CN102675279A - 用于治疗或预防黄病毒属感染的噻吩类似物 - Google Patents
用于治疗或预防黄病毒属感染的噻吩类似物 Download PDFInfo
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- CN102675279A CN102675279A CN2012100812804A CN201210081280A CN102675279A CN 102675279 A CN102675279 A CN 102675279A CN 2012100812804 A CN2012100812804 A CN 2012100812804A CN 201210081280 A CN201210081280 A CN 201210081280A CN 102675279 A CN102675279 A CN 102675279A
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- Prior art keywords
- alkyl
- substituted
- cyclohexyl
- trans
- compound
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- 238000011282 treatment Methods 0.000 title abstract description 13
- 206010054261 Flavivirus infection Diseases 0.000 title abstract description 8
- 230000002265 prevention Effects 0.000 title abstract description 7
- 150000003577 thiophenes Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 197
- 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 abstract description 73
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 6
- -1 Cyclohexyl Chemical group 0.000 claims description 159
- 150000003254 radicals Chemical class 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 230000003612 virological effect Effects 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 33
- 239000003112 inhibitor Substances 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 17
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 239000003001 serine protease inhibitor Substances 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 10
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 10
- 229960000329 ribavirin Drugs 0.000 claims description 10
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 10
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 239000002955 immunomodulating agent Substances 0.000 claims description 8
- 229940121354 immunomodulator Drugs 0.000 claims description 8
- MDDXNVPRRYHPMO-UHFFFAOYSA-N methyl 3-amino-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C#CC(C)(C)C)=CC=1N MDDXNVPRRYHPMO-UHFFFAOYSA-N 0.000 claims description 8
- 230000017105 transposition Effects 0.000 claims description 8
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 7
- 108010047761 Interferon-alpha Proteins 0.000 claims description 7
- 102000006992 Interferon-alpha Human genes 0.000 claims description 7
- 108091005804 Peptidases Proteins 0.000 claims description 7
- 239000004365 Protease Substances 0.000 claims description 7
- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 7
- 101710102218 Serine protease inhibitor Proteins 0.000 claims description 7
- 230000000692 anti-sense effect Effects 0.000 claims description 7
- WPMJNLCLKAKMLA-VVPTUSLJSA-N chembl3039503 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 WPMJNLCLKAKMLA-VVPTUSLJSA-N 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 6
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229940021747 therapeutic vaccine Drugs 0.000 claims description 6
- UJJWIWKVHFEOGC-IFSQOONMSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](N2N=NC=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](N2N=NC=C2)CC1 UJJWIWKVHFEOGC-IFSQOONMSA-N 0.000 claims description 5
- BQWNFSIZZJRQGF-VVPTUSLJSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](F)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](F)CC1 BQWNFSIZZJRQGF-VVPTUSLJSA-N 0.000 claims description 4
- HZGVSNYUDXKRGO-IFSQOONMSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](N2N=CN=C2)CC1 HZGVSNYUDXKRGO-IFSQOONMSA-N 0.000 claims description 4
- HZGVSNYUDXKRGO-PVPVSOICSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@H](N2N=CN=C2)CC1 HZGVSNYUDXKRGO-PVPVSOICSA-N 0.000 claims description 4
- NTVXCKOALKBIOR-UBBSCCEASA-N C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)[C@@H]1CC[C@@H](C)CC1 NTVXCKOALKBIOR-UBBSCCEASA-N 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- QDXQQJHQGYQPST-UHFFFAOYSA-N methyl 5-(3,3-dimethylbut-1-ynyl)-3-[[4-(1,2,4-triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound S1C(C#CC(C)(C)C)=CC(NC2CCC(CC2)N2N=CN=C2)=C1C(=O)OC QDXQQJHQGYQPST-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- WPMJNLCLKAKMLA-UGLKCIBTSA-N C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@H]1CC[C@@H](O)CC1 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@H]1CC[C@@H](O)CC1 WPMJNLCLKAKMLA-UGLKCIBTSA-N 0.000 claims description 3
