CA2508990C - 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
- CA2508990C CA2508990C CA2508990A CA2508990A CA2508990C CA 2508990 C CA2508990 C CA 2508990C CA 2508990 A CA2508990 A CA 2508990A CA 2508990 A CA2508990 A CA 2508990A CA 2508990 C CA2508990 C CA 2508990C
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- CA
- Canada
- Prior art keywords
- methyl
- phenyl
- cyclohexyl
- amino
- 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.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 210
- 238000000034 method Methods 0.000 title description 25
- 206010054261 Flavivirus infection Diseases 0.000 title description 6
- 238000011282 treatment Methods 0.000 title description 6
- 230000002265 prevention Effects 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 241000710781 Flaviviridae Species 0.000 claims abstract description 17
- 208000036142 Viral infection Diseases 0.000 claims abstract description 13
- 230000009385 viral infection Effects 0.000 claims abstract description 13
- -1 cyano, hydroxyimino Chemical group 0.000 claims description 269
- 125000000217 alkyl group Chemical group 0.000 claims description 86
- 125000000623 heterocyclic group Chemical group 0.000 claims description 84
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 63
- 125000003545 alkoxy group Chemical group 0.000 claims description 48
- 229910052736 halogen Inorganic materials 0.000 claims description 45
- 150000002367 halogens Chemical class 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 230000003612 virological effect Effects 0.000 claims description 44
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 41
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 41
- 239000003795 chemical substances by application Substances 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 229910052703 rhodium Inorganic materials 0.000 claims description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
- 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
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 23
- 125000004104 aryloxy group Chemical group 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 17
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 15
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 11
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 11
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 11
- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 11
- 101710102218 Serine protease inhibitor Proteins 0.000 claims description 11
- 239000003001 serine protease inhibitor Substances 0.000 claims description 11
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 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 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 239000003242 anti bacterial agent Substances 0.000 claims description 7
- 230000000692 anti-sense effect Effects 0.000 claims description 7
- 229960000329 ribavirin Drugs 0.000 claims description 7
- 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 7
- 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 6
- 125000003725 azepanyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 229940021747 therapeutic vaccine Drugs 0.000 claims description 6
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 5
- 102000053642 Catalytic RNA Human genes 0.000 claims description 5
- 108090000994 Catalytic RNA Proteins 0.000 claims description 5
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 5
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- 108010050904 Interferons Proteins 0.000 claims description 5
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 5
- 244000272459 Silybum marianum Species 0.000 claims description 5
- 235000010841 Silybum marianum Nutrition 0.000 claims description 5
- 108010046075 Thymosin Proteins 0.000 claims description 5
