OA12622A - Thiophene derivatives as antiviral agents for flavivirus infection. - Google Patents
Thiophene derivatives as antiviral agents for flavivirus infection. Download PDFInfo
- Publication number
- OA12622A OA12622A OA1200300320A OA1200300320A OA12622A OA 12622 A OA12622 A OA 12622A OA 1200300320 A OA1200300320 A OA 1200300320A OA 1200300320 A OA1200300320 A OA 1200300320A OA 12622 A OA12622 A OA 12622A
- Authority
- OA
- OAPI
- Prior art keywords
- phenyl
- thiophene
- carboxylic acid
- compound
- amino
- Prior art date
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- 239000003443 antiviral agent Substances 0.000 title claims description 16
- 206010054261 Flavivirus infection Diseases 0.000 title description 5
- 150000003577 thiophenes Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 722
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 208000036142 Viral infection Diseases 0.000 claims abstract description 10
- 230000009385 viral infection Effects 0.000 claims abstract description 10
- 241000710781 Flaviviridae Species 0.000 claims abstract description 8
- -1 2- phenylethenyl Chemical group 0.000 claims description 1135
- 125000000217 alkyl group Chemical group 0.000 claims description 223
- 125000000623 heterocyclic group Chemical group 0.000 claims description 180
- 125000003342 alkenyl group Chemical group 0.000 claims description 126
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 125
- 125000000304 alkynyl group Chemical group 0.000 claims description 118
- 239000002253 acid Substances 0.000 claims description 113
- 125000003118 aryl group Chemical group 0.000 claims description 107
- 229910052739 hydrogen Inorganic materials 0.000 claims description 100
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 93
- 229910052799 carbon Inorganic materials 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 85
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 78
- 239000000203 mixture Substances 0.000 claims description 72
- 239000003795 chemical substances by application Substances 0.000 claims description 56
- 230000003612 virological effect Effects 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
- 125000001544 thienyl group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 108060004795 Methyltransferase Proteins 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 17
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical group CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 12
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 150000003536 tetrazoles Chemical class 0.000 claims description 11
- NUJXFKHOOMJUPO-UHFFFAOYSA-N methyl 3-[(2,4-dichlorobenzoyl)-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=CC=C(Cl)C=C1Cl NUJXFKHOOMJUPO-UHFFFAOYSA-N 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 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 9
- 229960000583 acetic acid Drugs 0.000 claims description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 229960000329 ribavirin Drugs 0.000 claims description 9
- 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 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 102000053642 Catalytic RNA Human genes 0.000 claims description 7
- 108090000994 Catalytic RNA Proteins 0.000 claims description 7
- 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 7
- 229930105110 Cyclosporin A Natural products 0.000 claims description 7
- 108010036949 Cyclosporine Proteins 0.000 claims description 7
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 7
- 108010046075 Thymosin Proteins 0.000 claims description 7
- 102000007501 Thymosin Human genes 0.000 claims description 7
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 7
- 229960003805 amantadine Drugs 0.000 claims description 7
- 230000000692 anti-sense effect Effects 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 229960001265 ciclosporin Drugs 0.000 claims description 7
- 229930182912 cyclosporin Natural products 0.000 claims description 7
- 108091092562 ribozyme Proteins 0.000 claims description 7
- 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 7
