JP2013512247A5 - - Google Patents
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- JP2013512247A5 JP2013512247A5 JP2012541151A JP2012541151A JP2013512247A5 JP 2013512247 A5 JP2013512247 A5 JP 2013512247A5 JP 2012541151 A JP2012541151 A JP 2012541151A JP 2012541151 A JP2012541151 A JP 2012541151A JP 2013512247 A5 JP2013512247 A5 JP 2013512247A5
- Authority
- JP
- Japan
- Prior art keywords
- amino
- dimethyl
- thiophene
- benzoyl
- carboxylic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000001875 compounds Chemical class 0.000 claims description 126
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 64
- -1 —NH 2 Chemical group 0.000 claims description 43
- 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 26
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[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
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 230000017105 transposition Effects 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 241000710781 Flaviviridae Species 0.000 claims description 5
- 108010050904 Interferons Proteins 0.000 claims description 5
- 102000014150 Interferons Human genes 0.000 claims description 5
- 208000036142 Viral infection Diseases 0.000 claims description 5
- 229940079322 interferon Drugs 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- 102100040018 Interferon alpha-2 Human genes 0.000 claims description 4
- 108010047761 Interferon-alpha Proteins 0.000 claims description 4
- 102000006992 Interferon-alpha Human genes 0.000 claims description 4
- 108010079944 Interferon-alpha2b Proteins 0.000 claims description 4
- HAGOOSUDXBHSMT-IYARVYRRSA-N S1C(C#CC(C)(C)C)=CC(N([C@@H]2CC[C@@H](O)CC2)C(=O)C=2C=CC(Cl)=CC=2)=C1C(O)=O Chemical compound S1C(C#CC(C)(C)C)=CC(N([C@@H]2CC[C@@H](O)CC2)C(=O)C=2C=CC(Cl)=CC=2)=C1C(O)=O HAGOOSUDXBHSMT-IYARVYRRSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 229940065638 intron a Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 229940002988 pegasys Drugs 0.000 claims description 4
- 108010092853 peginterferon alfa-2a Proteins 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 2
- BURHMQWZAVCJQB-UHFFFAOYSA-N 3-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound CC(C)(C)C#CC=1C=CSC=1C(O)=O BURHMQWZAVCJQB-UHFFFAOYSA-N 0.000 claims description 2
- KWKCSVSLEKTKLY-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1,3-dimethoxypropan-2-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C(COC)COC)C(=O)C1=CC=C(Cl)C=C1Cl KWKCSVSLEKTKLY-UHFFFAOYSA-N 0.000 claims description 2
- PBLLBBNJLUNGQA-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1,3-dioxan-5-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2COCOC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O PBLLBBNJLUNGQA-UHFFFAOYSA-N 0.000 claims description 2
- VYMARQHNGPZNCI-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-methoxypropan-2-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C(C)COC)C(=O)C1=CC=C(Cl)C=C1Cl VYMARQHNGPZNCI-UHFFFAOYSA-N 0.000 claims description 2
- JVLQOOCNJXQWGQ-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-methylpiperidin-1-ium-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid;chloride Chemical compound Cl.C1CN(C)CCC1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl JVLQOOCNJXQWGQ-UHFFFAOYSA-N 0.000 claims description 2
- MKRZVIZUUCWRDB-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-methylsulfonylpiperidin-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CC2)S(C)(=O)=O)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O MKRZVIZUUCWRDB-UHFFFAOYSA-N 0.000 claims description 2
- NTGGXFHJTLLUPU-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-pyrimidin-2-ylpiperidin-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CC2)C=2N=CC=CN=2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O NTGGXFHJTLLUPU-UHFFFAOYSA-N 0.000 claims description 2
- KXPYCFRMQXOHKU-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(2,2,2-trifluoroethyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(CC(F)(F)F)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O KXPYCFRMQXOHKU-UHFFFAOYSA-N 0.000 claims description 2
- NBWWZQBKAJYUSU-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(2-methoxyethyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(CCOC)C(=O)C1=CC=C(Cl)C=C1Cl NBWWZQBKAJYUSU-UHFFFAOYSA-N 0.000 claims description 2
