AU2006246227B2 - Compounds and methods for the treatment or prevention of flavivirus infections - Google Patents
Compounds and methods for the treatment or prevention of flavivirus infections Download PDFInfo
- Publication number
- AU2006246227B2 AU2006246227B2 AU2006246227A AU2006246227A AU2006246227B2 AU 2006246227 B2 AU2006246227 B2 AU 2006246227B2 AU 2006246227 A AU2006246227 A AU 2006246227A AU 2006246227 A AU2006246227 A AU 2006246227A AU 2006246227 B2 AU2006246227 B2 AU 2006246227B2
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- Australia
- Prior art keywords
- trans
- methyl
- thiophene
- amino
- carboxylic acid
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- 150000001875 compounds Chemical class 0.000 title claims description 309
- 238000000034 method Methods 0.000 title claims description 67
- 238000011282 treatment Methods 0.000 title claims description 7
- 206010054261 Flavivirus infection Diseases 0.000 title description 6
- 230000002265 prevention Effects 0.000 title description 3
- -1 thiophene compound Chemical class 0.000 claims description 316
- 125000000217 alkyl group Chemical group 0.000 claims description 250
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 119
- 125000000623 heterocyclic group Chemical group 0.000 claims description 119
- 125000000304 alkynyl group Chemical group 0.000 claims description 106
- 125000003118 aryl group Chemical group 0.000 claims description 102
- 125000001072 heteroaryl group Chemical group 0.000 claims description 99
- 125000003342 alkenyl group Chemical group 0.000 claims description 98
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 91
- 229910052757 nitrogen Inorganic materials 0.000 claims description 70
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 67
- 239000011734 sodium Substances 0.000 claims description 59
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 53
- 230000003612 virological effect Effects 0.000 claims description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 46
- 241000711549 Hepacivirus C Species 0.000 claims description 45
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- 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 42
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 34
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- 125000001424 substituent group Chemical group 0.000 claims description 28
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
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- 125000004104 aryloxy group Chemical group 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
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- YPQKLYKBVPUWAG-UHFFFAOYSA-N methyl 3-[1,3-bis[tri(propan-2-yl)silyloxy]propan-2-ylamino]-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCC(CO[Si](C(C)C)(C(C)C)C(C)C)NC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 YPQKLYKBVPUWAG-UHFFFAOYSA-N 0.000 description 1
- XCGYGTXIMOMXFU-UHFFFAOYSA-N methyl 3-[1,3-dihydroxypropan-2-yl-(4-methylcyclohexanecarbonyl)amino]-5-(4,4-dimethylcyclohexyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC(C)(C)CC2)=CC=1N(C(CO)CO)C(=O)C1CCC(C)CC1 XCGYGTXIMOMXFU-UHFFFAOYSA-N 0.000 description 1
- NSMUNRCXDBJSNW-UHFFFAOYSA-N methyl 3-[1,4-dioxaspiro[4.5]decan-8-yl-(4-methylcyclohexanecarbonyl)amino]-5-(1-hydroxy-4,4-dimethylcyclohexyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2(O)CCC(C)(C)CC2)=CC=1N(C(=O)C1CCC(C)CC1)C(CC1)CCC21OCCO2 NSMUNRCXDBJSNW-UHFFFAOYSA-N 0.000 description 1
- JGHMTFPYGOMSIB-UHFFFAOYSA-N methyl 3-[1,4-dioxaspiro[4.5]decan-8-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C=CC(N(C2CCC3(CC2)OCCO3)C(=O)C2CCC(C)CC2)=C1C(=O)OC JGHMTFPYGOMSIB-UHFFFAOYSA-N 0.000 description 1