- 102000007501 Thymosin Human genes 0.000 claims description 5
- 229960004308 acetylcysteine Drugs 0.000 claims description 5
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 5
- 229960003805 amantadine Drugs 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
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- 229940079322 interferon Drugs 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 108091092562 ribozyme Proteins 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 5
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims description 5
- HQBQRPMEFPOVLG-UHFFFAOYSA-N 3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(OC)CCC1N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C(=O)C1CCC(C)CC1 HQBQRPMEFPOVLG-UHFFFAOYSA-N 0.000 claims description 4
- 241001024304 Mino Species 0.000 claims description 4
- HSEDSCPERRHAHJ-UHFFFAOYSA-N 3-[(4-carboxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C1CCC(C(O)=O)CC1 HSEDSCPERRHAHJ-UHFFFAOYSA-N 0.000 claims description 3
- YFLXLTMBSIBJFX-UHFFFAOYSA-N 3-[(4-hydroxyiminocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C1CCC(=NO)CC1 YFLXLTMBSIBJFX-UHFFFAOYSA-N 0.000 claims description 3
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 claims description 3
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 159000000000 sodium salts Chemical group 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 4
- CKVYPTIWERNFSU-UHFFFAOYSA-N 3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C1CCC(O)CC1 CKVYPTIWERNFSU-UHFFFAOYSA-N 0.000 claims 3
- 239000003963 antioxidant agent Substances 0.000 claims 3
- PWKUJELUZICZFM-UHFFFAOYSA-N 3-[(3-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C1CC(O)CCC1 PWKUJELUZICZFM-UHFFFAOYSA-N 0.000 claims 2
- HWYFKCSXDHOHRG-UHFFFAOYSA-N 3-[(4-hydroxy-4-methylcyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C1CCC(C)(O)CC1 HWYFKCSXDHOHRG-UHFFFAOYSA-N 0.000 claims 2
- KQNJFWKYCOSRHN-UHFFFAOYSA-N 3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-(4-methoxyphenyl)thiophene-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=CC(N(C2CCC(O)CC2)C(=O)C2CCC(C)CC2)=C(C(O)=O)S1 KQNJFWKYCOSRHN-UHFFFAOYSA-N 0.000 claims 2
- PLAQJAAXXUBONJ-UHFFFAOYSA-N 3-[(4-methylcyclohexanecarbonyl)-(4-oxocyclohexyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C(O)=O)C1CCC(=O)CC1 PLAQJAAXXUBONJ-UHFFFAOYSA-N 0.000 claims 2
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- GYEQPFHUEQWUQN-UHFFFAOYSA-N 5-(4-acetylphenyl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC(=CC=1)C(C)=O)C(O)=O)C1CCC(O)CC1 GYEQPFHUEQWUQN-UHFFFAOYSA-N 0.000 claims 2
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- 125000000753 cycloalkyl group Chemical group 0.000 description 10
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- SWIOGPHKKZUDIC-UHFFFAOYSA-L dichlororuthenium(2+) Chemical compound Cl[Ru+2]Cl SWIOGPHKKZUDIC-UHFFFAOYSA-L 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- VDQVEACBQKUUSU-UHFFFAOYSA-M disodium;sulfanide Chemical compound [Na+].[Na+].[SH-] VDQVEACBQKUUSU-UHFFFAOYSA-M 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
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- 239000003623 enhancer Substances 0.000 description 1
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- DCFSEYROOMXMCG-UHFFFAOYSA-N ethyl 2-(2-methylprop-2-enoxy)pent-4-enoate Chemical compound CCOC(=O)C(CC=C)OCC(C)=C DCFSEYROOMXMCG-UHFFFAOYSA-N 0.000 description 1
- GGGVQRNVJMPQTE-UHFFFAOYSA-N ethyl 2-hydroxy-4-methylcyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCC(C)CC1O GGGVQRNVJMPQTE-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
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- 125000001153 fluoro group Chemical group F* 0.000 description 1
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- 238000004108 freeze drying Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