- LPWNNRFFJGOEKN-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(4,4-difluorocyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(F)(F)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O LPWNNRFFJGOEKN-UHFFFAOYSA-N 0.000 claims description 2
- ZLZKGNCRXGJBOG-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(4-oxocyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(=O)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O ZLZKGNCRXGJBOG-UHFFFAOYSA-N 0.000 claims description 2
- DVKAZZAFTYBIBP-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(oxan-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCOCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O DVKAZZAFTYBIBP-UHFFFAOYSA-N 0.000 claims description 2
- RBXCYJQSDQDLTI-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(oxolan-3-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2COCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O RBXCYJQSDQDLTI-UHFFFAOYSA-N 0.000 claims description 2
- JUFWROUHJJOECC-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-[1-(2,2-difluoroethyl)piperidin-4-yl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CC(F)F)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O JUFWROUHJJOECC-UHFFFAOYSA-N 0.000 claims description 2
- NVWUPEMFXAHJEL-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-[1-(2-methylpropanoyl)piperidin-4-yl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1CN(C(=O)C(C)C)CCC1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl NVWUPEMFXAHJEL-UHFFFAOYSA-N 0.000 claims description 2
- JEEOYPYOQVHPTC-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-ethylamino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(CC)C(=O)C1=CC=C(Cl)C=C1Cl JEEOYPYOQVHPTC-UHFFFAOYSA-N 0.000 claims description 2
- MNKCSQMRVFMBPB-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-methylamino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C)C(=O)C1=CC=C(Cl)C=C1Cl MNKCSQMRVFMBPB-UHFFFAOYSA-N 0.000 claims description 2
- SGQLPEMPVMPRNR-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-propan-2-ylamino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(Cl)C=C1Cl SGQLPEMPVMPRNR-UHFFFAOYSA-N 0.000 claims description 2
- CXJVWFOGCVHFKQ-UHFFFAOYSA-N 3-[(2,4-dimethylbenzoyl)-(4-hydroxycyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound CC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 CXJVWFOGCVHFKQ-UHFFFAOYSA-N 0.000 claims description 2
- AOWPCMNNWKHMEE-UHFFFAOYSA-N 3-[(2-amino-4-chlorobenzoyl)-[4-[methyl(2-methylpropanoyl)amino]cyclohexyl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1CC(N(C)C(=O)C(C)C)CCC1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1N AOWPCMNNWKHMEE-UHFFFAOYSA-N 0.000 claims description 2
- DKOJRDPYSCBWQX-UHFFFAOYSA-N 3-[(2-chloro-4-methylbenzoyl)-(4-hydroxycyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound ClC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 DKOJRDPYSCBWQX-UHFFFAOYSA-N 0.000 claims description 2
- FXUMYKGLQZKAEV-UHFFFAOYSA-N 3-[(4-chloro-3-fluorobenzoyl)-(4-hydroxycyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(O)CC2)C(=O)C=2C=C(F)C(Cl)=CC=2)=C1C(O)=O FXUMYKGLQZKAEV-UHFFFAOYSA-N 0.000 claims description 2
- VQBGEWVEDKRADV-UHFFFAOYSA-N 3-[cyclobutyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O VQBGEWVEDKRADV-UHFFFAOYSA-N 0.000 claims description 2
- BFGYAEYPEBLYSC-UHFFFAOYSA-N 3-[cyclohexyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCCCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O BFGYAEYPEBLYSC-UHFFFAOYSA-N 0.000 claims description 2
- CCPFITPFDGSRRP-UHFFFAOYSA-N 3-[cyclopentyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O CCPFITPFDGSRRP-UHFFFAOYSA-N 0.000 claims description 2
- KLTNNDIUICSBFR-UHFFFAOYSA-N 3-[cyclopropylmethyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(CC2CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O KLTNNDIUICSBFR-UHFFFAOYSA-N 0.000 claims description 2
- PKEAKMDQXCCAPM-UHFFFAOYSA-N 3-[tert-butyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C(=O)C=2C(=CC(Cl)=CC=2)Cl)C(C)(C)C)=C1C(O)=O PKEAKMDQXCCAPM-UHFFFAOYSA-N 0.000 claims description 2
