyl)amine 0, OH \x , N^^NH group]-1-ketopentyl]amino]-3-methylbutyl] HU ο·' Analysis data: MS: [M-18]H4-458.0 D.7.3 I on the palm tt Chemical name: HS f&quot; Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Amino]amino]amino]-2-[(4-(4-methylphenyl)butanyl)amino]-1-one 0, NH-pentyl]amino]-3-mercaptobutyl Base] H 〇Λ Analytical data: MS: [M-18]H+ 474.0

95014 -156- 1345465

D.7.4 D.7.5 D.7.6

Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]][[(2RS)-2 - phenyl)amino]-1-benzylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 447.2 Chemical name: Dihydroxy decane, [(lR )-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(2-(4-isopropylphenoxy)ethenyl) Analytical data: MS: [M-18JH+ 491.5 Chemical name: dihydroxyborane, [(lR)-l-[[( 2S)-5-[[imino(nitroamino)methyl]amino]-2-[(5-fluorenyl-5-phenylpentanyl)amino]-1-ketopentyl Amino]-3-methylbutyl] Analytical data:

MS: [M-18]H+ 489.5_Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino] -2-[[(4RS)-l-[(l,l-didecylethoxy)carbonyl]hexahydropyridine·4-carbonyl]amino]-1-oneylpentyl]amino]-3 -nonylbutyl] Analytical data: D.7.8

MS: [M-18JH+ 526.1 Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-) [(4-Diethylamino)methylamino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data:

D.7.9

MS: [M-18]H+508.1_Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino) ]-2-[((E)-2-Methylhex-2-enyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: [ M-18]H+ 443.0 95014 -157- 1345465 D.7.10 Chemical name: Dihydroxyboron, [(lR)-l-[[(2S)-5-[[imino][y]amino]methyl Amino]-2-[(,secen-3-carbonyl)amino]-1-3⁄4ylpentyl]amino]-3-decylbutyl] Analytical data: MS: [M-18JH+425.6 D.7.11

Chemical name for benzene: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino]-2-[(4- Isopropylamino)amino]-1-Sylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18JH+461.3 D.7.12 Chemical name: Dihydroxyboron ,[(lR)-l-[[(2S)-5-[[imino(indolyl)indolyl]amino]-2-[(5-yl-f-thiophen-2-yl) Amino]-1-propenylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+439.3 D.7.13 Ο N.\x NH o人0 Chemical name : Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(phenylamino)amino) ]-1-decylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18JH+419.4 D.7.14 Pair of palmity ^r1

NHΛη o human chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]-2-[((E --2-butenyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 383.2 D.7.15

ΝνΑν^β-0Η Ϊ H OH Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2 -[((E)-penta-2,4-dienyl)amino]-1-indolylyl]amino]-3-methylbutyl]analytical data: MS: [M-18JH+ 395.4 95014 -158- 1345465 D.7.16 Pair of palms

:H

0* Chemical name: Dihydroxy fl^,[(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(3,3 -Methyl-butanyl)amino]-1-freeylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18JH+413.0 D.7.17

Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino)]amino]-2-[[5- (2,5-Dimethylphenoxy)-2,2-didecylpentenyl]amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS : [M-18JH+ 547.2 D.7.18

NsANXr〇H £ H OH Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[ (2,2-Dimercaptomethyl)amino]-1-decylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18JH+427.5 D.7.19 I Palmitic i H 0h NH A 〇'0 Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]] -2-[[4-(.cephen-2-yl)butanyl]amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: [M-18] H+ 467.5 D.7.20

For the chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]-2-[[5- (4-Fluorophenyl)indolyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 493.4 D.7.21 I « Palm tt, NH. Human 0 Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino]-2-[(2,2 -Dimethylhexyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 441.0 95014 -159* 1345465

D.7.22 Sr&quot;, human NH chemical name: dihydroxy hydrazine, [(1R)-1-[[(2S)·5-[[imino(nitroamino)methyl]amino]-2 -[(hexyl-2,4-enyl)amino]-1-mentylpentyl]amino]-3-methylbutyl] Η K 〇-~〇 Analytical data: MS: [M-18JH+ 409.3 D.7.23 I Witt \χ S human r 〇-~0 Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](phosphinyl) fluorenyl) Amino]-2-[[3-(»ceren-2-yl)propenyl]amino]-1-decylpentyl]amino]-3-methylbutyl] Analytical data: MS : [M-18JH+451.4 D.7.24 I to itt \ x&quot; Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino) Amidino]amino]-2-[(5-cyclohexylpentanyl)amino] ketopentyl]amino]-3-mercaptobutyl] H-in Analysis data: MS: [M-18 ]H+ 481.1 D.7.25 H f 'Y^^Y^^nV^'n^'b-oh :o \jf ^N' NH Chemical name: dihydroxyborane, [(lR)-l-[[( 2S)-5-[[imino(nitroamino)methyl]amino]-2-[((3R)-3,7-dimethyloct-6-enyl)amino]- 1-ketopentyl]amino]-3-mercaptobutyl] Η 1. 〇~〇 Analytical data: MS: [M-18]H+ 467.3 D.7.2 6 I to palmity Q \Ν(Η Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]] -2-[[3-[(4-methylindolyl)thio]propanyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Η T o-^o Analytical data: MS: [M-18]H+ 507.0 D.7.27 For palmity °Ό^αΝΛ I, H heart\χ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5 -[[imino(nitroamino)indolyl]amino]-2-[(4-pyrrol-1-ylindolinyl)amino]-1-ketopentyl]amino]- 3-mercaptobutyl] HL 0&quot; ^0 Analytical data: MS: [M-18]H+ 484.4 95014 -160- 1345465 D.7.28 ΦτΜ/Γ /〇〇, NH0&quot; Chemical name: Dihydroxy hydroxy, [ (lR)-l-[[(2S)-5-[[imino(decylamino)methyl]amino]-2-[(5-yl-2-ylbenzoyl)) Amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18JH+ 466.9 D.7.29; h 〇, N*^^NH Chemical name: dihydroxy boron Alkane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[((2S)-2. fluorenyl)) ]] ketopentyl]amino]-3-methylbutyl] Η 1. 0 is 0 Analytical data: MS: [M-18]H+ 399.0 D.7.30 1 to T = χ ^NH Chemical name: Dihydroxyborane, [(1R)-1-[[(2S)-5-[[imine] (nitroamino) fluorenyl]amino]-2-[(cyclopropanecarbonyl)amino]-1-decylpentyl]amino]-3-methylbutyl] H 1. 〇_% Analytical data: MS: [M-18JH+383.0 D.7.31 I to palm tt 0 X. ^ \χ Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[ Amino (nitroamino) fluorenyl]amino]-2-[(4-ethoxybenzylidenyl)amino]-1-ketopentyl]amino]-3-mercaptobutyl ] HA Analytical data: MS: [M-18]H+463.5 D.7.32 I to Ttt 0 , H OH \x Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5- [[Iminoamino(nitroamino)methyl]amino]-2-[((E)-3-(4-bromophenyl)prop-2-enyl)amino]-1-one Analyl data: MS: [M-18]H+ 523.6 D.7.33 For palmity 'Human chemical name: Dihydroxyborane, [(lR)-l- [[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[(2S)-2-(6-methoxyoxy-2-yl)-propyl Mercapto]amino]-1-ketopentyl]amino]-3-methylbutyl] H 〇Λ Analytical data: MS: [M-18]H+527 .5

95014 -161 - 1345465 D.7.34 I on the palm ft,.汾发化学名: Dihydroxyboron, [(lR)-l-[[(2S)-5·[[imino(de)amino]methyl]amino]-2-[[1-( 4-methoxyphenyl)-cyclopropanecarbonyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Η 1, 〇-^〇 Analytical data: MS: [M-18 ]H+ 489.4 D.7.35 1 pair of palms tt I ι Η in \χ , Ν^^^ΝΗ Chemical name: dihydroxyborane, [(lR)4-[[(2S)-5-[[imino] Nitroamino)methyl]amino]-2-[(3-fluoro]&gt; 4-methoxyphenylhydrazino)amino]-1-ketopentyl]amino]-3-methyl Butyl] Η Λ 0 Analytical data: MS: [M-18]H+ 466.9 D.7.36 I Mtk Ο 0Η \χ ,Ν*^ΝΗ Chemical name: Dihydroxyborane, [(lR)-l-[[( 2S)-5-[[imino(nitroamino)methyl]amino]-2-[[(E)-3-(naphthalen-2-yl)prop-2-enyl]amino ]-1-ketopentyl]amino]-3-mercaptobutyl] Η U Ο·~Ο Analytical data: MS: [M-18]H+495.0; 1H-NMR: (DMS0+D20, 343 K): 8.06 (s, 1H); 7.95 (d, J=9.0 Hz, 1H); 7.94 (m, 2H); 7.72 (d, 1H); 7.61 (d, J=14.9 Hz, 1H); 7.55 ( d, J=9.0 Hz, 1H); 7.55 (m, 2H); 6.89 (d, J=14.9 Hz, 1H); 4.40 (m, 1H); 3.30-3.10 (m, 3H); 1.82 (m, 1H); 1.73-1.53 (m, 4H); 1.50-1.32 (m, 2H); 0.87 (d, J=6.1 Hz, 3H); 0.86 (d, J=6.1 Hz, 3H). D.7.37 1 pair Gong tt F^AC 0 , OH \χ Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]] -2-[(4-Alkyl-3-indenyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Η I· 〇~〇 Analytical data: MS: [ M-18JH+ 451.3 D.7.38 I ntit O 0 Xx* N NH Η I. o' Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Amino]amino]amino]-2-[[[[[(9H- -9-yl) methoxy]carbonyl]amino]]]]]]]]]]]]] ]]-3-mercaptobutyl] Analytical data: MS: [M-18]H+ 622.2 95014 -162- 1345465 D.7.39 Chemical name: Dihydroxyboron, [(lR)-l-[[(2S) -5-[[imino(decylamino)indolyl]amino]-2-[(4-]ylbenzimidyl)amino]-1-3⁄4ylpentyl]amino]-3 -Methylbutyl] Analytical data: MS: [M-18JH+497.1 D.7.40, ΝΗ\λη H I. ο- Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)- 5-[[imino(jingenyl)methyl]amino]-2-[(3-butenyl)amino]-1-3⁄4 pentyl ] Amine-yl] -3 Yue methylbutyl] Analytical data: MS: [M-18] H + 383.2 D.7.41 «chiral I Β

〇-〜〇 Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino]-2-[(Ten Amidino)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 483.4

D.7.42

Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]][[4-(ethylidene) Amino)butanyl]amino]-1-ketopentyl]amino]-3-mercaptobutyl] Analytical data: MS: [M-18]H+442.2 D.7.43

For palm chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(6- Phenylhexyl)amino]-1-ketopentyl]amino]-3-methylbutyl]- Analytical Data: MS: [M-18JH+ 489.27

D.7.44

For the chemical name of the palm: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]-2-[(5- Peptidyl pentyl)amino]-1-ketopentyl]amino]-3-methylbutyl]- Analytical data: MS: [M-18]H+ 475.23 95014 -163- 1345465 D.7.45

Chemical name for the name of the palm: dihydroxyborane, [(1R)-1-[[(2S&gt;5-[[iminoamino(nitroamino)methyl]amino]-2-[(3-曱) Oxypropionyl)amino]-1-ketopentyl]amino]-3-methylbutyl]-analytical data: MS: [M-18]H+401.16 D.7.46

Capsule 〇 々〇 々〇 chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino (nitroamino) fluorenyl]amino]-2- [[2,2-Dimethyl-3-(2-methylpropenyl)-cyclopropanecarbonyl]amino]-1-ketopentyl]amino]-3-decylbutyl]-analytical data : MS: [M-18JH+ 465.29 D.7.47

I

NH o 乂O Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(3 -Methoxycyclohexylcarbonyl)amino]-1-ketopentyl]amino]-3-methylbutyl]-Analytical Data: MS: [M-18]H+ 455.57 D.7.48 Chemical Name: II Hydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[[3-(1Η-叫-朵- 3-yl)-propenyl]amino]-1-ketopentyl]amino]-3-methylbutyl]-analytical data: MS: [M-18JH+486.24 D.7.49

For the palm chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino]-2-[((RS )-2-cyclopent-2-enyl-ethenyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: [M-18JH+ 422.99 D. 7.50

For the palm chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(5- Erythrophen-2-yl-pentenyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 481.19 95014 -164- 1345465 D.7.51 Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(6- BenQ-heptyl)amino]-1-S-pentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 441.24 D.7.52

For the chemical name of Nadu: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(7- _ _ - 醯 ) ) ) -1- -1- -1- -1- -1- -1- -1- -1- 分析 分析 分析 分析 分析 分析 分析 分析 分析 分析 分析 分析 分析 : M M M M M M M M M M M M M M M

For the chemical name of the palm: dihydroxyborane, [(1R)-1-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(hexidine) Amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [Μ-18]H+413.06 Ref. D.7.54

〇-~0 For palm chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino]_2_[( Heptinyl)amino]-1-enylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18JH+ 427.14 D.7.55 for palmity

NH Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5,[[imino(nitroamino)indolyl]amino]-2-[(3-octyloxy) Amino-propylamino)-1-aminopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 499.17 D.7.56 I Wttt -•N. 丨々0 Chemical name: Dihydroxyboron, [(lR)-l-[[(2S)-5-[[imino(de)amino]indolyl]amino]-2-[(stupid) <RTI ID=0.0>#</RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; 0 S 7 Η 1. O' Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2 -[(undec-2-enyl)amino]-1-83⁄4ylpentyl]amino]-3-decylbutyl] Analytical data: MS: [Μ-18]H+481.41 D.7.58 1 atn. Chemical name: η n dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[( 9-decene fluorenyl)amino]-1-ketopentyl]amine, 1 NH \anh yl]-3-methylbutyl] h L o-^o Analytical data: MS: [M-18JH+ 467.31 D.7.59 丨 掌 化学 chemical name: human a-〇H dihydroxyborane, [(lR) -l-[[(2S)-5-[[imino(nitroamino)), ke, ίίΗ methyl]amino]-2-[(tetradecyl)amino]-1-one Amidyl NH amine Η 1. 0^*0 yl]-3-methylbutyl] Analytical data: MS: [M-18]H+ 525.10

Other compounds prepared according to the above Example 1X7 procedure are reported in Table D-7A.

Table D-7A Example No. Structure Chemical Name and Analytical Data D.7.60 | For T-T Properties 0 N. 〇H \χ κ r 0^*0 Chemical Name: Dihydroxyborane, [(lR)-l-[[( 2S)-5-[[imino(nitroamino)methyl]amino]-2-[(ll-azylundecenyl)amino]-1-ketopentyl]amine ]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 508.5 D.7.61 1 pair of palmity \χ Η Τ 0』々0 Chemical name: dihydroxyborane, [(lR)-l-[ [(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(9-cyano-nano)amino]-1-ketopentyl]amino] -3-Methylbutyl] Analytical data: MS: [M-181H+480.1 Example D.8 decylamine,]\-[(18,211)-1-[[[(1))-1-[(338 ,48,68,7311)-hexahydro_3^5,5_trimethyl 95014-166- 1345465 -4,6- ▼Hyunji_1,3,2-benzodioxide Linguin-2- 3-methylbutyl]amino]yl]-2-hydroxypropyl]-

Palm

Add TB (220 mg, 1.28 mmol, 1.2 eq. The solution was stirred for 10 minutes. The mixture was brought to 〇_5. Cool under the arm, add NMM (0.35 mL, 3.2 mmol, 3 eq.), then add the (2S)-amino-(3R)-hydroxy-butyric acid decylamine of Example C.3, 1^-[( 18)-1-[[[(111)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2 - benzodioxanthene-2-yl]-3-methylbutyl]amino]amino]hydrochloride (430 mg, 1.067 mmol, 1 eq.). The solution was stirred for 2 hours, then poured into water (200 mL) and extracted with ethyl acetate (1 mL). The organic layer was washed with the following solution: citric acid 2% (20 mL), sodium bicarbonate 2% (20 mL), and NaCl 2% (25 mL). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated, evaporated, evaporated, A white solid was taken in EtOAc (EtOAc)EtOAc. The yield was 20%. Analytical data: melting point l〇8-ll〇°C, TLC tannin (n-hexane/ethyl acetate 1/1, rf 0.33). EA calculated C (66.91%), Η (10_26%), N (5.38 % ), B (2.08%); found C (66.82%), Η (10.61%), Ν (5.35%), Β (1.93%). 95014 • 167· 1345465 1H-NMR (DMSO-dg) 5h : 8.81 (1H, db); =8.6, 1.8) ; 3.92 (1H, m) ; 2.52 (1H, m) ; 2.20 (1H, m), 2.17 (2H, t, J=7.1) ; 2.00 (1H, m); 1.83 (lH, t , J = 5.8); 1.78 (lH5m); 1.64 (lH, m); 1.62 (lH, m); 1.49 (2H, m); 1.34 (lH5d, J = 10.0); 1.31-U7 (21H, m); 1.04 (3H, d, J = 6.4); 0.91-0.83 (9H, m); 0.81 (3H, s). Other compounds prepared according to the above procedure include the following: Example D.8.1 (2S)-2-[ (benzyloxycarbonyl)amino]-4-methylpentamidine,]\-[(18,211)-1-[[[(11〇-1-[(338,48qiu, 731〇-hexahydro-33) ,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-2- Hydroxypropyl]-

Analytical data: TLC (CHC13 9 / MeOH 1, Rf 0_63), melting point 38-40 ° C, EA calc. C (64.60%), H (8.54%), N (6.85%); found C (62.44%) , Η(8·24 % ), Ν (7.47%). ^NMRCDMSO-de) 5η : 8.78(lH,br); 7.82 (1Η, d, J=8.60 Hz) ; 7.52 (1H, d, J=8.1 7.40-7.27 (6H, m) ; 5.02 (2H, br s) ; 5.00 (1H, d, J=5.1); 4.28 (1H, dd, J=8.6, J=4.2) ; 4.12 (1H, q , J 7.8); 4.05 (1H, dd, J=8.6, J=1.8); 3.94 (lH,m); 2.52 (lH3m); 2.19 (lH,m); 2.01 (lH,m); 1.83 (lH, t, J = 5.8); 1.78 (lH, m); 1.74-1.55 (5H, m); 1.46 (2H, m); 1.32 (lH, d, J = 10-1); 1.24 (3H, s); L_22(3H,s); 1.04(3H,d,J=6.2); 0.91-0.82 (12H,m); 0.80 (3H, s). 95014 • 16S· 1345465 Example D.8.2 KKU-diketonyl-1 ,3_diar-isoindol-2-yl)·decylamine-N-[(lS),(2R)-2-hydroxyl-[[(lR)-l-[(3aS,4S,6S ,7aR)-six-gas-3a,5,5-trimethyl-4,6-methylalkyl-lj3,2-benzodioxosin-2-yl-3-methylbutyl]amino Amino group]-propyl b analysis data: TLC (CHC13 9 / MeOH 1, Rf 0_83), EA calculated value C (66.52%), H (8.43%) , N (6.37%); found C (66.76%), Η (8·48 # % ), N (6.31%). NMRCDMSO-dg: 8.80 (lH, br); 7.85 (4H, m), 7.67 (1H, d, J = 8.80 Hz); 4.93 (1H, d, J=5.5), 4.28 (1H, dd, J=8.6, 4.0) ; 4.04 (1H, dd) ; 3.92 (lH,m); 3.56(2H,t, J=8.1); 2.49 (lH,m); 2.23-2.12 (3H, m) ; 2.00 (1H, m); 1.82 (lH,t,J=6.6); 1.78 (lH,m ); 1.73-1.53 (5H, m); 1.48 (2H, m); 1.33 (1H, d, J = 10.1); 1.3M.17 (20H, m); 1.03 (3H, d, J = 6.2); 0.84 (6H, d, J=6.6) ; 0.80 (3H, s). Other compounds and systems prepared according to the procedures of Examples D.8, D.8.1 and D.8.2 above are reported in Table D-8. . Table D-8 Example No. Chemical Name D.8.3 4-(pyridin-3-yl)benzamide, N-[( 1S ,2R)-1 -[[[(1R)-1 -[(3aS,4S , 6S,7aR)-hexahydro-3a,5,5-trimethyldecyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino ]carbonyl]-2-hydroxypropyl]. 95014 -169- 1345465 D.8.4 I 2-pyridinium carboxamide, bucket [(13,21〇-1-[[[(lR)-l-[(3aS) ,4S,6S,7aR)-Hexahydro-3\5,5-trimethyl-4,6-methylalkyl-1,3,2-isodioxanthene-2-yl]-3-indole Butyl]amino]carbonyl]-2-hydroxypropyl]. D.8.5. For palmar Η 1 ------------------- Tridecyl decylamine ,:^-[(13,211)-1-[[[(111)-1-[(3&amp;3,43,68,7&amp;11)-hexahydro-3a,5,5-trimethyl-4, 6-Methyl-1,3,2-benzene dioxobicin-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]. D.8.6 4-phenylbenzamide, 沁[(18,211)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-A hydrogen-3&amp;,5,5-trimethyl -4,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]. D. 8.7 1 pair of palms Χ〇^-Η ^&lt;ξχ 2,2-dimethyl decylamine, N-[(1S,2R)-l-[[[(lR)-l- [(3aS,4S,6S,7aR)-hexahydro-3\5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]- 3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]. D.8.8 1 Pair of palm (4-phenoxy)benzamine, N-[(lS,2R)-l- [[[(lR)-l-[(3aS,4S, 6S,7sR)-hexanitro-3a,5,5-dimethyl-4,6-nonylalkyl-1,3,2-benzo[ Oxyborium oxa-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]. D.8.9 1 pair of palm tt 5-butyl-2-pyridine carboxamide, N -[(lS,2R)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)-hexahydro-3a,5,5-tridecyl-4,6-methylalkyl- 1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]. 95014 -170- D.8.10 I 4-propoxybenzamide, N-[(lS,2R)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)-hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzoquinonedioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-2-hydroxypropene.. D.8.11 3-(3-pyridyl)benzamide, N-[(lS,2R)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)- Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-indole-2-yl]-3-methylbutyl]amino]carbonyl ]-2 -hydroxypropyl]. D.8.12 6-Phenyl-2-pyridinecarboxamide, N-[(lS,2R)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR )-six-rat-3a,5,5-dimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino ] carbonyl]-2-hydroxypropyl]. D.8.13 | Pair tt ~. 3-propoxybenzamide, N-[(lS,2R)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)-hexahydro-3a,5,5- Tridecyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl] D.8.14 | For palmar 1-bromoindole-2-carboxamide, N-[(lS,2R)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)- Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl ]-2-hydroxypropyl]. D.8.15 1 to ttt 6-bromobenzene-2-carboxyguanamine, 沁[(岱,21〇-l-[[[(lR)-l-[(3aS,4S ,6S,7aR)-A Hydrogen-3^5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-indenyl Butyl]amino]]yl]-2-hydroxypropyl]. 95014 -171 - D.8.16 . For phenyl-3-styl-based carbamide,]^-[(13,211;)-H[[( lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5·trimethyl-4,6-methylalkyl-1,3,2- benzodioxan 2·yl]-3-mercaptobutyl]amine based]_2-hydroxypropyl]. D.8.17 4-(2-fluorophenyl)benzamide, N-[(lS,2R)- L-[[[(lR)-i-[(3aS,4S, 6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-nonyl-1,3,2-benzene Diboron圜-2-yl]-3-methylbutyl]amino]carbonyl]-2-hydroxypropyl]. For use in Examples D.8.3, D.8.7, D.8.11, D.8.12 and D.8.13 The intermediate 1345465 carboxylic acid was synthesized according to the literature procedure. The compound 2,2-dimercaptodecanoic acid was prepared as described in Roth et al., CA. 1992, 35, 1609-1617, and the compound 4-(3-pyridyl)benzoic acid, 3-(3-pyridyl)benzoic acid and 6-phenyl-2-pyridine acid retardant are based on the work of Gong et al., n/e«, 2000, (6), The procedure described in 829-831 is made. The compound 3-propoxybenzoic acid is prepared according to the procedure described by Jones in /. CAew. 1943, 430-432. Example D.8.18 ❿ 2-p ratio tillage Carboxylamidine,]\-[(18)-1-[[[(11〇-1-[(338,48,68,7&amp;11)_hexahydro-33,5,5-trimethyl-4 ,6-Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-amineindolylethyl]

This compound has been derived from the example C.3 (2S)-2-amino-3-aminomercaptopropylamine, team [(111)-1-[(3&amp;3,45,68,7311)-six Hydrogen-3〇trimethyl-4,6-methylalkyl-1,3,2-benzene 95014-172-1345465 and dioxonium-2-yl]-3-methylbutyl] hydrochloride , basically according to the procedures of the above examples D.8, D.8.1 and D.8.2. 1H-NMR (DMS0-d6): 9.20 (1H, d, J = 1.29 Hz); 9.02 (1H, d, J = 8.52 Hz); 8.91 (1H, d, J = 2.45 Hz); 8.81-8.76 (2H , m) ; 7.42 (1H, s) ; 6.95 (1H, s); 5.00-4.80 (1H, m) ; 4.30-4.08 (1H, m) ; 2.85-2.72 (1H, m) ; 2.62-2.56 (2H , m) ; 2.25-2.15 (1H, m) ; 2.06-1.98 (1H, m) ; 1.84 (1H, t, J=5.54 Hz); 1.81-1.76 (1H, m) ; 1.72-1.58 (2H, m 1.32-1.26 (1H, m); 1.23(8H,d, J=5.36Hz); 0.85-0.79 (9H, m). Example D.8.19 Indoleamine, N-[(lS)-l-[ [[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine伍-2-yl]-3-methylbutyl]amino]carbonyl 1-2-aminemethylaminoethyl]

This compound has been subjected to the example of (2S)-2-amino-3-amine-branched propylamine C.3, ❿ team [(111)-1-[(3&amp;8,43,68&gt;11) -hexahydro-3屯5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl] hydrochloride Initially, it was basically made according to the procedures of Examples D.8, D.8.1 and D.8.2 above. Example D.8.20 4-butylbenzamide, N-[(1S)-1-[[[(1R) small[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-three Mercapto-4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl]-2-aminecarboxyethyl ] 95014 •173- 1345465

This compound has been derived from the example C.3 of (2S)-2-amino-3-amine-mercaptopropylamine, 1^-[(1 ft)-1-[(3&amp;8,48,68,7311 )-Hexahydro-33,5,5-dimethyl-4,6-fluorenyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl] The acid salt was initially prepared essentially according to the procedures of Examples D.8, D.8.1 and D.8.2 above. Example D.9 Φ guanamine, N_[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)_hexahydro·3ι5,5_trimethyl-4,6 -Mexyl-1^3,2-benzodioxoindol-2-yl]-3-methylbutyl]amino]p-]-2-indole (4-methylbenzhydryl) Amino 1 ethyl]·

The citric acid (330 mg, 1.95 mmol, L2 eq.) was dissolved in dry DMF (20 mL) and EtOAc (EtOAc, EtOAc, The solution was stirred for 10 minutes, cooled at 〇-5 ° C, and NMM (〇_53 mL, 4.9 mmol, 3 eq.) was added with &lt;2&gt; (4-mercaptophenyl)amino]propanamine, N-[(lR)-l-[(3aS,4S,6S, 7aR)-hexa-argon-3a,5,5-dimethyl- 4,6-Azepine-1,3,2-benzodioxan, oxa-2-yl]-3-methylbutyl]-, hydrochloride (800 mg, 1.58 mmol, 1 eq. The resulting mixture was stirred at room temperature for 3 hours. The solution was poured into water (200 ml), extracted with ethyl acetate (100 ml), citric acid solution 95014-174. 1345465 2% (50 ml), sodium bicarbonate 2% (50 ml), NaCl 2% (50 ml) wash. The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated and evaporated from Et. The suspension was filtered and dried to give a white solid. The yield was 33%. Melting point: 134 ° C -136 ° C, TLC oxime (solvent n-hexane / ethyl acetate, Rf 0.5) · EA calculated C (69.33%), Η (9.37%), N (6.74%), B (1.73%); measured values C (%), Η (%), Ν (23%), Β (%).

1H NMR (DMSO-d6) 8.74 (1H, d, J = 3.5 Hz); 8.25 (1H, t, J = 5.6); 7.95 (1H, d, J = 7.9); 7.71 (2H, d, J = 8.1 7.25 (2H, t, J=8.1) ; 4.59 (1H, m) ; 4.1 (1H, dd, J=1.8, 8.8); 3.49 (2H,m); 2.59 (lH,m); 2.35 (3H , s) ; 2.20 (lH, m); 2.09 (lH, t, J = 7.3); 2.02 (lH, m); 1.83 (1H, t, J = 5.5); 1.78 (lH, m); 1.62 (2H , m); 1.44 (2H, m); 1.36-1.21 (17H, m); 1.25 (3H, s); 1.22 (3H, s); 0.85 (3H, t, J = 6.8); 0.80 (9H, m ). Example D.10

2-S-decylamino-3-(hexylamino)-propanamide, 1\-[(18)-1-[[(111) small [(338,48,68,7珏11 )-Hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino group Carbonyl]

The citric acid (170 mg, 0.98 mmol, 1.2 eq.) was dissolved in anhydrous DMF (15 mL) and EtOAc ( EtOAc (EtOAc) The solution was stirred for 20 minutes and cooled at 0-5 ° C. and 95014 -175· 1345465

NMM (0.271 ml, 2.46 mmol, 2.5 equivalents) was added as in Example C.5 2-S-amino-3-(hexylamino)-propanamine, N-[(lS)-l-[ [(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxine圜-2-yl]-3-methylbutyl]amino]amino], hydrochloride (400 mg, 0.82 mmol, 1 eq.), and the resulting mixture is allowed to fall at room temperature 3 hours. The solution was poured into water (150 ml), extracted with ethyl acetate (1 mL), EtOAc (2 mL (50 mL), sodium hydrogen carbonate 2% (50 mL), NaCI. )washing. The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated and evaporated. The suspension was filtered and dried to give a white solid. Yield 47% » Analytical data: melting point 135-137 ° C, TLC oxime (solvent hexane / ethyl acetate 2 / 1, Rf = 0.27). EA calculated C (67.64%), Η (10_35%), N (6.96%); measured value C (66.93%), Η (10.29%), Ν (7.14%).

^NMRCDMSO-dg) 5η : 8.67 (1Η, d, J=2.9 Hz); 7.83 (1H, d, J=8.2); 7.67 (1H, t, J=5.5) ; 4.41 (1H, m) ; 4.10 ( 1H, dd, J=1.5, 8.6) ; 3.25 (2H, m); 2.56 (lH,m); 2.20 (lH,m); 2.13-1.95 (5H, m) ; 1.84 (1H, t, J=5.5 1.78 (lH,m); 1.64 (2H,m); 1.46 (4H,m); 1.35-1.15 (27H, m); 0.84 (9H, m); 0.79 (3H, s). Example D.ll 2-S-decylamino-3-(4-fluorosulfonylamino)propanamine, N_[(1S)-1-[丨(1R)-l-[(3aS,4S,6S) ,7aR)·Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxolybdenyl-2-yl]-3-methylbutyl] Amino]carbonyl] 95014 -176-

1345465 citric acid (160 mg '0.94 mmol) was dissolved in anhydrous DMF (20 mL) and TBTU (300 mg, 0.94 m., 1.2 eq.) was added at room temperature under nitrogen. The solution was stirred for 20 minutes at 〇5. (; cooled down, and added NMM (0.259 ml, 2_36 mmol, 2.5 equivalents) and Example C.6 2-S- φ Amino-3-(4-fluoroyl-decylamino)propanamide , N-[(lS)-l-[[(lR)-l-[(3aS,4S,6S, 7aR)-hexahydro-3a,5,5-tridecyl-4,6-nonyl-- 1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]amino]], hydrochloride (43 mg, 0.78 mmol, 1 eq) The resulting mixture was stirred at room temperature for 2 hours. The solution was poured into water (200 ml), extracted with ethyl acetate (1 mL) and washed with the following solution: citric acid 2% (50 ml) , sodium bicarbonate 2% (50 ml), NaCl 2% (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated and purified by EtOAc (solvent hexane-ethyl acetate 2/1). Evaporate the solvent and add n-hexane to obtain 1 gram of solid. Yield 19%. Analytical data · · melting point 83-85 ° C, TLC oxime (solvent hexane / acetic acid B Ester 2/1, Rf = 0.53). 1H NMR (DMSO-d6) δ η: 8.45 (1H, d, J = 3.8 Hz); 7.83 (3H, m); 7.63 (1H, t, J = 6.2); (2H, tsJ=8.8); 4.40 (lH,m); 4.12 (1H, dd, J=1.5, 8.6); 2.95 (2H,m); 2.64 (lH,m); 2.21 (lH,m); 2.17 (2H, t, J=7.3); 2.01 (lH,m); 1.83 (1H, t, J=5.5); 1.78 (1H, m); 1.62 (2H, m); 1.45 (2H, m); -1.1 (23H, m); 0.87-0.8 (9H, m); 0.79 (3H, s). 95014 •177· 1345465 Example D.12 2-S-decylamino-3-(3,4- Dimethoxyphenylacetamido)propanamine, N-[(lS)_l-[[(lR)-l_[(3aS,4S,6S,7aR)-hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]

The citric acid (80 mg '0.48 mmol, 1.2 eq.) was dissolved in dry DMF (20 mL) and TBTU (150 mg, 0.48 m. The solution was allowed to mix for 20 minutes, cooled at 〇-5 ° C, and NMM (0.13 mL, 1.2 mmol, 2.5 eq.) was added with 2-S-amino-3-(3,4) of Example C. -didecyloxy benzylamino) propylamine, ^-[(13)-1-[[(111)-1-[(3aS,4S,6S,7aR)-:^ hydrogen-3a ,5,5S methyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]amino], hydrochloric acid Salt (23 mg, 〇. 4 mmoles 1 equivalent) and the resulting mixture was stirred at room temperature for 2 hours. The solution was poured into water (200 ml), extracted with ethyl acetate (1 mL), and washed with the following solutions: citric acid 2% (50 ml), sodium bicarbonate 2% (50 ml), NaCl 2 % (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated, and then purified by EtOAc (EtOAc). The solvent was evaporated to give 100 mg of a glassy solid. The yield was 35.7%. Analytical data: TLC Shixi gum (solvent burned / ethyl acetate 1 / 1, r f. = 〇 53). EA calculated value C (67.13%), Η (9.25%), N (6.02%); measured Value C (65.38 95014 •178-1345465 % ), Η (9.20%), Ν (5.49). 1HNMR(DMSO-d6) 8.65 (1Η, d, J=3.5 Hz); 7.84 (2H,m); 6.83 ( 2H, m) ; 6.72 (1H, dd, J=1.7, 8.1) ; 4.43 (1H, m) ; 4.10 (1H} dd, J=1.8, 8.6); 3.72 (3H, s) ; 3.70 (3H, s ;3.30 (2H, m) lH,m); 1.63 (2H, m) ; 1.43 (2H, m) ; 1.35-1.15 (23H, m) ; 0.87-0.8 (9H, m) ; 0.79 (3H, s). Example D.13 2- S-decylamino-3-(phenylureido)propanamine, N_[(lS)-l-[[(lR)-l-[(3aS,4S,6S, 7aR)-hexaza_3a ,5,5-Dimethyl_4,6-Methylidyl-1,3,2·Benzodioxane-2 -yl]-3-methylbutyl]amino]carbonyl]

ΗΝ 〇6 Add citric acid (170 mg, 0.99 mmol, 1.2 eq.) to dry DMF (20 mL) and add TBTU (310 mg, 0.99 mmol, 1.2 eq.) at room temperature under nitrogen. . The solution was stirred for 20 minutes, cooled at 〇 5 ° C, and NMM (0.27 mL, 2.4 mmol, 2.5 eq.) was added with &lt;EMI ID=9.1&gt; Amidoxime has [(18)-1-[[(1)-)-[[3,48,63,7311)-hexahydro-3a,5,5-trimethyl-4,6-methyl -1,3,2-benzodioxoloxyl-indolyl]-3-mercaptobutyl]amino]amino], hydrochloride (420 mg, 0.82 mmol, i equivalent), and The formed / / compound was mixed for 2 hours under 〇C. The solution was poured into water (200 ml), extracted with ethyl acetate (1 mL) and washed with EtOAc: EtOAc (EtOAc) % (5〇95014 -179· 1345465 ml). The organic solution was dried over anhydrous sodium sulfate, dried, evaporated, and evaporated in diethyl ether (20 ml). Purification (n-hexane / ethyl acetate 1-8). The yield was 25%.

