JP2000513711A

JP2000513711A - 癌の治療法

癌の治療法

Info

Publication number: JP2000513711A
Authority: JP; Japan
Prior art keywords: ylmethyl; glycyl; substituted; methionine; alkyl
Prior art date: 1996-04-18
Legal status : Pending

Application number

JP09537313A

Other languages

English (en)

Japanese (ja)

Inventor

ジツブス，ジヤクソン・ビー

コール，ナンシー・イー

オリフ，アレン・アイ

Original Assignee

メルクエンドカンパニーインコーポレーテッド

Priority date

1996-04-18

Filing date

1997-04-15

Publication date

2000-10-17

1996-06-07 Priority claimed from GBGB9611982.1A external-priority patent/GB9611982D0/en

1997-04-15 Application filed by メルクエンドカンパニーインコーポレーテッド filed Critical メルクエンドカンパニーインコーポレーテッド

2000-10-17 Publication of JP2000513711A publication Critical patent/JP2000513711A/ja

Status Pending legal-status Critical Current

Links

206010028980 Neoplasm Diseases 0.000 title claims abstract description 47
201000011510 cancer Diseases 0.000 title claims abstract description 40
102000004357 Transferases Human genes 0.000 claims abstract description 97
108090000992 Transferases Proteins 0.000 claims abstract description 97
238000000034 method Methods 0.000 claims abstract description 77
239000003112 inhibitor Substances 0.000 claims abstract description 36
229940124639 Selective inhibitor Drugs 0.000 claims abstract description 28
239000003528 protein farnesyltransferase inhibitor Substances 0.000 claims abstract description 11
-1 cyclic amine Chemical class 0.000 claims description 368
125000003118 aryl group Chemical group 0.000 claims description 242
125000000623 heterocyclic group Chemical group 0.000 claims description 232
150000001875 compounds Chemical class 0.000 claims description 182
229910052739 hydrogen Inorganic materials 0.000 claims description 127
239000001257 hydrogen Substances 0.000 claims description 127
125000000753 cycloalkyl group Chemical group 0.000 claims description 110
RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 110
150000002431 hydrogen Chemical class 0.000 claims description 90
125000000217 alkyl group Chemical group 0.000 claims description 83
235000001014 amino acid Nutrition 0.000 claims description 74
150000001413 amino acids Chemical class 0.000 claims description 67
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 63
229910052794 bromium Inorganic materials 0.000 claims description 60
229910052801 chlorine Inorganic materials 0.000 claims description 60
229910052731 fluorine Inorganic materials 0.000 claims description 59
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 55
150000003839 salts Chemical class 0.000 claims description 52
229910052757 nitrogen Inorganic materials 0.000 claims description 45
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 44
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 43
229920006395 saturated elastomer Polymers 0.000 claims description 40
125000001424 substituent group Chemical group 0.000 claims description 38
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
125000004432 carbon atom Chemical group C* 0.000 claims description 36
PFMUCCYYAAFKTH-YFKPBYRVSA-N Gly-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CN PFMUCCYYAAFKTH-YFKPBYRVSA-N 0.000 claims description 34
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 32
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 32
125000003107 substituted aryl group Chemical group 0.000 claims description 30
QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 claims description 28
UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 claims description 28
QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 claims description 28
125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 claims description 26
125000003342 alkenyl group Chemical group 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 23
125000001072 heteroaryl group Chemical group 0.000 claims description 23
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 22
235000004279 alanine Nutrition 0.000 claims description 22
229910052799 carbon Inorganic materials 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 22
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 21
230000002401 inhibitory effect Effects 0.000 claims description 21
150000004702 methyl esters Chemical class 0.000 claims description 21
229910052717 sulfur Inorganic materials 0.000 claims description 20
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 claims description 19
229910052720 vanadium Inorganic materials 0.000 claims description 18
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
229910052760 oxygen Inorganic materials 0.000 claims description 17
238000000338 in vitro Methods 0.000 claims description 16
IPSFOLSLIUIMKK-LURJTMIESA-N methyl (2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate Chemical compound CSCC[C@@H](C(=O)OC)NC(=O)CN IPSFOLSLIUIMKK-LURJTMIESA-N 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 13
125000005842 heteroatom Chemical group 0.000 claims description 13
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 12
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
125000002619 bicyclic group Chemical group 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
229910052698 phosphorus Inorganic materials 0.000 claims description 10
IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 9
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 8
125000005002 aryl methyl group Chemical group 0.000 claims description 8
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
229940016590 sarkosyl Drugs 0.000 claims description 8
108700004121 sarkosyl Proteins 0.000 claims description 8
KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 8
XBZOQGHZGQLEQO-IUCAKERBSA-N Lys-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCCN XBZOQGHZGQLEQO-IUCAKERBSA-N 0.000 claims description 7
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
150000002019 disulfides Chemical class 0.000 claims description 7
239000011574 phosphorus Substances 0.000 claims description 7
PRGUXYFOEDWESW-QMMMGPOBSA-N propan-2-yl (2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate Chemical compound CSCC[C@H](NC(=O)CN)C(=O)OC(C)C PRGUXYFOEDWESW-QMMMGPOBSA-N 0.000 claims description 7
KVFGDOPIXKWWOH-KRWDZBQOSA-N (2s)-4-methylsulfanyl-2-[pentoxy(3-phenylpropanoyl)amino]butanoic acid Chemical compound CCCCCON([C@@H](CCSC)C(O)=O)C(=O)CCC1=CC=CC=C1 KVFGDOPIXKWWOH-KRWDZBQOSA-N 0.000 claims description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 6
LXHVDHCVOHXJTE-UWVGGRQHSA-N CCN1CCC[C@H]1C(=O)N[C@@H](CCSC)C(O)=O Chemical compound CCN1CCC[C@H]1C(=O)N[C@@H](CCSC)C(O)=O LXHVDHCVOHXJTE-UWVGGRQHSA-N 0.000 claims description 6
125000001931 aliphatic group Chemical group 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
125000002883 imidazolyl group Chemical group 0.000 claims description 5
239000006187 pill Substances 0.000 claims description 5
DFNPCBBBVQMXBS-STQMWFEESA-N propan-2-yl (2s)-2-[[(2s)-1-ethylpyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoate Chemical compound CCN1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)OC(C)C DFNPCBBBVQMXBS-STQMWFEESA-N 0.000 claims description 5