- DMTBZKHSEPBSDO-KTSLABGISA-N S1C(I)=CC(N([C@@H]2CC[C@@H](O)CC2)C(=O)[C@@H]2CC[C@@H](C)CC2)=C1C(=O)OC Chemical compound S1C(I)=CC(N([C@@H]2CC[C@@H](O)CC2)C(=O)[C@@H]2CC[C@@H](C)CC2)=C1C(=O)OC DMTBZKHSEPBSDO-KTSLABGISA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 3
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- GSVOVRREKYZZNE-UHFFFAOYSA-N methyl 5-(3,3-dimethylbut-1-ynyl)-3-[[4-(triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound S1C(C#CC(C)(C)C)=CC(NC2CCC(CC2)N2N=NC=C2)=C1C(=O)OC GSVOVRREKYZZNE-UHFFFAOYSA-N 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 239000011251 protective drug Substances 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 2
- 125000005914 C6-C14 aryloxy group Chemical group 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- RDQQTRLJVBILSZ-IYARVYRRSA-N chembl3121502 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCN(C)CC1 RDQQTRLJVBILSZ-IYARVYRRSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
- SFCSESWOFLHNMP-SHTZXODSSA-N S1C(I)=CC(N(C2CCC3(CC2)OCCO3)C(=O)[C@@H]2CC[C@@H](C)CC2)=C1C(=O)OC Chemical compound S1C(I)=CC(N(C2CCC3(CC2)OCCO3)C(=O)[C@@H]2CC[C@@H](C)CC2)=C1C(=O)OC SFCSESWOFLHNMP-SHTZXODSSA-N 0.000 claims 2
- 230000003078 antioxidant effect Effects 0.000 claims 2
- 230000002584 immunomodulator Effects 0.000 claims 2
- GQXVVAHUWNBYEE-UHFFFAOYSA-N methyl 5-(3,3-dimethylbut-1-ynyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C#CC(C)(C)C)=CC=1NC(=O)OC(C)(C)C GQXVVAHUWNBYEE-UHFFFAOYSA-N 0.000 claims 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 241000710781 Flaviviridae Species 0.000 abstract description 14
- 208000036142 Viral infection Diseases 0.000 abstract description 8
- 230000009385 viral infection Effects 0.000 abstract description 8
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 abstract description 2
- 239000012453 solvate Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 110
- 239000000203 mixture Substances 0.000 description 67
- 239000000243 solution Substances 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 41
- 241000711549 Hepacivirus C Species 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
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- 239000007787 solid Substances 0.000 description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 229940047124 interferons Drugs 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
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- 230000002829 reductive effect Effects 0.000 description 17
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- 239000004480 active ingredient Substances 0.000 description 14
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
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- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 7
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- RJGHQTVXGKYATR-UHFFFAOYSA-L dibutyl(dichloro)stannane Chemical compound CCCC[Sn](Cl)(Cl)CCCC RJGHQTVXGKYATR-UHFFFAOYSA-L 0.000 description 6
- 210000003494 hepatocyte Anatomy 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 6
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Biochemistry (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
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| US7569600B2 (en) | 2005-05-13 | 2009-08-04 | Virochem Pharma Inc. | Compounds and methods for the treatment of prevention of Flavivirus infections |
| EP2344201A1 (en) * | 2008-09-17 | 2011-07-20 | Nektar Therapeutics | Oligomer-protease inhibitor conjugates |
| BRPI0922364A2 (pt) | 2008-12-03 | 2017-08-29 | Presidio Pharmaceuticals Inc | Composto, composição farmacêutica e uso de um composto |
| AU2010276441B2 (en) * | 2009-07-21 | 2015-07-02 | Gilead Sciences, Inc. | Inhibitors of Flaviviridae viruses |
| EP2507249B1 (en) * | 2009-09-09 | 2015-11-11 | Gilead Sciences, Inc. | Inhibitors of flaviviridae viruses |
| MX2012006026A (es) * | 2009-11-25 | 2012-08-15 | Vertex Pharma | Derivados de acido 5-alquinil-tiofen-2-carboxilico y usos para tratamiento o prevencion de infecciones por flavivirus. |