Analytical data: TLC tannin (solvent hexanyl acetate / ethyl acetate 18, R f = 〇 4) _ ^ NMRC DMSO-^) 5h: 8.73 (1H, d, J = 3.1 Hz); 8.64 (1H, br s) 7.97 (1H, d, J=8.2); 7.36(2H, d, J=8.1); 7.19 (2H, t, J=8.1); 6.87 (1H, t, J=8.1); 6.1(lH,t , J=6.0); 4.44 (lH,m); 4.10 (1H, dd, J=1.8, 8.6); 3.41 (lH,m); 3.22 (lH,m); 2.59 (lH,m); 2.19 (lH , m); 2.10 (2H, t, J = 7.3); 2.02 (1H, m); 1.84 (lH, t, J = 5.5); 1.78 (lH, m); 1.64 (2H, m); 1.46 (2H , m); 1.35-1.15 (23H, m); 0.87-0.8 (9H, m); 0.79 (3H, s). Example D.14 2_Aminoacetamide, N-[(lSH-[[[ (lR)_l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- benzodioxanthene- 2-yl]-3-methylbutyl]amino 1carbonyl]-4-[[imino(indolyl)methyl]amino]butyl], hydrochloride

N-methylmorpholine (275 μL, 2.5 mmol) was added to a solution of N-Boc-glycine (383 mg, 2.18 mmol) in anhydrous dichloromethane (20 mL). The mixture was cooled to -15 ° C and then isobutyl methacrylate (286 μl '1.2 mmol) was added slowly. After 15 minutes, the (2S)-2-amino-5-[[imino(wall amine)methyl]amino] decylamine N-[(lR)-l- of Example C.1 was added. [(3aS,4S,6S, 95014-180- 1345465 幻幻-六氢士一义三曱基彳巴 alkyl 汔^benzodioxanthene)]-3-methylbutyl]-salt Acid salt (i.oo gram, 2 〇 millimolar) with another n-methylmorpholine (275 μl, 2.5 mmol) "&gt; The reaction mixture was taken at _15〇c _1 〇β(: 4 leaflets were disturbed, and then the plants were reduced to a small volume and separated between ethyl citrate (1 (10) ml) and water (50 ml). The aqueous phase was further extracted with ethyl acetate (2 mL). The combined organic phases were dried over sodium sulfate and evaporated and evaporated. mjjjjjjjjjjjjj The solid was collected by decantation and dried under vacuum (1.18 g, 95%). A portion of this b?c-protected intermediate (1.08 g, 1.73 mmol) was dissolved in THF (15 ml) ), then add 4N solution of HC1 in dioxane. Stir at room temperature 5 The mixture was concentrated <RTI ID=0.0></RTI> </ RTI> <RTI ID=0.0></RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; 1H NMR (DMSO-d6): 8.76 (1H, d, J = 3.1 Hz); 8.68 (1H, d} J = 8.1); 8.56 (1H, br); 8.06 (3H, m) ; 7.91 (2H, br) 4.43 (1H, m) ; 4.14 (1H, dd, J= _ 8.6, J=1.6) ; 3.60 (2H, m) ; 3.15 (2H, br) ; 2.67 (1H, m) ; 2.23 (1H, m ); 2.04 (lH,m); 1.87 (1H, t, J=5.8) ; 1.81 (lH,m); 1.75-1.60 (3H, m) ; 1.52 (3H,m); 1.41-1.28 (3H,m 1.27 (3H, s); 1.23 (3H, s); 0.86 (3H, d, J=6.4); 0.84 (3H, d, J=6.4); 0.81 (3H, s). Example D.15 3 -Aminopropylamine,]\-[(18)-1-[[[(111)小[(333,48,68,7311)-hexahydro-33,5,5-trimethyl-4, 6-Methyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl 1 amide 1 carbonyl H-[[imino(decylamino)methyl) Amine]butyl]; hydrochloride 95014-181 -

1345465 3-[[(1,1-Dimercaptoethoxy)carbonyl]amino]propanamide group [(18)-1-[[[(111)-1-[( 333,48,65,7&amp;11)-hexahydro-3屯5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl] 3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)indolyl-]amino]butyl]-(42 mg, 0.075 mmol) in diethyl ether ( In a solution cooled at 〇 ° C, a 10% v/v solution (2 ml) of hydrogenated hydrogen in diethyl ether was added. The mixture was stirred for 5 hours while allowing to warm to room temperature. The solid formed was collected by EtOAc (EtOAc) elute LC-MS 538.7, MH+.ESIPOS; AQA; spray 4kV/demister: 20V/probe 250 C. Other compounds made from the corresponding Boc protecting compounds of Table D.3 according to the above examples, Reported in Table D-15 below. Table D-15 Example number structure Chemical name and analytical data D.15.1 | Phenyl chemical name: CH HS (4RS)-hexahydropyridine-4-carboxamide, N-[(lS)-H[[(lR )-H (3aS, 4S, 6S, 7aR) - six. s hydrogen-3a, 5,5-trimethyl*4,6-methylalkyl-1,3,2-benzoan\anh dioxonium-2-yl]-3-methylbutyl]amino Carbonyl H-group]-4-[[imino(nitroamino)methyl]amino]butan 0 vo group], HC1 salt Analytical data: MS: MH+ 578.1 95014 • 182· 1345465

D.15.2 掌 掌 掌 CH CH s Chemical Name: (RS)-Hexahydropyridine-2-carboxyguanamine, N-[(lS)-l-[[[(lR)-H(3aS,4S,6S ,7aR)·six gas-3a,5,5-trimethyl*4,6-methylxyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl]*4-[[imino(nitroamino)methyl]amino]butyl]; HC1 salt Analytical data: MS: ΓΜΗ1+ 578.2 D.15.3 丨财掌性 CH H human chemistry Name: (2S)-hexa-argonpyridine-2-carboxamide, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-A argon-3a, 5,5-trimethyl 6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]*4-[[ Amino (nitroamino)methyl]amino]butyl]; HC1 salt Analytical data: MS: ΓΜΗ1+ 578.2 D.15.4 -----. «掌性 π坪办Η Λ 〇Chemical name · (2R )-Hexahydropyridine-2-carboxamide, N-[( 1S)· 1-[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2- benzodiazepine boron-2-yl]-3-methylbutyl]amino]carbonyl]-4·[[imino (Nitroamino)methyl]amino]butyl]; HC1 salt Analytical data: MS: ΓΜΗ1+578.8 Example D.16 Other Synthesis of the compound Following the procedure of Example D.9-D·13, the following compound was obtained by the reaction of phthalic acid with the intermediate of Example C.9. D.16.1 Indoleamine, N-[(1S)-1-[[[(1R)-1-[(3,5,48,68>11)-hexa-argon-:^,5,5-trimethyl *4,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]·2_(ethylamino)ethyl D.16.2 guanamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl 4, 6- ΙΛν Methyl-1,3,2- benzodioxanthene-2-yl]-3-methyl&gt;»mercaptobutyl]amino]carbonyl]-2-(9-yl group Hydroxylamine)ethyl]- 95014 -183 - 1345465

D.16.3 Indoleamine, N-[(1S)-1-[[[(1R)-1-[(335,43,65,7&amp;1〇-hexahydro-33,5,5-trimethyl) 4,6-Methyl-alkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-(pentyl-ureido)ethyl ]- L. You _^h D.16.4 Amidoxime, N-[(1S)-1-[[[(1R)-1-[(333,48,65,7311)-hexahydro-3\5 ,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-(methane sulfonate Amidino)ethyl]-o=s=o 1 D.16.5 guanamine, N-IXlSW-mGiO-l-^aSAS/SJaR)-hexahydro-3a,5,5-trimethyl 4,6 -Methyl-l,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-[(ethoxycarbonyl-grain)- Amines]ethyl]- D.16.6 4_butylphthalamide N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro- 3a,5,5-trimethyl 4,6-methylalkyl-l,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2- [(芊-oxycarbonylguanamine) ethyl]- lH NMR (DMSO-d6): 9.79 (1H, d); 8.32 (1H, d); 7.8 (2H, d); 7.3 (8H, m); 5.05 ( 2H, q) 4.7 (1H, q); 4.1 (1H, d); 3.45 (2H, m); 2.6 (3H, m); 2.2 (1H, m); 2.0 (1H, m); 1.85 (2H, m); 1.65 (4H, m); 1.3 (5H, m); 1.25 (6H, d) 0.9 (3H, t); 0.80 (9H, m). Melting point 95o-100oC. 3.0 ^ D.16.7 4-butyl benzylamine, N -[(1S)-1-[[[(1R)-1-[(335,35,65,7&amp;11)-hexahydro-3&amp;,5,5-trimethyl*4,6-methylalkyl -l,3,2- benzodioxanthene-2-yl-]-3-methylbutyl]amino]carbonyl]-2-(lH-pyrazine)ethyl]- o D.16.8 Indoleamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-tridecyl 4,6-methane -1,3,2-benzodioxan group-2-yl]-3-mercaptobutyl]amino]carbonyl]-2-[(indolyl carbonyl decylamine) ethyl]- lH NMR (DMSO-d6): 8.69 (1H, d); 7.85 (1H, d); 7.35 (5H, m); 7.05 (1H, t); 5.05 (2H, m) 4.45 (1H, q); 4.1 (1H , d); 3.3 (2H, m); 2.65 (1H, m); 2.2 (1H, m); 2.1 (3H, m); 1.85 (2H, m); 1.65 (2H, m); 1.45 (2H, m); 1.25 (22H, m); 0.8 (12H,m) 1 pair of palms

95014 184· 1345465

4-phenyloxybenzene f decylamine, N-[(1S)-1-[[[(1R)-1 [(3aS,4S,6S,7aR)-^ fi.-3a,5,5-=. f methylalkyl-1,3,2-benzodioxanol-2-yl]-3-methylbutyl]amino]carbonyl]-2-[(indolylcarbonyl decylamine)ethyl]- 'H NMR (DMSO-d6): 9.8 (1H, d); 8.4 (1H, d); 7.9 (2H, d); 7.4 (2H, t); 7.3 (6H, m); 7.25 (2H, m) ; 7.05 (4H, m); 5.05 (2H, q) 4.7 (1H, q); 4.05 (1H, d); 3.45 (2H, m); 2.65 (1H, m); 2.2 (1H, m); (1H, m); 1.80 (2H, m); 1.65 (2H, m); 1.3 (4H, m); 1.25 (6H, d) 0.8 (9H, m). Melting point 100o-103oC·

Example D.17

4-butylbenzamide, team [(18)-1-[丨[(1 dress-1-[C8,48,68,7311)-hexahydro-33,5,5-trimethyl- 4,6-Methyl-1,3,2-benzodioxanol-2-yl]_3-methylbutyl]amino]carbonyl]-2-(aminoethyl)-hydrochloric acid Example D.16.6 4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)-hexahydro-3a,5, 5-trimercapto-4,6-methylalkyl-1,3,2-benzodioxan-2-denyl-2-methylbutyl]aminocarbyl]-2-[(oxime Carbonyl decylamine)ethyl]-(4 mg, 0.62 mmol) is dissolved in 1,4-dioxane (1 mL) and methanol (5 mL). To this solution, Pd/C 10% (40 mg) and 4NHC1 1,4-dioxane (1.1 equivalent) were added. The mixture was hydrogenated at 1 bar. Upon completion of the reaction, Pd/C was filtered on celite, and the solvent was removed under reduced pressure to give a white foam. Yield 95%, 320 mg. Analytical data: 1H NMR (DMSO-d6): 8.76 (1H, d); 8.55 (1H, d); 8.15 (3H, br s); 7.95 (2H, d); 7.25 (2H, d); 4.8 (1H , m); 4.2 (1H, d); 2.80 (1H, m); 2.62 (2H, t); 2.23 (lH, m); 2.04 (lH, m); 1.87 (lH, t); 1.80 (lH, m); 1.75-1.50 (2H, m), 95014 -185-1345465 (2H, m); 1.41-1.20 (6H, d), (6H, m); 1.0-0.80 (3H, d) ; (3H, d) ; (3H, s), (3H, t). Example D.18 2-S-(4-butylbenzimidyl)-3-(2-pyroxycarbonylamino)-N-[ (lS)-l-[[(lR)-l_[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- Benzo-dioxaboron-2-yl]-3-methylbutyl]amino 1 carbonyl 1

2-Pyridinecarboxylic acid (76 mg, 0.61 mmol, 1.1 eq.) was dissolved in dry DMF (5 mL) and TBTU (2 mg, 0.61 m. equivalent). The solution was stirred for 15 minutes at 〇-5. Cool under the arm, and add NMM (0.20 mL, 1.85 mmol, 3.3 eq.) with 4-butyl benzoamine from Example D.17, &gt; 1-[(13)-1-[[[ (1«&gt;1-[(3&amp;3,43,63,7311)-hexahydro-3\5,5-trimercapto-4,6-nonylalkyl-1,3,2-stupid Oxyborax, 2,2-yl]-3-methylbutyl]amino]amino]-2-(aminoethyl) hydrochloride (31 mg, 〇.56 mmol, 1 equivalent And the resulting mixture was stirred for 4 hours at 25 ° C. The solution was poured into water (1 mL), extracted with ethyl acetate (5 mL) and washed with the following solution: 2% citric acid (50 ml), shirt &lt;:: 12% (5 ml), sodium bicarbonate 2% (50 ml), &gt;^ (: 12% (5 ml). The organic solution was dried over anhydrous sodium sulfate. , filtered, evaporated, and suspended in diethyl ether-hexane-hexanes to give a white solid, which was filtered and dried in vacuo to give a white powder. 95014 • 186·1345465 yield 52%. Analytical data: melting point 70-72 ° C. ^NMRCDMSO^): 9.20 (lH, s); 9.0 (lH, t); 8.85 (lH, d); 8.8 (lH, d); 8.78 (1H, d) ; 8 .60 (1H, d) ; 7.82 (2H, d) ; 7.35 (2H, d) ; 4.8 (1H, m) ; 4.1 (lH, d); 3.80 (lH, m); 3.62 (lH, m); 2.82 (lH,b); 2.65 (2H,m); 2.2-2.0 (2H, m) ; 1.80 (1H, m) ; 1.75-1.50 (2H, m), (2H, m) ; 1.41-1.20 (6H , d), (6H, m) ; 1.0-0.80 (3H, d) ; (3H, d) ; (3H, s), (3H, t). Example D.19

4-butylbenzamide, 1\-[(18)-1-[[[(11〇-1-[] 8,48,68,7211)-hexahydro-33,5,5-trimethyl Benzyl-4,6-methylalkyl-1,3,2-benzodioxan-indole-2-yl]-3-methylbutyl]amino]ylidene 2-[4-gas-benzene continued Amine

4-butylbenzamide of Example D.17,

7aR)-hexahydro-3a,5,5-tridecyl·4,6-nonanyl-1,3,2-benzodioxine 圜_2·yl]-3-mercaptobutyl] The amino group] is exemplified as the oxoamine amide)ethyl]- (2 75 g, 5.02 mmol, 1 equivalent), dissolved in anhydrous dichloromethane in 〇_5 〇c. In this solution, 'additional gasification of 4-fluorophenylsulfonate (1.07 g, 5.52 mmol, 1.1 eq)) and after a few minutes, N-mercapto-formoline (M) was added dropwise ( 1_11 grams, 11.04 millimoles, 2.2 equivalents). The mixture was stirred at 〇 5 ° C for 30 minutes and then at 10 ° C for 1 hour. The solvent was removed under reduced pressure, and the crude material was dissolved in ethyl acetate, and then 2% (5 liters) of citric acid solution, followed by carbon 95014 • 187·1345465 sodium hydride 2% solution (50 ml) Wash with 2% sodium chloride solution (5 mL). The solution was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The crude material was purified by silica gel chromatography (eluent ethyl acetate / n-hexanehexane / /). The collected fractions were evaporated under reduced pressure and the white solid was suspended in diethyl ether. Dry down and get white wax. Yield 60%, 2 g. Analytical data: ^NMRCDMSO^): 8.60 (lH,d); 8.30 (lH,d); 7.85 (3H,m); 7.8 (2H, d); 7.38 (2H, d); 7.30 (2H, d); 4.62 (1H, m) ; 4.15 (1H, d) ; 3.25 (2H, br); 2.61 (3H, m); 23-2.0 (1H, m) ; (lH, m); 1.80 (lH, m); 1.75-1.50 (2H, m), (2H, m) ; 1.41-1.20 (6H, d), (6H, m) ; 1.0-0.80 (3H, d) ; (3H, d) ; (3H, s) , (3H, t). Example D.20 4-butylbenzamide,]V-[(lS)_l-[[[(lR)-l-[(3aS,aS,6S,7aR)·six Hydrogen-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-]-3-methylbutyl]amino]carbonyl]-2 -[(2,5-dimethyl-2H-pyrazole)carbonylamino]ethyl]_

4-butyl benzoguanamine of Example D.17, N-[(1S)_H[[(1R) small [(3aS,4S,6s, 7aR)-hexahydro-3a,5,5-trimethyl 4,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]amino]-2-[(indoleoxycarbonyl decylamine) Ethyl]_(〇9 g, 1.64 mmol, 1 eq.) was dissolved in anhydrous dichloromethane (1 mL). The resulting solution was cooled to 〇 ° &lt; T &lt; 5 ° C, and N-methyl-mirafine (0.381 g, 95014 • 188·1345465 3.78 mmol, 2.3) was added. In the mixture, add gasification 13 dimethyl_1H_pyrazole-5-carbon hydrazine plus [55458_67_8]) (〇.286 mg, 18 mmol, u equivalent b. The mixture was stirred for 1 hour, then the temperature was raised To 20. 〇. The mixture was evaporated under reduced pressure, suspended in ethyl acetate (5 mL), 2% citric acid (30 mL), 2% sodium bicarbonate (30 ml), 2% gasification The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude material was purified by silica gel chromatography (solvent ethyl acetate / n-hexane 8/2). The collected fractions were obtained as a white powder, which was suspended in a riddle and filtered to give the desired compound. Yield: 65%, 650 mg. Rf. 0.62. Analytical data: melting point 62-64 ° C. 1H NMR (DMSO-d6): 8.82 (lH, d); 8.40 (2H, m); 7.85 (2H, d); 7.3 (2H, d); 6.5 (1H, s); 4.8 (lH, m); (lH,d); 3.9 (3H, s); 3.61 (2H,m); 2.65 (3H,m); 2.25 (lH,m); 2.15 (3H,s); 2.0(lH,m); 1.80 ( lH,m); 1.75-1.50 (4H, m) ; 1.41-1.20 (5H, m), (6H, m) ; 0.90 (3H, t) ; 0.8 (9 H, m); Example D.21 4-butylbenzamide, 1\-[(18)-1-[[[(111)-1-[(338,38,68,731〇-hexahydro-- ,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan group-2-yl+3-mercaptobutyl]amino]carbonyl]-2-( 4-methylphenylureidosulfonylamino)ethyl]-

95014 •189- 1345465

4-butyl benzoguanamine of Example D.17, N-[(lS)-l-[[[(lR)-l_[(3aS,4S,6S, 73 ft)-hexahydro-3屯5 ,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]]yl]-2-[( The oxime oxoamine ethyl)-(7 g, 1.27 mmol, 1 eq.) was dissolved in anhydrous THF (1 mL) and the solution was then cooled at &lt; Added triethylamine (0.4 ml, 1.8 mM, 2.2 eq.) and gasification of the example G_IX (4-mercaptophenyl)-velocyl-continuous (0.34 g, ι·38 mmol) 1_09 equivalent). The suspension was stirred at 25 ° C for 1 hour, then poured into a 1% solution of citric acid (30 mL) and extracted with ethyl acetate (5 mL). The organic solution was washed with a 2% solution of sodium chloride, dehydrated and dried under anhydrous sodium sulfate, and then evaporated to give a crude material which was purified by chromatography. - 己院 l / l) Rf 〇 · 64. The collected fractions were evaporated and the oil was co-evaporated with diethyl ether to give a white foam. Yield 31%, 280 mg. Analytical data: melting point 115-120 it

^NMRCDMSO-de): 8.80 (1H, s); 8.40 (1HS d); 7.82 (2H, d); 7.3 (2H, d); 7.25 (2H, d) ; 7.00 (2H, d) ; 4.62 (1H , m) ; 4.15 (1H, d) ; 2.61 (3H, m); 2.3-2.0 (3H, s) ; 1.80 (lH, m); 1.75 (2H, m), 1.6 (4H, m), 1.2 ( 13H, m) ; 0.9 (3H, s), 0.8 (9H, m) Example D.22 4-phenoxybenzamide, N-[(lS)-l-[[[(lR)-l- [(3aS, 4S, 6S, 7aR)-hexahydro-3玨,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl] -3-mercaptobutyl]amino]carbonyl 1-2-(3-phenyl-ureido)ethyl]- 95014 -190-

1345465 4-phenoxybenzamide which is derived from Example D.25.2, small [(3aS,4S,6S,7aR)-hexahydro-3\5,5-trimethyl-4,6-methyl- i,3,2-benzodioxanthene-2-yl]-3-f-butyl]amino]amino);]_2-(amino)ethyl hydrochloride (1 g, 17 mmol) The ear '1 equivalent) was dissolved in anhydrous dioxane (3 mL) and N-methyl-fifelin (0.2 g, 18.8 mmol, 1.1 equivalent) was added. The solution was cooled at 〇 - 5 ° C, and phenyl isocyanate (0.22 g, 17-7 mmol, 1.1 eq.) in dichloromethane. The mixture was stirred at 〇_5〇c for 1 hour. The solution was washed with a sodium carb. 2% solution (50 mL), dried over anhydrous sodium sulfate and evaporated. The crude material was suspended in diethyl ether (2 mL), stirred for 2 hrs, filtered and evaporated and evaporated. (: Drying, white powder was obtained. Yield 74.3%, 0.84 g. Analysis data: melting point 143-145 ° C φ ^NMRCDMSO^) : 8.9 (lH, d); 8.75 (1H, s); 8.59 (1H, d) 7.95 (2H, d); 7.45 (2H, t); 7.35 (2H, d); 7.2 (3H, m); 7.1 (4H, m); 6.9 (lH, m); 6.25 (lH, t 4.65 (lH,m); 4.10 (lH,d); 3.65 (lH,m); 3.4 (lH,m); 2.6 (lH,m); 2.2 (lH,m); 2.1 (lH,m) 1.85 (2H, m); 1.65 (2H, m), l_3 (3H, m); (6H, d); 0.80 (9H, t). Example D.23 4-butylbenzamide, N- [(lS)-l-[[[(lR)-l-[(3aS, aS,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-methylalkyl-l,3 ,2-benzodioxanthene-2-yl-]-3-methylbutyl] 95014 .191· 1345465 Aminocarbonylcarbonyl]-2·(4-methylphenyl sulfhydryl) Kib

4-butyl benzoguanamine from Example D.17, N_[(1S) small [[[((8), s[[3, s, s, s, s, s, s, s, s, s, s, s Trimethyl-4,6-methylalkyl-i,3,2- benzodioxanthene: yl]-3-fylbutyl]amino]carbonyl]·2_(aminoethyl)hydrochloride The salt (56 mg, 1.07 mmol, 1 eq.) was dissolved in anhydrous di-methane (2 mL), and the solution was cooled at 0-5t: Ν-methyl-morpholine (0125 ml) , 1.129 mmol, 1.1 eq.); with 4-methyl-toluene isocyanate (〇22 g, i 12 mmol, 1.1 eq.), and the mixture was stirred at room temperature for 2 hr. The acid solution was washed with 2% (20 ml) of a solution of sodium sulphate (2 ml) and then evaporated to dryness. The solvent was evaporated, and the crude material was suspended in n-hexane (20 ml). The mixture was stirred at room temperature for 1 hour, dried, and dried under vacuum at 50 ° C to give white powder. 75.6%, 0.55 g. Analytical data: melting point 168-170 ° C. ^NMRCDMSO^): 10.8 (lH, s); 8.75 (lH, d); 8.35 (lH, d); 7.75 (4H, m); 7.35 (5H, m); 6.65 (1H, t); 4.5 (1H, t) ; (lH,d); 3.5(lH,m); 3.25 (lH,m); 2.65 (3H, m); 2.3(3H,d); 2.2(lH,m); 2.1(lH,m); 1.80 ( 2H, m) ; 1.65 (4H, m), 1.3 (12H, m) ; 0.80 (12H, m). 95014 -192- 1345465 Example D.24 Synthesis of other compounds according to the procedure of Example D.18-D.23 The following compounds can be obtained from the intermediates of Examples D.17 or D.25 with commercially available carboxylic acids, mercapto halides, sulfonyl halides, isocyanates, sulfonyl isocyanates, or with Examples G. 14. G.15 and G.16 compounds are prepared by reaction. All of the compounds obtained were identified by 1H-NMR characterization. D.24.1 -^ F Chemical name: decylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5 -trimethyl-4,6-methylalkyl-1,3,2-benzodioxazole, 2-3-yl]-3-methylbutyl]aminocarbyl]-2-[4-fluoro- Phenylsulfonamide]ethyl]- D.24.2 〇y 0 Chemical name: decylamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR) -hexahydro-3\5,5-trimethylidene*4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino] Amino]-2-[(4-sulfolaminophenyl)carbonylguanidinyl]ethyl]-analytical data: 'H NMR (DMSO-d6): 8.8 (1H, d); 8.55 (1H, t 8.35 (1H, d); 7.92 (2H, d); 7.88 (2H, d); 7.45 (2H, s); 4.6 (1H, t); 3.5 (2H, m); 2.2 (1H, m) 2.1 (2H, m); 2.05 (1H, m); 1.8 (2H, m); 1.6 (2H, m); 1.45 (3H, m); 1.25 (24H, m); 1.65 (4H, m), 0.80 (12H, m). Melting point 178°-1810C. D.24.3 Chemical name: 4-butylbenzamine, N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl-]-3-A Benzyl]amino]carbonyl]-2-(acetamido)ethyl]- D.24.4 Chemical Name: 4-butylbenzamide , N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S,7aR)-hexa-argon-3a, 5,5-tridecyl-4,6-methylalkyl- 1,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-(decane continual amino)ethyl]- 95014 -193 - 1345465

D.24.5 Chemical name: 4-butylbenzamide, Ν-[( 1S)-1-[[[(1R)-1 -[(3 aS,aS,6S,7aR)-hexa-argon-3a, 5,5-trimethyl&gt;4,6-methylalkyl-1,3,2- benzodioxopropan-2-yl-]-3-methylbutyl]amino]carbonyl]-2 -(propylureido)ethyl]· Analytical data: 'H NMR (DMSO-d6): 8.9 (1H, s); 8.6 (1H, d); 7.8 (2H, d); 7.25 (2H, d) ; 6.2 (1H, t); 6.05 (1H, t); 4.5 (1H, t); 4.05 (1H, t); 3.4 (1H, m); 2.9 (1H, m); 2.65 (2H, t); 2.2 (1H, m); 2.0 (1H, m); 1.8 (2H, m); 1.65 (4H, m); 1.2 (15H, m), 0.80 (16H, m). D.24.6 I οΛ (Χ Χ Name: 4-butylbenzamide, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,aS,6S,7aR)-hexahydro-3〇trimethyl]&gt; 4,6-Methyl-1,3,2- benzodioxanthene-2-yl-]-3-methylbutyl]amino]carbonyl]-2-[(4-mercapto) )carbonylamino]ethyl]- D.24.7 Chemical name: 4-butyl carbamide, N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-methylbutyl] Amino]carbonyl]-2-[(l,l-dimethylethoxycarbonyl)amino]ethyl]-analytical data: 'H NMR (DMSO-d6): 8.8 (1H, s); 8.25 (1H, d); 7.8 (2H, d); 7.3 (2H, d); 6.9 (1H, t); 4.65 (1H, t); (1H, d); 2.65 (2H, m); 2.2 (1H, m); 2.1 (1H, m); 1.8 (2H, m); 1.6 (4H, m); 1.3 (20H, m); 0.80 (12H,m). D.24.8 I to palmity.~) Chemical name: 4-butylbenzamine, N-[(lS)-l-[[[(lR)-l-[(3aS ,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-anthracene Butyl]amino]carbonyl]-2-[(.塞 phen-2-ylcarbonyl)amino]ethyl]- D.24.9 Λ... 〇Λο Chemical name: guanamine, N-[(lS)-l-[[[(lR)-l-[(3aS ,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-anthracene Butyl]amino]carbonyl]-2-[(.cephen-2-ylcarbonyl)amino]ethyl]- D.24.10 I-to-zero chemical name: 4-butylbenzamide, N -[( 1S)-1 -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-tridecyl-4,6-methylalkyl-1, 3,2-benzoxa-oxaboron-2-yl]-3-methylbutyl]amino]carbonyl]-2-(hexanolamino)ethyl]-

95014 •194· 1345465

D.24.11 Chemical name: 4-butylbenzene f-amine, N-[(lS)-l-[[[(lR)-l-[3aS, aS,6S,7aR]-hexa-argon-3a,5, 5-trimethyl-4,6-methylalkyl 1,3,2-benzodioxan-2-yl-]-3-methylbutyl]amino]carbonyl]-2-(cyclopropane Carbonylamino)ethyl]- D.24.12 I to palmity HH^, 0 6 Chemical name: 4-butylphthalide, 乂[(13)-1-[[[(111)-1-[ (333,43,63,7 also)-hexahydro-3〇trimethyl 4,6-methylalkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl Amino]carbonyl]-2-(3-styl-ureido)ethyl]- D.24.13 o~° Chemical name: 4-butylbenzamide, N-[(lS)-l- [[[(lR)-l-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzo[ Oxyboron-2-yl]·3-methylbutyl]amino]carbonyl]-2-[(N-methyl-2-pyrrolylcarbonylguanamine)ethyl]- D.24.14 ^V; 1 HN 〇, chemical name: 4-butylbenzamine, N-[(lS), l-[[[(lR)-l-[3aS, aS,6S,7aR]-hexa-argon-3a,5 ,5-trimethyl-4,6-nonylalkyl 1,3,2-benzodioxan-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-[ (3,4-dimethoxyphenyl)ethylammonium]ethyl]- D.24.15 I to palmity 〇Λο Chemical name: 4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexa-argon-3a,5,5- Trimethyl-4,6-T-alkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-(nicotinone) Amino)ethyl]- D.24,16 Chemical name: 4-butylbenzamine, N-[(lS)-l-[[[(lR)-l-[3aS, aS,6S, 7aR]-hexahydro-3a,5,5-trimercapto-4,6-nonylalkyl 1,3,2-benzodioxoborer-2-yl-]-3-mercaptobutyl] Amino]carbonyl]-2-[(4-benzylamino)benzimidino]ethyl]-

95014 •195· 1345465

D.24.17 Chemical name: 4-butylbenzamide, N-[( 1S)-1 -[[[(1R)- l-[3aS, aS,6S,7aR]-hexa-argon-3a,5, 5-trimethylphosphonium 6-methylalkyl 1,3,2-benzodioxanthene-2-yl-]-3-methylbutyl]amino]]yl]-2-[(1Η-tetra Imidazole-5-yl-acetamido)ethyl)-analytical data: *H NMR (DMSO-d6): 9 (1H, s); 8.55 (1H, d); 8.5 (1H, br); 2H, d); 7.3 (2H, t); 4.6 (1H, t); 3.4 (2H, m); 2.65 (2H, m); 2.2 (1H, m); 2.1 (1H, m); 1.8 (2H , m); 1.6 (4H, m); 1.3 (14H, m); 0.9-0.80 (12H, m). D.24.18 I to palmity.七-3 Chemical name: 4-butyl benzylamine, N-[( 1S)-1 -[[[(1R)- l-[(3aS,aS,6S,7aR)-hexahydro-3a,5 ,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl-]-3-methylbutyl]amino]carbonyl]-2-[( 4-methylsulfonylphenyl)carbonylamino]ethyl]- D.24.19 1 iittt. :Heart chemical name: guanamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl *4,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-(in the base ketoamino group) Ethyl]- D.24.20 I Pair of palmity ^Vxy^ °X~&gt; n,h Chemical name: 4-butylbenzamide, N-[( 1S)-1 -[[[(1R)- 1 -[(3aS,aS,6S,7aR)-AiL -3a,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl- ]-3-mercaptobutyl]amino]carbonyl]-2-[(4-(2H,-tetrazol-5-yl)phenyl)alkylamino]ethyl]- D.24.21 03⁄4 Chemical name: 4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS,aS,6S,7aR)-hexahydro-3a,5,5 -tridecyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-[( L-isoxazol-5-yl)-carbonylamino]ethyl]-

95014 196- 1345465

D.24.22 For palm flies _ ό II Ν Chemical name: 4-butyl benzylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3 aS,aS,6S, 7aR)-hexahydro-3&amp;,5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxan-2-yl-]-3-methylbutyl] Amino]benzyl]-2-[(4-carbylphenyl)nonindolyl]ethyl]-analytical data: lH NMR (DMSO-d6): 8.6 (1H, d); 8.3 (1H, d); 8.1 (1H, t); 8.02 (2H, d); 7.98 (2H, d); 7.8 (2H, d); 7,25 (2H, d); 4.6 (1H, t); 4.15 (lH , d); 3.2 (2H, m); 2.2 (1H, m); 2.1 (1H, m); 1.8 (2H, m); 1.6 (4H, m); 1.3 (12H, m); 0.9-0.80 ( 12H, m). D.24.23 ^^ΟγΚν^Ν^0ν/ 11 : Η 1 /~~7\ / ° sh °'uX . Gas '&gt; Ν' Chemical name: 4-butylbenzamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,aS,6S,7aR)-hexahydro- 3a,5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxanol-2-yl-]-3-mercaptobutyl]amino]carbonyl]- 2-[(l-Methyl-1H-imidazole&gt;4-)sulfonylamino]ethyl]- D.24.24 orrzl^0 t) Chemical name: 4-butylbenzamine, N-[ ( 1S)-1 -[[[(1R)-1 -[(3aS,aS,6S,7aR)-hexahydro-3a,5,5-trimethyl*4,6-methylalkyl-1,3, 2-benzodioxol-indole-2-yl-]-3-methylbutyl]amino]carbonyl]-2-[(2-p-septene)-moleylamino]ethyl]-D. 24.25 Product; A Chemical name: 4-butylbenzamide, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,aS,6S,7aR)-hexahydro-3a, 5,5-trimethyl-4,6-methylxyl-1,3,2-benzodioxan-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2 -(6-morpholine-4-nicotinoindolyl)ethyl]- D.24.26 /ηνΙ^χ oAtv〇 Chemical name: 4-butylbenzamide, N-[(lS)- L-[[[(lR)-l-[(3aS, aS,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzo) Dioxonium 11 -2-yl-]-3-methylbutyl]amino]carbonyl]-2-(2-pyridyl-4-pyrazolecarbonyl) Yl) ethyl] -

95014 197- 1345465

D.24.27 n-&lt;-rt JO&quot; Chemical name: 4-butylbenzamide, Ν·[( 1S)-1 -[[[(1R)-1 -[(333,63,7 )-Hexahydro-30,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl-]-3-methylbutyl]amino] <RTIgt; </RTI> </RTI> <RTIgt; 8.4 (2H, d); 7.8 (2H, d); 7.3 (2H, d); 7.25 (2H, d); 4.6 (1H, t); 4.2 (lH, d); 2.65 (3H, m); 2.2 (4H, m); 2.0 (1H, m); 1.8 (2H, m); 1.6 (4H, m); 1.3 (12H, m); 0.9-0.80 (12H, m). D.24.28 I Tt is called chemical name: 4-phenoxybenzamide, N-[( 1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a , 5,5-trimethyl*4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino]carbonyl]-2- [(芊 oxycarbonyl decylamine) ethyl]- D.24.29 1 Pairs of retinoic c^〇Fja° Chemical name: 4-phenyloxybenzamide, N-[(lS)-l-[[[ lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine- 2-yl]_3_methylbutyl]amino]]yl]-2-[4-fluoro-benzenesulfonate ]ethyl]- D.24.30 to palmity 1 NN, chemical name: 4-phenoxybenzamine, N-[(lS)-l-[[[(lR)-l-[(3aS,aS ,6S,7aR)-Hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- benzodioxan 1-2-yl-]-3-methyl Butyl]amino]carbonyl]-2-[(2,5-dimethyl-2H-pyrazole)carbonylamino]ethyl]- D.24.31 σ ^ Chemical name: 4-phenyloxybenzoquinone Amine, N-[( 1S)-1 -[[[(1R)-1 -[(338,43,63,7〇11)-hexahydro-3a,5,5-trimethyl-4,6- Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-(4-phenylphenylguanidino)ethyl ]- D.24.32 Chemical name: 4-butylbenzamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a ,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanol-2-yl]-3-mercaptobutyl]amino]carbonyl]_2_(4 - stupid benzoguanamine)ethyl]-

95014 -198- 1345465

D.24.33 Chemical name: 4-butyl carbamide, Ν·[( 1 S)-l -[[[(1R)-1 -[(3aS,4S,6S,7aR)-hexahydro-3a, 5,5-trimethyl*4,6-methylalkyl-1,3,2- benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]-2-( 3-phenylpropynylamino)ethyl]- D.24.34 Chemical name: 4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[( 3aS, aS, 6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-indole-2-yl-]-3 -Methylbutyl]amino]]yl]-2-(2-carbyl-3-indolylamino)ethyl]- D.24.35 ό Chemical name: 4-butylbenzamide, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,aS,6S,7aR)-hexahydro-3a,5,5-trimethyl 4,6-nonanyl-1 ,3,2-benzodioxanthene-2-yl-]-3-methylbutyl]amino]carbonyl]-2-(D-pyramide fluorenylamino)ethyl]-analyte Data: 'H NMR (DMSO-d6): 9.85 (1H, d); 8.3 (1H, d); 8.1 (1H, t); 7.8 (3H, m); 7.3 (2H, d); 4.7 (1H, t); 4.15 (1H, d); 3.9 (1H, m); 3.5 (2H, m); 2.65 (3H, m); 2.2 (2H, m); 2.0 (3H, m); 1.8 (3H, m ); 1.6 (4H, m); 1.3 (11H, m); 0.9-0.80 (12H, m). D.24.36 0 Chemical name: 4-butyl Benzylamine, N-[( 1S)-1 -[[[(1R)-1 -[(3aS,aS,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6 -decyl-1,3,2-benzodioxan-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-(1-a sylvanic S&amp; Hexahydrogen, N-[(1S)-1 -[[[(1(R))) -1 -[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2- benzodioxan-2- 3-methylbutyl]amino]carbonyl]-2-(3-phenyl-yl)ethyl]- 95014 199- 1345465 D.24.38 Chemical name: decylamine, N-[( 1S )-1 -[[[(1R)- l-[(3aS,aS,6S,7aR)-hexa-argon-3a,5,5-trimethyl A6-methylalkyl-1,3,2-stuppy Oxyboron group-2-yl-]-3-methylbutyl]amino]carbonyl]-2-(acetamido)ethyl]- Example D.25 Synthesis of other compounds According to the procedure of Example D17, The following compounds can be prepared starting from the compounds of Examples D.16.8 and D.16.9.