PFJBRLADDVKCGK-ZDUSSCGKSA-N (2S)-2-[3-methylbutanoyl(pentoxy)amino]-4-methylsulfanylbutanoic acid Chemical compound CCCCCON([C@@H](CCSC)C(O)=O)C(=O)CC(C)C PFJBRLADDVKCGK-ZDUSSCGKSA-N 0.000 claims description 4
PDTLSIUBYNDOHS-LBPRGKRZSA-N (2S)-4-hydroxy-2-(5-pentoxypentanoylamino)butanoic acid Chemical compound CCCCCOCCCCC(=O)N[C@@H](CCO)C(O)=O PDTLSIUBYNDOHS-LBPRGKRZSA-N 0.000 claims description 4
QTGHDUCWDMAXFE-LWKPJOBUSA-N (2s)-4-hydroxy-2-[(2-methyl-3-phenylpropanoyl)-pentylsulfanylamino]butanoic acid Chemical compound CCCCCSN([C@@H](CCO)C(O)=O)C(=O)C(C)CC1=CC=CC=C1 QTGHDUCWDMAXFE-LWKPJOBUSA-N 0.000 claims description 4
VPVDOFJMUINSGB-LBPRGKRZSA-N (2s)-4-hydroxy-2-[3-methylbutanoyl(pentoxy)amino]butanoic acid Chemical compound CCCCCON([C@@H](CCO)C(O)=O)C(=O)CC(C)C VPVDOFJMUINSGB-LBPRGKRZSA-N 0.000 claims description 4
PSKCSAPEAFENPC-LWKPJOBUSA-N (2s)-4-hydroxy-2-[pentoxy(3-phenylbutanoyl)amino]butanoic acid Chemical compound CCCCCON([C@@H](CCO)C(O)=O)C(=O)CC(C)C1=CC=CC=C1 PSKCSAPEAFENPC-LWKPJOBUSA-N 0.000 claims description 4
JTHYTTAMRPUVFT-BDYUSTAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-4-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=NC=C1 JTHYTTAMRPUVFT-BDYUSTAISA-N 0.000 claims description 4
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 4
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
YUTRYUWIOMSYBY-NRFANRHFSA-N C(CCCC)ON([C@@H](CCSC)C(=O)O)C(CCC1=CC=CC2=CC=CC=C12)=O Chemical compound C(CCCC)ON([C@@H](CCSC)C(=O)O)C(CCC1=CC=CC2=CC=CC=C12)=O YUTRYUWIOMSYBY-NRFANRHFSA-N 0.000 claims description 4
SUYFDMQBZCATRT-AMGKYWFPSA-N C(CCCC)ON[C@@H](CC(O)C(C=CCC)=O)C(=O)O Chemical compound C(CCCC)ON[C@@H](CC(O)C(C=CCC)=O)C(=O)O SUYFDMQBZCATRT-AMGKYWFPSA-N 0.000 claims description 4
108010076830 Thionins Proteins 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
150000002596 lactones Chemical class 0.000 claims description 4
239000002932 luster Substances 0.000 claims description 4
KSRIGEDVURVPEB-XCZPVHLTSA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-4-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=NC=C1 KSRIGEDVURVPEB-XCZPVHLTSA-N 0.000 claims description 4
WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 claims description 4
229960002195 perazine Drugs 0.000 claims description 4
238000006467 substitution reaction Methods 0.000 claims description 4
150000003457 sulfones Chemical class 0.000 claims description 4
CSSIJCNUWSQRSC-QEOTZNIISA-N (2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](NC[C@@H](N)CS)C(C)C CSSIJCNUWSQRSC-QEOTZNIISA-N 0.000 claims description 3
LRICZMUKYVXXAT-VXKWHMMOSA-N (2s)-2-[[2-[[(2s)-1-[3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-[(2-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound COC1=CC=CC=C1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@H]1N(C(=O)CCC=2N=CNC=2)CCC1 LRICZMUKYVXXAT-VXKWHMMOSA-N 0.000 claims description 3
KKKDZZRICRFGSD-UHFFFAOYSA-N 1-benzylimidazole Chemical compound C1=CN=CN1CC1=CC=CC=C1 KKKDZZRICRFGSD-UHFFFAOYSA-N 0.000 claims description 3
125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 3
LBHNZGNSUMLAQN-IFUPQEAVSA-N 4-[[2-[[(2s)-4-(3-chlorophenyl)-2-(2-methylsulfonylethyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile;dihydrochloride Chemical compound Cl.Cl.C([C@@H]1CCS(=O)(=O)C)N(C=2C=C(Cl)C=CC=2)C(=O)CN1CC1=NC=CN1CC1=CC=C(C#N)C=C1 LBHNZGNSUMLAQN-IFUPQEAVSA-N 0.000 claims description 3