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- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QDUXDCXILAPLAG-UHFFFAOYSA-N hydron;1-methylpiperidine;chloride Chemical compound Cl.CN1CCCCC1 QDUXDCXILAPLAG-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- WYXXLXHHWYNKJF-UHFFFAOYSA-N isocarvacrol Natural products CC(C)C1=CC=C(O)C(C)=C1 WYXXLXHHWYNKJF-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229930007744 linalool Natural products 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical group 0.000 description 1
- 230000004904 long-term response Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- UYLHDRWQEQNJFY-UHFFFAOYSA-N methyl 3-(1-hydroxypropan-2-ylamino)-5-phenylthiophene-2-carboxylate Chemical compound OCC(C)NC1=C(C(=O)OC)SC(C=2C=CC=CC=2)=C1 UYLHDRWQEQNJFY-UHFFFAOYSA-N 0.000 description 1
- MPJUACLUAMMYLO-UHFFFAOYSA-N methyl 3-[(1-fluoro-4-methylcyclohexanecarbonyl)-propan-2-ylamino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(C)C)C(=O)C1(F)CCC(C)CC1 MPJUACLUAMMYLO-UHFFFAOYSA-N 0.000 description 1
- QSMNUBRLJWVKDI-UHFFFAOYSA-N methyl 3-[(1-methylpiperidin-3-yl)methylamino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NCC1CCCN(C)C1 QSMNUBRLJWVKDI-UHFFFAOYSA-N 0.000 description 1
- ITFTXKSFCJVRAC-UHFFFAOYSA-N methyl 3-[(2-acetamido-4-methylcyclohexanecarbonyl)-propan-2-ylamino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(C)C)C(=O)C1CCC(C)CC1NC(C)=O ITFTXKSFCJVRAC-UHFFFAOYSA-N 0.000 description 1
- GAXWATOOVOVBBX-UHFFFAOYSA-N methyl 3-[(4-hydroxyiminocyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(=NO)CC1 GAXWATOOVOVBBX-UHFFFAOYSA-N 0.000 description 1
- FRSWWNLPGVGCMM-UHFFFAOYSA-N methyl 3-[(4-oxocyclohexanecarbonyl)-propan-2-ylamino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(C)C)C(=O)C1CCC(=O)CC1 FRSWWNLPGVGCMM-UHFFFAOYSA-N 0.000 description 1
- MSCVWVRJZGPSMR-UHFFFAOYSA-N methyl 3-[(5-methyl-3,6-dihydro-2h-pyran-2-carbonyl)-propan-2-ylamino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(C)C)C(=O)C1CC=C(C)CO1 MSCVWVRJZGPSMR-UHFFFAOYSA-N 0.000 description 1
- SPYICMNEOGKMNP-UHFFFAOYSA-N methyl 3-[1-[tert-butyl(dimethyl)silyl]oxypropan-2-ylamino]-5-phenylthiophene-2-carboxylate Chemical compound CC(C)(C)[Si](C)(C)OCC(C)NC1=C(C(=O)OC)SC(C=2C=CC=CC=2)=C1 SPYICMNEOGKMNP-UHFFFAOYSA-N 0.000 description 1
- DKEDBTCOUACYFG-UHFFFAOYSA-N methyl 3-[1-azidopropan-2-yl-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(C)CN=[N+]=[N-])C(=O)C1CCC(C)CC1 DKEDBTCOUACYFG-UHFFFAOYSA-N 0.000 description 1
- PIKUYGZQOSADLH-CRAIPNDOSA-N methyl 3-[[(2r,5r)-5-methyloxane-2-carbonyl]-propan-2-ylamino]-5-phenylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C(C)C)C(=O)[C@H]1CC[C@@H](C)CO1 PIKUYGZQOSADLH-CRAIPNDOSA-N 0.000 description 1
- RZYLOBBUEWSONL-UHFFFAOYSA-N methyl 3-amino-5-bromothiophene-2-carboxylate Chemical compound COC(=O)C=1SC(Br)=CC=1N RZYLOBBUEWSONL-UHFFFAOYSA-N 0.000 description 1
- TWEQNZZOOFKOER-UHFFFAOYSA-N methyl 3-aminothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1N TWEQNZZOOFKOER-UHFFFAOYSA-N 0.000 description 1
- HSLZXALEQUIDCT-UHFFFAOYSA-N methyl 3-bromo-5-phenylthiophene-2-carboxylate Chemical compound BrC1=C(C(=O)OC)SC(C=2C=CC=CC=2)=C1 HSLZXALEQUIDCT-UHFFFAOYSA-N 0.000 description 1
- JEBMUYVIOTULIC-UHFFFAOYSA-N methyl 5-(3-fluorophenyl)-3-(propan-2-ylamino)thiophene-2-carboxylate Chemical compound CC(C)NC1=C(C(=O)OC)SC(C=2C=C(F)C=CC=2)=C1 JEBMUYVIOTULIC-UHFFFAOYSA-N 0.000 description 1
- GDCDRUGIAQQYKT-UHFFFAOYSA-N methyl 5-(3-fluorophenyl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound COC(=O)C=1SC(C=2C=C(F)C=CC=2)=CC=1N(C(=O)C1CCC(C)CC1)C1CCC(O)CC1 GDCDRUGIAQQYKT-UHFFFAOYSA-N 0.000 description 1
- JWGYYGHNONYRSO-UHFFFAOYSA-N methyl 5-bromo-3-(1,4-dioxaspiro[4.5]decan-8-ylamino)thiophene-2-carboxylate Chemical compound S1C(Br)=CC(NC2CCC3(CC2)OCCO3)=C1C(=O)OC JWGYYGHNONYRSO-UHFFFAOYSA-N 0.000 description 1