Example No. Structure Chemical Name and Analytical Data D.25.1 For Zero Property | — Chemical Name: Indoleamine, Ν-[( 1 S)-l-[[[(1R)-1 -[(3aS,aS,6S, 7aR)-hexahydro-3a,5,5-trimethyl&gt;4,6-nonylalkyl-1,3,2-benzodioxoborer-2-yl-]-3-mercaptobutyl Amino]]amino]-hydrochloride CM Analytical data: lHNMR (DMSO-d6): 8.4 (1H, d); 8.25 (1H, d); 8.15 (3H, Br s); 4.58 (1H, m); 4.2 (1H, m); 3.1 (1H, m); 2,9 (1H, m); 2.8 (1H, m); 2.4 (4H, m); 1.9 ( 1H, m); 1.85 (1H, m); 1.65 (2H, m); 1.50 (2H, m); 1.35 (1H, m); 0.85 (12H, m). D.25.2 1 Pair of palm chemical name: 4-phenyloxybenzamide, N-[( 1S)-1 -[[[(1R)小[(3&amp;3,43,63,7311)-hexahydro-3a,5,5-triterpene Methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-(amino)ethyl]-hydrochloride &gt; Analytical data: 'H NMR (DMSO-d6): 8.72 (1H, d); 8.54 (1H, d); 7.45 (2H, t); 7.22 (1H, t); 7.05 (4H, m); (1H, m); 4.21 (1H, d); 3.25 (1H, m); 3.15 (1H, m); 2.8 (1H, m); 2.25 (1H, m); 2.05 (1H, m); 1H, t); 1.82 (1H, m) 1.65 (2H, m); 1.28 (3H, s); 1.22 (3H, s); 0.85 (9H, m). Example D.26 4-butylbenzamide, N-[(lR)-l_ [[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine Boron-2-yl]-3-methylbutyl]amine 95014 •200- 1345465 base] base 1-2·[(4-methylbenzhydryl)aminopurine ethyl]

According to the same procedure used to prepare the compound of Example D.17, the intermediate 孪 butyl benzoylamine, N-[(irH-[[[(i(R)) is a small [[3] ,5_Trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-(amine The base ethyl)-hydrochloride salt was prepared using D_aspartate as a starting material. Then, the intermediate described later was reacted with 4-methylbenzoic acid according to the procedure described in Example D.18. The title compound was obtained. ^NMRCMeOD-d^: 8.88 (2H, d); 8.45 (2H, m); 7.8 (2H, d); 7.7 (2H, d); 7.35 (2H, m); 7.25 (2H, d) ; 4.75 (1H, m) ; 4.1 (1H, d) ; 3.8 (1H, m); 3.65 (2H, m); 2.65 (3H, m); 2.2 (1H, m) ; 2.1 (lH, m ); 1.8(2H,m); 1.6 (4H,m); 1.3-1.1 (2H,m); 0.9-0.80 (14H, m). Example El dihydroxyborane, [(lR)-H[(2S) )-5-[[imino(indolyl)methyl]amino]-2-[(2-chalycolyl)amino H-fluorenylpentyl]amino]-3-methyl Butyl]-puppet 1345465 Example D.1.1 of indole-2-carboxyguanamine, N-[(lS)-l-[[[(lR)-i_[(3aS,4S,6S,7aR)- Hexahydro-3a,5,5- Methyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]_3_methylbutyl]-amino]yl]-4-[[imino] Exactly amino) mercapto]amino]butyl]-(564 mg '0.90 mmol), 2-methylpropyldihydroxyborane (222 mg ' 2.19 mmol) and 4N hydrogenated hydrogen A mixture of oxyluline solution (225 μl) in a mixture of methanol and hexanes 40: 60 (10 ml) was stirred at room temperature for 4 hr. hexane (4 ml) was added and the mixture was stirred for a while, then The hexane layer was removed, fresh hexane (5 mL) and 2-methylpropyldihydroxyborane (100 mg, 0.99 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The layer was washed with hexane (2 x 5 mL). The residue obtained after concentration of the methanol phase was purified by chromatography on silica gel column, first with ethyl acetate' followed by 40:40:20 acetone: decyl alcohol: The mixture was dissolved in a mixture of ethyl acetate (250 mL) and methanol (6 mL). Concentrated. The residue was dried in vacuo <RTI ID=0.0></RTI> to <RTI ID=0.0>

Melting point 170-190 ° C lHNMR (DMSO-d6): 8.76 (1H, m); 8.51 (2H, br); 8.09-7.09 (5H, m); 7.88 (2H, br); 7.60 (2H, br); 4.67 (lH,m); 3.17 (2H,m); 2.58 (lH,m); 1.81 (2H,m); 1.56 (3H,m); 1.38-1.11 (4H, m) ; 0.83 (lH,m) 0.81 (1H} m) ; 0.74 (3H, d, J=6.4) ; 0.74 (3H, d, J=6.4). Elemental analysis calculated: C54.33% H6.43% N 17.28% B 2.22% Value C 54.87% H 6.64% N 17.00% B 2.12% Other compounds prepared essentially according to the above experimental procedure are reported in Tables 95014-202-1345465 El. Table E-l

Example No. Structure Chemical Name 舆 Analytical Data E.1.1 S χ0&quot; Chemical Name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino](nitroamino)] fluorenyl Amino]-2-[((2E)-3-ethoxycarbonyl-l-oxoprop-2-alkenyl)amino]-1-3⁄4ylpentyl]amino]-3-methylbutyl] ΝΗ Λ Λ 0 Analytical data: 1H-NMR (MeOH-d4): 7.07 (1H, d, J = 15.6 Hz); 6.74 (1H, d, J = 15.6 Hz); 4.64 (1H, dd, J= 6.3, 8.1); 4.25 (2H, q, J= 7.1); 2.75 (1H, t, J=7.4); 2.0-1.6 (5H, m); 1.34 (2H, m); 1.31 (3H, t, J =7.1); 0.92 (6H, d, J=6.6). E.1.2 I Pair of palmity \χ κ τ 〇-~0 Chemical name: Dihydroxyborane, [(1R)-1-[[(2S&gt; 5-[[imino(nitroamino)indolyl]amino]-2-[(2-pyroxycarbonyl)amino]-1-ketopentyl]amino]-3-methylbutyl Analytical data: lH-NMR (DMSO-d6): 9.18 (1H, br); 8.96 (1H, d, J = 8.2); 8.87 (1H, d, J = 2.4 Hz); 8.76 (2H, m) 8.51 (1H, br); 8.3-7.5 (2H, br); 4.63 (1H, m); 3.13 (2H, m); 2.53 (1H, m); 1.9-1.1 (7H, m); 0.73 (6H , d, J=6.6). E.1.3 1 pair of palmity 0, 014 \χ Chemical name: dihydroxyborane, [(lR)-l-[[(2S) )-5-[[imino(nitroamino)indolyl]amino]-2-[(4-butylbenzylidenyl)amino]-1-indolyl]amino]- 3-Methylbutyl] η ro' Analytical data: 1H-NMR (DMSO-d6): 8.68 (1H, d, J = 2.5 Hz); 8.51 (1H, br); 8.48 (1H, d, J = 7.8 Hz); 8.3-7.5 (2H, br); 7.80 (2H, d, J=8.1); 7.27 (2H, d, J=8.1 Hz); 4.59 (1H, m); 3.15 (2H, m); 2.61 (2H, t, J=7.7); 2.54 (1H, m); 1.9-1.1 (11H, m); 0.89 (3H, t, J=7.3); 0.77 (3H, t, J=6.8); (6H, d, J=6.6). E.1.4 I 対 palm chemical name: dihydroxyboron, [(lR)-l-[[(2S)-5-[[imino] mercaptoamine Methyl]amino]-2-[(2-indolyl)amino]-1-decylpentyl]amino]-3-methylbutyl], ν^Νη H into the analytical data: 1H-NMR (DMSO-d6): 8.77 (1H, br); 8.76 (1H, d, J = 8.0); 8.51 (1H, br); 8.50 (1H, s); 8.0 (4H, m); 7.5 (2H, br); 7.6 (2H, m); 4.67 (1H, m); 3.17 (2H, m); 2.57 (1H, m); 1.9-1.1 (7H, m); 0.73 (6H, d, J=6.6).

95014 203 - 1345465

Chemical name: Dihydroxyboron, [(lR)-l-[[(2S)-5-[[imino(indolyl)indolyl]amino]-2-[(3-(l, 3-Dihydro-1,3-dione-2H-iso-4-indol-2-yl)-1-ketopropylamino)-1-ketopentyl)amino)-3-methylbutyl Analytical data: lH-NMR (DMS0-d6): 8.59 (1H, br); 8.43 (1H, br); 8.27 (1H, d, J = 7.9 Hz); 7.82 (4H, m); 8.2-7.5 (2H, br); 4.31 (1H, m); 3.77 (2H, m); 3.08 (2H, m); 2.51 (3H, m); 1.7-1.1 (7H, m); 0.78 (6H, m). Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(indolyl))]amino]-2-[[2-(2- Methoxyethoxy)ethinyl]amino H-«ylpentyl]amino]-3-mercaptobutyl], HCl1 salt analytical data: lH-NMR (MeOH-d4): 4.65 (1H, Dd, J=6.1, 8.6 Hz); 4.04 (2H, s); 3.70 (2H, m); 3.60 (2H, t, J=4.04) 3.42 (3H, s); 3.30 (2H, t, J= 6.9 2.75 (1H, t, J=7.5); 2.0-1.6 (5H, m); 1.34 (2H, m); 0.92 (6H, d, J=6.6)._Chemical name: dihydroxyborane, [ (lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(2-butoxyethyl)amino]-1 - reticyl amyl]amino]-3-methylbutyl] Analytical data: lH- NMR (MeOH-d4): 4.65 (1H, dd, J = 6.1, 8.6 Hz); 3.98 (2H, s); 3.54 (2H, t, J = 6.6); 3.28 (2H, t, J = 6.9); 2.77 (1H, t, J=7.6); 2.0-1.3 (11H, m); 0.95 (3H, t, J=7.58); 0.92 (6H, d, J=6.6)._chemical name: dihydroxyborane ,[(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[[2-[2-(2-methoxy B) Oxy)ethoxy]ethinyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 4.66 (1H, dd , J=6.0, 8.8 Hz); 4.06 (2H, AB q, J=15.7); 3.7 (6H, m); 3.58 (2H, m); 3.37 (3H, s); 3.29 (2H, t, J= 6.9); 2.75 (1H, t, J=7.7); 2.0-1.6 (5H, m); 1.34 (2H, m); 0.92 (6H, d, J=6.6)._:_chemical name: dihydroxy boron院,[(1R)-1-[[(2S)·5·[[imino(desylamino)indolyl]amino]-2-[[2-(ethylamino)ethyl) Amino]-1-mentylpentyl]amino]-3-methylbutyl], HCl salt analysis data: 1H-NMR (MeOH-d4): 4.61 (1H, dd, J=5.7, 8.9 Hz) 3.86 (2H, s); 3.37 (3H, s); 3.30 (2H, t, J= 7.0); 2.75 (1H, t, J=7.7); 2.01 (3H, s); 2.0-1.6 (5H, m); 1.33 (2H, m); 0.92 (6H, d, J=6.6). 95014 204- 1345465

E.1.10 1 #掌性0 \\ 〇\ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amine) Alkyl]-2-[[4&gt;(methoxycarbonyl)butanyl]amino]-1-phenentylpentyl]amino]-3-methylbutyl] Analytical data: *H NMR (DMSOK16): 8.50 (1H , br); 8.44 (1H, d, J-5.6 Hz); 8.17 (1H, d, J=7.5); 7.92 (2H, br); 4.37 (1H, m); 3.58 (3H, s); 3.14 ( 2H, m); 2.57 (1H, m); 2.30 (2H, t, J=7.3); 2.19 (2H, t, J=7.5); 1.75 (2H, quintuple, J=7.3); 1.71 (lH , br); 1.64-1.39 (4H, br); 1.23 (2H, m); 0.86 (2H, m); 0.82 (3H, d, J = 6.4); 0.81 (3H, d, J = 6.4). .1.11 1 pair of palmity οα0γΛ4, NH 'Human HU o-^o Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino) Methyl]amino](indol-2-yloxy)ethenyl)amino H-ketopentyl]amino]-3-methylbutyl] Analytical data: lHNMR (DMSO-d6): 8.81 (1H, br); 8.51 (1H, br); 8.40 (1H, d, J = 7.5 Hz); 7.88 (2H, br); 7.83 (2H, m); 7.75 (1H, m); 7.44 (1H, m); 7.35 (1H, m); 7.26 (2H, m); 4.69 (2H, m); 4.51 (1H, m); 3.12 (2H, m); 2.60 (1H, m); 1.78 (1H, m ); 1.73-1.39 (3H, m); 1.39-U1 (3H, m); 0.80 (6H, m). E.1.12 | Chemical Name: Dihydroxyborane, [(lR)-l-[[( 2S)-5-[[imino(nitroamino)methyl]amino]-2-[(3-sulfeno-2-yl-propionyl)amino]-1-oneyl 0, H OH \x Η I· 〇 々〇 々〇 pentyl]amino]-3-methylbutyl] Analytical data: !H NMR (DMSO-d6): 8.65 (1H, br); 8.49 (1H, br) ; 8.20 (1H, d, J=8.2 Hz); 7.86 (2H, br); 7.27 (1H, dd, J=4.9, J=0.9); 6.91 (1H, dd, J=5.1, J=3.4); 6.84 (1H, m); 4.38 (1H, m); 3.11 (2H, m); 3.02 (2H, m); 2.56 (1H, m); 2.50 (2H, m); 1.69 (1H, m); -1.35 (4H, m); 1.27 (1H, m); 1.20 (1H, m); 0.82 (3H, d, J=6.4); 0.81 (3H, d, J=6.4). E.1.13 | Sex 9l hi? Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)] fluorenyl]]][2-[2- (2-Nitrophenyl)ethylidene]amino]-3-methylu 5 s ^ butyl]HC1 salt HC, Λτ 〇 is. Analytical data: lHNMR (DMSO-d6): 8.69 (1H, br); 8.51 (1H, br); 8.41 (1H, d, J = 7.9 Hz); 7.87 (2H, br); 7.40 (1H, m); 7.32 (1H, m); 7.26 (2H, m); 4.42 (1H, ra); 3.66 (2H, m); 3.14 (2H, m); 2.60 (1H, m); 1.73 (1H, m); 1.68 -1.40 (4H, m); 1.26 (2H, m); 0.83 (3H, d, J=6.4); 0.82 (3H, d, J=6.4).

95014 205 - 1345465

E.1.14 'Human H o-^o sputum chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino)methyl]] Amino]-2-[(l-keto-4-(1-butylhexafluoropyridine*4-yl)butyl)amino]-1-ketopentyl]amino]-3-methyl Butyl] Analytical data: lH NMR (DMS0-d6): 8.60 (1H, br); 8.50 (1H, br); 8.10 (1H, br); 8.00 (2H, br); 4.36 (1H, m); (2H, br); 2.86 (2H, br); 2.50 (1H, m); 2.27 (1H, br); 2.11 (2H, m); 1.76-1.34 (11H, m); 1.34-0.98 (11H, m 0.87 (3H, t, J=7.1 Hz), 0.82 (3H, d, J=6.4); 0.81 (3H, d, J=6.4). E.1.15 1 CNr^ Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(1-octanesulfonyl)amino]-1 -ketopentyl]amino]-3-methylbutyl], HCl salt - 〇-% Analytical data: [H NMR (DMS0-d6): 8.80 (1H, br); 8.50 (1H, br); 7.87 (2H, br); 7.52 (1H, d, J=8.6 Hz); 3.92 (1H, m); 3.15 (2H, m); 2.94 (2H, t, J=7.7); 2.62 (1H, m) 1.75-1.43 (7H, m); 1.38-L31 (4H, m); 1.24 (8H, s); 0.92-0.75 (9H, m). E.1.16 o Chemical name: dihydroxyborane, [( lR)-l-[[(2 S)-3-[(4-methyl alum) (2) into γ〇Η. , NH °^α Amino]-2-[(decylamino)]-l-ketopropyl]amino]-3-methylbutyl] Analytical data: lH NMR (CD30D): 7.73 ( 2H, d, J=8.0 Hz); 7.28 (2H, d, J=8.0); 4.78 (1H, t, J= 6.5); 3.82 (1H, dd, J=6.9, 13.5); 3.61 (1H, dd , J=6.9, 13.5); 2.74 (1H, m); 2.39 (3H, s); 2.24 (2H, t, J=7.4); 1.6-1.15 (17H, m); 0.89 (6H, m); 0.80 (3H, d, J=6.5). E.1.17 1 Pair of Spherical HS f&quot; Chemical Name: Dihydroxyborax, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[ (Into the γ-methyl group)amino]-1-ketobutyl]amino]-3-mercaptobutyl] Analytical data: 'H NMR (DMSO-d6): 8.58 (1H, br); 7.70 (1H, d, J=8.6 Hz), 4.93 (1H, br); 4.31 (1H, dd, J= 4.0, 8.6); 3.96 (1H, m); 2.56 (1H, m); 2.18 (2H, m); 1.60 (1H, m); 1.49 (2H, m); 1.35-1.15 (14H, m); 1.03 (3H, d, J = 6.4); 0.83 (9H, m). E.1.18 1 Chemical name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[[10-(l,3-diketo-1,3-di-argon-iso) [啕哚-2-yl)-fluorenyl]amino]-1-ketobutyl]amino]-3-methylbutyl] Analytical data: 'H NMR (DMSO-d6): 8.55 (1H, Br); 7.84 (4H, m); 7.69 (1H, d, J=8.4 Hz), 4.94 (1H, d, J= 5.4); 4.30 (1H, dd, J= 4.0, 8.6); 3.95 (1H, m); 3.55 (2H, m); 2.55 (1H, m); 2.17 (2H, m); 1.65-1.35 (5H, m); 1.3-1.1 (12H, m); 1.02 (3H, d, J = 6.4); 0.83 (9H, m).

95014 • 206 · 1345465 Other compounds made according to the procedure described above for Example E.1 are reported in Table E-1A.

Table E-1A Example No. Structure Chemical name and analytical data E.1.19

Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[((RS)-10 -N-yl-2-cyclopentylindolyl)amino]-1-propylpentyl]amino]-3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 4.57 (1H, m); 3.29 (2H, m); 3.20 (2H, m); 2.76 (1H, t, J=7.5Hz); 2.43 (2H, t, J=7.1); 2.05 (1H, m); 2.0-1.1 (11H, m); 0.93 (6H, d, J-6.6)._

E.1.20 E.1.21 E.1.22

Palm

For palm chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(10- (l,3-Dihydro-1,3-dione-2H-iso&quot;5丨哚-2-yl)-1-ketoindolyl)-)amino]-1-ketopentyl] Amino]-3-methylbutyl] Analytical data: lH-NMR (MeOH-d4): 7.82 (4H, m); 4.52 (1H, m); 3.66 (2H, t, J = 7.3); 2H, m); 2.75 (1H, m); 2.24 (2H, t, J = 7.3 Hz); 1.9-1.2 (20H, m); 0.91 (6H, d, J=6.6)._ Chemical name: Dihydroxyl Borane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(2-cyclopentyl-10-(1) ,3-dihydro-1,3-diketo-2H-iso-purin-2-yl)-1-ketoindolyl)-)amino]-1-one-pentyl]amino]-3 - mercaptobutyl] Analytical data: 1H-NMR (MeOH-d4): 7.82 (4H, m); 4.57 (1H, m); 3.66 (2H, t, 3=73); 3.28 (2H, m); 2.75 (1H, m); 2.05 (1H, m); 2.0-1.1 (30H, m); 0.91 (6H, two d, J=6.6).__ Chemical name: dihydroxyborane, [(lR)-l -[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]_2-[[7-(methoxycarbonyl)heptyl]amino]-]- benzyl Amino]-3-methylbutyl] Analytical data: *H NMR (DMSO-d6): 8.60 (1H, d, J=8.4 Hz); 8.50 (1H, br); 8.06 (1H, d, J=7.9); 7.92 (2H, br); 4.36 (1H, m); 3.58 (3H, s); 3.13 (2H, m); 2.55 (1H, m); 2.28 (2H, t, J=7.5); 2.12 (2H, m); 1.69 (1H, m); 1.49 (7H, m); 1.24 (7H, m); 0.81 (6H, m)._ Other compounds prepared according to the procedure described above for Example El are reported in Table E-1B. 95014 -207-

1345465

Table E-IB Example No. Structure Chemical Name 舆 Analytical Data E.1.23 . Pair tt Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[( 4-phenylbutenyl)amino]-1-ketobutyl]amino]-3-methylbutyl] Analytical data: *H NMR (MeOH-d4): 7.29-7.13 (5H, m); 4.53 (1H, d, J=3.9); 4.21-4.14 (1H, m); 2.72 (1H, d, J=7.6); 2.65 (2H, t, J=7.6); 2.34 (2H, t, J=7.5 2.10-2.89 (2H, m); 1.70-1.59 (1H, m); 1.37-1.27 (2H, m); 1.21 (3H, d, J=6.4); 0.94-0.89 (6H, m). .1.24 «Plank 〇HO Human chemical name: Dihydroxyboron, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(undecylaminocarbonyl)amino]-] <RTI ID=0.0></RTI> 3.16 (2H, t, J=6.9); 2.74 (1H, t, J=7.6); 1.76-1.66 (1H, m); 1.58-1.46 (3H, m); 1.42-1.30 (26H, m); (3H, d, J=6.4). E.1.25 1 Pair of palmity I Ϊ Human B k Chemical name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2 -[(l-bromo-2-indenyl)amino]-1-ketobutyl]amino]-3-methylbutyl] Analytical data: lH NMR (MeOH-d4): 8.37 (1H, d, J = 8.52); 7.99 (2H, dd, J = 8.2, J = 13.0); 7.75-7.60 (2H, m); 4.82 (1H, d, J =4.19); 4.31-4.23 (1H, m); 2.81 (1H, dd, J=6.10, J=9.14); 1.77-1.64 (1H, m); 1.48-1.38 (2H, m); 1.36 (3H, d, J=6.38); 1.0-0.9 (6H, m). E.1.26 I-pair chemical name: dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy- 2-[(6-Bromo-2-indolyl)amino]-1-ketobutyl]amino]-3-indenylbutyl] Analytical data: *H NMR (MeOH-d4): 8.49 (1H, s); 8.17 (1H, d, J=1.4); 7.99 (1H, dd, J=1.65, J=8.66); 7.95 (2H, dd, J=2.70, J=8.62); 7.69 ( 1H, dd, J=1.90, J=8.77); 4.81 (1H, d, J=4.26); 4.38-4.30 (1H, m); 2.77 (1H, t, J=7.63); 1.71-1.59 (1H, m); 1.40-1.33 (2H, m); 1.31 (3H, d, J=6.39); 0.94-0.90 (6H, m).

Other compounds made according to the procedure described above for Example E.1 are reported in Table E-1C. Starting with examples D.8.19 and D.8.20 compounds. 208- 95014 1345465

Table E-1C

Example No. Structure Chemical Name 舆 Analytical Data E.1.27 Ο 011 Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S)-3·amine f keke·2-[(癸)) amine Analytical data: 1H-NMR (MeOH-d4): 4.76 (1H, t, J = 6.0); 2.58-2.52 (3H, m); 2.14-2.09 (2H, m); 1.64-1.52 (1H, m); 1.51-1.40 (2H, m); 1.30-1.12 (14H, m); 0.84-0.80 (9H, m). 1.28 ° V m Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-3-aminocarbamido-2-[4-butyl(benzylidene)amino]-1 -Kenylpropyl]amino]-3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 7.78 (2H, d, J = 8.24 Hz); 7.32 (2H, d, J = 8.22 Hz); 5.16 (1H, T, J=6.52); 2.91 (2H, dd, J=2.09 Hz, J=6.53 Hz); 2.78 (1H, t, J=7.59 Hz); 2.74-2.66 (2H, m 1.72-1.60 (3H, m); 1.44-1.30 (5H, m); 1.00-0.9 (9H, m). Other compounds prepared according to the procedure described above for Example E.1 are reported in Table E. In -1D, starting with the compounds of Examples D.2.9 and D.2.10. Table E-1D Example No. Structure Chemical Name and Analytical Data E.1.29 1 Palm-forming property 0 LH CH H , Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-2-[(癸醯))amino]-1-keto-5-ureido-pentyl]amino]-3·methylbutyl] Analytical data: 1H-NMR (DMSO-d6): 8.56 (1H, s); 8.07 (1H, d, J=8.03 Hz); 5.96 (1H, t, J=5.18 Hz); 5.38 (2H, s); 4.42-4,20 (1H, m); 3.01-2.85 (2H, m) 2.65-2.40 (1H, m); 2.25-2.00 (2H, m); 1.70-1.52 (2H, m); 1.52-1.40 (3H, m); 1.40-1.10 (16H, m); 0.90-0.75 ( 9H, m). 95014 209- 1345465 E.1.30 I nta Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-2-[(4-butylbenzylidene))) ]-1-keto-5-yl-pentyl]amino]-3-methylbutyl] T ! if ^ 0 S 0 08 H 1 Analytical data: 1H-NMR (MeOH-d4+DMSO-d6 ): 7.80 (2H, d, J=8.08 Hz); 7.28 (2H, d, J=8.16 Hz); 4.58 (1H, t, J=7.4l Hz); 3.00 (2H, t, J=6.72 Hz) ; 2.63 (2H, t, J = 7.64 Hz); 1.82-1.74 (2H, m); 1.68-1.52 (4H, m); 1.52-1.36 (2H, m); 1.34-1.26 (2H, m); (2H, t, J = 7.23 Hz); 0.89 (3H, t, J = 7.35 Hz); 0.84 (6H, d, J = 6.55 Hz). Example E.2

Dihydroxyborane, [(1R)-1-[[(2S)-S-[丨imino(fluorenylamino)methyl]amino]-2-[(fluorenyl)amine]- 1-ketopentyl]amino]-3-methylbutyl]-

癸醯 癸醯 实例 实例 实例 实例 实例 实例 ( ( [(18)-1-[[[(111)-1-[(3&amp;3,48,63&gt;11)-hexahydro-3a,5,5- Trimethyl-4,6-nonylalkyl-1,3,2-benzodioxolybdenyl-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imine Base (nitroamino)methyl]amino]butyl]-(77 mg, 0.12 mmol) dissolved in Et20 (1 mL), and carefully added HC1 37% (2 mL) at 0 °C ). The reaction mixture was allowed to warm to room temperature and was shaken overnight. The mixture was concentrated to dryness <RTI ID=0.0> The solvent was evaporated, and the title compound was crystalljjjjjjjjjjj NMR (DMSO+D2 Ο, 343 K): 4.20 (m, 1H); 3.13 (m, 2H); 3.05 (m} 1H); 2.10 (t, J=6.2 Hz, 2H); 1.69 (m, 1H) 1.53-1.40 (m, 4H); 1.39-1.20 (m, 95014 -210-1345465 14H); 0.84 (m, 9H). LC-MS 468.9, MH+. ESI POS ; AQA ; spray 4kV / demister : 20V / probe 250 C. Other compounds made essentially according to the experimental procedure above are reported in Table E-2. Table E-2 Example Structure No. E.2.1 Chemical Name and Analytical Data

E.2.2 E.2.3 eft'

Ο - on the palm of the hand

On the palm of the hand E.2.4

For the palm of the hand =Η OH NHo people Ε.2.5

Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(l-feeding 癸Amino]-1-ketopentyl]amino]-3-mercaptobutyl] Analytical data: MS: MH+ 468.9; 1H-NMR: (DMS0+D20, 343 K): 4.20 (m, 1H 3.13 (m, 2H); 3.05 (m, 1H); 2.10 (t, J=6.2 Hz, 2H); 1.69 (m, 1H); 1.53-1.40 (m, 4H); 1.39-1.20 (m, 14H); 0.84 (m, 9H)._ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino][]-amino)methyl]amino ]-2-[(octyl)amino]-1-benzylpentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 441.4_ Chemical name: Dihydroxyborane, [ (lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(l-phenylcyclopentylcarbonyl)amino]-1- Glycosyl]amino]-3-mercaptobutyl] Analytical data: MS: ΓΜ-181Η+487.0_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5- [[Iminoamino(nitroamino)methyl]amino]-2-[((2R)-2-phenylbutylidene)amino]-1-indolyl]amino]indole- Methyl butyl] Analytical data: MS: [M-181H+461.2_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[ (nitroamino)methyl]amino]-2-[[4-(l,l-dimethylethyl)cyclohexylcarbonyl]amino]-1-ketopentyl]amino]- 3-methylbutyl] Analytical data: MS: [M-181H+ 481.1 95014 -211 - 1345465

E.2.6 | Name of the chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-) [(trans-4-pentylcyclohexylcarbonyl)amino]-1-ketopentyl]amino]-3-mercaptobutyl], human r 0 is. Analytical data: MS: ΓΜ-181Η+ 495.4 E.2.7 Cr^yr \ jr Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino](nitroamine) Methyl]amino]-2-[(4-phenylbutylidene)amino]-1-phenylpentyl]amino]-3-methylbutyl] hr 〇-~0 Analytical data: MS: ΓΜ,181Η+461.4 E.2.8 O \ on \x Chemical name: Dihydroxylacane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]] Amino]-2-[(4-(l,l-dimethylethyl)phenylindolyl)amino]-1-ketopentyl]amino]-3-methylbutyl] ^NH Η 1. Analytical data: MS: [M-181H+ 475.1 E.2.9 I to palmity ° Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Nitroamino)methyl]amino]-2-[(indolyl)amino]-1-ketopentyl]amino]-3-methylbutyl] κ r 0_~0 Analytical data: MS: ΓΜ-181Η+ 455.1 E.2.10 1 pair  χ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino) Methyl]amino]-2-[(2-»塞吩甲酝)amino]-1-ketopentyl]amino]-3-methylbutyl] ^NH. 0』々0 Analysis Data: MS: ΓΜ-181Η+ 425.3 E.2.11 I-pair i Sex FO vw \ Γ Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[( 2,3-Difluorobenzhydryl)amino]-1-ketopentyl]amino]-3-methylbutyl] H 〇-&lt;'〇 Analytical data: MS: ΓΜ-18]Η + 455.0 E.2.12 j to palm tt 0 \x〇H Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino][]-amino] fluorenyl Amino]-2-[(taudecyl)amino H-ketopentyl]amino]-3-methylbutyl] H 1. Λ Analytical data: MS: "M-181H+497.2 E .2.13. Factory material 〇τ drinking chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino (nitroamino) fluorenyl] yl]]]-[[2 -(2-iodophenyl)ethinyl]amino]-1-ketopentyl]amino]-3-methylbutyl] H in analytical data: MS: "M-181H+558.9

95014 -212· 1345465

E.2.14 «The palm chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)f-yl]amino]-2-[ (cyclohexylcarbonyl)amino]-1-phenoxypentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+425.0_ Ε.2.15 E.2.16 E.2.17 E.2.18

• NH Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)f-yl]amino]-2-[(2-A) Benzobenzhydryl)amino]-1·ketopentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-181Η+ 433.0_ Chemical name: Dihydroxyborane, [(lR )-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[((2S)-2-phenylpropanyl)amino]-1 -ketopentyl]amino]-3-mercaptobutyl] Analytical data: MS: ΓΜ-181Η+447.3_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5 -[[imino(nitroamino)methyl]amino]-2-[(2,2-dimethylbutanyl)amino]-1-one-pentyl]amino]-3-yl Phenylbutyl] Analytical data: MS: "M-181H+413.3_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino)(nitroamino) Methyl]amino]-2-[(喳林-2-carbonyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+470.0 _

E.2.19

For the chemical name of the palm: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(壬- 2-Alkenyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: fM-181H+ 453.1_

E.2.20

I Pair tt M'v^nX^°h 1 H OH , NH I. Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(indolyl)methyl]amino]-2-[(2-indenyl) Hexylcarbonyl)amino]-1-propenylpentyl]amino]-3-methylbutyl] Analytical data: MS: fM-181H+ 439.4_ E.2.21

«The palm chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]-2-[(g- 2-Nynyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+425.4_ 95014 -213 - 1345465

E.2.22 E.2.23 E.2.24 E.2.25 E.2.26 Ε.2.27 Ε.2.28 Ε.2.29 95014

〇-~〇

«The palm of the hand

ΝΗ 掌 掌 人 Ο 零

OH, ΝΗ 掌 化学 chemical name: dihydroxy decane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-) [2-(3,4-Dimethylphenoxy)ethinyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+ 477.3_ Chemical name: Dihydroxybutter, [(1R)-1-[[(2S)-5·[[imino(des)amino]methyl]amino]-2-[((RS&gt; 4-ethyloctyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-181Η+469.5_ Chemical name: Dihydroxyboron k, [(lR )-l-[[(2S)-5-[[iminoamino(nitroamino)indolyl]amino]-2-[(hexahydro-2,5-nonylalkyl fluorene, Shuangwu -3a(lH)-Enteryl)amino]-1-propenylpentyl]amino]-3-methylbutyl] Analytical data:

^〇Η ΟΗ 0,0 ο Λ〇rrWc' \艾对掌性-214- MS: ΓΜ-181Η+463.5_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5 -[[imino(nitroamino)methyl]amino]-2-[(bicyclo[2.2.1]heptane-2-carbonyl)amino]-1-methylpentyl]amine ]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 437.4_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Amino group] fluorenyl]amino]-2-[(5-fluorenylhexyl)amino]-1-decylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+ 427.0_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]-2-[ (2,4-Dimercaptopyrazole-5-carbonyl)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+454.3_ Chemistry Name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(furan-3-carbonyl) Amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-18]H+ 408.8 Chemical name: Dihydroxyborane, [(lR)-l-[ [(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(2-cycloheptyl) ) H- group BenQ pentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 453.2 1345465

E.2.36

Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(l-fluorenyl) Propane carbonyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-181Η+397.2_ Chemical name: dihydroxyborane, [(lR)-l -[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(3-methylbutanyl)amino]-1-indolyl]amino group ]-3-Methylbutyl] Analytical data: MS: [M-181H+399.4_ Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Nitroamino)methyl]amino]-2-[(3-phenylpropenyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-181Η+447.3_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[ [(E)-3-(3-Mercaptophenyl)propenyl]amino]-1-decylpentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 459.5_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(2-gold) <RTIgt;Cryptane-1-ylethyl)amino]-1-ketoindolyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+491.2_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-) ((RS)-2-methylbutylidene)amino]-1-mentylpentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 398.9_ Chemical name: Dihydroxyborane ,[(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(2-phenylethenyl)amino]-1 -ketopentyl]amino]-3-methylbutyl] E.2.37

Analytical data: MS: [M-181H+ 433.4_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino) ]-2-[[2-(4-Methoxyphenyl)ethinyl]amino]-1-phenoxypentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+ 463.5 95014 -215- 1345465

E.2.38 Chemical name: Dihydroxy oxime, [(lR)-l-[[(2S)-5-[[imino(indolyl)methyl]amino]-2-[[2- (4-Hhenylphenyl)ethinyl]amino]-1-pyylpentyl]amino]-3-methylbutyl] η Λ 0 Analytical data: MS: ΓΜ-181Η+511.3 E.2.39 1 #掌性人B/OH 0 V. ^ \ X Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino)methyl]] Amino]-2-[((RS)4-indolyl octyl)amino]-1-benzylpentyl]amino]-3-methylbutyl] o*N^o Analytical data: MS: ΓΜ -181Η+455.0 E.2.40 Φνννφ F. 'X Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino]-2-[(2-gas 5-methylbenzyl hydrazino)amino]-1-mentylpentyl]amino]-3-mercaptobutyl] mr 〇-~〇 Analytical data: MS: ΓΜ-181Η+ 451.4 E.2.41 j on palmity \χ κ T o-~o Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amine) Alkyl]-2-[[2-(bicyclo[2.2.1]heptan-2-yl)ethenyl]amino]-1-one-pentyl]amino]-3-methylbutyl] Data: MS: ΓΜ-181Η+ 451.0 E.2.42 I Pair of palmity \ f Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamine) Methyl]amino]-2-[(4-phenoxybutylidene)amino]-1-propenylpentyl]amino]-3-mercaptobutyl], human ^ Analytical data: MS: ΓΜ-181Η+ 477.4 E.2.43 | For zero Oyy \χ N^^NH HI* 〇~〇 Chemical name: Dihydroxy boron good [(lR)-l-[[(2S)-5-[[imine (nitroamino)methyl]amino]-2-[(2-indolylcarbonyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: [M-181H+419.9 E.2.44 I to palm tt O^v^^JyOH a \jf, human r o'N^o Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino) ]-2-[(3-»Bipyridylcarbonyl)amino]-1-propenylpentyl]amino]-3-mercaptobutyl] Analytical data: MS: ΓΜ-181Η+420.3 E.2.45 |掌 ft V. ^ 'Human chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)] fluorenyl]amino]-2 -[(tridecyl)amino]-1-ketopentyl]amino]-3-mercaptobutyl] H |. o~M^o Analytical data: MS: ΓΜ-181Η+511.6 95014 • 216· 1345465

E.2.46

E.2.50

E.2.51

E.2.52

Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(8-phenyloctyl) Amino]-1-pyridylpentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+517.3_ Chemical name: Dihydroxyborane, [(lR)-l-[ [(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[4-(4-methanesulfonylphenyl)&gt;4-retinyl]amino group ]-1-Benylpentyl]amino]-3-mercaptobutyl] Analytical data: MS: ΓΜ-181Η+ 553.3_ Chemical name: Dihydroxyboron, [(lR)-l-[[(2S) -5-[[imino(nitroamino)methyl]amino]-2-[[3-(indol-2-ylthio)-propenyl]amino]-1-ketopentyl Amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 529.3_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[ Amino (nitroamino)methyl]amino]-2-[[2-[(phenylmethyl)thio]ethenyl]amino H-ketopentyl]amino]-3- Methyl butyl] Analytical data: MS: ΓΜ-181Η+479.5_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](decylamino) Methyl]amino]-2-[(3-methylthiopropionyl)amino]-1-ketopentyl]amine ]-3-methylbutyl] Analytical data: MS: [M-181H+416.9_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Nitroamino) fluorenyl]amino]-2-[((2S)-l-ethinyltetrahydropyrrole-2-carbonyl)amino]-1-ketopentyl]amino]-3- Methyl butyl] Analytical data: MS: ΓΜ-181Η+454.1_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino) Methyl]amino]-2-[[trans-3-(2-bromophenyl)propenyl]amino]-1-mentylpentyl]amino], 3-methylbutyl] E. 2.53

Analytical data: MS: ΓΜ-181Η+ 523.0_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)] fluorenyl]amino group ]-2-[[2-(tetrazol-1-yl)ethenyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M- 181H+ 425.0 95014 -217- 1345465

E.2.54

Ο '0 «The chemical name of the palm: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino[]-amino)methyl]amino]-2-[ [2*(pyrimidin-2-ylthio)ethinyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Ε.2.55 Ε.2.56 Ε.2.57 Ε.2.58 Ε.2.59 E.2.60 95014

〇-

E.2.61

-218-

Analytical Data: MS; ΓΜ-18ΊΗ+ 467.0_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino) ]-2-[[2&lt;4-Ethyloxy)ethylidene]amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: HVI-181H +476.9_ Chemical name: Dihydroxyborane, [(1R)-1-[[(2S&gt;5-[[iminoamino(nitroamino)methyl]amino]-2-[[2-( 2,5-Dimethylphenyl)acetate]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 461.4_ Chemical name: II Hydroxyborane, [(lR)-l-[[(2S)-5-[[imino(indolyl)methyl]amino]-2-[(8-keto-8-phenyl) Octyl)amino]-1-propenyl]amino]-3-methylbutyl] Analytical data: MS: fM-18]H+531.0_ Chemical name: Dihydroxyborane, [(lR)- L-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[2-(2-chalcylthio)ethinyl]amino]- 1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-181Η+515.6_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)- 5-[[imino(nitroamino)indolyl]amino]-2-[[(RS)-2-cyclopentylhexanyl) Amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-18ΊΗ+481.1 Chemical name: Dihydroxyborane, [(1R)-l-[[ (2S)-5-[[imino(nitroamino)methyl]amino]-2-[[3-(4-mercaptophenyl)propenyl]amino]-1-keto Amyl]amino]-3-mercaptobutyl] Analytical data: MS: [M-181H+459.0_ Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-5-[ [Iminoamino(nitroamino)methyl]amino]-2-[[4-(4-methoxyphenyl)-butanyl]amino]-1-ketopentyl]amino]-3 - mercaptobutyl] Analytical data: MS: [Μ-18ΊΗ+491.6 1345465

E.2.62 E.2.63 E.2.64 E.2.65 E.2.66 E.2.67 E.2.68 E.2.69 95014

For the palm of the 〇-々〇 chemical name: dihydroxyboran, [(lR)-l-[[(2S)-5-[[imino]] (2-嚷-phen-3-yl-ephthyl)amino]-1-phenoxypentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+438.9_ for zero

OH

JjH

NH h 〇 : M ruj OH , ljlH 〇-&lt;〇

Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)f-yl]amino]-2-[[2-(dimethyl) Amino)Ethylamino]-1-ylidylpentyl]amino]_3-methylbutyl] Analytical data: MS: [M-181H+ 400.2_ Chemical name: Dihydroxyboron, [(lR )-l-[[(2S)-5-[[imino(decylamino)methyl]amino]-2-[[5-idyl-5-(喽 -3--3-yl)pentyl) Amidino]amino]-1-decylpentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-181Η+494.9_ Chemical name: Dihydroxyborane, [(lR)-l -[[(2S)-5-[[imino(nitroamino)f-yl]amino]-2-[(ethyl)amino]-1-oneylpentyl]amino]- 3-Methylbutyl] Analytical data: MS: ΓΜ-181Η+ 357.2_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] mercaptoamine Methyl]amino]-2-[(2-ethylthioethenyl)amino]-1-propenylpentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+417.4_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-) [(10-Hydroxyfluorenyl)amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: ΓΜ-2 Η201Η+ 467.0_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(2 - thiol ethyl keto)amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: [M-181H+ 402.9_ Chemical name: dihydroxyborane, [ (lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[((pyridin-2-sulfonyl)) B&amp; Amino]-1-ketopentyl]amino]-3-decylbutyl] Analytical data: MS: [M-181H+ 503.1

-219- 1345465

〇-~. Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[3-(benzenesulfonate) Base group) propyl sulfhydryl]amino]-lW pentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+510.9_ Chemical name: E.2.74

Dihydroxyboron, [(lR)-l-[[(2S)-5-[[imino(indolyl)methyl]amino]-2-[[(RS)-tetrahydrofuran- 3-carbonyl]amino]-1-ylpentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+413.2_ Chemical name: Dihydroxyborane, [(lR)- L-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(indol-1-sulfonyl)amino]-1-ketopentyl) Amino]-3-mercaptobutyl]- Analytical data: MS: ΓΜ-181Η+505.23_ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[亚Amino (nitroamino)methyl]amino]-2-[(indol-2-sulfonyl)amino]-1-ketopentyl]amino]-3-methylbutyl]- Analytical data: MS: [M481H+ 505.49_ Chemical name: Dihydroxyborane, [(1R)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]]- 2-[(Benzenesulfonyl)amino]-1-phenylpentyl]amino]-3-fylbutyl]- Analytical Data: MS: [M-181H+455.37 Based on the above Example E.2 Other compounds made by the procedure are reported in Table E-2A.