RMZQNOARFIICNW-DEOSSOPVSA-N 4-[[5-[[(2s)-4-(2,3-dimethylphenyl)-2-(2-methoxyethyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1CCOC)N(C=2C(=C(C)C=CC=2)C)C(=O)CN1CC1=CN=CN1CC1=CC=C(C#N)C=C1 RMZQNOARFIICNW-DEOSSOPVSA-N 0.000 claims description 3
125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 3
125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 3
125000006189 4-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
RTVOEPCPPNTPRP-NRFANRHFSA-N [(3s)-3-butyl-4-(2-imidazol-1-ylethylsulfonyl)piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1S(=O)(=O)CCN1C=CN=C1 RTVOEPCPPNTPRP-NRFANRHFSA-N 0.000 claims description 3
PVYWVOMHDKGWBJ-QFIPXVFZSA-N [(3s)-3-butyl-4-[3-(1h-imidazol-5-yl)propyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CCCC1=CNC=N1 PVYWVOMHDKGWBJ-QFIPXVFZSA-N 0.000 claims description 3
STGUUQDDIYWJJD-MHZLTWQESA-N [(3s)-3-butyl-4-[[3-(2-phenylethyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CCC1=CC=CC=C1 STGUUQDDIYWJJD-MHZLTWQESA-N 0.000 claims description 3
SUNRCDSJBVJKOF-DEOSSOPVSA-N [(3s)-3-butyl-4-[[3-(3-methylbut-2-enyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC=C(C)C SUNRCDSJBVJKOF-DEOSSOPVSA-N 0.000 claims description 3
OLSVEEWCYNTQJD-LJAQVGFWSA-N [(3s)-3-butyl-4-[[3-(naphthalen-1-ylmethyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)N3C[C@@H](N(CC3)CC=3N(C=NC=3)CC=3C4=CC=CC=C4C=CC=3)CCCC)=CC=CC2=C1 OLSVEEWCYNTQJD-LJAQVGFWSA-N 0.000 claims description 3
AEKIOMXHUIEHTI-PMERELPUSA-N [(3s)-3-butyl-4-[[3-(naphthalen-2-ylmethyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)N3C[C@@H](N(CC3)CC=3N(C=NC=3)CC=3C=C4C=CC=CC4=CC=3)CCCC)=CC=CC2=C1 AEKIOMXHUIEHTI-PMERELPUSA-N 0.000 claims description 3
QHKXREACPVGZHL-SANMLTNESA-N [(3s)-3-butyl-4-[[3-[(4-methoxyphenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(OC)C=C1 QHKXREACPVGZHL-SANMLTNESA-N 0.000 claims description 3
OITGWZQOTKBNHC-MHAHJAEUSA-N [(3s)-4-[(2r)-2-amino-3-hydroxyheptadecyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1[C@H](CCCC)N(C[C@@H](N)C(O)CCCCCCCCCCCCCC)CCN1C(=O)C1=CC=CC2=CC=CC=C12 OITGWZQOTKBNHC-MHAHJAEUSA-N 0.000 claims description 3
IVFJZZVFLCGKMR-MOPGFXCFSA-N [(3s)-4-[(2r)-2-amino-3-hydroxypropyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1CN(C[C@@H](N)CO)[C@@H](CCCC)CN1C(=O)C1=CC=CC2=CC=CC=C12 IVFJZZVFLCGKMR-MOPGFXCFSA-N 0.000 claims description 3
SFMJVGMTFJODNJ-CGAIIQECSA-N [(3s)-4-[2-amino-3-(2-hydroxyphenyl)propyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC(N)CC1=CC=CC=C1O SFMJVGMTFJODNJ-CGAIIQECSA-N 0.000 claims description 3
AVXFQBJAVCGIFW-FLDQDSGZSA-N [(3s)-4-[2-amino-3-(2-phenylmethoxyphenyl)propyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC(N)CC1=CC=CC=C1OCC1=CC=CC=C1 AVXFQBJAVCGIFW-FLDQDSGZSA-N 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
210000004556 brain Anatomy 0.000 claims description 3
229930195733 hydrocarbon Natural products 0.000 claims description 3
150000002430 hydrocarbons Chemical class 0.000 claims description 3
KXWULRSLTPLVDC-ZDUSSCGKSA-N methyl (2s)-2-(isoquinoline-1-carbonylamino)-4-methylsulfanylbutanoate Chemical compound C1=CC=C2C(C(=O)N[C@@H](CCSC)C(=O)OC)=NC=CC2=C1 KXWULRSLTPLVDC-ZDUSSCGKSA-N 0.000 claims description 3
MBPQSJQKBMFGNV-ZCYQVOJMSA-N methyl (2s)-2-[[2-[[(2s)-1-[2-(dimethylamino)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)CN(C)C MBPQSJQKBMFGNV-ZCYQVOJMSA-N 0.000 claims description 3
ZPSOILKVHRWGCY-HVCNVCAESA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[(2s)-5-oxopyrrolidine-2-carbonyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)[C@@H]1CCC(=O)N1 ZPSOILKVHRWGCY-HVCNVCAESA-N 0.000 claims description 3