- FKSYKJKBAIOVLP-UHFFFAOYSA-N methyl 5-bromo-3-[(4-methylcyclohexanecarbonyl)-propan-2-ylamino]thiophene-2-carboxylate Chemical compound S1C(Br)=CC(N(C(C)C)C(=O)C2CCC(C)CC2)=C1C(=O)OC FKSYKJKBAIOVLP-UHFFFAOYSA-N 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
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- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- VJYJOJXVMHQJIY-UHFFFAOYSA-N morpholine;thiophene Chemical compound C=1C=CSC=1.C1COCCN1 VJYJOJXVMHQJIY-UHFFFAOYSA-N 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- PWBJWDKDPAPGED-UHFFFAOYSA-N n'-chlorobutanediamide Chemical compound NC(=O)CCC(=O)NCl PWBJWDKDPAPGED-UHFFFAOYSA-N 0.000 description 1
- PRSBCBHCICEWIB-UHFFFAOYSA-N n-(4-hydroxycyclohexyl)-4-methyl-n-(5-phenylthiophen-3-yl)cyclohexane-1-carboxamide Chemical compound C1CC(C)CCC1C(=O)N(C=1C=C(SC=1)C=1C=CC=CC=1)C1CCC(O)CC1 PRSBCBHCICEWIB-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 239000002687 nonaqueous vehicle Substances 0.000 description 1
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- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
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- 235000019833 protease Nutrition 0.000 description 1
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- OIMWEHOYHJJPJD-UHFFFAOYSA-N pyridine;pyrimidine Chemical compound C1=CC=NC=C1.C1=CN=CN=C1 OIMWEHOYHJJPJD-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 102220262397 rs772216758 Human genes 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000003381 stabilizer Substances 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
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 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
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 229960000790 thymol Drugs 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
- 230000014621 translational initiation Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- ITHPEWAHFNDNIO-UHFFFAOYSA-N triphosphane Chemical compound PPP ITHPEWAHFNDNIO-UHFFFAOYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| AT (1) | ATE466856T1 (https=) |
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| DE102004061746A1 (de) * | 2004-12-22 | 2006-07-06 | Bayer Healthcare Ag | 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 |
| PE20070814A1 (es) * | 2005-12-22 | 2007-08-16 | Smithkline Beecham Corp | Compuestos derivados de 2-carboxitiofeno como inhibidores de la polimerasa del virus de la hepatitis c (hcv) |
| WO2008017688A1 (en) * | 2006-08-11 | 2008-02-14 | Smithkline Beecham Corporation | 2-carboxy thiophene derivatives as anti-viral agents |
| WO2008043791A2 (en) * | 2006-10-13 | 2008-04-17 | Smithkline Beecham Corporation | Thiophene derivatives for treating hepatitis c |
| CA2670260A1 (en) * | 2006-11-15 | 2008-05-22 | Virochem Pharma Inc. | Thiophene analogues for the treatment or prevention of flavivirus infections |
| ES2381410T3 (es) | 2007-05-04 | 2012-05-28 | Vertex Pharmceuticals Incorporated | Terapia de combinación paa el tratamiento de infecciones por VHC |
| GB0712393D0 (en) * | 2007-06-26 | 2007-08-01 | Smithkline Beecham Corp | Compounds |
| US9962368B2 (en) | 2009-01-09 | 2018-05-08 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US9095572B2 (en) | 2009-01-09 | 2015-08-04 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US9162980B2 (en) | 2009-01-09 | 2015-10-20 | Board Of Regents Of The University Of Texas System | Anti-depression compounds |
| US8362277B2 (en) | 2009-01-09 | 2013-01-29 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| EP2385829B1 (en) | 2009-01-09 | 2018-08-01 | Board of Regents of the University of Texas System | Pro-neurogenic compounds |
| 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 |