Table E-2A Example No. Structure Chemical Name and Analytical Data E.2.75 | For palm chemical name: SH § f&quot; Dihydroxyboron, [(lR)-l-[[(2S)-5-[[imine (nitroamino) fluorenyl]amino]-2-[[6-(ethylindolyl)hexyl]amino]-1-yl H 0 , OH \χ pentyl]amino] -3-methylbutyl] Η 1. - Other public analysis data: 0 v〇MS: "M-181H+470, 2 95014 220- 1345465

E.2.76 | Finance tt ο* nine. Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]][[(RS)-2 -(4-Phenylphenyl)propanyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical Data: MS: [M-181H+481.1 E.2.77 1 « Palm ft \χ〇Η H 1· Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-] 2-[[2-(4-Alkyloxy)ethanoyl]amino]-1-ketopentyl]amino]-3-methylbutyl] Analytical data: MS: ΓΜ-181Η+ 524.1 E.2.78 I-to-palmity&quot;ΧΧγtherapy々χ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino]alkylamino) Amino]-2-[[3-(4-ethylphenyl)propanyl]amino]-1-propenylpentyl]amino]-3-methylbutyl] S human r analysis Data: MS: ΓΜ-181Η+ 475.2 E.2.79 I-pair XYSM/r Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitro Amino)methyl]amino]-2-[3-[4-(heptyloxy)phenyl]-ureido]-1-mentylpentyl]amino]-3-methylbutyl] oxime Data: MS; ΓΜ-181Η+ 54S.3 E.2.80 Chemical name: Dihydroxyboron ,[(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(5-ketohexyl)amino]-] 1-ketopentyl]amino]-3-methylbutyl], -n/, *NH H 4 0* Analytical data: MS: [M-18]H+ 427.2 E.2.81 I For palmity, NH H 1. Eight chemical names: dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[ (2RS)-l-[(l,l-didecylethoxy)carbonyl]hexahydropyridine-2-carbonyl]amino]-1-ketopentyl]amino]-3-decylbutyl Analytical data: MS: [M-18]H+ 526.2 Example E.3 Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(4-butylbenzene) Mercapto)amino]-1-ketobutyl]amino 1-3-methylbutyl] 221 - 95014

1345465 4-butylbenzamide of Example D.3.179, N-[(1S,2R)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro) 3a,5,5-trimethyl _4 6-methyl benzodioxon 2·yl]-3-methylbutyl]amino]-carbonyl]-2.hydroxypropyl]-( 1.38 g, 2.63 mmol, '2_mercaptopropyldihydroxyborane (75 g, 7 37 mmol) and 2 n aqueous hydrochloric acid (2 mL) in methanol (2 mL) and hexane (2 〇 ml) The mixture in the heterogeneous mixture was stirred at room temperature for 16 hours. The mixture was diluted with methanol (2 ml) and agar (20 ml), and then the courtyard layer was removed. Ethyl acetate (50 ml) was added to the sterol layer and then concentrated. The residue was dissolved in ethyl acetate and the mixture was concentrated. This step was repeated (2_3 times) until an amorphous white solid was obtained. Then, a solid was prepared by B_(1〇_15 ml), and the supernatant was removed by decantation. Repeat this step 4 times. After trituration with additional B &amp; (15 mL), a white solid was collected by filtration and dried under vacuum and room temperature (0.724 g, 70% yield). Xin 1H NMR (MeOH-d4): 7.83 (2H, d, J = 8.2); 7.34 (2H, d, J = 8.2); 4.77 (1H, d, J = 6.4), 4.36-4.28 (1H, m) 2.77 (1H, t, J=7.6); 2.71 (2H, t, J=7.6); 1.72- 1.58(3H,m); 1.46-1.32 (4H,m); 1.29 (3H,d,J=6.4 ; 0.97 (3h, U=7.34); 0.94 (6H, dd, J=U, 6.6) Other compounds prepared according to the procedure described above for Example E.3 are reported in Table E-3. 95014 • 222· 1345465 Table E-3

Example No. Structure Chemical Name and Analytical Data E.3.1. Palmity °HO Human H &amp; Chemical Name: Dihydroxydecane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[ (2-Teylmethylamino)amino]cyanobutyl]amino]-3-methylbutyl] Analytical data: 'HNMR (MeOH-d4): 8.51 (1H, s); 8.10-7.95 ( 4H, m); 7.66-7.58 (1H, m); 4.84 (1H, d, J=4.1); 4.42-4.33 (1H, m); 2.77 (1H, t, J=7.6); 1.75-1.62 (1H , m); 1.41-1.36 (2H, m); 1.34 (3H, d, J=6.4); 0.94 (6H, d, J=6.5). E.3.2 〇Η〇人Η °Η Chemical name: Dihydroxyl Decane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(p-tolyloxyethylamine)-1-ketobutyl)amino)-3-yl Analytical data: 'H NMR (MeOH-d4): 7.14 (2H, d, J = 8.5); 6.92 (2H, d, J = 8.6); 4.63-4.59 (3H, m); 4.31-4.24 (1H, m); 2.75 (1H, t, J=7.5); 1.72-1.60 (1H, m); 1.38-1.33 (2H, m); 1.31 (3H, s); 1.17 (3H, d, J= 6.4); 0.95-0.92 (6H, m). E.3.3 Η. ----------^^^γΝΝ^ΑΝΑΒ-ί3Η 〇HO-^S,fc Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3- Hydroxy-2-[(tridecyl)amino]-1-propenylbutyl]amino]-3-methylbutyl] Analytical data: Melting point 97-116 ° C. 4 NMR (MeOH-d4) : 4.55 (1H, d, J=3.9); 4.23-4.16 (1H, m); 2.73 (1H, t, J=7.6); 2.36-2.30 (2H, m); 1.73-1.60 (3H, m); 1.40-1.26 (20H, m); 1.22 (3H, d, J=6.4); 0.97-0.90 (9H, m). E.3.4 1 recognize 0' ° for palm OCX. Into H k Chemical name: dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(phenyl-2-indolyl)amino]-1-indenyl) Butyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOH-d4): 8.44 (1H, s); 8.04 (2H, d, J = 8.6); 7.98 (1H, d, J=7.9); 7.87 (1H, d, J=8.7); 7.71-7.61 (2H, m); 4.10-4.02 (2H, m); 2.36 (1H, dd, J=6.5, 8.7); 1.40-1.26 (1H, m); 1.12 (3H, d, J=5.9); 1.07-0.87 (2H, m); 0.74 (3H, d, J=6.6); 0.72 (3H, d, J=6.6). 3.5 ^ «The palm chemical name: dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(4-phenyl adenyl)amino]-1 - ketobutyl]amino]-3-mercaptobutyl] Analytical data: mp 200-208 ° C. lH NMR (MeOH-d4): 8.00 (2H, d, J = 8.4); 7.79 (2H, d, J=8.4); 7.70 (2H, d, J=7.3); 7.49 (2H, t, J=7.5); 7.41 (1H, t, J=7.3); 4.80 (1H, d, J=4.1) 4.38-4.31 (1H, m); 2.78 (1H, t, 1=7.6); 1.73-1.62 (1H, m); 1.41-1.35 (2H, m); 1.31 (3H, d, J=6.4); 0.94 (6H, d, J=6.5). E.3.6 I against the palm tt. Human H ^ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(2,2-didecyl-fluorenyl)amino]- 1-ketobutyl]amino]-3-mercaptobutyl] Analytical data: *H NMR (MeOH-d4): 4.40 (1H, m); 4.05-3.95 (1H, m); 1.65-1.55 ( 1H, m); 1.50-1.40 (2H, m); 1.25-1.15 (14H, m); 1.10 (6H, d, J=8.8); 1.06 (3H, d, J=6.3); 0.82-0.88 (9H , m).

95014 -223 · 1345465

E.3.7 Non-zero chemical name: Dihydroxydecane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(4-phenoxy)]amino] -1- ketobutyl]amino]-3-methylbutyl] Analytical data: 'H NMR (DMS0-d6+ MeOH-d4): 7.90 (2H, d, J=8.7); 7.38 (2H, t , J=7.9); 7.16 (1H, t, J=7.4); 7.02 (4H, t, J=8.6); 4.53 (1H, d, J=4.83); 4.10-3.95 (2H, m); 2.53- 2.44 (1H, m); 1.62-1.48 (1H, m); 1.22-1.49 (2H, m); 1.09 (3H, d, J=6.35); 0.83-0.76 (6H, m). E.3.8 HO^\ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[[4-(l-propoxy)butyl) Amino]-1- butylbutyl]amino]-3-methylbutyl] Analytical data: lH NMR (MeOH-d4): 7.88 (2H, d, J = 8.9); 7.02 (2H, d , J=8.9); 4.76 (1H, d, J=4.0); 4.32 (1H, dq, J=4.2, 6.4); 4.03 (2H, t, J=6.5); 2.76 (1H, t, J=7.6 1.89-1.79 (2H, m); 1.72-1.60 (1H, m); 1.36 (2H, t, J=6.9); 1.28 (3H, d, J=6.4); 1.08 f3H, t, J=7.4 ); 0.93 (1H, dd, J=1.8, 6.6) E.3.9 For palmity CIH Chemical name: Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2- [(3-Pyridin-3-yl-stupyl)aminopurine- Ketobutyl]amino]-3-methylbutyl], hydrochloride salt, mp.: NMR (MeOH-d4): 8.90 (1H, s); 8.58 (1H, d, J = 4.26); 8.22 (1H, t, J=1.59); 8.21-8.16 (1H, m); 7.97 (1H, m); 7.93-7.89 (1H, m); 7.66 (1H, t, J=7.78); 7.60-7.54 (1H, m); 4.80 (1H, d, J=4.41); 4.38-4.28 (1H, m); 2.77 (1H, t, J=7.63); 1.71-1.60 (1H, m); 1.39-1.33 ( 2H, m); 1.29 (3H, d, J=6.38); 0.95-0.90 (6H, m). E.3.10 Chemical name: dihydroxyborane, [(lR)-l-[[(2S,3R) 3-hydroxy-2-[(3-propoxyphenylidene)amino] ketobutylbutyl]amino]-3-mercaptobutyl] Analytical data: lH NMR (MeOH-d4) : 7.49-7.44 (2H, m); 7.41 (1H, t, J=7.82); 7.18-7.12 (1H, m); 4.76 (1H, d, J=4.21); 4.36-4.27 (1H, m); 4.02 (2H, t, J=6.45); 2.77 (1H, t, J=7.61); 1.90-1.79 (2H, m); 1.72-1.60 (1H, m); 1.40-1.34 (2H, m); 1.29 (3H, t, J=6.39); 1.08 (3H, t, J=7.42); 0.94 (6H, d, J=6.48). E.3.11 1 nti± Chemical name: dihydroxyborane, [(lR) -l-[[(2S,3R)-3-hydroxy-2-([3-phenylbenzoyl)amino]-1-ylphenyl]amino]-3-methylbutyl] Analytical data: lK NMR (MeOH-d4): 8.18 (1H, t, 1.7); 7.92-7.85 (2H, m); 7.73-7.69 (2H, m); 7.61 (1H, 7, J=7.8); 7.52-7.46 (2H , m); 7.43-7.37 (1H, m); 4.81 (1H, d, J=4.3); 4.38-4.31 (1H, m); 2.78 (1H, t, J=7.6); 1.72-1.62 (1H, m); 138 (2H, t, J=8.7); 1.31 (3H, d, J=6.4); 0.94 (6H, d, J=6.5). 95014 224· 1345465 E.3.12 Chemical name: OCa 丄dihydroxy Borax, [(lR)-H[(2S,3R)-3-carbyl-2-[(4·{2-fluoro]V 丫1 B-based) benzhydryl)amine Η-«基丁Amino]-3-methylbutyl] Analytical data: 0H 〇 human 〇H lH NMR (MeOH-d4): 8.04-7.99 (2H, m); 7.75-7.69 (2H, m); 7.59-7.53 (1H, m); 7.47-7.40 (1H, m); 7.34-7.28 (1H, m); 7.28-7.20 (1H, m); 4.81 (1H, d, J=4.2); 4.39-4.30 (1H, m); 2.79 (1H, 7.63); 1.74-1.62 (1H, m); 1.42-1.34 (2H, m); 1.32 (3H, d, J=6.39); 0.98-0.92 (6H, m). Example E .4 dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-indole[4-(3-pyridyl)benzylidenyl]amino] ketobutyl Amino]-3-mercaptobutyl

Example D.8.3 4-indopyridin-3-yl)benzamide, 1\[-[(13,211)-1-[[[(111)-1-[(3aS,4S,6S,7aR )-Hexahydro-3\5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino Alkyl]-2-propyl]-(155 mg, 0.283 mmol), 2-methylpropyldihydroxyborane (81 mg, 0.793 mmol) and 2N aqueous hydrochloric acid (0.3 mL) A mixture of methanol (3 ml) and hexanes (3 ml) in a mixture was stirred at room temperature for 24 hours. The hexane layer was removed and the methanolic layer was washed with fresh hexanes (about 5 mL). Ethyl acetate (1 mL) was added to a methanol layer and then concentrated. The residue was dissolved in ethyl acetate and the mixture was concentrated. This step was repeated (2_3 times) until an amorphous white solid was obtained. Next, the solid was triturated with diethyl ether (5 mL) and the supernatant was removed by decantation. Repeat this step. The residue (126 mg) was combined with a similar product (140 mg) and dissolved in ethyl acetate (about 4 liters) and hexanes (2 liters). 〉Valley solution with NaQ saturated solution (7 ml) and 1〇% 95014 •225-1345465

A mixture of NaHC〇3 (2 ml) was washed. The layers were separated and the aqueous was washed further ethyl acetate (2x 20 mL). The combined organic phases were dried with sodium sulfate and concentrated. The residue was dissolved in ethyl acetate (ca. 2 mL) and the minimum amount of decyl alcohol, then concentrated to a small volume (approximately 5 ml of white formed by filtration and dried under vacuum and 5 (TC) , 65% total yield). 1H NMR (MeOH-d4): 8.90 (1H, s); 8.49 (1H, d, J = 4.0); 8.20 (1H, d, J = 8.1); 8.06 (2H, d , J = 8.1); 7.85 (2H, d, J = 8.1); 7.58 (1H, t broad, J = 6.0); 4.80 (1H, d, J = 3.9); 4.40-4.29 (1H, m); 2.78 (1H, t, J=7.5) ; 1.73-1.61 (1H, m) ; 1.38 (2H, t, J=6.9) ; 1.31 (3H, d, J=6.3) ; 0.94 (6H, d, J=6.31 Other compounds prepared according to the procedure described above for Example Ε4 are reported in Table Ε-4.

Example No. Structure Chemical name and analytical data Ε.4.1 1 Pair of palmity 1. People. η Chemical name: dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(2-pyry) carbonyl]amino]-1-mentylbutyl] Amino]-3-methylbutyl] Analytical data: !Η NMR (MeOH-d4): 9.29 (1H, d, J=1.3); 8.86 (1H, d, J=1.3); 8.76-8.74 (1H , m); 4.75 (1H, d, J=3.2); 4.43-4.36 (1H, m); 2.77 (1H, t, J=7.6); 1.72-1.60 (lH,m); 1.40-1.36 (2H, m); 1.27 (3H, d, J=7.6); 0.92 (6H, d, J=7.6). Ε.4.2 . Name of the palm chemical: dihydroxyboron, [(lR)-l-[[( 2S,3R)-3-Hydroxy-2-[(5-butyl-acridin-2-carbonyl)amino]-1-benzylbutyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOH-d4): 8.55 (1H, s); 8.04 (1H, d, J = 7.97); 7.84 (1H, d, J = 7.96); 4.73 (1H, d, J = 2.15); 4.42 -4.33 (1H, m); 2.81-2.71 (3H, m); 1.75-1.6 (3H, m); 1.5-1.3 (5H, m); 1.27 (3H, d, J=5.64); 1.02-0.95 ( 3H, m); 0.94-0.89 (6H, m).

95014 -226· 1345465

Chemical name: Dihydroxyboron, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(6-phenyl-pyridine-2-carbonyl)amino]-1-yl) Butyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOH-d4): 8.20 (2H, d, J = 7.52); 8.18-8.12 (1H, m); 8.11-8.06 ( 2H, m); 7.60-7.43 (3H, m); 4.77 (1H, d, J=2.66); 4.48-4.40 (1H, m); 2.77 (1H, t, J=7.54); 1.73-1.60 (1H m); 1.37 (2H, d, J=7.3); 1.31 (3H, d, J=6.36); 0.92 (6H, d, J=6.55)

Example Ε·5 Dihydroxyborane, [(lR)-l-[[(2S)-3-(2-pyroxycarbonylamino)-2-indole (4-butylbenzylamino) H- Ketopropyl propyl]amino]-3-methylbutyl]

2-S-(4-butylbenzimidyl)-3-(2-pyroxycarbonylamino)1[(18)-1-[[(1 ft)_1-) from Example D.18 [(3,43,63,7)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine 圜_2_yl] Benzyl butyl]amino]amino]] (120 mg '0.19 mmol, 1 eq.) was dissolved in hexane (2 mL) and n-hexane (2 mL). In this solution, isobutyldihydroxyborane (6 mg, 0.57 mmol) is added with 4NHC1 1,4-dioxane (〇7〇, 〇28 mmol, 1.5). equivalent). The resulting mixture was mixed at room temperature for one hour, n-hexane was removed, the methanolic solution was washed with n-hexane (2 mL) and evaporated under reduced pressure. The crude material was suspended in a test/positive-cooked/4 ml), and the mixture was stirred and transferred to a phoenix to obtain a white powder. Yield, 69 mg. Analytical data: melting point 145-150. (: 95014 • 227- 1345465 1H NMR (MeOD-d4): 9.3 (lH, s); 8.85 (lH, s); 8.75 (lH, s); 7.8 (2H, d); 7.3 (2H, d); 5.1 (2H, t); 4 (2H, t); 2.8 (1H, t); 2.75 (2H, t); 1.65 (3H, m); 1.4 (4H, m) ; 1.0 (3H, t) 0.9 ( 6H, dd). Other compounds prepared according to the procedure described above for Example E.5 are reported in Table E-5. Table E-5 Example Number Structure Chemical Name and Analytical Data E.5.1 ^ΝΗ 〇人化学Name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(ethylamino)-2-[(decylamino)]-1-one-propyl)] ]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 4.70 (1H, d); 3.50 (2H, m); 2.75 (1H, t); 2.25 (2H, t); (1H, t); 1.95 (3H, s); 1.65 (3H, m); 1.35 (14H, m); 0.9 (9H, m) E.5.2 〇丫Chemical name: dihydroxyborane, [(lR) -l-[[(2S)-3-(propylureido)-2-[(4-butyl)-benzylidinyl]-1-ketopropyl]amino]-3-indenyl Butyl] Analytical data: 'H NMR (MeOD-d4): 7.80 (2H, d); 7.28 (7H, m); 4.45 (1H, br); 3.7 (1H, br); 3.1 (2H, t); 2.65 (2H, t); 1.7-1.2 (10H, m); 0.9 (12H, m) E.5.3 〇 IIl 1 Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-3-(decanesulfonylamino)-2-[(4-butyl)- phenylamino) ]-1-Methoxypropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.80 (2H, d); 7.28 (7H, m); 3.65 (2H, m 3.0 (3H, s); 2.8 (1H, br); 1.65 (3H, m); 1.35 (4H, m); 0.9 (12H, m). Melting point 120°-123°C E.5.4 0 ^ ΟΗ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-[2-(lH-pyrazole)ethyl]-2-[(4-butyl)-benzoguanamine ]]-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.68 (2H, d); 7.65 (1H, d); 7.43 (1H , d); 7.27 (1H, m); 7.24 (2H, d); 5.06 (1H, t); 4.54 (2H, m); 2.60 (2H, m); 1.5 (3H, m), 1.60-1.3 ( 4H, m); 0.86 (3H, t); 0.80 (6H, d). 228 · 95014 1345465

E.5.5 . For palmity 8 k H NH °^XX Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(methanesulfonylamino)-2-[(4 -butyl)- benzoamido]-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.85 (2H, d); 7.75 (2H, d); 7.35-7.25 (4H, dd); 4.85 (1H, t); 3.9 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2.4 (3H, s), 1.65 (3H, m); 1.35 (5H, m); 1.05-0.80 (9H, m). E.5.6 Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-3-[ (Benzyloxycarbonyl, carbonylbenzyloxyamino)-2-[(4-butylbenzylidinium)]-1-ketopropyl)amino)-3-indenylbutyl) Analytical data: 'H NMR (MeOD-d4): 7.80 (2H, d); 7.28 (7H, m); 5.2 (2H, dd); 3.6 (2H, d); 2.8 (1H, t); 2.75 (2H, t) 1.65 (3H, m); 1.3 (4H, m); 1.0 (9H, m). Melting point 92°-96°CE 5.7 0 LH OH NH. ~) Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-[(» 塞 phen-2-ylcarbonyl)amino]-2-[(4-butyl phenyl) Amidino)]-l-ketopropyl]amino]-3-methylbutyl] Analytical data: *H NMR (MeOD-d4): 7.80 (2H, d); 7.7 (2H, m); 7.3 (2H, d); 7.2 (1H, t); 4.9 (2H, dd); 3.9 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 1.65 (3H, m); (4H, m); 1.0 (3H, t) 0.9 (6H, dd). E.5.8 O \ OH NH Chemical Name: Dihydroxyboron, [(lR)-l-[[(2S)-3- (Ethylamino)-2-[4-butyl-benzoguanidino]]-1-ketopropyl]amino]-3-decylbutyl] Analytical data: 'H NMR (MeOD- D4): 7.8 (2H, d); 7.3 (2H, d); 4.8 (1H, m); 3.7 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2 (3H, s 1.65 (3H, m); 1.4 (4H, m); 1.0-0.9 (3H, t), |6H, dd). Melting point 107°-109°CE5.9 Λ οΛ0 Chemical name: dihydroxyborane, [ (lR)-l-[[(2S)-3-[(5,6-hydroxycarbonyl)amino]]-2-[(decylamino)]-l-ketopropyl]amino ]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): t 7.7 (2H, d); 7.15 (1H, t); 4.8 (1H, m); 3.7 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2,25 (2H, t) 1.65 (3H, m); 1.4 (14H, m); 1.0-0.9 (3H, t). E.5.10 I Ϊ OCvggc^ Chemical name: dihydroxyborane, [(lR)-l-[[ (2S)-3-(Hexylamino)-2-[(4-butylbenzylidinium)]-l-ketopropyl]amino]-3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.8 (2H, d); 7.3 (2H, d); 3.7 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2.2 (2H, t); 1.65 (5H, m); 1.4 (9H, m); 1.0-0.9 (12H, t).

95014 -229- 1345465

E.5.11 E.5.12 E.5.13

F

E.5.15

Chemical name: Dihydroxydecane, [(1R)-1-[[(2S)-3-[4-|l- oxasulfonamide]-2-[(4-butylbenzylidene)) ]-1-3⁄4 propyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.95 (2H, dd); 7.8 (2H, d); 7.3 (4H, m); 4.8 (1H, m); 3.4 (2H, m); 2.85 (1H, t); 2.7 (2H, t); 1.7 (3H, m); 1.4 (4H, m); 1.0-0.9 (9H , t). Melting point 130°-132°C. Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-[4-fluoro-benzenesulfonamide]_2_[(癸蕴Amino]-1-ketopropyl]amino]-3-mercaptobutyl] Analytical data: Ή NMR (MeOD-d4): 7.95 (2H, dd); 7.35 (2H, t); 4.45 (1H, t); 3.0 (2H, m); 3.4 (2H, m); 2.1 (2H, t); 1.65-1.35 (3H, m); 1.25 (14H, m); 0.85 (9H, m). Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-3-(hexylamino)-2-[(decylamino)]-l-ketopropyl] Amino]-3-mercaptobutyl] Analytical data: 'H NMR (MeOD-d4): 4.45 (1H, t); 3.3 (2H, m); 2.1 (4H, tt); 1.65-1.35 (3H, m); 1.25 (18H, m); 0.85(12H,m).___ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(hexylamino)-2- [(Cyclopropylcarbonylamino)]-1 -ketopropyl] '3-methylbutyl]3-methylbutyl]amino]carbonyl]-2-(cyclopropylcarbonylamino)ethyl]-analytical data: 'H NMR (MeOD-d4): 7.8 ( 2H, d); 7.2 (2H, d); 4.6 (1H, br); 3.4 (2H, m); 3.0 (2H, s); 2.7 (2H, m); 1.5 (4H, m); 1.3 (3H , m); 1.2 (4H, m); 0.9-0.6 (15H,m).___ Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-3-[(3,4- Dimethoxyphenyl)Ethylamino]-2-[(4-butylbenzylidinium)]-l-ketopropyl]amino]-3-methylbutyl] Analytical data: Melting point 150°-152°C 'H NMR (MeOD-d4): 7.7 (2H, d); 7.2 (2H, d); 6.8 (1H, s); 6.75 (2H, m); 4.7 (1H, m) ; 3.7 (6H, m); 3.54 (2H, s); 3.35 (2H, s); 2.66 (3H, t); 1.6 (2H, t); 1.4-1.2 (2H, m); (2H, m) ; (2H,m); 0.9 (3H, t), 0.8 (6H, d).___ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-[lN-fluorenyl) -2-pyrrolylcarbonylamino]-2-[(4-butylazinocarbyl)amino]-1-indolyl]amino]_3·decylbutyl] Analytical data: *H NMR (MeOD-d4): 7.8 (2H, d); 7.3 (2H, d); 6.9 (1H, d); 6.7 (1H, d); 6 (1H, t); 4.8 (1H, t); 3H, s); 3.7 (2H, m); 2.7 (3H, m); 1.65 (3H, m); 1.35 (4H, Mi; 0.9-0.6 (9H, m). Melting point 130M35°C·

95014 - 230- 1345465 E.5.17 °HN^ &quot; '〇H Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-3-[4-amine sulfonyl) ][2-(4-butylbenzylidene)amino]-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.95 (4H, dd); 7.8 (2H, d); 7.3 (2H, d); 4.9 (1H, t); 3.7 (2H, d); 2.7 (2H, t); 2.6 (1H, t); (3H, m); 1.2 (4H, m); 0.95-0.8 (9H, m). Melting point 156°-159°CE5.18 o L ^ , NM 0 Chemical name: dihydroxydecane, [(lR)-l -[[(2S)-3-(nicotinoguanidino)-2-[(4-butylbenzylidinium)]-l-ketopropyl]amino]-3-mercaptobutyl Analytical data: lHNMR(MeOD-d4): 9.1 (1H, s); 8.8 (1H, d); 8.4 (1H, d); 7.8 (2H, d); 7.7 (1H, t); 7.3 (2H , d); 4.9 (1H, t); 3.7 (2H, m); 2.7 (2H, t); 2.6 (1H, t); 1.6 (3H, m); 1.4-1.2 (7H, m); 0.95- 0.8 (9H, m). E.5.19 λ ό Chemical Name: Dihydroxyborane, [(1R)-1 -[[(2S)-3-(3-phenylureido)-2-(4-butyl) Benzoguanidino)-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 8.8 (1H, d); 7.35 (2H, d) ; 7.25 (2H, d); 7.2 (2H, t 6.9 (1H, t); 4.7 (1H, t); 3.7-3.4 (2H, m); 2.7 (2H, t); 2.6 (1H, t); 1.6 (3H, m); 1.4-1.2 ( 4H, m); 0.95-0.8 (9H, m). E.5.20 ° ^Νη&quot; °Η °^S〇L ^/^so2ch3 Chemical name: dihydroxyborane, [(lR)-l-[[( 2S)-3-[(4-Methanesulfonyl)benzamideamino]-2-[(4-butylphenylguanidino)]-1-ketopropyl]amino]-3- Methyl butyl] Analytical data: 'H NMR (MeOD-d4): 8.0 (4H, m); 7.8 (2H, d); 7.25 (2H, d); 4.9 (1H, br); 3.75 (2H, m 3.2 (3H, s); 2.7 (2H, t); 2.6 (1H, t); 1.6 (3H, m); 1.4-1.2 (4H, mj; 0.95-0.8 (9H, m). -170. (:. E.5.21 For zero-value 0 5w OH w. ό Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(3-phenylureido)-2-) (decylamino)-1-ketopropyl]amino]-3-decylbutyl] Analytical data: lH NMR (MeOD-d4): 7.35 (2H, d); 7.28 (2H, dd) ; 7.0 (2H, t); 3.6 (2H, d); 2.75 (1H, t); 2.2 (2H, t); 1.65 (3H, m); 1.3 (14H, m); 0.9 (9H, m) E .5.22 , ^^^^人β·0Η 0 ^νηΗ όΗ Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(nicotinoguanidino)]-2-( <RTI ID=0.0></RTI> </RTI> <RTIgt; ; 8.3 (1H, d); 7.5 (1H, t); 4.9 (1H, m); 3.9-3.6 (2H, m); 2.75 (1H, t); 2.2 (2H, t); 1.65 (3H, m ); 1.3 (14H, m); 1.0-0.9 (9H, m). Melting point 136°-141°C. 95014 -231 · 1345465

E.5.23 E.5.24 E.5.25 E.5.26 E.5.27 95014

0 on palm

Palm

232 - Chemical name: Dihydroxydecane, [(lR)-l-[[(2R)-3-(4-methylphenylcarbonyl)-2-(decylamino)-1-propanyl-propyl Amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 8.85 (2H, d); 8.0 (2H, d); 7.3 (4H, m); 5.0 (lH, m); 3.9 (2H, m); 2.75 (3H, m); 1.65 (3H, m); 1.3 (9H, m); 0.9 (9H, m) Chemical name: dihydroxyborane, [(lR)- L-[[(2S)-3-[4-(lH-tetrazolyl)-phenylcarbonylamino]-2-[(4-butyl-carboxamido)]-l-ketopropyl Amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 8.15 (2H, d); 7.9 (2H, d); 7.8 (2H, d); 7.3 (2H, d 5.0 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.65 (3H, m); 1.3 (4H, m); 0.9 (9H, m) _ Melting point &gt; 250 ° C.

Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(2-isoxazolylcarbonylamino)-2-[(4-butylbenzamide)]] -l-ketopropyl]amino]-3-methylbutyl] Analytical data: *H NMR (MeOD-d4): 8.4 (1H, s); 7.7 (2H, d); 7.2 (2H, d 6.9 (1H, s); 4.9 (1H, t); 3.8 (2H, m); 2.7 (1H, t); 2.6 (2H, t); 1.5 (3H, m); 1.25 (4H, m) ; 0.8 (9H, m) mp 175°-180°C. Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-3-[l-methyl-1H-imidazole-4- Aminesulfonyl]-2-[(4-butylphenylhydrazino)amino]-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD- D4): 8.8 (2H, d); 8.7 (2H, s); 7.3 (2H, d); 4.9 (1H, br); 3.8 (3H, s); 3.5 (2H, m); 2.8 (1H, t ); 2.7 (2H, t); 1.65 (3H, m); 1.35 (4H, m); 0.9 (9H, m), melting point 120°-123°C._ Chemical name: dihydroxyborane, [(1R -1[[(2S)-3-[6-morpholin-4-yl-pyridin-3-amine sulfonyl]-2-[(4-butylacylmethyl)amino]- 1-ketopropyl]amino]-3-methylbutyl] hydrochloride analysis data: 'H NMR (MeOD-d4): 8.35 (1H, s); 8.1 (1H, d); 7.8 (2H , d); 7.3 (3H, m); 4.9 (1H, br); 3.9 (4H, t); 3 .8 (4H, t); 3.5 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.65 (3H, m); 1.35 (4H, m); 0.9 (9H, m). Melting point 182 ° -184 ° C.

1345465

E.5.28 Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-3-(6-morpholinylnicotinamide)-2-[(4&gt; butylphthalamidine) Amino]-1-ketopropyl)amino)-3-indenylbutyl) Analytical data: lH NMR (MeOD-d4): 8.5 (1H, s); 7.9 (1H, d); (2H, d); 7.2 (2H, d); 6.7 (1H, d); 4.9 (1H, t); 3.8 (2H, ts); 3.7 (4H, d); 3.4 (4H, d); 2.65 ( 1H, t); 2.6 (2H, t); 1.60 (3H, m); 1.25 (4H, m); 0.9 (9H, m). Melting point 178°-180°CE5.29 0 V. OH c« r /* , ίί Chemical Name: Dihydroxydecane, [(lR)-l-[[2S)-3-(4^(l,3-dimethyl-1H-pyrazole-5-carbonylamino)-2) -[(4-Butyl albendyryl)amino]-1-ketopropyl)amino]&gt; 3-methylbutyl) hydrochloride salt. Data: Ή NMR (MeOD-d4): 7.8 (1H, d); 7.3 (2H, d); 6.65 (1H, s); 5.0 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 3H, s); 1.60 (3H, m); 1.35 (4H, m); 0.9 (9H, m). E.5.30 to palmity 丄 °, Η chemical name: dihydroxyborane, [(lR)-l -[[(2S)-3-[4-fluoro- oxasulfonamide]-2-[(4-phenoxybenzylidinyl)amino]-1-ketopropyl]amino]-3 -mercaptobutyl] Analytical data: 'HN MR (MeOD-d4): 7.95 (2H, m); 7.9 (2H, d); 7.4 (2H, m); 7.3 (2H, t); 7.25 (1H, t); 7.1 (2H, d); (2H, d); 3.4 (2H, m); 2.8 (1H, br); 1.7 (1H, m); 1.40 (2H, m); 0.9 (6H, d). Melting point 150°-155°CE5.31 Palmity I 0〇ΧΧυ^Λν\〇^ 0,νηη Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(4-(l,3-dimethyl-1H) -pyrazole-5-carbonylamino)-2-[(4-phenoxybenzylidene)amino]-1-ketopropyl)amino)-3-methylbutyl)carbonylamino Ethyl)-analytical data: 'H NMR (MeOD-d4): 7.9 (2H, d); 7.45 (2H, t); 7.25 (1H, t); 7.11 (2H, d); 7.05 (2H, d 6.55 (1H, s); 5.0 (1H, t); 4.1 (3H, s); 3.9 (2H, m); 2.8 (1H, t); 2.25 (3H, s); 1.6 (1H, m) ; 1.35 (2H, m); 0.9 (6H, d). Melting point 145. -148.0. E.5.32 σ io Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(4-phenylureido)-2-[(4-phenoxy) Benzomidine)amino]4-ketopropyl)amino)-3-indenylbutyl) Analytical data: 'H NMR (MeOD-d4): 7.9 (2H, d); 7.40 (2H, t 7.35 (2H, d); 7.25 (3H, m); 7.10 (2H, d); 7.05 (3H, d); 3.75 (2H, m); 2.8 (1H, t); 1.75 (1H, m) 1.4 (2H, m); 0.9 (6H, d) · melting point 155 ° -158 ° C.