- JARYWUSNBQQCLK-UHFFFAOYSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[(2-fluoro-4-methylbenzoyl)-(4-hydroxycyclohexyl)amino]thiophene-2-carboxylic acid Chemical compound FC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 JARYWUSNBQQCLK-UHFFFAOYSA-N 0.000 claims description 2
- RGOKCNBSFCCMJH-UHFFFAOYSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[(4-fluorobenzoyl)-(4-hydroxycyclohexyl)amino]thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(O)CC2)C(=O)C=2C=CC(F)=CC=2)=C1C(O)=O RGOKCNBSFCCMJH-UHFFFAOYSA-N 0.000 claims description 2
- CPXYBXFTEYLSEH-QAQDUYKDSA-N BrC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound BrC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 CPXYBXFTEYLSEH-QAQDUYKDSA-N 0.000 claims description 2
- FLZHELOCIQGFHP-IYARVYRRSA-N C1=C(F)C(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(F)C(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 FLZHELOCIQGFHP-IYARVYRRSA-N 0.000 claims description 2
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- XCWWWQQOLKGAQS-SAABIXHNSA-N C1C[C@@H](COC)CC[C@@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1N Chemical compound C1C[C@@H](COC)CC[C@@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1N XCWWWQQOLKGAQS-SAABIXHNSA-N 0.000 claims description 2
- WVQJBLVLIQITPO-QAQDUYKDSA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl WVQJBLVLIQITPO-QAQDUYKDSA-N 0.000 claims description 2
- WVQJBLVLIQITPO-CALCHBBNSA-N C1C[C@@H](OC)CC[C@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl Chemical compound C1C[C@@H](OC)CC[C@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl WVQJBLVLIQITPO-CALCHBBNSA-N 0.000 claims description 2
- YOFRMGSSLOVAOT-IYARVYRRSA-N CC1=CC(Cl)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound CC1=CC(Cl)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 YOFRMGSSLOVAOT-IYARVYRRSA-N 0.000 claims description 2
- FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-UHFFFAOYSA-N 0.000 claims description 2
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 2
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 claims description 2
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- SXVBPPKFXXBGNZ-QAQDUYKDSA-N OC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound OC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 SXVBPPKFXXBGNZ-QAQDUYKDSA-N 0.000 claims description 2
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- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000000692 anti-sense effect Effects 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 239000002955 immunomodulating agent Substances 0.000 claims description 2
- 229940121354 immunomodulator Drugs 0.000 claims description 2
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- 239000003112 inhibitor Substances 0.000 claims description 2
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 2
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 229940106366 pegintron Drugs 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
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- 229960000329 ribavirin Drugs 0.000 claims description 2
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
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| US61/374,396 | 2010-08-17 | ||
| PCT/US2010/057719 WO2011068715A1 (en) | 2009-11-25 | 2010-11-23 | 5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections |
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| WO2011011303A1 (en) | 2009-07-21 | 2011-01-27 | Gilead Sciences, Inc. | Inhibitors of flaviviridae viruses |
| ES2559437T3 (es) | 2009-09-09 | 2016-02-12 | Gilead Sciences, Inc. | Inhibidores de virus de la familia Flaviviridae |
| AP3576A (en) | 2010-01-15 | 2016-02-08 | Gilead Sciences Inc | Inhibitors of flaviviridae viruses |
| CA2785563C (en) | 2010-01-15 | 2019-05-14 | Gilead Sciences, Inc. | Inhibitors of flaviviridae viruses |
| EP2585448A1 (en) * | 2010-06-28 | 2013-05-01 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| EP2595983A1 (en) * | 2010-07-22 | 2013-05-29 | Novartis AG | 2,3,5-trisubstituted thiophene compounds and uses thereof |
| WO2013009678A2 (en) * | 2011-07-08 | 2013-01-17 | Indiana University Research And Technology Corporation | Compositions and methods for the treatment of norovirus infection |
| AU2012280959B2 (en) * | 2011-07-13 | 2015-08-06 | Gilead Sciences, Inc. | Thiophen-2-carboxylic acid derivatives useful as inhibitors of Flaviviridae viruses |