| JP2013512247A (ja) * | 2009-11-25 | 2013-04-11 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス感染症の治療または予防のための５−アルキニル−チオフェン−２−カルボン酸誘導体およびそれらの使用 |
| 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 |
| WO2012006070A1 (en) * | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| AU2011292040A1 (en) * | 2010-08-17 | 2013-03-07 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of Flaviviridae viral infections |
| EP2651906A4 (en) | 2010-12-17 | 2014-06-25 | Cocrystal Discovery Inc | INHIBITORS OF HEPATITIS C VIRUS POLYMERASE |
| AU2012280959B2 (en) * | 2011-07-13 | 2015-08-06 | Gilead Sciences, Inc. | Thiophen-2-carboxylic acid derivatives useful as inhibitors of Flaviviridae viruses |
| WO2013016492A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Thiophene compounds |
| WO2014055142A1 (en) | 2012-06-20 | 2014-04-10 | Cocrystal Discovery, Inc. | Inhibitors of hepatitis c virus polymerase |
| 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 |
| US8759544B2 (en) | 2012-08-17 | 2014-06-24 | Gilead Sciences, Inc. | Synthesis of an antiviral compound |
| AU2013305591B2 (en) | 2012-08-24 | 2017-04-13 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| WO2015070237A1 (en) | 2013-11-11 | 2015-05-14 | Board Of Regents Of The University Of Texas System | Neuroprotective chemicals and methods for identifying and using same |
| WO2015070234A2 (en) | 2013-11-11 | 2015-05-14 | Board Of Regents Of The University Of Texas System | Neuroprotective compounds and use thereof |
| 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 |
| MX2020011912A (es) | 2018-05-09 | 2021-01-29 | Cocrystal Pharma Inc | Terapia de combinacion para el tratamiento del virus de la hepatitis c (vhc). |
| US12274700B1 (en) | 2020-10-30 | 2025-04-15 | Accencio LLC | Methods of treating symptoms of coronavirus infection with RNA polymerase inhibitors |
Family Cites Families (6)
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| WO1995005170A1 (en) * | 1993-08-13 | 1995-02-23 | Warner-Lambert Company | Methods of inhibiting hiv and inhibiting the activation of hiv |
| US5734081A (en) * | 1994-08-05 | 1998-03-31 | Warner-Lambert Company | Arylthio compounds |
| KR20020060160A (ko) * | 1999-08-12 | 2002-07-16 | 파마시아 이탈리아 에스.피.에이. | 3(5)-아미노-피라졸 유도체, 이의 제조 방법 및항종양제로서의 이의 용도 |
| US20030096737A1 (en) * | 2001-04-19 | 2003-05-22 | Anita Diu-Hercend | Caspase inhibitors and uses thereof |
| US6887877B2 (en) * | 2001-06-11 | 2005-05-03 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of Flavivirus infections |
| 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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2003
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- 2003-12-09 EP EP03767343A patent/EP1569929B9/en not_active Expired - Lifetime
- 2003-12-09 AU AU2003291885A patent/AU2003291885A1/en not_active Abandoned
- 2003-12-09 WO PCT/CA2003/001912 patent/WO2004052885A1/en not_active Ceased
- 2003-12-09 DK DK03767343.1T patent/DK1569929T3/da active
- 2003-12-09 MX MXPA05006196A patent/MXPA05006196A/es active IP Right Grant
- 2003-12-09 AT AT03767343T patent/ATE466856T1/de active
- 2003-12-09 CA CA2508990A patent/CA2508990C/en not_active Expired - Fee Related
- 2003-12-09 NZ NZ540799A patent/NZ540799A/en not_active IP Right Cessation
- 2003-12-09 BR BR0316771-2A patent/BR0316771A/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1569929B9 (en) | 2011-09-14 |
| NZ540799A (en) | 2008-09-26 |
| JP2006510636A (ja) | 2006-03-30 |
| JP4926403B2 (ja) | 2012-05-09 |
| BR0316771A (pt) | 2005-10-25 |
| EP1569929A1 (en) | 2005-09-07 |
| WO2004052885A1 (en) | 2004-06-24 |
| MXPA05006196A (es) | 2006-01-27 |
| ATE466856T1 (de) | 2010-05-15 |
| CA2508990A1 (en) | 2004-06-24 |
| AU2003291885A1 (en) | 2004-06-30 |
| EP1569929B1 (en) | 2010-05-05 |
| DK1569929T3 (da) | 2010-08-16 |
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