95014 233 - 1345465

E.5.33 Chemical name: Dihydroxydecane, [(lR)-l-[[(2S)-3&lt;4-phenyl benzoate)-2-[(4-butylbenzylidene)amine Analytical data: lH NMR (MeOD-d4): 7.9 (2H, d); 7.8 (2H,d); 7.75 (2H, d); 7.70 (2H, d); 7.45 (2H, t); 7.35 (1H, d); 7.30 (1H, d); 5.0 (1H, t); 3.95 (2H, m); 2.8 (1H, t ); 2.7 (2H, t); 1.65 (3H, m); 1.4 (2H, m); 1.0 (3H, t) 0.9 (6H, d)_ melting point 178M80°C E.5.34 ^Cr^yv^r Chemistry Name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(4-phenyl)carbazide)-2-[(4-phenoxybenzyl)amino] -1-ketopropyl)amino)-3-methylbutyl) Analytical data: 'H NMR (MeOD-d4): 7.9 (4H, m); 7.80 (2H, d); 7.70 (2H, d ); 7.4 (4H, m); 7.20 (1H, t); 7.05 (4H, d); 5.0 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 1.6 (1H, m) 1.4 (2H, m); 0.9 (6H, d). Melting point 158o-160°CE5.35 % Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(phenyl propyl) Indole)-2-[(4-butylbenzylidene)amino]-1-mentylpropyl)amino)-3-methylbutyl) Analytical data: lH NMR (MeOD-d4): 7.85 (2H, m); 7.4 (2H, d ); 7.5 (1H, d); 7.45 (2H, m); 7.35 (2H, d); 5.0 (1H, t); 3.95 (2H, m); 2.8 (1H, t); 2.7 (2H, t) ; 1.7 (3H, m); 1.4 (4H, m); 1_0 (3H, t) 0.9 (9H, m). Melting point 138°-140°CE5.36 / . ^对笨性&quot;XX Chemical Name: Dihydroxyborane, [(lR)-l-[[(2S)-3-(4-methylphenylsulfonyl)-ureido]-2-[(4 -butylbenzylidene)amino]-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.85 (2H, d); 7.75 (2H, d); 7.3 (2H, d); 7.25 (2H, d); 4.7 (1H, t); 3.65 (2H, m); 2.75 (1H, t); 2.7 (2H, t); 3H, m); 1.4 (4H, πό; 1.0-0.9(9H,m). Melting point 175.-177.匚. E.5.37 J HN Γ Chemical name: dihydroxyborane, [(lR)-l-[ [(2S)-3-(4-(2-(4-pyridyl)-1,3-oxazolidinecarbonylamino))-2-[(4-butyl-carboxamyl)amino]- 1-ketopropyl)amino)-3-methylbutyl) Analytical data: *H NMR (MeOD-d4): 8.7 (2H, d); 8.45 (lH, s); 8.05 (2H, d) 7.8 (2H, d); 7.3 (2H, t); 4.0 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.7 (3H, m); &amp;H,m); 0.9 (3H, t); 0.8 (6H, dd). Melting point 155°-158°C. 95014 234 - 1345465

E.5.38 〆k〆〇H 丨 to palmity 0 〇Chemical name: dihydroxyborane, [(lR)-l-[[(2S)-3-(l-nonanesulfonyl hexamidine pyridine*4 -carbonylamino)-2-[(4-butylbenzamide)]-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4 ): 9.9 (1H, br); 8.35 (1H, t); 7.8 (2H, d); 7.3 (2H, d); 4.9 (1H, t); 3.7 (4H, m); 2.8 (3H, s) ; 2.75 (4H, m); 2.3 (1H, m); 1.85-1.6 (7H, m); 1_3 (4H, m) 0_9 (9H, m); melting point 170°-173°CE 5.39 H ^ Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-[(2-喽))sulfonylamino]-2-[(4-butylbenzoquinone)]- 1-Methylpropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.95 (1H, dd); 7.8 (2H, d); 7.58 (1H, dd); 7.32 (2H, d); 7.18 (1H, dd); 4.8 (1H, m); 3.23 (2H, m); 2.66 (1H, t); 1.3-1.23 (8H, m); 0.9 (3H, t) , 0.8 (6H, d). E.5.40 0 \ OH NH Chemical name: Dihydroxyboron, [(1R)-1 -[[(2S)-3-(4-( 1H-1,2,4- Triazol-1-yl)obetylcarboxamide]]-2-[(4-butylazinocarbyl)amino]-l-ketopropyl]amino]-3-methylbutyl] Acid analysis data: 'H NMR (MeOD -d4): 9.8 (1H, s); 8.6 (1H, s); 8.08 (2H, d); 8.01 (2H, d); 7.8 (2H, d); 7.3 (2H, d); 5.05 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.6 (3H, m); 1.3 (4H, m); 1.0 (3H, t); 0.9 (6H, dd Melting point 192°-195°CE5.41 i^Vxr«Yisi6- 0 OH HN, °^X Chemical name: Dihydroxyborane, [(lR)-l-[[(2R)-3-(4-A) Phenylcarbonylcarbonyl)-2-(decylamino)-1-ketopropyl]amino]-3-methylbutyl] Analytical data: 'H NMR (MeOD-d4): 7.85 (2H, d); 7.8 (2H, d); 7.35 (4H, m); 5 (1H, m); 4.05 (1H, m); 3.95 (1H, m); 2.75 (2H, t); 1.65 (2H, m 1.35 (10H, m): 1.0 (3H, t), 0.85 (6H, d). E.5.42, for palmity 〇^NH 〇H 乂ό Chemical name: Dihydroxyboron, [(lR)- L-[[(2S)-3-(4-Phenylureido)-2-(indolyl)-1-ketopropyl)amino)-3-indenylbutyl) E.5.43 person Chemical name: Dihydroxyborane, [(lR)-l-[[(2S)-3-acetamido-2-ylamino-1-ketopropyl]amino]-3-yl Phenylbutyl]

95014 -235 - 1345465 Example Fl an amine, [[18]_1-[[[(11〇小[(411,511)-4,5-dicyclohexyl-[1,3,2]diboron困-2-yl]-3-mercaptobutyl]amino]carbonyl]_4-indenylamino(nitroamino)methyl]amino]butyl

Dihydroxyborane as obtained in Example E.2, [(1R) small [[(2S)_5_[[iminoamino(nitroamino)methyl]amino]]-2-[(癸醯Amino]]1·ketopentyl]amino]-3-methylbutyl]-(125 mg, 0.26 mmol) in acetonitrile (〇. 5 mL) and di-methane (1 mL) In the suspension in the mixture, add a few drops of methanol until the solids are completely dissolved. (1R, 2R)-1,2-dicyclohexyl-l,2-ethanediol (61 mg, 0.26 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (yield) to 50. Then, the product was developed by hexane and the solvent was removed by decantation. The development was repeated twice more. The product was obtained as a solid (65 mg, 37% yield). Melting point 75-100 ° C. ^NMRCDMSO-de): 8.99 (1H, d, J = 2.5 Hz); 8.52 (lHsbr); 7.98 (lH5d, J = 8.05); 7.88 (2H, br); 3.48 (2H, d, J=5.7) ; 3.14 (2H, m) ; 2.55 (1H, m); 2.19 (lH,m); 2.10 (2H,m); 1.79 (2H,m); 1.74-1.35 (16H, m) 1.24 (22H, m); 1.12(5H,m); 0.89 (4H,m); 0.84 (9H,m). 95014 -236· 1345465 Example F.2 4-Phenylbutyramine, N-[( 1S)-1-[[[(1R)-1-[13,15-dioxo-14-shed snail [5.0.5.3I-fifteen-14-yl 1-3-methylbutyl I amine group]丨 基 4- 4- 4-[[imino[]-aminoalkyl)methyl-amino-butyl 1-

The title compound was prepared according to the procedure described above for Example F.1 using the appropriate dihydroxyborane starting material and dicyclohexyl-1,1 '-diol. Analytical results: 1H NMR (DMS0-d6): 8.79 (1H, d, J = 2_5 Hz); 8.52 (1H, br); 8.00 (1H, d, J = 7.94); 7.85 (2H, br); 7.31-7.23 (2H, m); 7.20-7.14 (3H, m); 4.40-4.30 (1H, m) ; 3.15 (2H, m) ; 2.55 (3H, m) ; 2.14 (2H, t, J=7.3 Hz); 1.78 (2H, q, J=7.3 Hz); 1.70-0.97 (27H, m); 0.84 (3H, ts J=6.7 Hz); 0.83 (3H, t, J=6.7 Hz).

Example F.2.1 4-butylbenzamine, N-[(1S,2R)-1-[丨[(1R)-1-[13,15-dioxo_14 boron dispiro[5.o. 5.3]15-u-yl]methylbutyl]amine-based machine base phydroxypropyl]-

Suitable compounds are prepared according to the procedure described above for Example F1, using a diboronylborane starting material with dicyclohexyl 4 丨, _ ^ ^ , monool. 95014 -237- 1345465 Analysis results: iHNMRCDMSO-cU: 8.98 (lH, sbr.); 8.00 (1H, d J=85); 7.81 (2H, d, J = 8'2); 7.31 (2H, d, J = 8.2) ; 5_03 (1H, d, J = 6.2); 4.49 (1H, dd, J = 8.5, 5.0); 4.07-3.98 (1H, m); 2.64 (1H, t, J = 7.6) ; 2.57- 2.50 (1H, m); 1.65-1.21 (21H, m); 1.14-1.00 (9H, m); 0.90 (3H, t, J=7.4); 0.85 (6H, d, 6.5). Example Gl 10_(1 , 3-diyl-1,3_diazo-isoindole-2-yl)-decanoic acid

Step 1 ·· 2-11-10-enyl-1,3-dione-1}dihydroisoindole in 10-undecen-1-ol (4.23 g, 24.8 mmol), adjacent Benzemethylene imine (3.65 g, 24.8 mmol) and triphenylphosphine (6.51 g, 24.8 mmol) in a mixture of anhydrous tetrahydropyrene (30 ml), slowly add DEAD (3.9 ml) A solution of '24.8 mmoles in anhydrous tetrahydrofuran (1 mL) while maintaining the temperature below 8-10 C. After 2 hours, additional dead (10 mL, 6.37 mmol) and triphenylphosphine (1.3 g, 4.96 mmol) were added and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and the residue was crystaljjjjjjjj The solid was removed by filtration and washed with diethyl ether (2 χ 5 mL). The combined ferric solution was concentrated and the residue was developed in a house (5 mL) at 40 C. The solid formed was removed by filtration and washed with hexane (2 EtOAc). The combined filtrate was concentrated, and the residue was purified by column chromatography eluting with EtOAc: EtOAc. The product was obtained as a low white solid (49 g, 66% yield). .

Melting point 25-30 ° C 95014 -238-1345465 IHNMR (DMSO-d6) 7.83 (4H, m); 5.76 (1H, m); 4.96 (1H, dq, J = 17.2, 1.6 Hz), 4.90 (1H, ddt , J=l〇.2} 2.2, 1.1) ; 3.54 (2H, t, J=7.1), 1.97 (2H, q, J=6.7) ; 1.56 (2H, m) ; 1.35-U5 (14H, m) Step 2: 10-(1,3-diketo-1,3-dihydroisoindole-2-yl)nonanoic acid 2-Step-I〇-alkenyl 13-diketone of Step 1. a solution of _13_dihydroisoindole (2 g, 6.68 mmol) and Aliquat® 336 (0.2 g) in a mixture of hexane (20 ml) and acetic acid (6 ml), adding force σ to Potassium peroxylate (2 76 g, 2 〇 φ mmol) in water (28 mL) was simultaneously cooled at 〇 ° C. The reaction mixture was mixed for 7 hours at room temperature, and then aqueous sodium hydrogen sulfite solution was added until the purple color disappeared. The mixture was then extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and concentrated. The residue was purified by column chromatography on a column of EtOAc. The product was obtained as a white solid (1.

Melting point 58-60 ° C 1H NMR (DMSO-d6) 11.95 (1H, br); 7.85 (4H, m); 3.55 (2H, t, J = 7.2 Hz); φ 2.17 (2H, t, J = 7.2 Hz ; 1.7-1.4 (4H, m) ; 1.22 (10H, m). Example G.2 6-(Benzenesulfonyl)hexanoic acid Addition of gasified benzenesulfonate (2.5 ml '19 mmol) to 6_Aminocaproic acid (1 g ' 7.62 mmol) in a solution of 2N NaOH (22 ml) and dioxane (3 ml) while stirring at 0 ° C - 5 ° C to make the mixture Warm to room temperature and stir for 1 hour. The reaction mixture was washed with ethyl acetate (5 mL) and then acidified to &lt The combined organic layers were dried over sodium sulfate and concentrated. The residue was triturated with hexane 95014 • 239·1345465. The solid was taken by filtration <RTI ID=0.0></RTI> and dried <RTI ID=0.0>

Melting point 113-115 ° C ^NMRCDMSO-d^ : 11.96 (lH, s); 7.79 (2H, m); 7.60 (4H, m); 2.71 (2H, m); 2.13 (2H, t, J = 7.14 Hz ; 1.38 (4H, m) ; 1.21 (2H, m). Example G.3 6-(ethanesulfonylamino)hexanoic acid • Will be gasified and burned (3·9 ml, 41.1 mmol) A solution in dioxanol (i〇 ml) was added to 6-aminocaproic acid (2 g, 15.2 mmol) in 1N NaOH (56 mL) and dioxane (1 mL) Stir in the solution while stirring at -5 C. The pH of the reaction mixture was adjusted to 8-9 by the addition of a 25% sodium hydroxide solution. The mixture was allowed to warm to room temperature and stirred for 3 min. An additional 25% NaOH solution was added to adjust the pH to about u. After 3.5 hours, 1N hydrochloric acid (15 ml) and ethyl acetate (6 mL) were added. The organic layer was dehydrated and dried with sodium sulfate and quenched. The residue was triturated with a mixture of slat (5 mL) and hexane (15 mL). The solid was collected by filtration and dried to give 13 g of the title compound (40%). 1H NMR (DMSO-d6): 11.9 (1H, s); 6.97 (1H, t, J = 5.7 Hz); 2.97 (2Hsq, J = 7.1); 2.88 (2H, q, J = 6.6); 2.2 (2H, t, J=7.3); 1.47 (4H,m); 1.29 (2H,m); 1-18 (3H, t, J=7.3). Example G.4 8-(Acylamino)octanoic acid A solution of ethanesulfonate (1.5 ml, 15.7 mmol) in dioxane (5 ml), added to 8-aminooctanoic acid (1 g, 6 28 mmol) in 95014 • 240· 1345465

In a solution of NaOH (22 ml) and dioxane (5 ml), while mixing at 〇 C -5 C, "warp the mixture to room temperature" and mix for a few minutes. During this time period, the pH was adjusted to 7-8 by adding a 25% NaOH solution at 1 hour intervals. The reaction mixture was washed with diethyl ether (30 mL). The pH was adjusted to 1-2 by the addition of 1NHC1, and the mixture was extracted with ethyl acetate (70 ml). The organic layer was dried over sodium sulfate and concentrated. The residue was triturated with an ether mixture. The solid was collected by hydrazine and dried in vacuo to give the title compound (yield: 38% yield). NMRC DMSO-c^): 11.9 (1H, s); 6.96 (1H, t, J = 6 Hz 2.96(2H,q,J= 7.1); 2.88 (2H, q, J=6.6) ; 2.2 (2H, t, J=7.3) ; 1.45 (4H,m); 1.26 (6H,m); 1.18 (3H, t, J = 7.3). Example G.5 3-Amino-2-S-indole (1,1-dimercaptoethoxycarbonyl)amino]-propionic acid benzyl ester • Step 1: Step Tris-butoxycarbonyl hydrazine _ aspartate [commercially available] φ

'L-aspartate (15 g, 0.113 mol, 1 eq.) and sodium carbonate (12 g, 0.113 mol) dissolved in water (225 ml) and 1,4-dioxane at room temperature (at room temperature) 225 ml). To this solution, di-tert-butyl dicarbonate (3 g, 〇.137 mol, 1.2 eq.) was added, and the mixture was stirred overnight. The solvent was evaporated under reduced pressure until the 1,4-dioxane was distilled off, and the pH was adjusted to 2 with HCl 1% to afford a white solid which was filtered, washed with water and dried. 95014 -241 · 1345465 Yield 91% ^ 24 g. Analytical data: melting point 175 ° C - 180 ° C (literature 175. (:) _ lH NMR (DMSO-d6) 12.5 (lH, br); 7.31 (lH, br); 6.91 (lH, br); 6.87 (1H, d, J=8.4 Hz); 4.23 (1H, q, J=7.7 Hz); 2.56-2.36 (2H, m) ; 1.38 (9H, s). Step 2: N-[(l,l-dimethyl) Ethoxycarbonyl)amino]-L-aspartate thioglycol

The compound was prepared according to Bioorg. Med. Chem., 6 (1998) 1185-1208. N-[(l,1-dimethylethoxycarbonyl)amino]cetillin (2〇7 g, 89] mmoles 1 equivalent) of Step 1 was dissolved in methanol (500 mL). A carbonation planer (15.97 grams, 49 millimoles, 0.55 equivalents) was added. The solvent was evaporated to give a white solid which was dissolved in N,N-dimethylformamide (2 mL). To the suspension, benzyl bromide (11.6 ml, 98 mmol, 1.1 eq.) was added dropwise, and the mixture was stirred overnight. The solvent was reduced under reduced pressure, water (3 mL) was added, and the mixture was extracted with ethyl acetate (200 ml), washed with brine (5 mL) and solvent was evaporated under reduced pressure. This was suspended in n-hexane (16 mL) and filtered and dried under vacuum to yield 14. The yield was 51%. Analytical data: melting point 113M15T: 1HNMR (DMSO-d6) 7.35 (6H, m); 7.13 (1H, d, J = 7.9 Hz); 6.94 (1H, brs); 5.10 (2H, s); 4.39 (1H, q, J=7.4 Hz) ; 2.6-2.4 (2H, m) ; 2.03 (2H, t, J=7.3); 1.37 (9H, s). Step 3: 3-Amino-2-S-[(l , l-Dimethylethoxycarbonyl)amino]-propionic acid decyl vinegar 95014 • 242· 1345465 乂. 〇-〇 步骤 Step 2 N-[(l,l-didecylethoxycarbonyl)amino]-L-aspartic acid ester (2 g, 6.3 mmol, 1 equivalent) dissolved in acetonitrile (8 〇 ml) with water (8 〇 ml). The solution was cooled to 〇-5 ° C and benzene diacetate (3 g, 9.3 mmol, 丨. 5 eq.) was added in portions. The mixture was stirred for 3 minutes and then at room temperature for 4 hours. The organic solvent was removed under vacuum and diethyl ether and #HC11N were added. The layers were separated and extracted with dichloromethane (100 mL) The organic solvent was dried over anhydrous sodium sulfate and evaporated under reduced pressure to yield &lt;RTI ID=0.0&gt;&gt;&&&&&&&&&&&&&&&&& J=7.7 Hz); 5.13 (2H, AB q, J=12.8) ; 4.01 (1H, m) ; 2.80 (2H, m) ; 1.38 (9H, s). Example G.6 (2S)-2-[ (l,l-dimethylethoxycarbonyl)amino]methylbenzhydryl)amino] A propionic acid

Step 1: 2-S-[(l,l-Dimethylethoxycarbonyl)amino]-3-(4-f-phenylbenzamide) propionate decyl vinegar

95014 -243 - 1345465 3-Amino-2-S-[(l,l-dimethylethoxycarbonyl)amino]-propionate propionate of Example G.5 (690 mg, 2.34 m Mohr, 1 equivalent) was dissolved in anhydrous dmf (2 mL) and added TBTU (900 mg, 2.98 mmol, 1.2 eq.). The mixture was stirred at room temperature for 10 minutes&apos; cooled to 〇_5»c in an ice bath and (0.51 mL, 4_68 mmol, 2 eq.) and 4-Mercaptobenzoic acid (380 mg,

2.81 millimoles, 1.2 equivalents). The mixture was stirred at room temperature for 3 hours, poured over water (100 mL) andEtOAc. The organic layer was washed with citric acid solution 2% (50 ml), sodium bicarbonate 2% (50 ml), EtOAc (50 ml), dried over anhydrous sodium sulfate, and evaporated under reduced pressure. 1 gram of oil. The yield is quantified. Analytical data: 1H NMR (DMSO-d6) 8.46 (1H, br, J = 5.7 Hz); 7.70 (2H, d, J = 8.0); 7.35-7.2 (8H, m); 5.07 (2H, s); 4.29 (1H, m) ; 3.67 (1H, m) ; 3.58 (1H, m); 2.36 (3H, s); 1.37 (9H, s).

Step 2: (2S)-2-[(l,l-Dimethylethoxycarbonyl)amino]-3-(4-methylbenzimidamide, propionic acid

2-S-[(l,1-Dimethylethoxycarbonyl)amino]-3-(4-mercaptophenylamino)-propionic acid decyl ester of Step 1 (930 mg, 2.25 m) Moor) was dissolved in decyl alcohol (25 ml) and Pd/C 10% (90 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. The Pd/C was filtered, and the solution was evaporated under reduced pressure to yield 650 m. The yield was 86%. Analytical data: 1H NMR (DMSO-d6): 12.5 (1H, br); 8.40 (1H, t, J = 5.7 Hz); 7.71 (2H, d, J = 8.05 Hz); 7.27 (2H, d, J=8.05 Hz) ; 7.09 (1H, d, J=7.9) ; 4.17 (1H, m); 3.57 (2H, m) ; 2.35 (3H, s) ; 1.37 (9H, m). Example G.7 2-S- [(l,l-Dimethylethoxycarbonyl)amino]-3-(hexylamino)propanoic acid hydrazine 乂ΛΑ Step 1: 2_s-[(l,1-dimethylethoxycarbonyl)amino group ]-3-(hexylamino)propionic acid decyl vinegar was dissolved in hexane (1.5 mg, 3.87 mmol, 1.2 eq. Ears, 1.2 equivalents), the mixture was stirred at room temperature for 20 minutes and then cooled to 〇-5 in an ice bath. Add 3-amino-2-S-[(l,1-dimethylethoxycarbonyl)amino]propionate propionate (950 mg, 3.22 mmol, 1 equivalent) of Example G.5 with nmm (1 〇 6 ml, 9.61 mmol) 2.5 equivalents. The mixture was stirred at room temperature overnight, poured over water (15 mL) andEtOAc. The organic layer was washed with citric acid solution 2% (50 ml), sodium bicarbonate 2% (5 mL), NaCI 2% (50 ml), dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The crude material was purified by chromatography on a Shih-Gui gel column (solvent: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The yield was 4%. Analytical data: ^NMRCDMSO-dg). δα: 7.87 (1Η, br t, J=6.2 Hz); 7.35 (5H, m); 7.14 (1H, d, J=8.2); 5.07 (2H, s); 4.14 (1H, m); 3.37 (2H, m); 2.00 (2H, t, J=7.1); 1.43 (2H, m); 1.36 (9H, s); 1.3-1.1 (4H, m); 0.83 (3H , t, J=7.1 Hz) Step 2: 2-S-[(l,l-Dimethylethoxycarbonyl)amino](hexylamino)propionic acid

call. Η 0 Dissolve 2-S-[(l,l-dimethylethoxycarbonyl)amino]-3-(hexamethylene)propionate (500 mg, 1.27 mmol) in Step 1. In methanol (15 ml), add Pd/C 10% (50 mg). The mixture was hydrogenated at atmospheric pressure for 1 hour. The Pd/C was filtered, and the solution was evaporated under reduced pressure to yield 300 mg of white solid. The yield was 78%. Analytical data: melting point 123-125 ° C.

^NMRCDMSO-dg). δΕ : 12.6 (1Η, br) ; 7.84 (1H, br t) ; 6.87 (1H, d, J=7.5 Hz) ; 4.00 (1H, m); 3.32 (2H, m); 2.04 (2H, t, J=7.5); 1.47 (2H,m); 1.38 (9H,s); 1.3-1.1(43⁄4 m); 0.85(3H,t,J=7.1Hz) Example G.8 2_S- Tri-butoxycarbonylamino-3-(4-fluorosulfonylamino)propionic acid 95014 -246- 1345465

Step 1: 2-S-[(l,1-dimethylethoxycarbonyl)amino]-3-(4-fluorosulfonylamino)propionic acid benzyl S

The 3-amino-2-S-[(l,1-dimethylethoxycarbonyl)amino]propionate propionate (1.25 g, 4.24 mmol, 1 eq.) of Example G.5 was dissolved. Anhydrous di-methane (2 mL) was passed and the solution was cooled to 0-5 ° C under nitrogen. TEA (0.65 ml, 4.67 mmol, L1 equivalent) and 4-fluoro-chlorobenzene (0.9 g, 4.67 mmol) were added in anhydrous methane (10 mL). The mixture was stirred at room temperature for 1 hr, then evaporated and evaporated. The yield was 99%. Analytical data: melting point 105-107 ° C · TLC tannin (solvent: n-hexane / ethyl acetate 1 / 1, Rf = 0.55). ^NMRCDMSO-dg). 7.91 (1Η, t, J = 6.2 Hz) 7.85 (2H, dd, J = 5.3, 8.8); 7.43 (2H, t, J = 8.8); 7.35 (5H, m); 7.15 (1H, d, J = 8.2); 5.09 (2H, s); 4.14 (lH,m); 3.10 (2H, m); 1.36 (9H, s). Step 2: 2-S-[(l,1-dimethylethoxycarbonyl)amino]_3_(4-fluoro) Sulfhydrylamino) 95014 •247- 1345465

2-S-[(l,l-Dimercaptoethoxycarbonyl)amino]-3-(4-fluorosulfonylamino)propionic acid decyl ester of Step 1 (1.8 g, 3.98 mmol) The ear was dissolved in methanol (30 ml) and Pd/C 10% (180 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. "Pd/C was filtered, and the solution was evaporated under reduced pressure to give 1.39 g of a pale oil. The yield was 97%. Analytical data: ^NMRCDMSO-dg). (5h*·12.7(lH,br); 7.83 (2H, dd, J=5.3, 8.8); 7.78 (1H, br t, J=5.5) ; 7.42 (2H, t , J=8.8); 6.87 (1H, d, J=8.6); 3.99 (1H, m); 3.03 (2H, m); 1.36 (9H, s). Example G.9 2-S-[(l, L-Dimethylethoxyxo)amino]-3-(3,4-dimethoxyphenylethylamino)-propionic acid

Step 1: 2-S-[(U-Dimethylethoxycarbonyl)amino] Winter (3 4 -Dimethoxyphenylethylamino)-propionic acid decyl vinegar 95014 -248 - 1345465

3,4-Dimethoxy-phenylacetic acid (720 mg, 3.66 mmol, 1.2 eq.) was dissolved in dry DMF (20 mL) and TBTU (1.17 g, 3.66 mmol, 1.2 eq) The mixture was stirred at room temperature for 20 minutes and then cooled to 〇-5 °C in an ice bath. Add 3-amino-2-S-tris-butoxycarbonylamino-propionic acid benzyl ester of Example G.5 (0.9 g, 3.05 mmol, 1 eq.) with NMM (1.0 mL, 9.15 mmol) Ear, 2.5 equivalents). The mixture was stirred at 0&lt;0&gt;C for 2 h then poured over water (200 mL) andEtOAc. The organic layer was washed with the following solution: citric acid 2% (20 ml), sodium bicarbonate 2% (20 ml), NaCl 2% (20 ml), dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude material was purified by chromatography (yield: n-hexane/ethyl acetate 1/1, Rf = 0.57). Yield 69

Analytical data: 1H NMR (DMSO-d6) (5H: 8.02 (1H, t, J = 5.7 Hz); 7.34 (5H, m); 7.17 (1H, d, J = 7.7); 6.82 (2H, m); 6.71 (1H, dd, J=1.5, 8.2); 5.03 (2H, s); 4.14 (lH,m); 3.71 (3H, s); 3.69 (3H, s); 3.39 (2H, m); 1.36 ( 9H, s). Step 2: 2-S-[(l,1-dimethylethoxycarbonyl)amino]-3-(3,4-dimethoxyphenylacetamido)-propionic acid 95014 • 249· 1345465

2-S-[(l,l-didecylethoxycarbonyl)amino]-3-(3,4-dimethoxyphenylacetamido)-propionic acid, benzyl ester of Step 1 (1 g, 2.1 mmol) was dissolved in methanol (30 mL) and Pd/C 10% (10 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. The Pd/C was filtered, and the solution was evaporated under reduced pressure to yield white crystals. The yield was 91%. Analytical data: WNMRPMSO-dd.SH: 12.7 (lH, br); 8.06 (lH, t, J = 5.9 Hz); 7.00 (1H, d, J = 8.05); 6.91 (2H, m); 6.80 (1H, Dd, J=1.5, 8.4); 4.08 (1H, m) ; 3.80 (3H, s) ; 3.78 (3H, s) ; 3.5-3.3 (2H, m) ; 1.36 (9H, s). Example G.10 2-[(l,l-dimethylethoxycarbonyl)amino]-3-(3-phenylureido)propanoid

HN 乂. ό Methyl ethoxycarbonyl)amino]-3-(3-phenylureido)propionic acid vinegar

'Example 3-Glycol-2-S-KU-dimethylethoxyxyl)amino]propionate propionate (L14 g, 3.87 mmol, 1 equivalent) at room temperature Dissolved in di-gas methane (20 ml). The solution was allowed to cool to 〇 - 5 ° C, and the iso-decanoic acid ester of bis-decane (5 95 014 - 250 · U4M65 house liter) was added dropwise (〇·42 ml ' 3.87 mmol, 1 equivalent). The cold liquid was stirred at room temperature for 1 hour, evaporated under reduced pressure, and purified by silica gel chromatography (solvent-n-hexane/ethyl acetate 1/1) to obtain 0.71 g of a glassy solid. In diethyl ether, a white solid was obtained. The yield was 44%. Analytical data: TLC gel (solvent n-hexane / ethyl acetate, Rf = 〇 44), melting point 48-50 ° C. 1H NMR (DMSO-d6)·dH: 8.68 (lH, s); 7.4-7.27 (8H, m); 7.22 (2H, t, J = φ 8·2 Hz); 6.90 (1H, t, J=7.3 6.26 (1H, t, J=5.7) ; 5.11 (2H, s) ; 4.12 (1H, m) ; 3.58 (lH,m); 3.28 (lH,m); 1.38 (9H,s). Step 2 : 2-[(l,l-Dimethylethoxycarbonyl)amino]phenylurea)propionic acid

Dissolving 2-S-[(l,1-dimethylethoxycarbonyl)amino]-3-(3-phenylureido)propanoic acid benzyl ester (0.7 g, 1.7 mmol) in Step 1 In sterol (25 ml), add Pd/C 10% (70 mg). The mixture was hydrogenated at atmospheric pressure for 1 hour. The Pd/C was filtered, and the solution was evaporated under reduced pressure to give the desired product. The yield is 87%. Analytical data: iHNMRPMSO-i^). (5H: 12.6 (lH, br); 8.66 (lH, s); 7.37 (2H, d, JB.l Hz); 7.21 (2H, t, J = 7.50); 7.08 (1H, d, J=7.9); 6.89 (1H, tjj=7.3); 6.21 (1H, t, J=5.9); 3.98 (lH,m); 3.54 (lH,m); 3.22 (lH,m) 1.38 (9H, s). Example G.ll 95014 -251 · 1345465 Synthesis of other compounds • The following compounds can be exemplified by the &amp; method described in steps 1 and 2 of G.6-G.10, from the example G· 5-3. Amino-2-S-[(l,l-dimethylethoxycarbonyl)amino]propionic acid succinic acid S is prepared starting from G.11.1 2-[(U-dimethyl Ethoxycarbonyl)amino]-3-(ethylguanidino)propionic acid λ G.11.2 2-[(1,1-dimethylethoxycarbonyl)amino]-3-(9-yl fluorenyl) Oxylamine carbaryl)) bismuth propionate. G.11.3 2-[(1,1-Dimercaptoethoxycarbonyl)amino]_3_(3·pentylureido)propionic acid, *N G.11.4 2-[(1,1_dimethyl B) Oxylamino)amino]·3·(decanesulfonylamino)propionic acid Vr/oH XNH o=s=〇G.11.5 2-[(1,1-dimethylethoxycarbonyl)amino] _3_[(ethoxycarbonylsuccinyl)-decylamine]ethyl]•propionic acid. 2 Example G.12 2-[(1,1-Dimethylethoxy)amino]_3_(3_芊Oxycarbonylamino)propionic acid

0 VNH (ΤΛ Step 1: Ν2-(Third-butoxycarbonyl)_L-2,3-diaminopropionate 讲. Speaking of 95014-252-1345465 makes it possible to obtain step 1 of the example G.5 or commercially available The third-butoxycarbonyl-l-aspartate (8 g, 0.034 mol, 1 eq.) was suspended in ethyl acetate (72 ml), acetonitrile (72 ml) and water (36 ml). Under c, iodobenzenediacetate (13.3 g, 0.041 mol, 丨_2 eq.) was added. The mixture was stirred at 1 〇 25 &lt;&gt; (: 3-4 hours, then a white solid appeared. It was washed with diethyl ether and dried under vacuum to give a white powder. The rate was 57% 4 g. Analytical data: melting point 21 (TC - 21 Γ (:. 矽 (methane methane / methanol / acetic acid _ 5 / 3 / l Rf0.5.1H NMR (DMSO-d6) 4.15 (lH, t); 3.15 (2H, m); 1.45 (9H, s); Step 2: 2-[(l'l-dimethylethoxycarbonyl)amine Base]_3(3_芊oxycarbonylamino)propionic acid

(X. human at 25 C such that the step 丄(N2_(T-butoxycarbonyl)_L-2,3-diaminopropionic acid (3.8 g, 0.018 mol' 1 equivalent) is dissolved in aqueous sodium carbonate solution 1〇% (2 2 when I) and 1,4-dioxane (38 ml). In this solution, add gas • bismuth citrate (3 ml, 0.020 mol, U equivalent) The solution was stirred for 3 hours at 25 ° C. Upon completion of the reaction, the mixture was poured into water (1 mL) and washed with diethyl ether (1 mL). (6 ml) 'until pH 2' and the obtained mixture was extracted with ethyl acetate (1 mL). The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. The solvent was obtained as a colorless oil, and white foam was obtained under vacuum. Yield 93%, 5.9 g.

Analytical data: Silicone (dialdehyde methane / methanol / acetic acid 5 / 3 / 1) Finance L 95014 • 253 · 1345465 1H NMR (DMSO-d6) 12.6 (lH, brs); 7.35 (5H, m); 6.94 (lH, d 5(2H, s); 4.1(2H,m); 1.4(9H,s). Example G.13 2-(Terti-butoxycarbamoyl)-3-oxazol-1-yl- Propionic acid

The intermediates were prepared according to the procedure described in Vederas, ./. dw. CAem. &amp; c., 1985, 707, 7105-7109. Example G.14 1-Activation of the base - hexahydro ρ than bite 4 after the rebellion

〇β^=0

Step 1: 1-[(1,1-Dimethylethoxycarbonyl)amino]•hexahydropyridine carboxylic acid

The hexahydropyridine-4-carboxylic acid (5 g, 38.7 mmol, ! equivalent) was dissolved in sodium carbonate solution (4.5 g, 42.61 mmol, 2.2 eq.) 70 ml with Μ•二氧陆园 (3〇 In milliliters). A solution of di-tert-butyl phthalate (93 g, 42 6 mM millimoles, 1.1 eq.) in 1,4-dioxane (40 ml) was added dropwise, and the resulting mixture was added. Stir at room temperature overnight. The organic solvent was removed under reduced pressure and the resulting solution was acidified with &lt The resulting suspension was filtered and the white solid was taken as a milliliter of silk. The mother liquor was 95014 • 254·1345465 and extracted with ethyl acetate (120 ml) and the solid was added. The organic solution was dried over anhydrous sodium sulfate. Analytical data: melting point 133-135 ° C. 1H NMR (DMSO-d6) 12.3 (1H, br s); 3.85 (2H, d); 2.8 (2H, br); 2.35 (lH, t); 1.8 (2H, d 1.4;ll(1,1-dimethylethoxycarbonyl)amino]-hexahydropyridine

1-[(1,1-Dimethylethoxycarbonyl)amino]-hexahydropyridine carboxylic acid (6 g ' 26.16 mmol' 1 equivalent) from step 1 was dissolved in methanol (15 mL) Medium, and adding carbonic acid planer (4.26 g, 13.08 mmol, 〇·5 equivalent) ^ Mix the mixture under the chamber for 2 hours 'The solvent was removed under reduced pressure. The crude material was dissolved in DMF (1 mL) and yttrium bromide (5, 37 g, 3,139 mM, i 2 §) was added dropwise. The mixture was stirred overnight at room temperature and poured into water (3 mL). The organic layer was dried with anhydrous sodium sulfate and evaporated and evaporated Yield 95%, 7 g. Analytical data: 1H NMR (DMSO-d6) 7.3 (5H, m); 5.1 (2H, s); 3.85 (2H, d); 2.8 (2H, br); 2.65 (lH, t); 1.8 (2H, d 1.4; llH, m). Step 3: hexahydropyridine-4-carboxylic acid decyl ester hydrochloride 95014-255 · 1345465

The 1-[(1,1-dimethylethoxycarbonyl)amine hexahydropyridine·4·carboxylate (7 g, 21.0 mmol) was dissolved in ι,4- Dioxane (2 ml). 4NHC1 (7.8 ml, 300 ml, 12 equivalents) in 1,4-dioxane was added to this solution, and the resulting solution was stirred at room temperature overnight. The solid was filtered, suspended in n-hexane (50 mL) and filtered to afford white solid. Yield 54%, 2.5 g. Analytical data: 1H NMR (DMSO-d6) 8.9 (2H, br); 7.35 (5H, m); 5.1 (2H, s) ; 3.25 (2H, d) ; 2.9 (2H, t) ; 2.75 (1H, m 2.0 ; 2 (2H, m) ; 1.8 (2H, m). Step 4: 1-A 炫 醯 - - 六 六 六 六 六 6

I. In a step 3, the hexahydropyridine-4-carboxylic acid benzyl ester hydrochloride (1 g, 3 9 mM '1 eq.) was dissolved in DMF (15 mL). , 4 millimolar, 1 equivalent) with gasified methane sulfonium. The mixture was stirred at room temperature for 1 hour and then poured into water (2 mL). The aqueous solution was extracted with ethyl acetate (9 mL). Yield 78%, 0.9 g. Analytical data: 95014 -256 - 1345465 1H NMR (DMSO-d6) 7.35 (5H, m); 5.1 (2H, s) ; 3.5 (2H, d) ; 2.8 (5H, m); 2.6 (1HS m) ; (2H, m) ; 1.6 (2H, m). Step 5: 1-Methanesulfonyl-hexahydropyridine 4-carboxylic acid

The methanesulfonyl-hexahydropyridine-4-carboxylic acid decyl ester from Step 4 (0.8 g, 26.7 mmol) was dissolved in ethyl acetate (1 mL) and methanol (1 mL). Pd/C 10% (80 mg) was added and the resulting mixture was argonized at 1 bar. The catalyst was filtered on celite and the solvent was removed under reduced pressure to give a white solid. Yield 73%, 0.4 g. Analytical data: 1H NMR (DMSO-d6) 12.4 (1H, br); 3.6 (2H, d); 2.9 (4H, m); 2.4 (1H, m); 2.0 (2H, m) ; 1.6 (2H} m ). Example G.15

Gasification (4-methylphenyl)-matrix-transverse

K-y-c, this compound is based on ed CAem. 1996, double 1243-1252. Briefly, a solution of isocyanate-based sulfonate (1.62 g, 11.5 mmol, 1 equivalent) was diluted in anhydrous diethyl ether and the resulting solution was applied to _5〇〇c &lt;T&lt;_4 Cool down under 〇t. To this solution, p-toluidine (1·23 g, 115 mmol, 1 equivalent) was added. The solution was stirred at _35t for 10 min and a suspension was obtained. &lt;RTI ID=0.0&gt;&gt; Yield 80%, 2.3 g. Analytical data: melting point 127-129° (:·1H NMR (DMSO-d6) 9.9 (1H, s); 7.3 (2H, d); 7.1 (2H, d); 2.25 (3H, s); Example G.16 Isoxazole-5-carboxylic acid

The desired carboxylic acid is prepared according to the procedure of Wolfang et al., 1986, 69-70. Useful Compound Activity The compounds of the present invention inhibit protein degradation body activity. The following table provides data relating to several example compounds of the invention which are related, for example, to the ability to inhibit the activity of a protein degrading agent. Methods and Compositions The compounds of the present invention inhibit the activity of a protein degrading agent, resulting in a protein which is directly or indirectly inhibited by a variety of intracellular functions associated with it. For example, a protein degradation inhibitor can modulate (e. g., cause) cell wilting in cells. The compound which induces sputum in the cytoplasm can kill tumor cells by using it. Thus, the compounds of the invention may treat cancer, tumors or other proliferative disorders. ::: Body: inhibit: protein degradation by the compounds of the invention. This or the immune and inflammatory response and cell viability of the 95014-258-^45465 gene regulation, play a suffix _ can inhibit ubiquitination / protein please disintegration function is also abnormal egg ... ί. This pathway is especially catalyzed by high and short-lived (IV) selective degradation of proteins. According to the specific embodiment of the present invention, the degradation of the blood stab technique of the present invention is "the degradation of the P53 纮", which is degraded by the ubiquitin-dependent pathway. The ubiquitination/proteolysis pathway also involves internalization. cell

Dirty scorpion... The treatment of the scorpion venom antigen into a binding type, using: the compound of the present invention can be used in many cell types of cell lysate myosin-dependent proteolytic system # this 'the utility of this compound Therapeutic agents can be included, such as treatment of various diseases or conditions associated with the body. Such a state, such as a prion protein (4), disintegrates a mammalian steroid associated with a disease or condition, and administers a therapeutically effective amount of a compound or composition of the invention. 2 Therapeutic effective amount, '' refers to the foot (4) prevention, mitigation of this technique. Any phenomenon known to be associated with a disease or condition, such as the cause or severity of the disease.