STTPMEVACJNPEF-YADHBBJMSA-N n-[[(2r)-2-amino-3-[(2s)-2-butyl-4-(naphthalene-1-carbonyl)piperazin-1-yl]propyl]sulfanylmethyl]acetamide Chemical compound C1CN(C[C@@H](N)CSCNC(C)=O)[C@@H](CCCC)CN1C(=O)C1=CC=CC2=CC=CC=C12 STTPMEVACJNPEF-YADHBBJMSA-N 0.000 claims description 3
ALSVYJWYFHSURP-JDXGNMNLSA-N propan-2-yl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-4-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC(C)C)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=NC=C1 ALSVYJWYFHSURP-JDXGNMNLSA-N 0.000 claims description 3
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 3
125000000547 substituted alkyl group Chemical group 0.000 claims description 3
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
239000003558 transferase inhibitor Substances 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
LAPHWKUNWCRZCI-SFTDATJTSA-N (2S)-2-[[(2S)-1-[2-(1H-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methoxy-(3-phenylpropanoyl)amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CON([C@@H](CCSC)C(O)=O)C(=O)CCC=2C=CC=CC=2)CCN1C(=O)CC1=CN=CN1 LAPHWKUNWCRZCI-SFTDATJTSA-N 0.000 claims description 2
NTRSFDJLDDPBQH-ZDUSSCGKSA-N (2S)-4-hydroxy-2-[4-methylpentanoyl(pentoxy)amino]butanoic acid Chemical compound CCCCCON([C@@H](CCO)C(O)=O)C(=O)CCC(C)C NTRSFDJLDDPBQH-ZDUSSCGKSA-N 0.000 claims description 2
YHCLTLZZKPKZIQ-LBPRGKRZSA-N (2s)-2-(isoquinoline-1-carbonylamino)-4-methylsulfanylbutanoic acid Chemical compound C1=CC=C2C(C(=O)N[C@@H](CCSC)C(O)=O)=NC=CC2=C1 YHCLTLZZKPKZIQ-LBPRGKRZSA-N 0.000 claims description 2
VOWJQSVTTNCIGG-GMAHTHKFSA-N (2s)-2-[[2-[[(2s)-1-(1h-imidazole-5-carbonyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1=CNC=N1 VOWJQSVTTNCIGG-GMAHTHKFSA-N 0.000 claims description 2
BBIMPJDOEHPCLJ-GMAHTHKFSA-N (2s)-2-[[2-[[(2s)-1-(2-aminoethyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1CCN BBIMPJDOEHPCLJ-GMAHTHKFSA-N 0.000 claims description 2
WGZXCXSLMXNADB-GMAHTHKFSA-N (2s)-2-[[2-[[(2s)-1-(3-aminopropanoyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)CCN WGZXCXSLMXNADB-GMAHTHKFSA-N 0.000 claims description 2
NIMQYCGHXAABQY-DMDYGQEQSA-N (2s)-2-[[2-[[(2s)-1-[(2r)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=1C2=CC=CC=C2C=CC=1)C1=CNC=N1 NIMQYCGHXAABQY-DMDYGQEQSA-N 0.000 claims description 2
RDGVOABWUWODLX-JZWVFAODSA-N (2s)-2-[[2-[[(2s)-1-[(2r)-2-aminopropanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)[C@@H](C)N RDGVOABWUWODLX-JZWVFAODSA-N 0.000 claims description 2
NIMQYCGHXAABQY-RNXOBYDBSA-N (2s)-2-[[2-[[(2s)-1-[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=1C2=CC=CC=C2C=CC=1)C1=CNC=N1 NIMQYCGHXAABQY-RNXOBYDBSA-N 0.000 claims description 2
HUBAHCJBIRMDBS-PMVMPFDFSA-N (2s)-2-[[2-[[(2s)-1-[(3s)-3,4-diamino-4-oxobutanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)C[C@H](N)C(N)=O HUBAHCJBIRMDBS-PMVMPFDFSA-N 0.000 claims description 2
XNLSOFWOAJBPRW-SFTDATJTSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[(2-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound COC1=CC=CC=C1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@H]1N(C(=O)CC=2NC=NC=2)CCC1 XNLSOFWOAJBPRW-SFTDATJTSA-N 0.000 claims description 2
NAPKHUSBDHTYQA-UNMCSNQZSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[(3-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound COC1=CC=CC(CN(C[C@H]2N(CCC2)C(=O)CC=2NC=NC=2)CC(=O)N[C@@H](CCSC)C(O)=O)=C1 NAPKHUSBDHTYQA-UNMCSNQZSA-N 0.000 claims description 2
SJXPMYBVFKOZTF-UNMCSNQZSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[(4-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C1=CC(OC)=CC=C1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@H]1N(C(=O)CC=2NC=NC=2)CCC1 SJXPMYBVFKOZTF-UNMCSNQZSA-N 0.000 claims description 2