- NKMNDFXAMGNIMF-UHFFFAOYSA-N methyl 3-bromo-5-(4,4-dimethylcyclohexen-1-yl)thiophene-2-carboxylate Chemical compound BrC1=C(C(=O)OC)SC(C=2CCC(C)(C)CC=2)=C1 NKMNDFXAMGNIMF-UHFFFAOYSA-N 0.000 description 1
- PEGSJNCGPSIJOX-UHFFFAOYSA-N methyl 3-bromothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1Br PEGSJNCGPSIJOX-UHFFFAOYSA-N 0.000 description 1
- DOJJLBZWLLHGAB-UHFFFAOYSA-N methyl 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCC3(CC=2)OCCO3)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 DOJJLBZWLLHGAB-UHFFFAOYSA-N 0.000 description 1
- VCKGKTQUZPVVFS-UHFFFAOYSA-N methyl 5-(1,4-dioxaspiro[4.5]decan-8-yl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC3(CC2)OCCO3)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 VCKGKTQUZPVVFS-UHFFFAOYSA-N 0.000 description 1
- XSKFBQUERIPAKH-UHFFFAOYSA-N methyl 5-(1,4-dioxaspiro[4.5]decan-8-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C1CCC2(CC1)OCCO2)C(=O)OC)C(=O)C1CCC(C)CC1 XSKFBQUERIPAKH-UHFFFAOYSA-N 0.000 description 1
- CXOZJRDPSBGTDT-UHFFFAOYSA-N methyl 5-(1-hydroxycyclohex-2-en-1-yl)-3-[(4-methylcyclohexanecarbonyl)-[4-(oxan-2-yloxy)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2(O)C=CCCC2)=CC=1N(C(=O)C1CCC(C)CC1)C(CC1)CCC1OC1CCCCO1 CXOZJRDPSBGTDT-UHFFFAOYSA-N 0.000 description 1
- LIXSQKKNCMTAOV-UHFFFAOYSA-N methyl 5-(2,6-difluorocyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1C(CCCC=1F)F)C(=O)OC)C(=O)C1CCC(C)CC1 LIXSQKKNCMTAOV-UHFFFAOYSA-N 0.000 description 1
- TZUJJCSDLZTBCF-UHFFFAOYSA-N methyl 5-(4,4-dimethylcyclohexen-1-yl)-3-[[4-(1,2,4-triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCC(C)(C)CC=2)=CC=1NC(CC1)CCC1N1C=NC=N1 TZUJJCSDLZTBCF-UHFFFAOYSA-N 0.000 description 1
- IPICGJKKANUVMD-UHFFFAOYSA-N methyl 5-(4,4-dimethylcyclohexyl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC(C)(C)CC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 IPICGJKKANUVMD-UHFFFAOYSA-N 0.000 description 1
- SWVLETVKMGFLHZ-UHFFFAOYSA-N methyl 5-(4,4-dimethylcyclohexyl)-3-[1,3-dioxan-5-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2CCC(C)(C)CC2)=CC=1N(C(=O)C1CCC(C)CC1)C1COCOC1 SWVLETVKMGFLHZ-UHFFFAOYSA-N 0.000 description 1
- OSUVFWFEGCZXCD-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C(=O)OC)C(=O)C1CCC(C)CC1 OSUVFWFEGCZXCD-UHFFFAOYSA-N 0.000 description 1
- PYNHJVXZJFCQHI-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-(2-methyl-3-oxo-2-azaspiro[4.5]decan-8-yl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C(CC1)CCC21CN(C)C(=O)C2 PYNHJVXZJFCQHI-UHFFFAOYSA-N 0.000 description 1
- PFVAJVRMWSPGKC-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-(3-oxo-2,5,6,7,8,8a-hexahydro-1h-indolizin-7-yl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C1CC2N(C(CC2)=O)CC1)C(=O)C1CCC(C)CC1 PFVAJVRMWSPGKC-UHFFFAOYSA-N 0.000 description 1
- UJPXPQITBKABOQ-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-[1-(2-methylpropanoyl)piperidin-4-yl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCN(C(=O)C(C)C)CC1 UJPXPQITBKABOQ-UHFFFAOYSA-N 0.000 description 1
- SCTGGEQFOGRINW-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[(4-methylcyclohexanecarbonyl)-[4-(1,2,4-triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C(CC1)CCC1N1C=NC=N1 SCTGGEQFOGRINW-UHFFFAOYSA-N 0.000 description 1
- QFIKJRHQBUOWDD-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[[4-(1,2,4-triazol-1-yl)cyclohexyl]amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1NC(CC1)CCC1N1C=NC=N1 QFIKJRHQBUOWDD-UHFFFAOYSA-N 0.000 description 1
- YBXCOOWWSWKENH-UHFFFAOYSA-N methyl 5-(cyclohexen-1-yl)-3-[cyclohex-3-en-1-yl-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2CCCCC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC=CC1 YBXCOOWWSWKENH-UHFFFAOYSA-N 0.000 description 1