A treatable disease or condition (abnormal physical symptoms) can be associated with either positive* or iso-hanging activity of the protein, such as the regulation of cell hole zero. , egg: quality degrading body is associated or expected to be induced by cells; weekly treatment = multiple diseases or conditions are known 'and include, for example, various cancers and swollen / including skin, prostate, colorectum, pancreas , kidney, ovary, 1 'liver, tongue, lung and smooth muscle tissue are associated. Preferred tumors that can be treated with egg degrading inhibitors, including but not limited to hematology; for example, leukemia, lymphoma, non-Hodgkin lymphoma, bone marrow cells 95014-259 « 1345465 tumor, multiple myeloma, and solid tumors, such as the colon Rectum, breast, prostate 'lung and pancreatic tumors. To elicit therapeutic effects, the protein degradation inhibitor can be administered to a patient in a single agent or in combination with one or more anti-tumor or anti-cancer agents and/or radiation therapy. Other anti-tumor or anti-cancer agents that may be co-administered with a protein degradation inhibitor, examples of which include, but are not limited to, doxorubicin, daunorubicin, methotrexate, vincristin, 6 - mercapto, arabinoside, cyclophosphamide, 5_fu, hexamethylene cyanide

Amines such as chloramine, cis-amine, edetrecin, pachtaxel, d〇cetaxd, t〇p〇tecan, Illinois (irinotecam), gemcitabine, L_pAM, bCNU and VP-16. Methods for measuring cell dying in vitro are known in the art and kits are commercially available. See, for example, Ap〇_〇NETM homogeneous cysteine

Aspartase _3/7 was detected from Promega, Madison, WI, USA (Technical Bulletin No. 295, Revision 2/02, Promega). Other diseases or conditions associated with protein degradation, including accelerated or enhanced proteolysis, occur in atrophic muscles, such as often associated with the activation of processes involving ubiquitin and requiring non-lysosomal ATp.

Accelerated or enhanced proteolysis can be the result of many, including septicemia, burns, trauma, cancer, infection, neurodegenerative diseases such as muscular dystrophy, acidosis or spinal/neural damage, corticosteroid use, Fever, stress and hunger. The compounds of the present invention can be tested for inhibition of muscle consumption by any of the various procedures known in the art, and are urinary excreted by a modified amino acid 3-methylhistamine (see Personnel, Federation Proc., 1978, 37, 229). For example, by degree, such as Young 95014 -260-1345465

The compounds of the invention may further be used to treat or prevent diseases or conditions associated with NF-/cB activity, including, for example, human immunodeficiency virus (HIV) infection, and due to, for example, transplant rejection, arthritis, infection, inflammatory bowel disease, An inflammatory condition caused by asthma, osteoporosis, osteoarthritis, psoriasis, restenosis, and autoimmune diseases. Therefore, a method for preventing NF-/CB activation in a patient suffering from such a disease is therapeutically advantageous. The inhibition of NF-/cB activity can be utilized, for example, Palombella et al., Ce//1994, 75, The DNA binding assay metric described in 773. Those skilled in the art can readily identify individuals who are susceptible or suspected of having the disease or condition using standard diagnostic techniques.

Example A Detection of chymotrypsinogen activity such as 20S human erythrocyte protein degrading protein (HEP) The protein degradation body chymotrypsinogen activity of the compound of the present invention was examined according to the following procedure.

The 20S Human Red Blood Cell Protein Degrading Body (HEP) ' purchased from Immatics Biotech (Tubingen, Germany) was at 0.2 μg/ml (about 0.6 nM catalytic position) in 〇.〇4% SDS 20 mM Tris buffer' Covered in 96-well microtiter plates. A fluorometer from the company (St. Louis, M0, USA) was added to the Suc-LLVY-AMC (Broken decyl fluorenyl-4-mercaptocoumarin) to a stock solution obtained from 10 mM. In the dimethyl sub-subtraction, the final concentration is 100. The reaction volume is microliters per well. After incubation at 37 ° C for various periods, the concentration of AMC (aminomercaptocoumarin) released on a Perkin Elmer HTS 7000 Plus microplate reader was determined to be 'excitation 370 nm' and emission was 95014. 261 · 1345465 465耄 microns. The activity of the protein degrading body is determined under conditions in which the hydrolysis of the substance linearly increases with time, and the change in the fluorescence signal is proportional to the concentration of the released AMC.

Example B Detection of α-Prochymosin Protoplast Activity The chymotrypsinogen from Sigma was purchased at 〇Ng/ml (, 2 pM catalytic position) at 〇5 M NaC1 5〇 The mM buffer is covered in a 96-well microtiter plate. (4) The self-purchasing company (9) L〇uisM〇, USA) is responsible for the quality of the camping light (Aia_pr〇n amidino-4-mercaptocoumarin) added to the stock solution obtained from 1 mM In the scorpion, the final concentration is 25 I. The reaction volume was 1 〇〇 microliter per well. After various periods of incubation at room temperature, the concentration of released AMC was determined on a Per] dn ElmerHTs 7000P1US microplate reader, 35 shots at 37 Å nm and emission at 465 nm. The chymotrypsinogen activity is enthalpy under conditions in which the hydrolysis of the substrate linearly increases with time, and the change in the Dengguang signal is proportional to the concentration of released AMC.

EXAMPLE C Determination of P HE value of HEP and prochymosin inhibitors ICm values are typically defined as the concentration of compound necessary to produce 5 % inhibition of enzyme activity. "The value of ^ is a useful index of the activity of the compound for its intended use." The protein degradation inhibitor of the present invention has a 1 (:5 〇 value less than about 1 microgram for the inhibition of human erythrocyte protein degradation (HEp). Mohr concentration can be considered to be active. In some embodiments, the inhibitor does not show some specificity for HEP, and inhibits chymotrypsinogen 95014-262-, 134546:) = busy 50 pairs of inhibition % of HEP. The ratio means chymotrypsin Ό/ IC50 (HEP), which is greater than about 1 〇〇. ', the inhibition of chymotrypsinogen activity of bovine α-chymotrypsinogen is based on the assumption of enzyme and different concentrations before adding the substance: the preparation is incubated at 37t for 15 minutes (or 胄α·皮凝The prolactin was originally tested for broth. Each experimental condition was evaluated in triplicate and the replication experiments were performed for the inhibitors described herein. The test compound identified above is considered to be active for the compound of the present invention to inhibit HEP with an ICw value of less than 1000 nanomoles/agriculture. Preferably, the present invention has an IC5 enthalpy for inhibiting HEp below the i(8) nanomolar concentration. More preferably, the compound of the present invention has an ICso value for inhibiting HEP of less than 10 nanomolar. In the tests identified above, it has been confirmed that the compounds of the present invention have a value for inhibiting HEP of less than 1 〇〇〇 nanomolar.

Example D

Cellular detection of protein-like prochymosin activity in Molt-4 cell line

The chymogen activity of the protein degrading body in Molt-4 cells (human leukemia) was detected according to the following procedure. A brief description of this method was previously published (Harding et al., //, wwo/., 1995, /55, 1767). Molt-4 cells were washed and resuspended in HEPES_buffered saline (5.4 mM KC1, 120 mM NaCl, 25 mM glucose, 1.5 mM MgS04, 1 mM pyruvate Na, 20 mM Hepes) and covered in 96_well micro Titrate the white plate to a final concentration of 6χ10ό cells/ml. Then, reduce the various 5χ proteins to 95014 •263 - 1345465 Disintegration Inhibitor Concentrate (or diluted DMS® for control) and add to plate t The final IX concentration, which was diluted 50-fold with hepes-buffered saline, was prepared from a 250X DMSO solution. After incubation at 37 ° C for 15 minutes, the fluorometer cells purchased from the enzyme system catalog number APC48 were able to pass through the culture (MeOSuc-FLF-AFC) (曱 醯 醯 醯 - - Phe-Leu-Phe-7) - Amidino-4-difluoromethylcoumarin) was added to each well at a final concentration of 25 _ from a 20 mM stock solution 'the reaction volume in DMS0 was 1 〇〇 microliter per well. The concentration of AFC released was from p〇iastar 〇ptima, bmG Labtechnologies microplate reader, using an excitation wavelength of 390 nm and an emission wavelength of 520 nm 'monitored every 1.5 minutes' for 3 minutes (22 cycles) . The protein degrading body activity is determined in a condition in which the hydrolysis is linearly increased with time, and the change in the fluorescence signal is positive with the concentration of the released AFC.

Example E Determination of ECs Depreciation of Protein Degradation Inhibitors in MOLT-4 Cell Lines EC: 50 values are typically defined as the minimum and maximum response to inhibition of enzyme activity (this assay is 〇% and 85_9, individually). %) The concentration of the compound required in the middle of the process. The £(:5() value is a useful indicator of the activity of the compound for its intended use. If the compound of the invention has an EC" of less than about 1 micromolar, it can be considered active. Protein in MOLT-4 cells The inhibition of the degradation-like chymotrypsinogen activity was determined by incubating the cells with different concentrations of the putative inhibitor at 37 ° C for 15 minutes before the addition of the substrate. Each experimental condition was evaluated in triplicate. And the replication assay is performed against the inhibitors described herein. 95014 - 264 - 1345465 If the EC" value of the compound of the invention for inhibition of protein degradation in MOLT-4 is below 10 micromolar, then it is It is considered to be active in the assays identified herein. Preferably, the compounds of the invention have an EC" value for protein degradation of less than 2 micromolar in m〇lt_4. The compounds of the invention are preferably The concentration of EC5 in the inhibition of protein degradation in M0LT-4 is less than 200 nanomolar. In the above-identified assay, it has been confirmed that the compound of the present invention inhibits the protein degradation body in MOLT-4 cells. ECS 〇 The value is less than 1 〇 micromolar concentration. Example F Detecting Protein Degradation The detection of the activity of the photoreceptor of the human protein is as described above and can be detected by the following modification. The reaction can be supplemented with i 2_ It is carried out in Tris·Glycerol buffer (pH 9.5) of mercaptoethanol, and the receptor may be a fluorescent precursor, such as a methoxy-based group--Phe--Arg-AMC (100 _). Under 37 C After incubation for various periods, the released concentration can be determined on a • F1U〇r〇Skan Π Spectrometer with a 390 nm excitation filter and a 460 nm emission filter. Protease activity can be The mass hydrolysis is measured linearly over time, and the change in fluorescence is proportional to the concentration of released AMC.

Example G The effect of an inhibitor of in vivo inhibition of cell muscle breakdown on the unweighted atrophy of the soleus muscle in juvenile rats can be as described, for example, by Tischler, 1990, 756, for example, 'young female history. Sprague-Dawley rats 95014 -265-1345465 (80-90 grams) can be suspended by the tail mold and hind limbs as described by Jaspers et al., ρ/· 1984, 57, 1472. The hind limbs of the animal can be raised above the scorpion floor of each of the individual animals, and the animals can freely obtain food and water and can be weighed at the time of suspension and the time of termination. During this suspension, the animal can be inspected daily to ensure that its toes are not in contact with the cage floor, and there is no swelling of the tail due to the mold. β Experimental Design - Part 1 Each experiment can be started by suspending 20 rats. The lines were randomly divided into 4 groups of 5 animals each. The sputum group can be suspended for 2 days, providing baseline data on the size of the soleus muscle in other animals that were suspended for a longer period of time. At the beginning of the study, the average body weight of the cohort was compared and used as a correction factor for body size differences. Group B can be a second control group with a soleus muscle of one limb treated with an aqueous solution of Mercury two days after no aggravation to confirm the ability to slow muscle atrophy in each group of animals during no weighting. On the 2nd day after the start of the unweighted, the aqueous solution of Mercury (2 mM; 4 μL / ι gram initial weight) was introduced into a soleus muscle. The contralateral muscle can be injected in the same volume 9 _ melon water (vehicle). The sputum can be kept under the pressure of Inn 〇 Var-Vet (10 μl / 1 gram body weight) during the on-site injection procedure. After the injection, the animals can be resuspended for 24 hours' and the soleus muscle can be removed. Each of the experimental and group 1) can be used to test each of two different specific embodiments of the disclosed compounds. The substance can be treated as B, and can be injected into the soleus muscle of one foot in the dimethyl protein degrading inhibitor contained in dimethyl sulphate ((10)), and only DMSO is injected into the contralateral soleus muscle. Therefore, each experiment contained two control groups and a test for the degradation of the proteosome inhibitor of the protein of the present invention. Five of these 95014 • 266 - 1345465 experiments were tested with different inhibitions of Panyu _ + + for the 'system' to provide a V value of 10 to test each inhibitor, and each can be tested in two different transports of the animal . Treatment of the soleus muscle - Part 1 After the animal has been sacrificed, the h, remove the soleus muscle, trim the fat and connective tissue, and carefully weigh it. The splicing, ·, s... has made the muscles homogenized in 10% trichloroacetic acid (TCA) and granulated by centrifugation to precipitate. Next, the pellets can be washed once with 10% TCA, fen,,,, ρ / 尤 滁 and washed once with ethanol: ether (1··1). Can make the most

The pellets afterwards were dissolved in 4 ml of sodium oxide t. The protein content of the sample can then be analyzed by the bile procedure using albumin as a standard. Data Analysis - Part 1 The effect of inhibitors on total muscle protein content can be tested primarily by comparison with untreated contralateral muscle pairs. The ratio of the computable content was then analyzed statistically by analysis of variance (&quot;AN〇VA&quot;). The left foot can always be the treated foot so that the protein content ratio can also be compared to: 绖 treated control animals. In this way, significant differences can be shown by comparing the protein content of both feet and the relative effectiveness of the tested inhibitors. The paired Student test can also be performed for each separate treatment. The '.'f treatment control data also provided an estimate of protein content on day 2. This allows for an approximation of protein changes within 24 hours of treatment for each of Groups B, C, and D. Experimental Design - Part 2 Each experiment may include 10 animals, of which the group of 5 animals is the effect of the inhibitor on the protein synthesis. In this study, it was not necessary to control the animals, and the muscles of the contralateral DMS treatment were used as inhibitors to treat the matched phase of the muscles. Each group can be injected as described in Section 1 for Groups C and D. The grading rate of protein synthesis can be analyzed in two soleus muscles twenty-four hours after treatment at 95014 - 267 · 1345465. Each muscle may be injected with 3H-phenylalanine (50 mM; 1 ml) in 0.9% saline solution (3 5 μl / 1 gram final weight). After fifteen minutes, the middle two-thirds of the muscles can be removed and the muscles can be treated as described below. Treatment of soleus muscle - Part 2 First, the muscles can be washed in 0.84% saline for 1 minute. The brine contains φ 〇.511^cycloheximide to stop protein synthesis, and 20 mM cyclic leucine to capture cells. Amphetamine. The muscles can then be homogenized in 25 ml of ice-cold 2% peroxyacid. The precipitated protein can be granulated by centrifugation. One liquid supernatant can be used for liquid scintillation counting, and another liquid fraction can be processed to convert the albinoic acid to phenethylamine, and the concentration of phenylalanine can be measured by fluorescence metering. . See, for example, Garlick et al., (10) 1980, 1980, 792, 719. This specific value provides intracellular specific activity. The specific activity of amphetamine in muscle protein can be determined after the protein is heated by heating in your Ηα. The released amino acid can be dissolved in a buffer. It is advisable to use one aliquot for scintillation counting and the other for phenylalanine, as for the supernatant fraction. The rate of fractionation of protein synthesis can be calculated as follows: protein specific activity/intracellular specific activity χ time. Data Analysis - Part 2 Analysis of protein synthesis can be based on pairing for each inhibitor. Comparison of the Student's paired t test of the contralateral muscles can determine whether the inhibitor has any effect on protein synthesis. Protein breakdown can be approximately at the rate of protein synthesis (from Part 2) plus the rate of protein growth (from Part 95014 - 268 · 1345465 where protein loss produces a negative protein growth. Inhibitor slows down proteins Loss without affecting the slowdown of protein degradation in protein lines. In vivo study substances for antitumor activity

A protein degradation agent inhibitor for in vivo studies can be formulated in an appropriate medium for intravenous or oral administration. For example, for intravenous administration, the compound can be dissolved in Q9% Naa or in Na (four), s〇lu coffee 5 and dimethyl hydrazine, for example, in a ratio of 87: ι〇: 3 (nine) V,)

i) st is calculated, qualitatively speaking, the ability to synthesize, the mixture of examples 投 is administered. The cell lines are different as follows: Human and mouse tumor cell lines derived from the source of the test can be used to test the antitumor activity of the compounds of the invention: H46(human, lung), a278 (human, ovary), pC-3 (human) , prostate), L〇v〇 (human, colon), HCT116 (human, colon), BXPC3 (human, septic) pANci (human, sputum), MX-1 (human 'breast), M〇LT (human , white disease), multiple myeloma (human, myeloid cell tumor), YC8 (mouse, lymphoma), U2i〇 (mouse, leukemia) '3LL (rat, lung). Animal species 5-6 week old immunologically active or immunodeficient mice were purchased from commercial sources, for example from Harlan (Correzzana, Mi Italy). The CD 1 nu/mi mouse line was kept under sterile conditions using sterilized pets, valerian, food and acidified water. Tumor cell implantation and growth 95014 -269-1345465 Solid tumor models of different tissue types (lung, ovary, breast, prostate, pancreas, colon) can be transplanted subcutaneously (sc.) to the area of immunocompetent mice (mouse mode) Or immuno-deprived mice (human model). The human tumor cell line originally obtained from ATCC can be modified to grow from a &quot;in vitro culture&quot;, &lt;11 in vivo&quot; to a solid tumor. Hematology human or mouse tumor models can be transplanted to different locations of immunocompetent mice (mouse tumors) or immuno-deprived mice (human white blood disease, lymphoma, and myeloid cell models) according to their highest tumor dose (iv, ip , ic or sc). Medication The rats with solid (segmented) or hematological tumors were randomly divided into experimental groups (10 mice/IE) 1 in solid tumors, and the mean tumor weight of the group was _mg is considered to start treatment; Rat with the largest tumor. The experimental group was randomly designated as a drug treatment and a control group. Animals may be treated intravenously N or orally, depending on the oral bioavailability of the compound, according to different treatment schedules: intravenously or twice a week, or by daily oral administration. In solid-state tumor mode, drug therapy can begin after tumor transplantation (Day 0), with tumor sizes ranging from 80-100 mg. The compound can be administered in a suitable volume and in a volume of H) ml/kg body weight/rat. Parameters for anti-tumor activity The following parameters can be used to estimate the anti-tumor activity: 95014 -270· 1345465 'Measured by caliper in each mouse; &quot; When compared with control mice, t I ί ^ red treated mice Survival time • Weight assessment of individual mice twice a week.

Tumor growth inhibition TO (% of primary tumor growth inhibition compared to vehicle-treated controls), or in the case of segmented tumors, relative tumor growth inhibition RTWI%, one week after the last drug treatment As assessed, and tumor weight (TW) can be calculated as follows: TW = 1/2 ab2 where a and b are the long and short diameters of the tumor mass, expressed in millimeters. Antitumor activity can be determined by tumor weight inhibition (TWI%), which is calculated according to the following formula: X 100

The growth method of primary solid tumors was monitored twice a week for RTWI% (relative percentage of primary tumor growth inhibition in comparison with the vehicle-treated control group), according to the following formula, in the final drug treatment Evaluation after the following week: RTWI% = 1〇〇 -

Average RV of treated mice vs. average RV of control mice

XlOO vt (tumor weight on day t) ^ ^ RV (initial tumor weight at the beginning of treatment) The percentage of tumor regression can be calculated from the perspective of tumor weight, which is calculated by degrading the tumor weight on a specific day. It was determined by the initial tumor weight of the experiment. 95014 • 271 · 1345465 On the hematological tumor model, tumor activity was measured as an increase in the mean survival time of the mice, which was expressed in the treatment group (τ) versus the control group (the mean survival time ratio (T/C%). At the end of the experiment (6 days after transplantation), the tumor-free animal line was excluded from the calculation and was considered to be a long-term survivor (LTS) and was evaluated for toxicity in tumor-bearing mice.

Toxicity can be assessed daily by total necropsy findings and weight loss. When death occurs before the death of the vehicle-treated control animals, or when significant weight loss (>20%) is found and/or the spleen and liver size decrease, the mice are considered to have died of toxicity. BWC% ( % change in body weight was evaluated as follows: 1〇0 _ (average mouse body weight on a given day / average body weight at the start of treatment) X 1〇〇. This value is determined one week after the last treatment of the test compound. Example 活 In vitro viability of cells

The 1 (:5() value of cell viability in the presence of the test compound is measured and can be determined according to the following procedure. Cells can be seeded at different densities in 96 well plates and then 'after 24 hours' use The yellow chlorophyll-AM viability assay is used to determine the optimal final density for each cell type. The cells can then be dosed at 100 microliters of the appropriate cell culture medium known to the artist. Next, inoculate in a 96-well plate. A serial dilution of the test compound can be made so that the concentration is twice the concentration desired to be evaluated. When 100 microliters of the dilution is then added to cover the 100 microliter medium. In the middle of the cells, a final concentration of, for example, 0, 11.7, 46.9, 95014 - 272 - 1345465 187.5, 375, and 750 nM can be obtained. The compound can be added to the plate three to four hours after seeding the cells, and then, The plate is cultured at 37*&gt;c and subjected to the desired time point (for example, one, two or three days). The calcein-AM viability test can be carried out at the desired time as described below. Manifolds and metal plates can be used. Aspirate the medium, Leave approximately 5 μL/well. The well can be washed three times with 200 μl of DPBS, each time with a manifold suction to leave 50 μL/well. Calcium Chlorophyll-am can be prepared in DPBS 8 _ Solution, and 150 microliters can be added to each well. The plate can then be incubated for 30 minutes. After incubation, the calcein can be pipetted and the cells can be washed with 200 microliters of DPBS as described above. After aspiration, the fluorescence can be measured using a Cytofluor 2300 Fluorescent Plate Reader. The negative control can contain medium without cells, and experiments can be performed in triplicate.

EXAMPLE L In Vitro Kinetics Experiments Compounds of the invention can be tested for protein degradation activity by using the compounds described in Rock et al, Ce//, 1994, 75, 761, as the protein degradation agent interacts with the test compound. When a complex is formed, according to this procedure, a dissociation constant of equilibrium is established (Κ〇. The reaction can be carried out using a 20S protein degradant activated by SDS from rabbit muscle, and the protein degrading body can be Suc-LLVY-AMC)抑制 Inhibition of NF-/cB activation can be tested for inhibition of NF-/cB activity by performing the assay described in Palombella et al, Ce//, 1994, 78, 773. For example, MG63 Bone 95014 • 273· 1345465 Cancer cells can be stimulated by treatment with TNF-α for the indicated time. Whole cell extracts can be prepared and detected by electrophoretic mobility shift using the human IFN-0 gene promoter. Analysis of PRDII probes. Example 化合物 Compound activity

Using the above-described Example C and the detection of the examples, the following Table F-1 demonstrates the utility of the compounds of the present invention for inhibition of protein degradation bodies. In the following table, for inhibition of HEP, Example C, on the IC5〇 of HEP inhibition, the compound of the invention having "+&quot; is less than 1000 nM; the compound of the invention having &quot;++&quot; is lower than 100 nM; and the compound of the invention having "+++" is less than 10 nM. In the following table, for inhibition of MOLT4, Example E, on the EC5 inhibition of HEP inhibition, the compound of the invention having "+" is lower than ΙΟΟΟΟηΜ; the compound of the invention having "++" is less than 2000 nM; The compound of the invention having "+++" is less than 200 nM. In the case of "&gt;+", the active system is greater than the limit of detection. The data is yet to be determined without the IC5 threshold or EC50 value.

Table F-1 Example number HEP (IC5〇) MOLT4 (ECs〇) D.1.1 -Η-+ D.1.2 -Μ- -Η- D.1.3 -Η-4- -Η- D.1.4 -Η-+ +-Η- D.1.5 +-Η- -R* D.1.6 -Η- D.1.7 ++ + D.1.8 -Η-+ -Η- D.1.9 -Η- D.1.10 -Η- D. 1.11 ++ D.1.12 -ΗΗ- ++ D.1.13 -Κ-+ + 95014 -274- 1345465

95014 D.1.14 -H- &gt;+ D.2 -Hl· -Kl· D.2.1 -HH- -H- D.2.2 -HH- &gt;+ D.2.3 HH- -HH- D.2.4 -HH - -hH- D.2.5 -H- D.2.6 -H- + D.2.7 HH- -HH- D.2.8 -H- -HH- D.2.9 -HH- -HH- D.2.10 -HH- - HH- D.3.1 -Hf D.3.2 +-H- -HH- D.3.3 +-H- -H- D.3.7 -HH- -HH- D.3.8 +++ -Hl· D.3.11 +- H- D.3.12 -HH- -H-+ D.3.15 -HH- D.3.24 -hH- -HH- D.3.26 -Hf- +-H- D.3.27 -H-+ -HH- D.3.29 -HH- D.3.31 -H- -H- D.3.32 +++ D.3.34 D.3.36 -H-+ +-H- D.3.37 +++ -HH- D.3.38 -Hl· -Hh D .3.39 -Hh -H-+ D.3.43 -H-+ D.3.49 -Hf ++ D.3.50 -hH- -Hf D.3.54 -H-+ -HH- D.3.55 -HH- D.3.57 - HH- -HH- D.3.58 -hhi- +++ D.3.59 +-H- ++ D.3.62 -hH- +-H- D.3.64 -hH- -HH- D.3.66 -H-+ - H-+ • 275 ·

1345465

D.3.67 -Hh -HH- D.3.68 -Hl· D.3.69 -H-+ D.3.70 -HH- -m- D.3.73 HH* +-H- D.3.75 -hH- -Hh D.3.76 -HH- D.3.77 -H-+ D.3.78 -Kf D.3.80 -Hf D.3.87 +-H- D.3.89 -HH- D.3.91 -HH- +++ D.3.92 -H-+ D .3.93 -Hf HH- D.3.94 -fH- -HH- D.3.96 -hH- -HH- D.3.97 -HH- -HH- D.3.102 -Hh -H- D.3.103 -H-+ -H - D.3.104 -Hh D.3.105 -H-+ -H- D.3.115 -HH- D.3.117 -HH D.3.119 +++ +-H- D.3.122 -fH- +++ D.3.124 - HH- +++ D.3.125 -HH- D.3.126 -H-+ -HH- D.3.128 +++ -H- D.3.129 -H-4- D.3.130 -HH- D.3.131 +-H - D.3.132 -H-4- D.3.133 +++ D.3.136 +++ &gt;-l· D.3.137 H-+ + D.3.138 ++ ++ D.3.161 -HH- D.3.174 - H- -H-+ D.3.175 ++ ++ D.3.176 +-H- +++

95014 • 276· 1345465

D.3.177 -HH- -HH- D.3.178 -H- HH- D.3.179 -HH- -HH- D.3.180 -Hl· -Hl· D.3.182 -H- -H- D.3.185 -HH- HH- D.3.186 -Hl· -hH- D.3.189 HH- -HH- D.3.190 4-H- -HH- D.3.191 -HH- -H-+ D.3.192 -H- 十 D.4.3 - Hh -HH- D.4.4 -HH- -fH- D.4.6 ++ HH- D.4.7 -H- -Hl· D.4.8 -Kf D.4.9 -H- -H-+ D.6.3 -HH- -Hh D.6.5 -H-+ -HH- D.6.8 ++ -HH- D.6.9 -Hl· +-H- D.7.1 -Hi- + D.7.2 -HH- + D.7.3 -HH- + D.7.4 -H-+ &gt;+ D.7.5 +++ D.7.6 -Hl· &gt;+ D.7.7 HH- &gt;4- D.7.8 -H-+ &gt;4- D.7.11 - H-+ + D.7.12 -HH- &gt;+ D.7.17 -HH- -H- D.7.19 -H-+ + D.7.20 -Hf + D.7.21 + D.7.23 +++ &gt;+ D .7.24 -H- D.7.25 + D.7.26 +++ + D.7.27 -Hf- + D.7.28 -H-+ &gt;+ D.7.30 ++ &gt;+ 95014 • 277· 1345465

95014 D.7.31 &gt;+ D.7.32 -HH- + D.7.33 -H-+ + D.7.35 -HH- &gt;+ D.7.36 4-H- + D.7.37 -Hl· &gt;+ D. 7.38 -H4- D.7.39 -HH- + D.7.41 -Hf 4-M- D.7.60 HH- + D.7.61 -HH- &gt;+ D.8 -Hl· D.8.4 -H- -Hl· D.8.5 -Hl· D.8.6 -Hh -Hf D.8.18 -hl· -H- D.8.19 -HH- -Hl· D.8.20 -fH- -HH- D.9 -H-+ -Hf D .12 -f+4- D.16.6 -Hh -Hh D.18 -H-+ -HH- D.19 -h-hf -H-+ D.24.3 +-H- HH- D.24.4 -HH- -Hf D.24.6 +-H- 4-H- D.24.8 +++ -HH- D.24.9 +++ -h++ D.24.10 4-H- +-H- D.24.11 +-H- HH- D.24.12 -HH- -HH- D.24.14 -HH- +++ D.24.15 -HH- D.24.16 +-H- E.1.1 +-H- &gt;+ E.1.2 HH- + E.1.3 +++ -H- E.1.4 -H-+ -H- E.1.5 -HH- &gt;4- E.1.6 ++ + E.1.7 +-H- + E.1.8 -HH- &gt;+ • 278 - 1345465

95014 E.1.10 -HH- E.1.11 -HH- -H- E.1.12 -Hl· &gt;f E.1.13 -Hl· + E.1.14 -HH- E.1.15 -HH- -H- E.1.16 -HH- -H-+ E.1.17 -Hh -Hf E.1.18 -lH- -HH- E.1.19 -HH- -H- E.1.20 -H-+ E.1.21 -iH- +++ E. 1.22 -HH- E.1.23 -Hl· -Hf- E.1.24 -HH- -Hf E.1.25 HH- E.1.26 +++ E.1.27 -Hh E.1.28 -H-+ ++ E.1.29 - H-+ -H- E.1.30 -HH- + E.2.1 -HH- HH- E.2.2 -H-+ -H- E.2.3 -hH- + E.2.4 &gt;+ E.2.5 -H- + + E.2.6 -HH- -H- E.2.7 -Hf + E.2.8 -m- + E.2.9 -fH- -H- E.2.10 &gt;+ E.2.11 -HH- &gt;+ E. 2.12 -H~f HH- E.2.13 -Hh + E.2.14 +++ &gt;+ E.2.15 -HH- E.2.16 -Hf &gt;+ E.2.18 -HH- + E.2.19 +-H- + E.2.20 -hhl· + E.2.21 HH- + E.2.22 -HH- -H- -279- 1345465

E.2.23 -HH- -H- E.2.24 -HH- &gt;+ E.2.25 +-H- + E.2.26 -Hf* &gt;+ E.2.27 -HH- &gt;4- E.2.28 -HH - &gt;+ E.2.29 -HH- + E.2.31 4-hh &gt;+ E.2.32 -H-+ &gt;+ E.2.33 -Hh + E.2.34 -HH- + E.2.35 &gt;+ E .2.36 4-H- &gt;+ E.2.37 +++ &gt;4- E.2.38 HH- X E.2.39 -HH- HH- E.2.40 -HH- + E.2.41 -HH- &gt;+ E .2.42 ΉΗ- E.2.45 -H-+ +++ E.2.46 -HH- ++ E.2.47 -tH* E.2.48 -Hh -H- E.2.49 -H-+ &gt;+ E.2.50 + ++ &gt;+ E.2.51 -H- &gt;+ E.2.52 + E.2.53 -H- &gt;+ E.2.54 -HH- &gt;+ E.2.55 HH- + E.2.56 -HH- + E .2.57 -HH- + E.2.58 HH- + E.2.59 +++ + E.2.60 -hh-h X E.2.61 +-H- + E.2.62 -Hh &gt;+ E.2.64 &gt;+ E .2.65 &gt;-h E.2.66 -H*+ &gt;+ E.2.67 + E.2.68 -Hl· &gt;+

95014 • 280- 1345465

95014 E.2.69 -Hf &gt;f E.2.70 -Hl· &gt;H- E.2.75 -H-+ &gt;+ E.2.76 -HH- + E.2.77 -HH- + E.2.78 -H-+ + E.2.79 -Hh -H- E.2.80 -H- + E.2.81 -H- + E.3 -Hl· HH- E.3.1 +-H- -Hf E.3.2 HH* E.3.3 -HH - HH- E.3.4 -H- -4-H- E.3.5 -Hl· -Hf E.3.6 -HH- -Hf E.3.7 -Hl· -HH- E.3.8 -Hf -Hh E.3.9 4 -H- HH- E.3.10 +++ +++ E.4 -HH- -H-+ E.4.1 -H- -H- E.4.2 -H- -Hl· E.4.3 -HH- -H -+ E.5 -HH- +++ E.5.1 -Hl· E.5.2 -1-+4- -fH- E.5.3 -H- -H- E.5.5 E.5.6 Hl· E.5.7 - hH- -HH- E.5.8 -hH- -hH- E.5.9 -HH- -hH- E.5.10 +-H- -H-+ E.5.11 -hH- -H-+ E.5.12 -M- + +-H- E.5.13 -H-+ +-H- E.5.16 4-H- E.5.17 +++ -H- E.5.18 +-H- -1-++ E.5.19 -H- 4- -ffh E.5.20 -Hl· -HH- • 281 -

1345465 E.5.21 -Hf HH- E.5.22 -HH- +-H- E.5.24 HH- -H- E.5.25 -Hf -Hl· E.5.26 -Hl· -H- E.5.27 -HH- - HH- E.5.28 -(-Η- -HH- E.5.29 -fH- -HH- E.5.30 -fH- -H- E.5.31 -H-+ +-H- E.5.32 -Hl· -Hl · E.5.33 -HH- 4-f E.5.34 -Hf -Hl· E.5.35 -HH- -Hl· E.5.36 -H- -H- E.5.37 +-H- -HH- E.5.40 Ί1 Ί Ί&quot; -h-Hh E.5.41 -H- F.1 F.2.1 -H- -H-

Pharmaceutical formula and dosage form

When used as a pharmaceutical, the compound of formula (I) can be administered in the form of a pharmaceutical composition. Such compositions can be administered by a variety of routes, including buccal, rectal, transdermal, subcutaneous, intravenous, intramuscular, and intranasal, and can be made in a manner known in the art of medicinal techniques. The invention also includes pharmaceutical compositions containing one or more of the above compounds of formula (I) as the active ingredient in combination with one or more pharmaceutically acceptable carriers. In making the compositions of the present invention, the active ingredient is typically mixed with the excipient, diluted by excipients, or enclosed in a carrier such as a capsule, sachet, paper or other container. When the excipient serves as a diluent, it can be a solid, semi-solid or liquid material which acts as a vehicle, carrier or vehicle for the active ingredient. Therefore, the composition may be in the form of tablets, pills, powders 95014-282-1345465, tablets, sachets, cachets, ugly agents, suspensions, emulsions, solutions, glycosides, aerosols (made as solids, Or in a liquid medium, containing, for example, up to H) by weight of active compound (iv), soft and hard gelatin capsules, test, sterile injectable solutions and aseptically packaged powders.

In preparing the formulation, the active compound can be ground to provide the appropriate particle size prior to combining with the soy ingredients. If the active compound is substantially insoluble, it can be ground to a particle size of less than 2 (8) mesh. If the active compound is substantially water soluble, the particles are adjusted by milling to provide a substantially uniform distribution in the formulation, e.g., about 4 mesh.

Some examples of suitable excipients include lactose, dextrose 1 sugar, flower germination, mannitol, starch, gum arabic, squaric acid, alginate, scutellaria, gelatin, shixi _, microcrystalline Cellulose, polyvinyltetrakis(tetra)ketone, cellulose, water, syrup and methylcellulose. These formulations may additionally comprise: a slip agent, such as talc, magnesium stearate and mineral oil; a wetting agent; an emulsifying and suspending agent; a preservative, such as a bitter formic acid and a vinegar; a sweetener; And a scenting agent. The compositions of the present invention can be formulated by the procedures known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a patient. The compositions may be formulated in unit dosage forms containing from about 5 to about 1 mg, more usually from about 10 to about 30 mg of active ingredient per dose. &quot;Unit dosage form, the term '" means a physically discrete unit suitable as a single dose for use by human patients and other mammals, each unit containing a predetermined amount of active substance calculated to produce the desired therapeutic effect, and Accompanying appropriate medical excipients. The active compound is effective to cover a wide range of dosages and is generally administered in an effective amount at a pharmaceutical level of from 95014 to 283 to ^345465. However, it should be understood that the amount of the compound actually administered is usually determined by the physician based on the condition of the association, including the condition to be treated, the route of administration chosen, the actual compound being administered, the age of the individual patient, Weight and response, the severity of the patient's symptoms, etc. For the preparation of a solid composition, such as a tablet, the main active ingredient is mixed with a pharmaceutical excipient to form a solid pre-formulation composition containing a homogeneous mixture of the compound of the invention. When the pre-formulated composition is said to be homogeneous, the activity is The ingredients are typically dispersed evenly throughout the composition such that the composition can be readily subdivided into equivalent effective unit dosage forms such as tablets, pills, and capsules. This solid pre-formulation is then subdivided into unit dosage forms of the type described above containing, for example, from 0.1 to about 500 mg of the active ingredient of the present invention. The tablets or pills of the present invention may be coated or otherwise blended to provide a dosage form which will provide the advantage of long term action. For example, a tablet or pill may contain an internal dose and an external dose component, the latter being in the form of a coating covering the former. The two components can be separated by an enteric layer which prevents disintegration in the stomach and allows the internal components to pass intact into the duodenum or be delayed. A wide variety of materials are available for use in such enteric layers or coatings, including a wide variety of polymeric acids, and mixtures of polymeric acids with materials such as shellac, wax alcohol, and cellulose acetate. The liquid form in which the compounds and compositions of the present invention can be incorporated for oral administration or administration by injection includes aqueous solutions, suitably flavored syrups, aqueous or oily suspensions, and flavoring emulsions with edible oils, such as cottonseeds. Oil, sesame oil, coconut oil or peanut oil' as well as elixirs and similar pharmaceutical vehicles 0 95014 -284. 1345465 Compositions for inhalation or insufflation, including solutions in pharmaceutically acceptable aqueous or organic solvents or mixtures thereof With suspension, and powder. The liquid or solid compositions may contain a suitable pharmaceutically acceptable excipient as hereinbefore described. In some embodiments, the composition is controlled by oral or nasal respiratory tract to provide a local or systemic effect. The composition can be atomized by inert gas. The atomized solution can be directly aspirated from the atomizing device, or the spray device can be connected to a mask tent or an intermittent positive pressure beer suction machine. The solution, suspension or powder composition can be administered orally or nasally from a device that delivers the formulation in an appropriate manner. The amount of the compound or composition to be administered to the patient will vary depending on the person being administered, the purpose of administration, such as prevention or treatment, the state of the patient, the mode of administration, and the like. In therapeutic applications, the composition can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the signs of the disease and its complications. Sufficient to achieve such an amount, is called &quot;therape effective amount,,. The effective dose is determined by the condition of the disease being treated, and by the judgment of the responsible clinician, such as the severity of the disease, the age, weight and general condition of the patient. The composition to be administered to a patient can be in the form of a pharmaceutical composition as described above. These compositions can be sterilized by conventional sterilization techniques or can be sterilized by filtration. The aqueous solution may be packaged&apos; used in its own right, or via; the dry formulation, which is administered in combination with a sterile aqueous carrier. The pH of the compound preparation is typically between 1 and 1, more preferably 5 to 9, and most preferably 7 to 8. It will be appreciated that the use of certain of the foregoing excipients, carriers or stabilizers will result in the formation of a pharmaceutical salt. ' 95014 1345465

The therapeutic dose of the compound of the present invention can be varied depending, for example, on the particular use of the treatment, the manner in which the compound is administered, the health and condition of the patient, and the judgment of the designated physician. The ratio or concentration of a compound of the invention in a pharmaceutical composition can vary depending on a number of factors, including dosage, chemical characteristics (e.g., hydrophobicity), and route of administration. For example, a compound of the invention can be provided in a physiological buffer solution containing from about 0.1 to about 10% w/v of the compound for parenteral administration. Some typical dosages range from about 1 microgram per kilogram to about 1 kilogram per kilogram of body weight per day. In some embodiments, the dosage range is from about 001 mg/kg to about 100 mg/kg body weight per day, and the dosage is also dependent on a number of variables, such as the type and extent of progression of the disease or condition, and the overall health of the particular patient. State, relative biological efficacy of the selected compound, excipient formulation, and route of administration. The effective dose can be extrapolated from the dose-response curve of the in vitro or animal model test system.