NSTOSYAYHNCROE-UPVQGACJSA-N (2s)-2-[[2-[[(2s)-1-[2-(dimethylamino)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)CN(C)C NSTOSYAYHNCROE-UPVQGACJSA-N 0.000 claims description 2
PJIRHLLXQXEKHG-SFTDATJTSA-N (2s)-2-[[2-[benzyl-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C=CC=CC=2)CCN1C(=O)CC1=CN=CN1 PJIRHLLXQXEKHG-SFTDATJTSA-N 0.000 claims description 2
WCICNWWHELSEFM-INIZCTEOSA-N (2s)-4-hydroxy-2-[pentoxy(3-phenylpropanoyl)amino]butanoic acid Chemical compound CCCCCON([C@@H](CCO)C(O)=O)C(=O)CCC1=CC=CC=C1 WCICNWWHELSEFM-INIZCTEOSA-N 0.000 claims description 2
LLWHJERHFOWCKW-BDYUSTAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(2-pyridin-2-ylacetyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CC=CC=N1 LLWHJERHFOWCKW-BDYUSTAISA-N 0.000 claims description 2
HFABAVNVKIGOQD-MMOCMJAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-3-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCCNC1 HFABAVNVKIGOQD-MMOCMJAISA-N 0.000 claims description 2
KZMFHSMLMMKVBK-AHWVRZQESA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-4-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCNCC1 KZMFHSMLMMKVBK-AHWVRZQESA-N 0.000 claims description 2
ZBBSQXCFADEMLA-XWGVYQGASA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[(2s)-5-oxopyrrolidine-2-carbonyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)[C@@H]1CCC(=O)N1 ZBBSQXCFADEMLA-XWGVYQGASA-N 0.000 claims description 2
BVVYOFGYTQLBKT-HVCNVCAESA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[(2s)-pyrrolidine-2-carbonyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)[C@@H]1CCCN1 BVVYOFGYTQLBKT-HVCNVCAESA-N 0.000 claims description 2
YRSFPIMTLHOOHE-AHWVRZQESA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-2-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=CC=N1 YRSFPIMTLHOOHE-AHWVRZQESA-N 0.000 claims description 2
HDWJGUSPAWNOSP-ZCYQVOJMSA-N (2s)-5-amino-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]-methylamino]-5-oxopentanoic acid Chemical compound C([C@H]1CN(CC(=O)N([C@@H](CCC(N)=O)C(O)=O)C)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 HDWJGUSPAWNOSP-ZCYQVOJMSA-N 0.000 claims description 2
PVPBBTJXIKFICP-UHFFFAOYSA-N (7-aminophenothiazin-3-ylidene)azanium;chloride Chemical compound [Cl-].C1=CC(=[NH2+])C=C2SC3=CC(N)=CC=C3N=C21 PVPBBTJXIKFICP-UHFFFAOYSA-N 0.000 claims description 2
125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 claims description 2
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
208000026310 Breast neoplasm Diseases 0.000 claims description 2
UUGYBWICSROEIS-LBPRGKRZSA-N C(C1=CC=CC=C1)OC([C@@H](NC(CN)=O)CCSC)=O Chemical compound C(C1=CC=CC=C1)OC([C@@H](NC(CN)=O)CCSC)=O UUGYBWICSROEIS-LBPRGKRZSA-N 0.000 claims description 2
DBBIPZHJCCFIJP-NPGWBMRXSA-N COC(=O)[C@H](CCSC)NC(=O)CN(CC1=CC=CC2=CC=CC=C21)C(CC3=CN=CN3)[C@@H]4CCCN4 Chemical compound COC(=O)[C@H](CCSC)NC(=O)CN(CC1=CC=CC2=CC=CC=C21)C(CC3=CN=CN3)[C@@H]4CCCN4 DBBIPZHJCCFIJP-NPGWBMRXSA-N 0.000 claims description 2
208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 2
206010025323 Lymphomas Diseases 0.000 claims description 2
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 2
DFZYCDAULQCYSM-NSHDSACASA-N N1=C(C=CC=C1)COC([C@@H](NC(CN)=O)CCSC)=O Chemical compound N1=C(C=CC=C1)COC([C@@H](NC(CN)=O)CCSC)=O DFZYCDAULQCYSM-NSHDSACASA-N 0.000 claims description 2
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 2
206010041067 Small cell lung cancer Diseases 0.000 claims description 2