| US8841340B2 (en) | 2012-08-17 | 2014-09-23 | Gilead Sciences, Inc. | Solid forms of an antiviral compound |
| US8759544B2 (en) | 2012-08-17 | 2014-06-24 | Gilead Sciences, Inc. | Synthesis of an antiviral compound |
| US8927741B2 (en) | 2012-08-17 | 2015-01-06 | Gilead Sciences, Inc. | Synthesis of an antiviral compound |
| GB201305376D0 (en) | 2013-03-25 | 2013-05-08 | Univ Leuven Kath | Novel viral replication inhibitors |
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| AP1019A (en) | 1996-10-18 | 2001-10-16 | Vertex Pharma | Inhibitors of serinre proteases, particularly hepatitis C virus NS3 protease. |
| EP1012180B1 (en) | 1997-08-11 | 2004-12-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor peptide analogues |
| ES2241157T3 (es) | 1997-08-11 | 2005-10-16 | Boehringer Ingelheim (Canada) Ltd. | Peptidos inhibidores de la hepatitis c. |
| AU756627B2 (en) | 1998-07-27 | 2003-01-16 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Diketoacid-derivatives as inhibitors of polymerases |
| US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| AR022061A1 (es) | 1998-08-10 | 2002-09-04 | Boehringer Ingelheim Ca Ltd | Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos. |
| UA74546C2 (en) | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
| EP1162196A4 (en) | 1999-12-27 | 2003-04-16 | Japan Tobacco Inc | COMPOUNDS WITH JOINED CYCLES AND THEIR USE AS MEDICAMENTS |
| US20040034041A1 (en) | 2000-05-10 | 2004-02-19 | Dashyant Dhanak | Novel anti-infectives |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| GB0017676D0 (en) | 2000-07-19 | 2000-09-06 | Angeletti P Ist Richerche Bio | Inhibitors of viral polymerase |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| ES2263687T3 (es) | 2000-11-20 | 2006-12-16 | Bristol-Myers Squibb Company | Inhibidores tripeptidicos de la hepatitis c. |
| WO2002057425A2 (en) | 2001-01-22 | 2002-07-25 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| AU2002252183A1 (en) | 2001-03-06 | 2002-09-19 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| EP1256628A3 (en) | 2001-05-10 | 2003-03-19 | Agouron Pharmaceuticals, Inc. | Hepatitis c virus (hcv) ns5b rna polymerase and mutants thereof |
| AR036081A1 (es) | 2001-06-07 | 2004-08-11 | Smithkline Beecham Corp | Compuesto de 1,2-dihidroquinolina, su uso para preparar una composicion farmaceutica, metodos para prepararlo y compuestos del acido 2-aminobenzoico n-alquilado de utilidad como intermediarios en dichos metodos |
| CN101624391A (zh) | 2001-06-11 | 2010-01-13 | 病毒化学医药公司 | 用作黄病毒感染抗病毒剂的噻吩衍生物 |
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| AR035543A1 (es) | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
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| JP4926403B2 (ja) * | 2002-12-10 | 2012-05-09 | ヴァイロケム ファーマ インコーポレイテッド | フラビウイルス感染の処置もしくは予防のための化合物および方法 |
| AU2003291886A1 (en) | 2002-12-10 | 2004-06-30 | Virochem Pharma Inc. | Thiophenederivatives for the treatment of flavivirus infections |
| WO2004092161A1 (en) | 2003-04-11 | 2004-10-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
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| DE102004061746A1 (de) | 2004-12-22 | 2006-07-06 | Bayer Healthcare Ag | Alkinyl-substituierte Thiophene |
| DE102005028077A1 (de) * | 2004-12-22 | 2006-07-13 | Aicuris Gmbh & Co. Kg | Alkinyl-substituierte Thiophene |
| BRPI0610283A2 (pt) | 2005-05-13 | 2010-10-19 | Virochem Pharma Inc | composto, uso do mesmo na preparação de um medicamento para o tratamento ou prevenção de uma infecção por vìrus de hepatite c, composição farmacêutica e combinação farmacêutica |
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-
2010
- 2010-11-23 JP JP2012541151A patent/JP2013512247A/ja active Pending
- 2010-11-23 MX MX2012006026A patent/MX2012006026A/es not_active Application Discontinuation
- 2010-11-23 AU AU2010326225A patent/AU2010326225A1/en not_active Abandoned
- 2010-11-23 CA CA2781614A patent/CA2781614A1/en not_active Abandoned
- 2010-11-23 EP EP10785560A patent/EP2504329A1/en not_active Withdrawn
- 2010-11-23 WO PCT/US2010/057719 patent/WO2011068715A1/en not_active Ceased
-
2012
- 2012-05-25 US US13/480,631 patent/US20130136719A1/en not_active Abandoned
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