| PH12012501216A1 (en) * | 2009-12-18 | 2012-11-05 | Boehringer Ingelheim Int | Hcv combination therapy |
| PT2523951E (pt) * | 2010-01-15 | 2015-09-14 | Gilead Sciences Inc | Inibidores de vírus flaviviridae |
| AU2011205744B2 (en) | 2010-01-15 | 2015-06-25 | Gilead Sciences, Inc. | Inhibitors of Flaviviridae viruses |
| TW201130502A (en) | 2010-01-29 | 2011-09-16 | Vertex Pharma | Therapies for treating hepatitis C virus infection |
| CA2800530A1 (en) * | 2010-05-28 | 2011-12-01 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| WO2011159826A2 (en) | 2010-06-15 | 2011-12-22 | Vertex Pharmaceuticals Incorporated | Hcv ns5b protease mutants |
| WO2012006070A1 (en) * | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| UY33473A (es) | 2010-06-28 | 2012-01-31 | Vertex Pharma | Compuestos y métodos para el tratamiento o la prevencion de infecciones por flavivirus |
| EP2585448A1 (en) | 2010-06-28 | 2013-05-01 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| WO2012010663A1 (en) * | 2010-07-22 | 2012-01-26 | Novartis Ag | 2,3,5-trisubstituted thiophene compounds and uses thereof |
| AU2011292040A1 (en) | 2010-08-17 | 2013-03-07 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of Flaviviridae viral infections |
| US8822520B2 (en) | 2010-09-22 | 2014-09-02 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic HCV inhibitors |
| TW201307334A (zh) | 2010-12-17 | 2013-02-16 | Cocrystal Discovery Inc | Ｃ型肝炎病毒聚合酶抑制劑 |
| WO2013009678A2 (en) * | 2011-07-08 | 2013-01-17 | Indiana University Research And Technology Corporation | Compositions and methods for the treatment of norovirus infection |
| EP2734515B1 (en) | 2011-07-13 | 2015-11-04 | Gilead Sciences, Inc. | Thiophen-2-carboxylic acid derivatives useful as inhibitors of flaviviridae viruses |
| AU2012286853A1 (en) | 2011-07-26 | 2013-05-02 | Vertex Pharmaceuticals Incorporated | Thiophene compounds |
| WO2013016499A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Methods for preparation of thiophene compounds |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| SE1450130A1 (sv) | 2011-10-21 | 2014-05-07 | Abbvie Inc | Förfaranden för att behandla hcv innefattande minst två direktverkande antivirala agenser, ribavirin men inte interferon |
| EP2583680A3 (en) | 2011-10-21 | 2013-06-12 | Abbvie Inc. | Mono (PSI-7977) or combination treatment of DAAs for use in treating HCV |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| CN103087052A (zh) * | 2011-10-31 | 2013-05-08 | 上海壹志医药科技有限公司 | 噻吩衍生物及其药物用途 |
| WO2014055142A1 (en) * | 2012-06-20 | 2014-04-10 | Cocrystal Discovery, Inc. | Inhibitors of hepatitis c virus polymerase |
| US8759544B2 (en) | 2012-08-17 | 2014-06-24 | Gilead Sciences, Inc. | Synthesis of an antiviral compound |
| US8841340B2 (en) | 2012-08-17 | 2014-09-23 | Gilead Sciences, Inc. | Solid forms of an antiviral compound |
| US8927741B2 (en) | 2012-08-17 | 2015-01-06 | Gilead Sciences, Inc. | Synthesis of an antiviral compound |
| EP2762124A1 (en) | 2013-01-31 | 2014-08-06 | IP Gesellschaft für Management mbH | Packaging comprising administration units of polymorphs, amorphous forms or solvates |
| TWI731854B (zh) | 2015-03-23 | 2021-07-01 | 美商共結晶製藥公司 | Ｃ型肝炎病毒聚合酶之抑制劑 |
| EA201892448A1 (ru) | 2016-04-28 | 2019-06-28 | Эмори Юниверсити | Алкинсодержащие нуклеотидные и нуклеозидные терапевтические композиции и связанные с ними способы применения |
| TWI833753B (zh) | 2018-05-09 | 2024-03-01 | 美商共結晶製藥公司 | 用於治療hcv之組合療法 |
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| CN1602308A (zh) * | 2001-06-11 | 2005-03-30 | 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 |
| WO2006072347A2 (de) * | 2004-12-22 | 2006-07-13 | Aicuris Gmbh & Co. Kg | Alkinyl-substituierte thiophene |
| WO2006072348A2 (de) * | 2004-12-22 | 2006-07-13 | Aicuris Gmbh & Co. Kg | Alkinyl-substituierte thiophene |
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| JPS57116077A (en) | 1981-01-12 | 1982-07-19 | Kanebo Ltd | Thieno(3,2-b)pyridinecarboxylic acid derivative |
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| JP2574085B2 (ja) | 1991-10-28 | 1997-01-22 | 株式会社トクヤマ | ３−アミノ−２−チオフェンカルボン酸誘導体の製造方法 |
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