The invention also includes a pharmaceutical kit which can be used, for example, to treat or prevent an inflammatory disease, which comprises - or a plurality of containers comprising a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I). If desired, such kits can incorporate one or more of the various conventional medical kit components, such as containers having one or more pharmaceutically acceptable carriers, other containers, etc., as will be apparent to those skilled in the art. The instructions, whether it is to make an insert or to make a mark t show the amount of ingredients to be administered, the dosing finger? | and / or a mixture of ingredients can also be included in the kit. Various modifications of the invention are apparent to those skilled in the art from the foregoing description. Within the scope of the request. In addition to those described in this application, such revisions are also intended to fall within the references cited in the accompanying text, including patents, published patent applications, and journal articles. The full text is hereby incorporated by reference.

95014 287 ·

Claims (1)

1345465 $093124291 Patent Application Chinese Shen% Patent Range Replacement (October 99) X. Patent application scope: A compound of formula (I) (I) or a pharmaceutically acceptable salt, stereoisomer or tautomeric form thereof, wherein: ^ is ^-^alkyl; r2 is -(CH2)eCH(R7)ZR8; _e is 0,1 2, 3 or 4; R7 is an alkyl group; H Ci〇 alkyl, Ci-C20 alkyl-S(=0)2·, Cg-C丨8 aryl-S(=〇)2_, h2NS (= 0) 2-, _803Ή or a protecting group; Ζ is 〇; Q is -β(οη) 2 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane vinegar contains 2 to 20 carbon atoms, and The case contains a hetero atom which may be Ν, S or ;; _ X is RAC(=0)-; RA is a c3 _C2G carbocyclic group substituted by 1-5 R2, as the case may be; or 1_5 R2, as the case may be a substituted heterocarbocyclyl; r2 1 is selected from the group consisting of CVC20 alkyl, C2-C2()alkenyl, C2_C2()alkynyl, 〇R2ia, _SR21a, -CN, halo, halo C^Cio alkyl, _nh2, alkyl), -N(c丨-Ci Q alkyl)2, -NHC(=〇)〇-Cl _Cl Q alkyl, _Ci 〇95014-99l001.doc 1345465 alkyl, -COOH, -(3(=0)0-(^-(^0 alkyl, -(:(=0)(^-C1()alkyl, -C(0)H, -SpOHVC丨〇alkyl , -S(=0)2-Ci-C1()alkyl, -ShCO-Qq 8 aryl, -SH&gt;)2 -C6-C〗 8 aryl, C3-C2Q carbocyclyl substituted by 1-5 R22, and heterocarbyl ring substituted by 1-5 R22, as the case may be; R is Η, Cl -C2 〇 An alkyl group, a -C2 fluorene group, a C2 -C2 fluorenyl group, a C3 _匸2 fluorene carbocyclic group or a heterocarbocyclic group; I R22 is selected from the group consisting of: Ci -C 〗 0 alkyl, C2 - Ci 〇, C 2 -Ci 〇 fast radical, phenyl, functional group, halo q-CM alkyl, qQ alkoxy, sulfur CrQ alkoxy, amine, Ci-C1G alkylamino, dialkylamine Base, carboxyl group, Ci-Cw alkyl-〇C(=〇)_, C! -C! 0 alkyl group-C(=0)-, c6-C! 8 aryl-0C(=0)-, Ci -C]! 0 calcination base - 0C (=0) NH-, C6 -C! 8 aryl-〇c(=〇)NH-, q -Cj 〇alkyl-C(=0)NH-, (VC10 Alkyl-C(=〇)〇-, (q-Cio alkyl-0)r-Ci-C10 alkyl, HCKQ-Cw alkyl. Alkyl-, -〇H, #-SH, -CN,- N3, -CNO, -CNS, Q -C!. Alkyl-S(=〇)-, q -C! 〇-基-S(=0)2 _, H2NS(=0)- and; 1' is 1,2,3,4,5,6,7 , 8, 9 or 10; and the above heterocarbocyclyl group is a saturated or unsaturated C 3 -C 2 fluorene carbocyclic group, wherein one or more of the CpCw carbocyclic groups are formed by a ring selected from 0, S And hetero atom substitution of N. 2. The compound of claim 1, wherein R is Ci-C4 alkyl. 3. The compound of claim 1 wherein R1 is 2-propyl. 95014-991001.doc * 2 - 4. A compound of the formula 1, wherein e is ο, 丨 or 2. • For example, in March, the compound of claim 1, wherein e is a compound of the formula 1, wherein q is a decanediol dihydroxyborane ester, a bismuth dihydroxyborane vinegar, a 1,2-ethane Glycol dihydroxyborane vinegar, hydrazine, 3-propanol dihydroxyborane ester, 1,2-propylene glycol dihydroxyborane ester, 2,3-butanol monodecyl borane ester, 1,1,2, 2-tetramethylethanediol dihydroxyborane θ 1,2~diisopropylethanediol dihydroxyborane ester, 5,6-nonanediol dimethyldiborate, 1,2 - dicyclohexylethane glycol dihydroxyborane ester, bis/hexyl-1,1-ol dihydroxyborane ester, diethanolamine dihydroxyborane ester S '2 a stupid base_1, 2-ethyl burning The diol di-base is esterified. The compound of claim 6 wherein q is a decanediol dihydroxyborane ester. The compound of claim 6 wherein q is a dicyclohexyl glycol dihydroxyboron. The compound of claim 6, wherein Q is i, 2_dicyclohexyl-ethane-oxime, 2-diol diboronyl borane. 10·If you print the item! a compound, wherein ... is an aryl group or a heteroaryl group having 3 to 2 % of a carbon atom forming a % and a ruthenium to 4 hetero atoms selected from the group consisting of 〇, N, and optionally 1-5 R 2i Replace. The compound of claim 1, wherein ... is a 7 (7) cycloalkyl or a q heterocyclic group (wherein one or more ring-forming carbon atoms are replaced by a hetero atom selected from the group consisting of ruthenium, S and N), Each case is substituted with 1-5 R2 1 as appropriate. The compound of claim 1, wherein rA is a C6_C18 aryl group optionally substituted with 1-3 R2?. 95014-99100i.d〇 (and 13. The compound of the request, wherein RA is via - like 2 milk is a stupidoxy group. Instead of the base 'halo group 4', the compound of claim 12, wherein 8 aryl Is at least one substituted. y 1S · a compound of formula 1 as claimed in claim 1, Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is CKC8 alkyl; R2 is Η or -(CH2)e CH(R7)ZR8; e is 0, 1, 2, 3 Or 4; R7 is H or q-C10 alkyl; Han is Η, Ci-Cio alkyl, C^-Cio alkyl-S(=0)2-, c6-C18 aryl-S(=0)2 -, H2NS (=0) 2-, -S03H or a protecting group; Z is hydrazine; Q is -B(OH)2, decanediol dihydroxyborane ester, diterpene dihydroxy pteroester, 1, 2-Ethylene diol diol via base shed ester, 1,3-propanediol diboryl borane ester, 1,2-propanediol dihydroxy borane ester, 2,3-butanediol di-boron borane, 1,1,2,2-tetradecylethane glycol dihydroxyborane ester, 1,2-diisopropylethane glycol dihydroxyborane ester, 5,6-nonanediol di-based group Pit ester, 1,2-dicyclohexylethane ketone, kiln, kiln, lacquer, lacquer, urethane, dicyclohexyl-m, ι'_diol, dihydroxyborane, diethanolamine Alkyl sulphate or 1,2-diphenyl-l,2-ethanediol dihydroxyboran ester; X is rac(=o)-; RA is optionally substituted with 1-5 R2 1 a c3-C2 fluorene carbocyclyl; or, as the case may be, substituted with 1-5 R2 1 a heterocarbocyclyl; R2 1 is selected from the group consisting of Cj-Cm alkyl, C2-C2 nonenyl, C2-C2Q alkynyl, CrC2Q alkoxy, Ci-C2 0 sulfur alkoxy, -OH , -CN, halo, halo q - C! 0 alkyl, - ΝΗ 2, alkyl),. Alkyl) 2, -NHC(=0)0-C! -C〗 〇Alkyl, -NHCPO% -C〗 〇Alkyl, ·(:(=〇)〇(:! 〇alkyl, -C( =0) C丨-C10 alkyl, alkyl, benzyl, -S(=0)-C6-C18 aryl, -S(=0)2-c6-C18 aryl, optionally 1-5 R22 a substituted C3-C2 fluorene carbocyclyl; and, optionally, a heterocarbocyclic group substituted with i_5 R22; R22 is selected from the group consisting of CVCm alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzene Base 'halo, halo (: 〗 - (: 10 alkyl, qQ alkoxy, qQ sulfur alkoxy, amine, C! decyl amine, two C!-C! Q alkylamine, carboxyl , C!-C! 〇alkyl-0C(=0)·, q-Cw alkyl-C(=0)·, c6-C18 aryl-0C(=0)-, C!-C! decane Base - 0C (=0) NH-, C6 - C! 8 aryl _ 〇 c (= 〇) nh-, C! -C! 〇-alkyl-C (=0) NH-, q 〇 alkyl < :(=0)0-, (C! -Ci 〇alkyl-〇)rC! -Cl Q alkyl, HCKCi -C! G alkyl-opq -C 〇alkyl-, 95014-991001.doc ^ 45465 '〇H, -SH, -CN ' -N3, -CNO, -CNS, C! -C!. Alkyl-S(=0)-, C]-C〗. Burning base-S(=0) 2 -, H2 NS (=0) - and 13⁄4 NS (=0) 2 -; and r &amp; 2, 3, 4, 5, 6, 7, 8, 9 or 10; A carbocyclic group is as defined in claim 1. 16'A compound of claim 15, wherein R1 is 2 propyl. As in June, the compound of claim 15 wherein Q is _B (〇j^2. The compound of claim 15, wherein Q is a ruthenium diol di-butylborate. For example, &quot;Xiao Xiangxiang 15 compound, wherein ra is C6-C〗 8 aryl substituted by 丨3 R2丨 as the case may be. 20. A compound according to claim 15 wherein RA is a heterocyclyl group as defined by claim 1 as replaced by W R21. 2l. The compound of claim 15, or the compound, the salt, the stereoisomeric or tautomeric form of the compound, wherein: R1 is 2-propyl; Q is -b(oh)2 Or a decanediol dihydroxyborane ester; and RA is optionally substituted by 1-3 R2 for C6_Cl8 aryl; or, as the case may be, substituted by R, as defined by the requester. The compound of the formula (I) of claim 1 is a soil. Q R1 (I) or a pharmaceutically acceptable salt thereof, in stereoisomeric or tautomeric form, wherein: 95014-99l001.doc -6 - 1345465 R is Ci-Cg alkyl; R2 is; e is ο, i or 2; R7 is hydrazine or methyl; R is H·, Ci-C 〇 〇, -S(=〇)2-Ci-C2 〇 base, -s(=o)2-nh2, -so3h Or a protecting group; Z is 0; Q is -B(OH&gt;2 or a cyclic dihydroxyborane ester, wherein the cyclic di-perylene ester contains 6 to 20 carbon atoms and contains at least one c Γ J 2 Q % and X is RAC (=0) --- RA is a heterocarbyl ring group substituted with 1-5 R 2 1 as appropriate (: 3 -C 2 fluorene carbocyclyl; or optionally substituted with 1-5 R 2 1 ; R 2 1 is selected from the group consisting of Group: -S(=0)2-C6.c base moiety; Ci-C2 decyl, C2-C2 nonenyl, C2-C2 decynyl, CVC20 alkoxy, Ci-C2 , -〇H, -CN, halo, halo c^-C^o, -NH2, -NHA-Cw alkyl), -Ν((ν(:1()alkyl)2, - NHC(=0)0-Ci-C1()alkyl, -ΝΗΟ^ΟΑ-Αο alkyl, _C(=0)0-C1 -Cl 〇院基, -c(=o)c丨-C丨〇 Burning base, -S(=0)-C丨-C! 〇 基, -S(=0)2_Ci-Ci 〇, -S(=〇)-C6-Ci8 aryl, -S(=〇 a 2-c6-Cl8 aryl group, optionally a c3-C2 fluorenylcarbocyclyl group substituted with 1-5 R2 2 and a heterocarbacyclyl group substituted with 1-5 R22, as the case may be; Groups of the following composition: 95014-991001.doc 1345465 Cl -Cl 〇, C2 -Cl 〇, C2 -Cl 〇, phenyl, halo, halo-Ci oxime, Ci -Cg Alkoxy group, Ci-Cg sulfur-sintered base, amine group, q-decylamino group, diqinylamine group, carboxyl group, q-Ci decyl-0C(=0)_, Ci-Ci〇 -C(=0)-, Cg-Cis aryl-0C(=0)-, q-Ci o alkyl-〇C(=0)NH-, c6 -Ci 8 aryl-0C(=0) NH-, Ci -Ci ο alkyl-C(=0)NH-, CVCw alkyl-C(=0)0-, (qC i. Alkyl-0)rq-CM alkyl, HCKCVCw alkyl-ox-cvc!. Alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, Q-alkyl-S (O)-, C] decyl-s(=o)2-, h2ns(=o)-, and h2ns(=o)2-; r is 2, 3, 4, 5, 6, 7, 8, 9 or 10; and the above heterocarbocyclic group is as defined in claim 1. 23. The compound of claim 22, wherein Ri is 2-propyl. 24. The compound of claim 22 wherein q is _B ( 〇H) 2. 25. The compound of claim 22, wherein Q is a decanediol dihydroxyboron ester. 26. The compound of claim 22, wherein rA is 8 aryl substituted by 13 R 2 视 as appropriate The compound of claim 22, wherein ra is a heterocarbocyclyl group as defined in claim 1 substituted by 13 r2丨. 28. The compound of claim 22 or pharmaceutically acceptable thereof a salt, stereoisomeric or tautomeric form, wherein: R1 is 2-propyl; Q is -B(OH)2 or benzoinoldicarbylborate; and RA is optionally 1-3 Substituting R2 for Γ Γ from sand μ to QC! 8 aryl; or 1-3 95014-991001.doc • 8 - 1345465 R21 substituted carbon ring . 29. The compound of formula (I) of claim 1 (I) or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is 2-propyl; R2 is -CH(CH3)OH; Q is -B(OH)2, decanediol dihydroxyborane ester, dicyclohexyl-1, fluorene-diol dihydroxyborane or 1,2-dicyclohexyl - ethane-1,2-diol dihydroxyborane ester; X is rac(=o)-; RA is a gold-steel alkyl-, bicycloheptyl-, substituted ring with 0-3 R2 1 a cyclopentyl group substituted with 0-2 R21; a cyclohexyl group substituted with 0-2 R2 1; a phenyl group substituted with 0-3 R21; a fluorenyl group substituted with 0-2 R21; - 1 R 2 1 substituted pyrinic group; quinolinyl group substituted by 0-1 R 2 1; imidazolyl group substituted by 0-1 R 2 1; tetrahydrop-folyl group substituted by 0-1 R21 ; 95014-991001.doc • 9- keto oxazolidinyl substituted by 0-1 R21; benzoxazolyl substituted by 0-1 R21; thiazolyl substituted by 0-2 R21; 0-2 R21 substituted furyl; tetrahydropyrrolyl substituted by 0-1 R21; hexahydropyridyl substituted by 0-1 R21; hexahydropyrrino substituted by 0-1 R21 Or a pyridyl group substituted by 0-1 R21; R21 is selected from the group consisting of: methyl-, ethyl-, propyl-, butyl-, pentyl-, hexyl-, heptyl-, vinyl -, propenyl-, butenyl-, decyloxy-, ethoxy, propoxy-, phenoxy-, fluoro-, chloro-, m-, thiol_c(=o)_, butyl -OC(=0)-, butyl-0C(=0)NH-, phenyl-, oxime-phenyl-, phenyl-phenyl, phenyl-, bromophenyl-, P-specific -and p is more than bite-. 30. A compound selected from the group consisting of: 荇-2-carboxyguanamine, from [(18)-1-[[[(111)_1-[(3&amp;3,43,68,7&amp;11)- Hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino] Carbonyl]-4-[[imino(indolyl)methyl]amino]butyl] 2-pyridinium carboxamide, 怍[(13)-1-[[[(111)-1- [(3&amp;3,43,63,7311)-hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl] -3-methylbutyl]amino]carbonyl]-4-[[imino(indolyl)methyl]amino]butyl]- 3-(1,3-dimercapto-1, 3-dioxane-iso-purine-2-yl)-propanolamine, scam [(18)-1-[[[(111)-1-[(3,48,68,7311)-hexahydro-3) Heart 5,5-trimethyl-4,6-nonyl-1,3,2-benzodioxosin-2-yl]-3-mercaptobutyl]amino]amino]- 4-[[imino(nitroamino)methyl]amino]butyl] 95014-991001.doc -10- 1345465 4-butylbenzamide, team [(18)-1-[[ [(11〇-1-[(338,48,68,7311)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan Indole-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(wall amine)methyl] Butyl] 3-[(1,1-dimethylethoxy)alkylamino]benzamide, N-[(lS)-l-[[[(lR)-l-[( 3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3- Methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]-2-(2-methoxyethoxy)acetamide, N- [(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-tridecyl-4,6-methylalkyl-1,3 , 2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)indenyl]amino]butyl 2-[2-(2-methoxyethoxy)ethoxy]acetamidine, 仏[(18)-1-[[[(1))-1-[(3,43,68; ^11)-Hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl] bucket[[imino(nitroamino)methyl]amino]butyl(E)-3-(ethoxycarbonyl)propenylamine, N-[(1S)-1- [[[(1R)-1-[(3aS,4S,6S,7aR)4 Hydrogen-3a,5,5-trimethyl-4,6-methyldinyl]-1,3,2-benzo[ Oxyboron-indolyl-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) Methyl]amino]butyl] 2-hexahydropyridin-1-yl-acetamide, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR )-Hexahydro-3〇trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]- 4-[[imino(tridodecyl)indenyl]amino]butyl] 4-(1-indolyl-hexahydropyridin-4-yl)-butanamine, &gt;^-[(18 )-1-[[[(111)-1-[(3 ugly 8,43,68,7811)-hexahydro-3&amp;,5,5-tridecyl-4,6-nonanyl-1, 3,2-benzodioxolan-2-yl]-3-methylbutyl]amino]]yl]-4-[[imino(nitroamino)methyl]amino] Butyl] 2_acetamido-acetamide, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-33,5, 5-trimethyl-4,6-anthracenyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[ Imino (nitroamino)methyl]amino]butyl] 4-(methoxycarbonyl)butanamine, N-[(lS)-l-[[[(lR)-l-[(3aS) ,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-anthracenyl-1,3,2-benzodioxan-2-yl]-3- Methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl] 4-(1-butyl-hexahydropyridine- 4-yl)-butanamine, hydrazine[(15)-1-[[[(111)-1-[(3&amp;8,48,68,7311)-hexahydro-3,5,5-triterpene 4-,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino] Exact amino group) methyl]amino]butyl] 95014-991001.doc 1345465 2-butoxyacetamide, 怍[(18)-1-[[[(111)-1-[(338, 48,68,7&amp;11)-Hexahydro-3屯5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan-2-indole-2-yl]-3 -nonylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]naphthalene-2-sulfonamide, from [(18)-1- [[[(111)-1-[(333,43,63,7&amp;11)-hexahydro-3&amp;,5,5-tridecyl-4,6-fluorenyl-1,3,2- Benzodiazepine 圜-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(indolyl)methyl]amino]butyl] (2S )-4-[[imino(wall-based amino)indolyl]amino]-2-[(2-indolyl)-amino]-pentamethyleneamine, bucket [(1!1)- 1-[(3,48,68,73 ft)-hexahydro-3 〇trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3 -methylbutyl](2S)-4-[[imino(renylamino)indolyl]amino]-2-[(l-naphthylfluorenyl)-amine ]· pentamidine, team [(111)-1-[(338,48,68,7汲)-hexahydro-3〇trimethyl-4,6-decyl-1,3,2-benzene And dioxonium-2-yl]-3-methylbutyl](2S)-4-[[imino(indolyl)methyl]amino]-2-[-|-- Aminoamine]-pentylamine, from [(1 ft)-1-[(338,48,68,7])-hexahydro-33,5,5-trimethyl-4,6-nonylalkyl -1,3,2-benzodioxanthene-2-yl]-3-methylbutyl] (2S)-4-[[imino(trans)amino)methyl]amino] -2-[(Phenylmethyl)amino]••pentamidine, &gt;^-[(111)-1-[(3&amp;8,43,68,7&amp;11)-hexahydro-315, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl] 1^-[(18)-1-[ [[(111)-1-[(3&amp;8,48,68,7311)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzophenan Oxyboron-indolyl-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(indolyl)methyl]amino]butyl]-N'-( 2-mercapto) intestinal sputum [(18)-1-[[[(111)-1-[(338,48,68,7811)-hexahydro-3&amp;,5,5-trimethyl-4, 6-decyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[iminoamino(nitroamino) Methyl]amino] ]-N'_Phenylurea [(18)-1-[[[(1))-1-[(3&amp;8,48,68,7&11)-hexahydro-3屯5,5- Tridecyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]_4_[[imino] Nitroamino)methyl]amino]butyl]-Ν'-heptylurea&gt;}-[(18)-1-[[[(111)-1-[(3&amp;8,48,68) ,7311)-hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl]-4-[[imino(decylamino)methyl]amino]butyl]-N'-(l-naphthyl)choline[(13)-1-[[ [(111) small [(3,43,68,7)-hexahydro-3屯5,5-trimethyl-4,6-decyl-1,3,2- benzodioxan Indole-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(terminal amino)methyl]amino]butyl]-indole-undecylurea 95014-991001.doc 1345465 1^-[(18,211)-1-[[[(1))-1-[(338,48,68,7311)-hexahydro-315,5-trimethyl-4, 6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]amino]-2-propyl-]-N·- Ketourea [(18)-1-[[[(111)-1-[(333,48,63,7&amp;11)-hexahydro-33,5,5-trimethyl-4,6-methane Base-1,3,2-benzene Dioxonium-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]-Ν·- [5-(ethoxycarbonyl)pentyl]urea dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-) 2-[[(2E)-3-(2-indolylphenyl)-1-one-propan-2-yl]amino]-1-ketopentyl]amino]-3-methylbutyl Dihydroxy sane, [(lR)-l-[[(2S)-5-[[imino(indolyl)methyl)amino]-2-[((E)-2- Methyl phenyl phenyl propylene sulfhydryl) amino group] · 1 · ketopentyl] amine group]_3_ decyl butyl] Once a boron-based compound, [(lR)-l-[[(2S)-5-[[imino]]amino]-2-[(4-(4-mercaptobenzene) Butyl) benzyl] keto]pentyl]amino]_3•methyldihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino)曱]]amino]-2-[((2RS)-2-phenylpropenyl)amino]-1-ketopentyl]amino]_3_methylbutyl] dihydroxy ranane, [ (1R)-1-[[(2S)_5-[[imino(nitroamino)indolyl]amino]-2-[(2-(4-isopropylphenyloxy)ethenyl) Amino]ketopentyl]amino]_3_methylbutyl] Dihydroxyborane, [(1R)-1-[[(2S)·5-[[imino(nitroamino)indolyl]amino]-2-[(5-keto-5-benzene) Ethyl pentyl)amino]-1-ketopentyl]amino]_3_mercaptobutyl] dihydroxyborane, [(lR)-l-[[(2S)-5-[[imine] (nitroamino)indenyl]amino]-2-[[(4RS)-l-[(l,l-didecylethoxy))]hexahydrop is a bit _4_ Amino]-1-ketopentyl]amino]-3-methylbutyl]dihydroxy sulane, [(lR)-l-[[(2S)-5-[[imino] Amino] benzyl]amino]-2-[(4-diethylaminophenylhydrazino)amino]_ι-ketopentyl]amino]_3•methylbutyl] dihydroxy sane ,[(lR)-l-[[(2S)-5-[[imino(a)amino)indolyl]-2-[((E)-2-fylhex-2- Iridyl)amino]-1-ketopentyl]amino]_3_methylbutyl] 95014-991001.doc 1345465 Di-based base, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl)amino]-2-[(p) Benzeno-3-yl)amino]-1-enylpentyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-5- [[Iminoamino(nitroamino)methyl]amino]-2-[(4-isopropylbenzylamino)amino]-1-enylpentyl]amino]·3_fluorenyl Butyl] dihydroxy shed, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(5-fluorenyl p) Phenyl-2-ylamino)-1-ketopentyl]amino]_3_mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[ [Iminoamino(nitroamino)methyl]amino]-2-[(benzylidene)amino]-1-ketopentyl]amino]_3_methylbutyl] Dihydroxy shed Alkane, [(lR)-l-[[(2S)-5-[[imino(indolyl)methyl)amino]-2-[((E)-2-butene) Amino]-1·-ylpentyl]amino]_3·methylbutyl] dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamine) Amino]]][[(()))]] Zhao Ji shed, [(lR)-l-[[(2S)-5-[[imino](颂Amino)mercapto]amino]-2-[(3,3-dimethyl-butan[1]yl)amino]-1-indenylpentyl]amino]_3_methylbutyl]dihydroxy Borane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[[5-(2,5-dimethyl) Phenoxy)-2,2-didecylpentenyl]amino]ketopentyl]amino]-3-methylbutyl]dihydroxyborane, [(1R)-1-[[( 2S&gt;5-[[imino(nitroamino)indolyl;j-amino]-2-[(2,2-dimercaptopentyl)amino]-1-ketopentyl]amine ]]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2- [[47-sept-2-yl)butanyl]amino]-1-ketopentyl]amino]_3_mercaptobutyl]dihydroxy side alkane, [(lR)-l-[[(2S) )-5-[[imino(nitroamino)methyl;j-amino]-2-[[5-(4-fluorophenyl)pentanyl]amino]-1-ketopentyl Amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-) 2-[(2,2-Dimercaptohexyl)amino]-1·ketopentyl]amino]-3-methylbutyl] Dihydroxy slate, [(lR)-l-[ [(2S)-5-[[imino group] Amino]-2-[(hexyl-2,4-enyl)amino]_1--ylpentyl]amino]-3-mercaptobutyl] 95014-991001.doc 1345465 Dihydroxyboron Alkane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[[3·(thiophen-2-yl)propene oxime] Amino]-1-ketopentyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Nitroamino)methyl]amino]-2-[(5-cyclohexylpentanyl)amino]-1-ketopentyl]amino]-3-mercaptobutyl] Dihydroxy sane ,[(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[((3R)-3,7-didecyl octyl) -6-Isodecyl)amino]-1-ketopentyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[ [Iminoamino(nitroamino)methyl]amino]-2-[[3-[(4-carbamimidyl)thio]propanyl]amino]-1-ketopentyl]amine Base]_3_decylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amine]][[ (4-pyrrol-1-ylphenylhydrazino)amino] ketopentyl]amino]_3-mercaptobutyl]dihydroxyborane, [(1R)-1-[[(2S&gt;5 -[[imino group (nitroamino group) Mercapto]amino]-2-[(5-fluoro-2-indolylbenzyl)amino]-1-indolyl]amino]_3-methylbutyl] dihydroxyborane ,[(lR)-l-[[(2S)-5-[[imino(de)amino)methyl]amino]-2-[((2S)-2-indolyl)-yl) ]_1_ketopentyl]amino]_3_mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino]] Amino]-2-[(cyclopropenylcarbonyl)amino]-1-ketopentyl]amino]_3_methylbutyl]dihydroxypalane, [(1R)-1-[[ (2S&gt;5-[[imino(nitroamino)methyl]aminoindolyl]-2-[(4-ethoxyphenylindolyl)amino]ylpentyl]amino]_3_ Methyl butyl W) dihydroxyborane, [(lR)-l-[[(2S)-5-[[iminoamino(nitroamino)methyl]amino]-2-[((E )-3-(4-bromophenyl)prop-2-enyl)amino]-1-ketopentyl·|amino]-3-mercaptobutyl]dihydroxyborane, [(lR )-l-[[(2S)-5-[[imino(decylamino)indolyl]amino]-2-[[(2S)-2-(6-methoxyindole-2-) ))-propyl fluorenyl]amino]-1-ketopentylamino]-3-methylbutyl] 』 dihydroxy sane, [(1R)-1-[[(2S)-5-[ [Imino group (terminal amino group) fluorenyl] amine group ]-2-[[l-(4-methoxyphenyl)-cyclopropanecarbonyl]aminoketone pentylyl]-t-butyl butyl] ^ i SJ 95014-991001.doc 1345465 Dihydroxy sane, [ (lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(3-fluoro)-4-oxobenzoquinone) Amino]-1-branched]ylpentyl]amino]_3-mercaptobutyl]dihydroxy sane, [(lR)-l-[[(2S)-5-[[imino](nitro Amino)methyl]amino]-2-[[(E)-3-(indol-2-yl)prop-2-enyl]amino]-1-ketopentyl]amino]_3 · Methyl butyl] a super-base, [(lR)-H[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(4-fluoro Benzyl-3-methylbenzyl)amino]-1-ketopentyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-5- [[imino (amino) sulfhydryl]amino]-2-[[[[[(9H- -9-yl) decyloxy]] yl]] yl]]]]]]]]]] _ketopentyl]amino]-3-methylbutyl] Dihydroxypalane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[(4-bromobenzopyranyl) Amino]-1-ketopentyl]amine;|_3_methylbutyl] Dihydroxy sane, [(1R)-1-[[(2S&gt;5-[[imino](nitro Amino)methyl]amino]-2-[(3-butenyl)amino]-1-ketopentyl]amino]_3_methylbutyl] dihydroxyborane, [(lR )-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]][[indolyl]amino]_1-ketopentyl]amine Base]_3_methylbutyl] dialkylborane, [(1R)-1-[[(2S&gt;5-[[iminoamino(nitroamino)methyl]amino]]-2-[ [4-(Ethylamino)butanyl]amino]butanylpentyl]amino]_3_decylbutyl] Di-boryl borane, [(lR)-l-[[(2S)-5-[[imino(indolyl)indolyl]amino]-2-[(6-phenylhexanyl) Amino] ketopentyl]amino]_3_methylbutyl f-based borane, [(lR)-l-[[(2S)-5-[[imino)(nitroamino) Methyl]amino]-2-[(5-phenylpentanyl)amino ketopentyl]amino]_3_methylbutyl]-^-based pentane, [(lR)-l- [[(2S)-5-[[imino(nitroamino)indolyl]amine]]-2_[(3-decyloxypropyl)amino]]indole-ketopentyl]amine Base]_3_methylbutyl]-f is calcined in the base, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amine f Ι2ΐ2,2 -Dimethyl-3_(2-methacryl)-cyclopropanecarbonyl]amino]-1-ketopentyl]amino]-3-methylbutyl]-f gas-based shed, IXlRH- tpS}·5·^imino(nitroamino)indolyl]amine^-2-[(3-methoxycyclohexyl)amino][indolyl]pentyl]amino]_3 _Methylbutyl]- 95014-991001.doc • 16 - 1345465 Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino)methyl]] Amino]-2-[[3-(1Η-indol-3-yl)-propenyl]amino]-1-ketopentyl]amino]-3-mercaptobutyl]-dihydroxy Borane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[((RS&gt;2-cyclopent-2-) Alkenyl-ethenyl)amino]] small ketopentyl]amino]-3-mercaptobutyl] dipyridyl, [(lR)-l-[[(2S)-5·[[ Imino (nitroamino) fluorenyl]amino]-2-[(5-pyrimidin-2-yl-indenyl)amino] cyanopentyl]amino]-3-methyl Butyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(6-keto-) Heptinyl)amino]-1-ketopentyl]amino]-3-mercaptobutyl]dicarbylborane, [(lR)-l-[[(2S)-5-[[ Amino (nitroamino) fluorenyl]amine _yl]-2-[(7-keto-octyl)amino]-1 ketopentyl]amino]-3-methylbutyl] By-borane, [(lR)-l-[[(2S)-5-[[imino(mercaptoamino)methyl]amino]][[hexyl)amino]- 1-ketopentyl]amino]_3_mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino](nitroamino)methyl) Amino]-2-[(heptinyl)amino]-1-ketopentyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-H[(2S) -5-[[imino(nitroamino)methyl]amino]-2-[ (3-octyloxy-propionyl)amino]_ι-ketopentyl]amino]_3·methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-5 -[[imino(nitroamino)methyl]amino]-2-[(benzothiasin-6-carbonyl)amino]_1-ketopentyl]amino]_3-mercapto Dihydroborane, [(lR)-l-[[(2S)-5-[[.imino)]amino]-2-[(11-2 -(ethenyl)amino]-1-ketopentyl]amino]_3_mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imine (nitroamino)methyl]amino]-2-[(9-nonenyl)amino]-1,ylpentyl]amine;j_3_methylbutyl]dihydroxy sane, [(lR)-l-[[(2S)-5-[[imino(des)amino)indolyl]-2-[(tetradecyl)amino]-1-one Amyl]amino]_3_methylbutyl] decylamine, 汴[(18,211)-1-[[[(111)-1-[(3&amp;8,48,68,7)-hexahydro) -3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] -2-hydroxypropyl]- 95014-991001.doc -17- (2S)-2-[(- oxycarbonyl)amino], 4-mercaptoamylamine, &gt; 1-[(18,2 ft)-1-[[[ 1_[(城43,63,7说)_hexahydro_3〇trimethyl_4,6-methylalkyl-1,3,2-benzodioxanthene]_3•methylbutyl Amino]carbonyl]2 hydroxypropyl]- 10-(1,3-diketo-1,3-dihydro-isoindolyl)-decanoic acid-decylamine _, N-[(lS) ,(2R)-2·hydroxyl 1-[[(1 ft)_1_[(3,48,68,7 _hexahydro_33,55_tridecyl-4,6-fluorenyl-1,3 , 2-benzodioxanthene: benzyl]-3-mercaptobutyl]aminocarbonyl]-propyl]- anthracene, N-[(lS)-l-[[[(lR)- L_[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methyl-1-,3,2-benzodioxon: base]-3 -Methylbutyl]amino]]yl]-2-[(4-mercaptobenzylglycyl)amino]ethyl]- 2-S-decylamino-3-3-(hexylamine) Base)-propanamide, &gt;^[(18)-1-[[(1 ft)-1-[(338,45,68,73 ft)-hexahydro-3&amp;,5,5-triterpenoid 4-,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] 2-S-decylamino -3-(4-Fluorosulfonylamino)propanamine, N-[(lS)-l-[[(lR)-l-[(3aS,4S,6S,7aR)-six -3a,5,5-trimethyl-4,6-methane basic oxime-oxo-indole-2-yl]-3-mercaptobutyl]amino]carbo] 2-S-branched Amino-3-(3,4-dimethoxyphenylethylamino) propylamine, N-[(lS)-l-[[(lR)-l-[(3aS,4S,6S, 7aR)-hexahydro-3a,5,5-trimercapto-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amine ]]carbonyl] 2-S-decylamino-3-(phenylureido)propanamine,;^-[(13)-1-[[(111)-1-[(335,48,68 ,7311)-hexahydro-3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl] 2-aminoacetamide, co-[(13)-1-[[[(11〇-1-[(3&amp;8,45,68,7〇11)-hexahydro-3) Indole-3,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]]yl]-4·[[ Imino (nitroamino)methyl]amino]butyl], hydrochloride 3-aminopropionamine, 怵[(18)-1-[[[(111)-1-[(3&amp ;3,48,65&gt;11)-hexahydro-315,5-trimethyl-4,6-sulfenyl-1,3,2-cracked dioxin oxazol-2-yl]-3- Nonylbutyl]amino]carbonyl]-4-[[imino(indolyl)methyl]amino]butyl]; hydrochloride (4RS)-six Hydropyridine-4-carboxyguanamine, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-A hydrogen-3a,5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino](nitro Amino)indolyl]amino]butyl], HCl1 salt 95014-991001.doc 1345465 (RS)-hexahydropyridin-2-carboxyguanamine, N-[(1S)-1-[[[(1R) )-1- [(3aS,4S,6S,7aR)-A hydrogen-3a,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxon- 2-yl]-3-methylbutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl]; HC1 salt (2S)-hexahydropyridine -2-carboxamide, N-[(1S)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro•33,5,5-tridecyl-4 ,6-Mercapto-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[iminoamine (nitroamine) Methyl]amino]butyl]; HC1 salt (2 ft) - hexahydrop than bite-2-rebel, N-[(1S)-1-[[[(1R)-1-[ (3aS,4S,6S,7aR)-hexanitro-3a,5,5-dimethyl-4,6-methylalkyl-1,3,2-benzoquinonedioxan-2-yl]- 3-mercaptobutyl]amino]carbonyl]-4-[[imino oximeylamino)methyl]amino]butyl]; HC1 salt Indoleamine, N-[(lS)-l-[[[(lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-曱alkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-2-(ethylguanidinyl)ethyl]-anthracene Amine, 沁[(18)-1-[[[(111)-1-[(338,43,68,7&amp;11)-hexahydro-3&amp;,5,5-trimethyl-4,6- Methyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]amino]-(9-ylmethyloxyamine-methylhydrazine Ethyl]- decylamine, called (18)-1-[[[(1,1))-1-[(333,43,68,7say)-hexahydro-3,7,5-triazine 4-,6-decyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]amino]-2-(pentyl-matrix Ethyl]- Indoleamine, 怵[(18)-1-[[[(1 ))-1-[(3&amp;3,48,63,7&amp;11)-hexahydro-3&amp;,5,5-tridecyl -4,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-2-(decanesulfonylamino) Ethyl]-decylamine, ke (18)-1-[[[(111)-1_[(3&amp;3,43,63,73 ft)-hexahydro-3&amp;,5,5-triterpene 4-,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]yl]-2-[(ethoxycarbonyl) Amber oxime)-decylamine)ethyl]-dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-] 2-[((2E)-3-ethoxycarbonyl-1-ketoprop-2-enyl)amino]-1-indenylpentyl]]amino]-3-mercaptobutyl]dihydroxy Borane, [(lR)-l-[[(2S)-5.