- FRKRFOAZSVJFDM-UHFFFAOYSA-N methyl 5-bromo-3-[(1,3-dimethyl-2,4-dioxo-1,3-diazaspiro[4.5]decan-8-yl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2CCC3(CC2)C(N(C)C(=O)N3C)=O)C(=O)C2CCC(C)CC2)=C1C(=O)OC FRKRFOAZSVJFDM-UHFFFAOYSA-N 0.000 description 1
- DNVFEPOGJHDYMJ-UHFFFAOYSA-N methyl 5-bromo-3-[(2,2-dimethyl-1,3-dioxan-5-yl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C2COC(C)(C)OC2)C(=O)C2CCC(C)CC2)=C1C(=O)OC DNVFEPOGJHDYMJ-UHFFFAOYSA-N 0.000 description 1
- YMZBNCXRVMHBHA-UHFFFAOYSA-N methyl 5-cyclohex-2-en-1-yl-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2C=CCCC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 YMZBNCXRVMHBHA-UHFFFAOYSA-N 0.000 description 1
- UODPHKFUTYRNDZ-UHFFFAOYSA-N methyl 5-cyclohex-2-en-1-yl-3-[(4-methylcyclohexanecarbonyl)-(4-oxocyclohexyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C2C=CCCC2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(=O)CC1 UODPHKFUTYRNDZ-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
- NUXCOKIYARRTDC-UHFFFAOYSA-N o-ethylhydroxylamine;hydron;chloride Chemical compound Cl.CCON NUXCOKIYARRTDC-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical group 0.000 description 1
- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 1
- 229950006081 taribavirin Drugs 0.000 description 1
- 229960002935 telaprevir Drugs 0.000 description 1
- BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 description 1
- 108010017101 telaprevir Proteins 0.000 description 1
- WYVFPGFWUKBXPZ-UHFFFAOYSA-N tert-butyl n-(4-oxocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(=O)CC1 WYVFPGFWUKBXPZ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- BMWZMDDFCPGUSM-UHFFFAOYSA-N thiophene-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CS1 BMWZMDDFCPGUSM-UHFFFAOYSA-N 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- DZXKSFDSPBRJPS-UHFFFAOYSA-N tin(2+);sulfide Chemical compound [S-2].[Sn+2] DZXKSFDSPBRJPS-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CMHHITPYCHHOGT-UHFFFAOYSA-N tributylborane Chemical compound CCCCB(CCCC)CCCC CMHHITPYCHHOGT-UHFFFAOYSA-N 0.000 description 1
- REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229950002810 valopicitabine Drugs 0.000 description 1
- ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical compound C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D333/40—Thiophene-2-carboxylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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| EP2543664A1 (en) | 2013-01-09 |
| CN101218224B (zh) | 2013-05-08 |
| CN101218224A (zh) | 2008-07-09 |
| HK1112910A1 (en) | 2008-09-19 |
| JP2008540463A (ja) | 2008-11-20 |
| EP2546246A2 (en) | 2013-01-16 |
| US20060276533A1 (en) | 2006-12-07 |
| US8158675B2 (en) | 2012-04-17 |
| ZA200709727B (en) | 2008-11-26 |
| KR20080016597A (ko) | 2008-02-21 |
| CA2607359A1 (en) | 2006-11-16 |
| ES2415742T3 (es) | 2013-07-26 |
| US20120164103A1 (en) | 2012-06-28 |
| US20100093775A1 (en) | 2010-04-15 |
| AP2007004245A0 (en) | 2007-12-31 |
| EA016071B1 (ru) | 2012-01-30 |
| SG161315A1 (en) | 2010-05-27 |
| EP1879879A1 (en) | 2008-01-23 |
| NZ563909A (en) | 2011-10-28 |
| JP5030947B2 (ja) | 2012-09-19 |
| EP1879879A4 (en) | 2010-03-10 |
| EP2546246A3 (en) | 2013-04-24 |
| CA2607359C (en) | 2011-08-09 |
| US7569600B2 (en) | 2009-08-04 |
| US8674118B2 (en) | 2014-03-18 |
| MX2007014117A (es) | 2008-02-05 |
| AU2006246227A1 (en) | 2006-11-16 |
| BRPI0610283A2 (pt) | 2010-10-19 |
| EP1879879B1 (en) | 2013-03-27 |
| EA200702493A1 (ru) | 2008-04-28 |
| WO2006119646A1 (en) | 2006-11-16 |
| CN102718744A (zh) | 2012-10-10 |
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