ATICIZQVYXZRKE-SANMLTNESA-N [(3s)-3-butyl-4-[[3-[(4-fluorophenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(F)C=C1 ATICIZQVYXZRKE-SANMLTNESA-N 0.000 claims description 2
DSPPCOUSGYJEON-UXHICEINSA-N [(3s)-4-[(2r)-2-amino-4-hydroxybutyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1CN(C[C@H](N)CCO)[C@@H](CCCC)CN1C(=O)C1=CC=CC2=CC=CC=C12 DSPPCOUSGYJEON-UXHICEINSA-N 0.000 claims description 2
QDVKETOAAQPNNT-ZSXSBBPPSA-N [(3s)-4-[3-amino-2-(naphthalen-2-ylmethylamino)propyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)N3C[C@@H](N(CC3)CC(CN)NCC=3C=C4C=CC=CC4=CC=3)CCCC)=CC=CC2=C1 QDVKETOAAQPNNT-ZSXSBBPPSA-N 0.000 claims description 2
125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 2
125000003435 aroyl group Chemical group 0.000 claims description 2
ZBKUMGBVZLQGRO-ZETCQYMHSA-N ethyl (2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CN ZBKUMGBVZLQGRO-ZETCQYMHSA-N 0.000 claims description 2
210000000867 larynx Anatomy 0.000 claims description 2
201000005249 lung adenocarcinoma Diseases 0.000 claims description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
GBDRMPRTNVKBAD-BYPYZUCNSA-N methyl (2s)-2,5-diamino-5-oxopentanoate Chemical compound COC(=O)[C@@H](N)CCC(N)=O GBDRMPRTNVKBAD-BYPYZUCNSA-N 0.000 claims description 2
LHABEFAAOYSPFO-ADHGMGHFSA-N methyl (2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoate Chemical compound CC(C)C[C@@H](C(=O)OC)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](NC[C@@H](N)CS)C(C)C LHABEFAAOYSPFO-ADHGMGHFSA-N 0.000 claims description 2
XBHIDWKJAGFKQB-UPVQGACJSA-N methyl (2s)-2-[[2-[[(2s)-1-(1h-imidazole-5-carbonyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1=CNC=N1 XBHIDWKJAGFKQB-UPVQGACJSA-N 0.000 claims description 2
OMJJXOGARPFMJT-UPVQGACJSA-N methyl (2s)-2-[[2-[[(2s)-1-(3-aminopropanoyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)CCN OMJJXOGARPFMJT-UPVQGACJSA-N 0.000 claims description 2
KKHKWUHYSPSTGC-OIKPOIBNSA-N methyl (2s)-2-[[2-[[(2s)-1-[(2r)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=1C2=CC=CC=C2C=CC=1)C1=CN=CN1 KKHKWUHYSPSTGC-OIKPOIBNSA-N 0.000 claims description 2
NGXKPLLTHVOWOD-UCFCWBNQSA-N methyl (2s)-2-[[2-[[(2s)-1-[(2r)-2-aminopropanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)[C@@H](C)N NGXKPLLTHVOWOD-UCFCWBNQSA-N 0.000 claims description 2
KKHKWUHYSPSTGC-URORMMCBSA-N methyl (2s)-2-[[2-[[(2s)-1-[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=1C2=CC=CC=C2C=CC=1)C1=CN=CN1 KKHKWUHYSPSTGC-URORMMCBSA-N 0.000 claims description 2
PNWWULIGMCXRNW-XWGVYQGASA-N methyl (2s)-2-[[2-[[(2s)-1-[(3s)-3,4-diamino-4-oxobutanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)C[C@H](N)C(N)=O PNWWULIGMCXRNW-XWGVYQGASA-N 0.000 claims description 2
IRYTXZYSQWNLMJ-AHWVRZQESA-N methyl (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 IRYTXZYSQWNLMJ-AHWVRZQESA-N 0.000 claims description 2
IDOPLSXAMKHPEG-VXKWHMMOSA-N methyl (2s)-2-[[2-[benzyl-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C=CC=CC=2)CCN1C(=O)CC1=CN=CN1 IDOPLSXAMKHPEG-VXKWHMMOSA-N 0.000 claims description 2
LMWZXKDVEIHYSV-XCZPVHLTSA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(2-pyridin-2-ylacetyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CC=CC=N1 LMWZXKDVEIHYSV-XCZPVHLTSA-N 0.000 claims description 2
SBVVZLWMKBDEEF-BDYUSTAISA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-4-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCNCC1 SBVVZLWMKBDEEF-BDYUSTAISA-N 0.000 claims description 2
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