[[imino(nitroamino)indolyl]amino]-2-[(2-p-rough carbonyl)amino] _1 ketopentyl]amino]_3_mercaptobutyl] di-perylene, [(lR)-l-[[(2S)-5-[[imino](nitroamino)) Amino]-2-[(4-butylphenylindolyl)amino][indolyl]pentyl]amino]_3_mercaptobutyl] 95014-99100l.doc 19 1345465 Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl)amino]-2-[(2) - mercapto)amino] ketopentyl]amino]_3_mercaptobutyl] dihydroxyborane, [(1R)-1-[[(2S&gt;5-[[imino] Nitroamino)methyl]amino]-2-[(3-(l,3-dihydro-1,3-dione-2H-isoindolin-2-yl)-1-one-propanyl Aminoamino]-1-mercaptoyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino] Amino)]mercapto]amino]-2-[[2-(2-decyloxyethoxy)ethenyl]amino]_ι-ketopentyl]amino]_3_methylbutyl] , HCl salt dihydroxyborane, [(lR)-l-[[(2S)-5·[[imino(nitroamino)indolyl]amino]-2-[(2-butoxy) Ethyl)amino]-1-ketopentyl]amino]_3_methylbutyl] Dihydroxyborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)methyl]amino]-2-[[2-[2-(2-曱 ethoxyethoxy)ethoxy]ethyl hydrazide]amino] ketopentyl]amino]-3-methylbutyl] dihydroxy sulane, [(lR)-l-[[(2S) )-5-[[imino(a)amino]mercapto]amino]-2-[[2-(ethylamido)ethinyl]amino]-; μ ketopentyl]amine Base]_3•mercaptobutyl], HCl salt dihydroxyborane, [(1R)-1-[[(2S)-5-[[imino(tetra)ylamino)indolyl]amino]-2 -[[4-(methoxycarbonyl)butanyl]amino]_ι-ketopentyl]amino]_3_mercaptobutyl]dihydroxy[,[(lR)-l-[[(2S)- 5-[[imino(nitroamino)methyl]amino]-2·[(2-(tea-2-yloxy)ethenyl]amino]_ι-ketopentyl)amine Base)_3 methyl butyl) Dialkylborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amine) ]]·2-[(3-ρ塞-phen-2-yl-propenyl)amino]-i-ketopentyl]amino]_3_methylbutyl]dihydroxy-paraffin, [(lR )-l-[[(2S)-5-[[imino(a)amino]methyl]amino]-2-[2-(2-phenylphenyl)ethenyl]amino]_3 _Methylbutyl]HC1 salt diradylborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[ (l-net-based 4-(1-butylhexahydropyridin-4-yl)butyl)amino] ketone keto.yl]amino]-3-methylbutyl] guanidine dipyridyl ,[(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl 1amino]-2-[(l-octyl)]amino] ι·ketopentyl]amino]·3·methyl]], HC1 salt label 95014-991001.doc •20-di-boron borane, [(lR)-l-[[(2S)-3 -[(4-methylbenzhydryl)amino]-2-[(decylamino)]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane , [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(indolyl)amino]-1-ketobutyl]amino]-3-methylbutyl] Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[[10-(l,3-dione-1,3-dihydro-isoindole-) 2-yl)-indenyl]amino]-1-ketobutyl;]amino]_3_ Mercaptobutyl]dicarbylborane, [(lR)-l-[[(2S)-5-[[imino(nitroamino)indolyl]amino]-2-[(l- Ketodecyl)amino]-1-ketopentyl]amino]_3·nonylbutyl] decylamine, N-[(lS)-l-[[[(lR)-l-[( 4R,5R)-4,5-Dicyclohexyl-[1,3,2]dioxaboron-2-yl]-3-indolylbutyl]amino]carbonyl]-4-[[imine (N-[(1S)-1-[[[(1R)-1-[13,15·dioxo]) ·14. Boron dispiro[5.0.5.3]-quinone-14-yl]-3-methylbutyl]amino]]yl]-4-[[imino([,]amino]yl]methyl] -Amino]butyl]- or a pharmaceutically acceptable salt thereof or a free base form. 31. A compound selected from the group consisting of: 2-[2-(2-methoxyethoxy)ethylammonium]acetamide, N_[(1S) small [[[(1 ft)-1) -[(3&amp;8,48,68,7311)-hexahydro-33,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxine - 2 -yl]-3-mercaptobutyl]amino]carbonyl]-4-[[imino(nitroamino)methyl]amino]butyl decylamine, N-[l-[[[ (lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine -2-yl]-3-methylbutyl]amino]carbonyl]methyl] 2-[2-(2-methoxyethoxy)ethoxy]ethylamine, &gt;^-[1 -[[[(111)-1-[(3&amp;8,48,68,711)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2 -benzodioxan oxo-2-yl]-3-methylbutyl]amino] benzyl]methyl] decylamine, 怵[(13)-1-[[[(1 尺)- 1-[(3&amp;8,48,68,7&amp;11)-hexahydro-33,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxan Indole-2-yl]-3-methylbutyl]amino]carbonyl]-5-ureidopentyl]-4-butylbenzamide, N-[(lS)-l-[[[ lR)-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxon- 2-yl]-3-methyl Amino]carbonyl]-54-hydroxypentyl]-]^-[(18)-1-[[[(111)-1-[(3 ug8,48,68,7&amp;11)-six Hydrogen-3&amp;,5,5-trimethyl-4,6-methylalkyl[S] 95014-991001.doc -21- 1345465 -1,3,2-benzodioxanthene-2-yl] -3-methylbutyl]amino]carbonyl]-4-[[imino(wall-based amino)methyl]amino]butyl]-NH4-butylphenyl)urea 1^-[( 18)-1-[[[(111)-1-[(3&amp;3,48,68,7))-hexahydro-33,5,5-trimethyl-4,6-anthracene 1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-4-[[iminoamino]methyl]amino Butyl]-N'-(4-heptyloxy 1phenyl)urea 4-(pyridin-3-yl)benzamide, N-[(1S,2R)-1-[[[(1R) -1- [(3aS,4S,6S,7aR)-hexahydro-315,5-trimethyl-4,6-fluorenyl-1,3,2- benzodioxan-2-yl ]-3-decylbutyl]amino]carbonyl]-2-hydroxypropyl] 2-pyridyl 11 carboxy guanamine, 怵[(18,211)-1-[[[(111)-1-[( 338,48,68,7 says)-hexahydro-3〇trimethyl-4,6-decyl-1,3,2-benzodioxan-2-yl]-3-methyl Butyl]amino]carbonyl]-2.hydroxypropyl] Twelve burned decylamine,]^-[(18,211)-1-[[[(111)-1-[(338,48,68,7311)-hexahydro-33,5,5-trimethyl-4 ,6-Methyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl 1amino]carbonyl]-2-hydroxypropyl] 4-phenylbenzene Indoleamine;;^-[(13,211)-1-[[[(111)-1-[(3,43,63,7311)-hexahydro-3a,5,5-trimethyl-4,6-曱alkyl-1,3,2-benzodioxazole oxyl-2-yl]-3-mercaptobutyl]amino]amino]-2-propyl] ">2-didecyl Indoleamine, N-[(1S,2R)-1-[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4, 6-Methyl-1,3,2-benzodioxazole oxyl-2-yl]_3_methylbutyl]amino]]yl]-2-propyl] (4-phenoxy)phenylamine, N-[(1S,2R)-1-[[[(1R)-1_[(秘来风~Noisy 6a,5,5-tridecyl) -4,6-decyl-1,3,2-benzodioxanthene-2-yl]_3_methylbutyl]amino]carbonyl]-2-hydroxypropyl] 5 dibutyl-2-:pyridinium carboxamide, Ke (10) 'Ye + town (10)) small [(3aS 4S 6S 7aR) j hydrogen-3a,5,5-diindenyl-4,6-fluorenyl -1,3,2-benzodioxole _2_基ι_3-methylbutyl]amino]]yl]-2-propyl propyl] 4-propoxy phenyl hydrazide, N_ [(1S, 2R) small [[[(1R) small [(3aS4S6S 7aR) hexa f -3a, 5, 5). Methyl 4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]_3_mercaptobutyl]amino]carbonyl]-2.hydroxypropyl] 3: (3-Pyridine benzepidine, N_[(1S, 2R) small [[[(1R&gt;1_[(3aS4S6S7aR)_>,-3a,f,5-dimethyl-4,6-A) -1,3,2-benzodioxanthene-2_yl]·3- ηylbutyl]amino]carbonyl]-2-hydroxypropyl] 6:phenyl-2dipyridylcarboxylate Amine, [(3aS 4S 6S 7 gas-3a,5,5-dimethyl-4,6-methylalkyl-l,3,2-benzodioxan-2-denyl]_3_^ 95014-991001 .doc -22- 1345465 butyl]amino]carbonyl]-2-hydroxypropyl] 3-propoxy, benzoguanamine, N-[(lS,2R)-l-[[[(lR)-i_[(3aS, 4S,6S,7aR)_hexahydro-3a,5,5-dimercapto-4,6-fluorenyl-1,3,2-benzodioxoline 圜_2-yl]_3_methyl Butyl]amino]carbonyl]-2-hydroxypropyl] 1-oxanaphthalene-2-carboxylated amine, N-[(lS,2R)-l-[[[(lR)-i.[(3aS ,4S,6S,7aR)-hexahydro-3a,5,5-dimercapto-4,6-fluorenyl-1,3,2-benzodioxanthene 圜_2_yl]_3_曱Alkyl]amino]amino]-2-propyl]6-indole-2-carboxylamine;;^-[(18,211)-1-[[[(1))-1-[( 3,48,68,7311)-hexahydro-33,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxan-2-one]-3- Methylbutyl]amino]carbonyl]-2-hydroxypropyl] 3-phenylbenzamide, team [(13,2!1)-1-[[[(111)-1_[(3%) 48,68,7&amp;11)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3- Methylbutyl]amino]carbonyl]-2-hydroxypropyl] 4-(2-fluorophenyl)benzamide, N-[(1S,2R)-1-[[[(1R)-1 - [(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxon-indole-2-yl] -3-methylbutyl]amine ]carbonyl]-2-hydroxypropyl] 2-pyridinium carboxamide, &gt;}-[(18)-1-[[[(1))-1-[(3,43,63,7311)- Hexahydro-33,5,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino] Carbonyl]-2-amine decylethyl] decylamine, team [(18)-1-[[[(111)-1-[(3&amp;8,43,68,7&amp;11)-hexahydro -3&amp;,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino] ]-2-Aminomethylaminoethyl] 4-butylbenzamide,]^-[(18)-1-[[[(111)-1-[(3&amp;8,48,68,7&amp;;11)-hexahydro-315,5-trimethylphenyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino ]carbonyl]-2-aminoindolyl] 4-butylbenzamide, 怵[(15)-1-[[[(1!1)-1-[(333,48,63,7311 )-Hexahydro-33,5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amine ]]carbonyl]-2-[(芊 oxycarbonyl decylamine)ethyl]-4-butylbenzamide, 汴[(13)-1-[[[(1 ))-1-[(333々 ,63,7311)-Hexahydro-3〇trimercapto-4,6-methylalkyl-1,3,2-benzodioxene value 圜-2-yl-]-3-mercaptobutyl] Amino]carbonyl]-2-(1Η-pyridyl Ethyl]-guanamine, 怵[(15)-1-[[[(111)-1-[(333,48,68,7311)-hexahydro-33,5,5-tridecyl- 4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]anthraceyl]-2-[(芊-oxycarbonyl decylamine )ethyl]- [Si 95014-991001.doc •23· 1345465 4-phenoxybenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS,4S, 6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl Amino]carbonyl]-2-[(benzyloxycarbonylguanamine)ethyl]- 4-butylbenzamide, 1^-[(18)-1-[[[(111)-1-[ (338,48,68,7311)-hexahydro-33,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxan-2-yl]- 3-mercaptobutyl]amino]yl]-2-(aminoethyl)-hydrochloride 2-S-(4-butylphenylguanidino)-3-(2-pyridinylcarbonyl) Amino)-,[[18]-1-[[(111)-1-[(3&amp;8,43,68,7311)-hexahydro-315,5-trimethyl-4,6-fluorene Alkyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl] 4-butylbenzamide, team [(18)-1 -[[[(111)-1-[(3&amp;8,43,68&gt;11)-hexahydro-33,5,5-trimethyl-4,6-decyl-1,3,2- Benzodiboron Won-yl] -3-methylbutyl] Amino]carbonyl]-2_[4-fluoro-benzenesulfonamide]ethyl]_ 4_butylbenzamide, ^^-[(18)-1-[[[(11^)-1-[ (338,38,68,7&amp;1^)-hexahydro-3&amp;,5,5-lubetrimethyl-4,6-methylalkyl-1,3,2-benzodioxon -yl-]-3-mercaptobutyl]amino]carbonyl]-2-[(2,5-dimercapto-2H-pyrazole)carbonylamino]ethyl]- 4-butylbenzamide , N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1 ,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-(4-methylphenylureidosulfonylamino)B 4-phenoxybenzamine, 汴[(18)-1-[[[(111)-1-[(3,43,68,7211)-hexahydro-3a,5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl]_3_methylbutyl]amino]carbonyl]-2-(3-phenyl- Pulse base) ethyl]- 4-butyl benzoguanamine, &gt;1-[(18)-1-[[[(111)-1-[(333々,68&gt;11)-hexahydro-33,5,5-triterpene] 4-,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-(4-mercaptobenzene Sulfhydryl ureido)ethyl;] decylamine, &gt;^-[(18)-1-[[[(1))-1-[(338,48,68,7))-hexahydro -33,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl] -2-[4-fluoro-benzenesulfonamide]ethyl]-guanamine, 1^-[(18)-1-[[[(111)-1-[(338,48,68,7311) -hexahydro-33,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxan-2-yl]-3-mercaptobutyl]amino ] 叛基]-2-[(4- 醯 醯 醯 phenyl)carbonyl decylamino]ethyl]· 4-butylbenzamide, team [(15)-1-[[[(11( -1-[(333々,63,7311)-hexahydro-33,5,5-trimethyl-4,6-nonyl-1,3,2-benzodioxan-2-yl ·]-3-mercaptobutyl]amino]carbonyl]-2-(acetamido)ethyl]- 4·butylbenzamide, N-[(lS)-l-[[[ lR)-l-[(3aS,aS,6S,7aR)-hexahydro-3a,5,5- 95014-99I001.doc -24· 1345465 tridecyl-4,6-methylalkyl-1,3,2 -benzodioxan -2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-(decanesulfonylamino)ethyl]-4-butylbenzoquinone,]^-[(18) -1-[[[(111)-1-[(338,&amp;8,68,73 ft)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxanthene-2-yl-]-3.methylbutyl]amino]carbonyl]-2-(propylureido)ethyl]-4-butylbenzamide N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S,7aR)·hexahydro-3a,5,5-trimethyl-4,6-fluorenyl-- l,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-[(4-methylphenyl)alkylamino]B 4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S,7aR)-hexahydro-3a,5,5- Triamyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]yl]]-2-[(l ,l-dimethylethoxyxo)amino]ethyl]- 4-butylbenzamide,;^-[(18)-1-[[[(111)-1-[(3%) 48,68,7&amp;11)-hexahydro-33,5,5- _trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl]-3 -mercaptobutyl]amino]carbonyl]-2-[(p-cephen-2-ylcarbonyl)amino]ethyl]_ anthraquinone, &gt; 1-[(18)-1-[[[ (1 foot)-1-[(338,48,68 ,7311)-hexahydro-33,5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxanthene-2-yl]-3-methylbutyl Amino]]yl][〇»cephen-2-ylidene)amino]ethyl]-4-butylbenzamide, N-[(lSH-[[[(lR)-l- [(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-l,3,2-benzodioxanthene-2-yl]- 3-mercaptobutyl]amino]carbonyl]-2-(hexanolamino)ethyl]- 4-butylbenzamide, ^[(18)-1-[[[(111)- 1_[3&amp;8 to 68,7&amp;11]-hexahydro-3 wood 5,5-trimethyl-4,6-methylalkyl 1,3,2-benzodioxine 圜_2_yl_ ]_3_Methylbutyl]amino]carbonyl]-2-(cyclopropylcarbonylamino)ethyl]-4-butylbenzamide, &gt; 1-[(18)-1-[[[ (111)-1-[(3,43,68,7311)-hexahydro-33,5,5-^trimethyl-4,6-methylalkyl-1,3,2-benzodioxine伍圜_2_基]_3_Methylbutyl]amino]carbonyl]-2_(3-phenyl-keto)ethyl]_ Φ·butylphthalamide,;^-[(13) -1-[[[(111)-1_[(3,48,68,7]_hexahydro_3,7,5,1,3,3,6-methyl-1-,3,2-benzo- Oxyborax, 圜_2_yl]_3_mercaptobutyl]amino]carbonyl]-2-[(N-fluorenyl-2-pyrrolylcarbonylguanamine)ethyl] _ 4-butylbenzamide, ke (15)-1-[[[(111)-1_[338成68,7311]-hexahydro-33,5,5-trimethyl-4,6- Methyl-1,3,2-benzodioxine 圜_2_yl_]_3_methylbutyl'^] Amino]carbonyl]-2-[(3,4-dimethoxyphenyl) Ethylamino]ethyl]- 4-butylbenzamide, &gt;^-[(18)-1-[[[(1)-1][(3,48,68,7&amp;11) )-hexahydro-3-7,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-indole-2-yl]_3_decylbutyl] 95014- 991001.doc •25·1 Amino]carbonyl]-2-(nicotin ketoamino)ethyl]-4-butylbenzamide, from [(18)-1-[[[(111) Small [333,33,65,7311)-hexahydro-33,5,5-trimethyl-4,6-nonyl 1,3,2-benzodioxan-2-yl-]-] -3-mercaptobutyl]amino]carbonyl]-2-[(4-thinylamino)benzamideamino]ethylindole-butylbenzamide, 怵[(18)-1 -[[[(1尺)小小[333#,68,731〇-hexahydro-33,5,5-trimethyl-4,6-nonylalkyl 1,3,2-benzodioxine - 2-yl-]-3-methylbutyl]amino]carbonyl]-2-[(1Η-tetrazol-5-yl-acetamido)ethyl)-4-butylbenzoguanamine, From [(18)-1-[[[(111)-1-[(338,33,68,7&amp;11)-hexahydro-3&amp;,5,5-tridecyl) -4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-[(4-mercaptosulfonate) Nonylphenyl)carbonylamino]ethyl]-decylamine, [[18]-1-[[[(11〇-1-[(338,48,68,7&amp;11)-hexahydro- 3 wood 5,5-trimethyl-4,6-decyl-1,3,2-benzodioxan-2-yl]-3-methylbutyl]amino]carbonyl]- 2-(in the base ketoamino)ethyl]-4-butylbenzamide, 沣[(15)-1-[[[(1))-1-[(335,38,63,7&amp;;11)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl Amino]]yl]-2-[(4-(2H-tetra-β-s--5-yl)phenyl)-Wenylamino]ethyl]- 4-butylbenzamide, co-[13 )-1-[[[(111)-1-[(3], 63,7&amp;11)-hexahydro-3〇trimethyl-4,6-nonanyl-anthracene, 3,2-benzene And dioxonium oxa-2-yl-]-3-methylbutyl]amino]carbonyl]-2-[(1-isoxazol-5-yl)-carbonylamino]ethyl]- 4 -butylbenzamide, 砵[(18)_1-[[[(1 尺)小小[(如8#,68,7&1〇-hexahydro-3〇tridecyl-4,6-曱Alkyl-1,3,2-benzodioxanthene-2-yl-]-3-methylbutyl]amino]carbonyl]-2-[(4-cyanophenyl) ruthenyl amine Ethyl]- 4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS,aS,6S,7aR)-hexahydro-3a,5 ,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-methylbutyl]amino]derivative]-2 -[(l-fluorenyl-1H-imidazole-4-)-nonylaminol]ethyl]-4-butylbenzamide, N-[(1S)-1-[[[(1R) small [(3aS, aS, 6S, 7aR)-hexahydro-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxan-2-yl-]-] -3-mercaptobutyl]amino]carbonyl]-2-[(2-sulfonyl)diamidinoamino]ethyl]- 'butylbenzamide,&gt;1-[(18)- 1-[[[(111)-1-[(3&amp;3々,68,7&amp;11)-hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2- Benzodioxanthene-2-yl-]-3-methylbutyl]amino]]yl]-2-(6-moffine-4-final amine amino)ethyl]- 4-butylbenzamine,:^-[(18)-1-[[[(111)-1-[(3&amp;8々,68,7&amp;11)-hexahydro-3&amp;, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-methylbutyl]amino]carbonyl]-2-(2) -pyridine-4-, thiazolylcarbonylamino)ethyl]--26· 95014-991001.doc 1345465 4·butylphthalamide, 怵[(18)-1-[[[(111)-1 -[(3 33,68,7311)-Hexahydro-30,5-trimethyl-4,6-nonylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-methyl Butyl]amino]carbonyl]-2-(4-mercaptophenylureidosulfonylamino)ethyl]-4-phenoxy azelaamine, N-[(1S)-1-[ [[(1R)小[(3&amp;8,48,63,7&amp;11)-hexahydro-3a,5,5-trimethyl-4,6-fluorenyl-1,3,2-benzo Dioxo-indole-2-yl]-3-methyl-butyl]amino]anthracene]-2-[(芊-oxycarbonylguanamine)ethyl]- 4_ phenoxybenzamide [(18)-1-[[[(111)-1-[(3&amp;3,48,68,7&amp;11)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl -1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]amino]][4-fluoro-benzenesulfonamide]ethyl]· 4-phenoxy alumine, from [(18)-1-[[[(111)-1-[(333,38,63,7])-hexahydro-33,5,5-triterpene Benzyl-4,6-methylalkyl-1,3,2-benzodioxole 圜-2-yl-]-3-methylbutyl]amino]]yl]-2-[(2, 5-dimercapto-2H-pyrazole)carbonylamino]ethyl]4-phenoxybenzamine, N-[(lS)-l-[[[(lR)-l-[(3aS ,4S,6S,7aR)-Hexahydro-3a,5,5-trimethyl-4,6-decyl-1,3,2-benzenedioxaboron-2-yl]-3-A Butyl]amino]carbonyl]-2-(4-phenylbenzylidinium)ethyl]- 4-butylbenzamide, N-[(lS)-l-[[[(lR )-l-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-decyl-1,3,2-benzodioxon- 2-yl]-3-mercaptobutyl]amino]carbonyl]-2-(4-phenyl amidino)ethyl]-4-butylbenzoguanamine, &gt; 1-[( 18)-1-[[[(111)-1-[(3&amp;8,43,68,7311)-hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3 ,2-benzodioxanthene-2-yl]-3-methylbutyl]amino]carbonyl]-2-(3-phenylpropynylamino)ethyl]- 4-butylbenzamine,;^_[(18)-1-[[[(111)-1-[(338,&amp;8,68,7&amp;11)-hexahydro-33,5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-mercaptobutyl]amino]carbonyl]-2-(2) -hydroxy-3-nicotinylamino)ethyl]-4-butylbenzamide, N-[(lS)-l-[[[(lR)-l-[(3aS, aS,6S ,7aR)-Al-3a,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxanthene-2-yl-]-3-methylbutyl] Amino]carbonyl]-2-(D-pyramide decylamino)ethyl]-4-butylbenzamide,:^-[(18)-1-[[[(111)-1 -[(3&amp;8, Wang 8,68,7&amp;11)-hexahydro-315,5-trimercapto-4,6-methylalkyl-1,3,2-benzodioxon-5 -yl-]-3-methylbutyl]amino]carbonyl]-2-(1-methanesulfonyl-hexahydropyridine-4-carbonylamino)ethyl]-decylamine, hydrazine [(18) )-1-[[[(1 ft)-1-[(3,8,43,68,7&amp; ft)-hexahydro-33,5,5-trimethyl-4,6-decyl- 1,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]amino]-2-(3-phenylindolyl)ethyl]-anthracene Indoleamine, from [(18)-1-[[[(111)-1-[(3&amp;8,33,68,7〇11)-hexahydro-33,5,5-trimethyl E SI 95014 -991001.doc -27- 1345465 -4, 6-decyl-1,3,2-benzodioxine 圜_2_yl+3-mercaptobutyl]amino]carbonyl]-2-(ethylamino)ethyl]_ 癸Indoleamine, 怵[(18)-1-[[[(111)-1-[(3 68 68,7&amp;11)-hexahydro-3\5,5-trimethyl-4,6-methane -1,3,2-benzoindole boron 圜 2 2 2 ] ] ] ] ] ] ] ] ] 几 几 几 几 几 几 几 几 几 几 几 几Amine, N-[(1S)-1-[[[(1R) small [(3,#&gt;63&gt; ft.)-hexahydro-3 〇trimethyl-4,6-methylalkyl-1,3, 2-Oxadioxanthene-2-yl-]-3-methylbutyl]amino]diyl]-2-amino]ethyl]-hydrochloride 4-butylbenzamide , team [(111) small [[[(111)-1-[(3&3,43,68,7311)-hexahydro-33,5,5-trimethyl-4,6-methyl-1-) ,3,2-benzodioxanthene-2-yl]-3-mercaptobutyl]amino]carbonyl]-2-[(4-mercaptobenzoyl)amino]ethyl] - Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(4-phenylbutanyl)amino]-1-ketobutyl]amino]- 3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(undecylaminocarbonyl)amino]-1-one) Butyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(l- Alkyl-2-indenyl)amino]-1-ketobutyl]amino]-3-methylbutyl] di-based boron, [(lR)-l-[[(2S,3R --3-carbyl-2-[(6-indolyl-2-indenyl)amino]-1-ketobutyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-Aminoindenyl-2-[[indolyl]amino]]-indolyl]propyl]amino]-3-methylbutyl] Hydroxyborane, [(lR)-l-[[(2S)-3-aminoindol-2-[4-butyl(benzylidene)amino]-1-ketopropyl]amino) ]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-2-[(indolyl)amino]_ι-keto]-5-ureido-pentyl Amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-2-[(4-butylbenzylidene))]] _5_ureido-pentyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[2S,3R)-3-hydroxy-2-[(2-naphthalene) Methyl fluorenyl) keto ketobutyl]amino]-3-methylbutyl] dihydroxyborane, [(lR)-H[(2S,3R)-3-hydroxy-2-[( p-Methyloxyacetamide)-1-ketobutyl)amino>&gt;3•methylbutyl)dihydroxyborane, [(lR)-l-[[(2S,3R)-3 -hydroxy-2-[(tridecyl)amino]-indole-ketobutyl Amino]-3-mercaptobutyl] 95014-991001.doc -28-dihydroxyborane, [(lR)-l-[[2S,3R)-3-hydroxy-2-[(荇- 2-sulfonyl)amino]-1-ketobutyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3- Hydroxy-2-[(4-phenylphenylindolyl)amino]-1-ketobutyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[ [(2S,3R)-3-hydroxy-2-[(2,2 dimethyl-indenyl)amino H-ketobutyl]amino]-3-methylbutyl]dihydroxyborane ,[(lR)-l-[[(2S,3R)-3-hydroxy-2-[(4-phenoxyphenylindolyl)amino]-1-ketobutyl]amino]-3 -Methylbutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[[4-(l-propoxy)butylbenzylidene] Amino]-1-ketobutyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[( 3-pyridin-3-yl-benzylidenyl)amino]-1-ketobutyl]amino]-3-mercaptobutyl], hydrochloride dihydroxyborane, [(lR)-l -[[(2S,3R)-3-hydroxy-2-[(3-propoxy-phenylindolyl)amino]-1-ketobutyl]amino]-3-mercaptobutyl] Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(3-phenylbenzene) Mercapto)amino]-1-ketobutyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2 -[(4-(2-fluorophenyl)phenylindolyl)amino]-1-ketobutyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l -[[(2S,3R)-3-hydroxy-2-[[4-(3-pyridyl)benzylidenyl]amino]-1-ketobutyl]amino]-3-mercaptobutyl Dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(2-pyroxycarbonyl)amino]-1-ketobutyl]amino] -3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(5′ butyl-pyridine-2-carbonyl)amino] 1-ketobutylbutyl]amino]-3-mercaptobutyl]dipyridyl bromide, [(lR)-l-[[(2S,3R)-3-carbyl-2-[(6) -Phenyl-p ratio nitr-2-carbonyl)amino]-1-ketobutyl]amino]-3-methylbutyl] Di-based sheds, [(1R)-1-[[ (2S)-3-(2-p ratio p-based alkylamino)-2-[(4-butylbenzylidinium)]-1-ketopropyl]amino]-3-indenyl Butyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(ethylamino)-2-[(indolyl)]-i-ketopropyl]amine ]]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(propylureido)-2-[( 4-butyl)-benzimidyl]-1-ketopropyl]amino]-3-mercaptobutyl] Di-based group, [(lR)-l-[[(2S)- 3-(曱 醯 醯 ) ))-2-[(4-butyl)-benzoquinone 95014-991001.doc •29- 1345465 醯amino]-1-ketopropyl]amino]-3- Methyl butyl] dihydroxyborane, [(lR)-l-[[(2S)-3-[2-(lH-pyrazole)ethyl]-2-[(4-butyl)-benzoquinone Amidino]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(decanesulfonylamino) )-2-[(4-butyl)-benzoguanidino]-1-ketopropyl]amino]-3-methylbutyl] di-based boron, [(1 ft)-1 -[[(28)-3-[(( 爷 魏 几 几 氧基 氧基 氧基 氧基 氧基 氧基 氧基 氧基 氧基 ) ) ] ) ) ) ) ) ))) Dihydroxyborane, [(lR)-l-[[(2S)-3-[deoxoster-2-ylcarbonyl)amino]-2-[(4-butylbenzimidino)]- 1-ketopropyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3_(ethylamino)-2-[4-butyl] -Benzylaminoamino]]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-[( Thiophene, 2-ylcarbonyl)amino]]-2-[(decylamino)]- 1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(hexylamino)-2-[(4 -butylphenylguanidino)]-1-copperylpropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-[ 4-fluoro-benzenesulfonamide]-2-[(4-butylphenylhydrazino)amino H-ketopropyl]amino]-3-mercaptobutyl]dihydroxyborane, [( lR)-l-[[(2S)-3-[4-fluoro-benzenesulfonamide]-2-[(indolyl)amino]-1-ketopropyl]amino]-3-methyl Butyl]dihydroxyborane, [(lR)-l-[[(2S&gt;3-(hexylamino)-2-[(decylamino)]-i-ketopropyl] Amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(hexanolamino)-2-[(cyclopropylcarbonylamino)]] -1-ketopropyl]amino]'-3-methylbutyl]3-methylbutyl]amino]carbonyl]-2-(cyclopropylcarbonylamino)ethyl]-dihydroxyborane , [(lR)-l-[[(2S&gt;3-[(3,4-Dimethoxyphenyl)acetamido]-2-[(4-butylphenylguanidino)]] Ketopropyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-[lN-methyl-2-pyrrolylcarbonylamino]] -2-[(4-butylphenyl)amino]-1-ketopropyl] Base]_3_mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-[4-aminesulfonylbenzylideneamino]_2-[(4-butyl) Benzyl hydrazino)amino]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(nicotine) Nonylamino)-2-[(4-butylbenzylidinium)]-1-ketopropyl]amino]methylbutyl] 95014-991001.doc •30· Dihydroxyborane, [(lR)-l-[[(2S)-3-(3-Phenylureido)-2-(4-butylphenylguanidino)-1- ketopropyl]amino]-3- Mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-[(4-oxasulfonyl)benzamide]-2-[(4-butylbenzene) Mercapto)]-l-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(3- 】 ))-2-(decylamino) kilopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)_3-(smoke Alkali-decylamino)-2-(decylamino)-1-ketopropyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[( 2R)-3-(4-mercaptophenylcarbonyl)-2-(decylamino)-1-ketopropyl]amino]-3-mercaptobutyl]dihydroxyborane, [( lR)-l-[[(2S)-3-[4-(lH-tetrazolyl)-benzene Rhenylamino]-2-[(4-butylbenzimidino)]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)- L-[[(2S)-3-(2-isoxazolylcarbonylamino)-2-[(4-butylbenzimidino)]-1-ketopropyl]amino]-3 -Methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-[l-fluorenyl-1H-imidazol-4-aminesulfonyl]-2-[(4- Butyl phenyl hydrazino)amino]-1-ketopropyl]amino]-3-mercaptobutyl] After decarboxylation, [(lR)-l_[[(2S)-3-[ 6-?-fu-p--4-yl-p-biti-3-amine aryl]-2-[(4-butylphenylhydrazino)amino]-1-ketopropyl]amino] _3_曱^ butyl] hydrochloride diboron borane, [(lR)-l-[[(2S)-3-(6-moffin based on decylamine)-2-[(4-butyl) Benzo phenyl)amino]-1-ketopropyl)amino)-3-indenyl butyl) [(lR)-l-[[(2S)-3-(4) - (l,3-dimercapto-purin-ρ ratio. Sodium-5-monoamino)-2-[(4-butylphenylhydrazino)amino]-1-ketopropyl)amino)_3_methylbutyl] hydrochloride dihydroxy boron Alkane, [(lR)-l-[[(2S)-3-[4-fluoro-benzenesulfonamide]-2-[(4-phenoxyphenyl)amino]-1-one Propyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(4-(l,3-dimercapto-1H-pyrazole) -5-carbonylamino)-2-[(4-phenoxyphenyl)amino]-1-ketopropyl)amino)_3_methylbutyl]carbonylamino]ethyl] - Dihydroxy shed, [(lR)-l-[[(2S)-3-(4-phenylureido)-2-[(4-phenoxyphenyl)amino]-1-one Propyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(4-phenylphenylguanamine)-2-[( 4-butyl alum 曱95014-991001.doc -31- 1345465 hydrazino)amino]-1-ketopropyl)amino)-3-methylbutyl) Dihydroxy sane, [(lR)- L-[[(2S)-3-(4-Phenylphenylguanamine)-2-[(4-phenoxyphenyl)amino]]-1- propylpropyl)amino)- 3-mercaptobutyl)dihydroxyborane, [(lR)-l-[[(2S)-3-(phenylpropionamide)-2-[(4-butylphenyl)amino) ]-1-ketopropyl)amino group -3-mercaptobutyl)dihydroxyborane, [(1R) small [[(2S)-3-(4-mercaptophenylsulfonyl)-ureido]-2-[(4-butylbenzene) Indenyl)amino]-1-ketopropyl]amino]-3-mercaptobutyl]dihydroxyborane, [(lR)-l-[[(2S)-3-(4-( 2-(4-Pyridyl)-1,3-oxexazole-4-carbonylamino))-2-[(4-butylphenylhydrazino)amino]-1-ketopropyl)amine Base]-3-methylbutyl) Dihydroxyborane, [(lR)-l-[[(2S)-3-(l-decanesulfonylhexahydropyridinylcarbonylamino)-2-[(4-butylphenylhydrazino) )]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[[2S)-3-[(2-thiophene)sulfonyl) Amino]_2-[(4-butylphenylguanidino)]-1-ketopropyl]amino]-3-methylbutyl]dihydroxyborane, [(lR)-l-[ [(2S)-3-(4-(lH-l,2,4-triazol-1-yl)benzamide)]-2-[(4-butylphenylhydrazone)amino]_1_ _propylpropyl]amino]_3_methylbutyl] hydrochloride diboron borane, [(lR)-l-[[(2R)-3-(4-methylphenylcarbonyl)_2· (decylamino)-1-ketopropyl]amino]-3-methylbutyl] Di-boron-boron, [(lR)-l-[[(2S)-3-(4-phenylureido)-2-(indolyl))-indolyl]amino]amino]- 3-methylbutyl] * U-phenylbenzamide, ls_dioxo [5.0.5.3]15--14-yl]-3-mercaptobutyl]amino]amino]2-hydroxypropyl]borane or its pharmaceutically acceptable Accepted salt or free form. 32. A composition comprising the compound according to the claim "one of the compounds and a pharmaceutically acceptable carrier.", 33. - an inhibitor of (4) an in vitro method of activity of a white matter degrading body, "including making a request A compound of any one of ι-31 is contacted with the protein degradation body. 0950950-991001.doc -32-^45465 34 A pharmaceutical composition for treating cancer comprising a therapeutically effective amount such as a request A compound of any one of 1-31. A pharmaceutical composition for treating cancer, wherein the cancer is selected from the group consisting of skin, prostate, colorectum, pancreas, kidney, ovary, breast, liver, tongue, Lung and smooth muscle tissue. A monthly pharmaceutical composition for treating cancer, wherein the cancer is selected From leukemia, lymphoma, non-H〇dgkin lymphoma, myeloid cell tumor, and multiple myeloma. 37. A pharmaceutical composition for the treatment of cancer according to claim 34, which further comprises a therapeutically effective amount of a compound according to any one of claims (4), in combination with two or more anti-tumor or anti-cancer agents and/or Radiation Therapy. 38. An in vitro method for inhibiting protein degradation A protein degradation product of a protein is contacted with a request. The method of claim 38, wherein the protein f is ubiquitin, wherein the protein is hydrazine. The method of claim 38, wherein the protein f is ubiquitin. τ A therapeutic (IV) for the treatment of accelerated or enhanced proteolysis comprising a therapeutically effective amount of a request. A pharmaceutical composition comprising a product of the present invention, which comprises a compound for inhibiting transcription factor npi b activity, such as one of claims 1-31. 43. A medical treatment for a disease or condition selected from the group consisting of a human immunodeficiency virus (mv) susceptibility composition $' or by 'the disease or condition is associated with transplant rejection, joint 95014-991001.doc [-33- 1345465 An inflammatory condition caused by inflammation, infection, inflammatory bowel disease, asthma, osteoporosis, osteoarthritis, psoriasis, restenosis, and autoimmune disease, which comprises a therapeutically effective amount as one of claims 1-31 Compound. 44. A compound which is [(lR)-l-[[(2S,3R)-3-hydroxy-2-[(6-phenyl-pyridin-2-carbonyl)amino]-1-one) Butyl]amino]-3-methylbutyl]dihydroxyborane or a pharmaceutically acceptable salt thereof. 95014-991001.doc 34·