- WUEPMEXUMQVEGN-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;2,2,2-trifluoro-n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethylamino]ethyl]acetamide Chemical compound OC(=O)C(F)(F)F.FC(F)(F)C(=O)NCCNCCNC(=O)C(F)(F)F WUEPMEXUMQVEGN-UHFFFAOYSA-N 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- NYYKDALOYDQKPA-UHFFFAOYSA-N 3-(n-(2,4-dichlorobenzoyl)anilino)-5-phenylthiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N(C=1C=CC=CC=1)C(=O)C1=CC=C(Cl)C=C1Cl NYYKDALOYDQKPA-UHFFFAOYSA-N 0.000 claims description 6
- BACMTCNFHNDMIM-UHFFFAOYSA-N 3-[(2-methylphenyl)sulfonylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=CC=CC=2)=C1 BACMTCNFHNDMIM-UHFFFAOYSA-N 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 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 6
- 229960004308 acetylcysteine Drugs 0.000 claims description 6
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- CORJOVCCNWIHJE-UHFFFAOYSA-N 3-[(2-chlorophenyl)sulfonylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NS(=O)(=O)C1=CC=CC=C1Cl CORJOVCCNWIHJE-UHFFFAOYSA-N 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 5
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 150000001805 chlorine compounds Chemical class 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 150000004678 hydrides Chemical class 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- NSTBKJQXCZFJQD-UHFFFAOYSA-N 3-(benzenesulfonamido)-5-phenylthiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NS(=O)(=O)C1=CC=CC=C1 NSTBKJQXCZFJQD-UHFFFAOYSA-N 0.000 claims description 4
- RBRIBDVYHLVUON-UHFFFAOYSA-N 3-[(2-fluorophenyl)sulfonylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NS(=O)(=O)C1=CC=CC=C1F RBRIBDVYHLVUON-UHFFFAOYSA-N 0.000 claims description 4
- HHSIYAYAFUPSSR-UHFFFAOYSA-N 3-[(2-methylphenyl)sulfonylamino]-5-(4-nitrophenyl)thiophene-2-carboxylic acid Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=CC(=CC=2)[N+]([O-])=O)=C1 HHSIYAYAFUPSSR-UHFFFAOYSA-N 0.000 claims description 4
- GVWAYNGOHLPMHK-UHFFFAOYSA-N 3-[(3,4-dichlorophenyl)sulfonylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NS(=O)(=O)C1=CC=C(Cl)C(Cl)=C1 GVWAYNGOHLPMHK-UHFFFAOYSA-N 0.000 claims description 4
- CDEZPEKCNFPDPF-UHFFFAOYSA-N 3-[(4-chloro-2,5-dimethylphenyl)sulfonylamino]-5-(4-chlorophenyl)thiophene-2-carboxylic acid Chemical compound C1=C(Cl)C(C)=CC(S(=O)(=O)NC2=C(SC(=C2)C=2C=CC(Cl)=CC=2)C(O)=O)=C1C CDEZPEKCNFPDPF-UHFFFAOYSA-N 0.000 claims description 4
- NXUAAIVUPKHHNC-UHFFFAOYSA-N 3-[(4-chloro-2,5-dimethylphenyl)sulfonylamino]-5-[4-(2-methylpropyl)phenyl]thiophene-2-carboxylic acid Chemical compound C1=CC(CC(C)C)=CC=C1C1=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(C)C=2)C)=C(C(O)=O)S1 NXUAAIVUPKHHNC-UHFFFAOYSA-N 0.000 claims description 4
- XOTWANLGDMFVLK-UHFFFAOYSA-N 3-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound CC1=C(C)C(OC)=CC(C)=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=CC=CC=2)=C1 XOTWANLGDMFVLK-UHFFFAOYSA-N 0.000 claims description 4
- TVZQQBXPOAOCMB-UHFFFAOYSA-N 3-[[3-(1-benzofuran-2-yl)phenyl]methyl-(4-chloro-2,5-dimethylphenyl)sulfonylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1=C(Cl)C(C)=CC(S(=O)(=O)N(CC=2C=C(C=CC=2)C=2OC3=CC=CC=C3C=2)C2=C(SC(=C2)C=2C=CC=CC=2)C(O)=O)=C1C TVZQQBXPOAOCMB-UHFFFAOYSA-N 0.000 claims description 4
- YUIZNFJAQDNHFE-UHFFFAOYSA-N 3-[butanoyl(methyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound S1C(C(O)=O)=C(N(C)C(=O)CCC)C=C1C1=CC=CC=C1 YUIZNFJAQDNHFE-UHFFFAOYSA-N 0.000 claims description 4
- UBAKMPJZPGNBRL-UHFFFAOYSA-N 5-(3,5-difluorophenyl)-3-[(2-methylphenyl)sulfonylamino]thiophene-2-carboxylic acid Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=C(F)C=C(F)C=2)=C1 UBAKMPJZPGNBRL-UHFFFAOYSA-N 0.000 claims description 4
- MNPSEJXQPRBIEG-UHFFFAOYSA-N 5-(3-cyanophenyl)-3-[(2-methylphenyl)sulfonylamino]thiophene-2-carboxylic acid Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=C(C=CC=2)C#N)=C1 MNPSEJXQPRBIEG-UHFFFAOYSA-N 0.000 claims description 4
- KIBUYVNUMTWMAH-UHFFFAOYSA-N 5-(4-carboxyphenyl)-3-[(2-methylphenyl)sulfonylamino]thiophene-2-carboxylic acid Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=CC(=CC=2)C(O)=O)=C1 KIBUYVNUMTWMAH-UHFFFAOYSA-N 0.000 claims description 4
- IVEHHMJVVPJWPX-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-[(2-methylphenyl)sulfonylamino]thiophene-2-carboxylic acid Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=C(C(O)=O)SC(C=2C=CC(Cl)=CC=2)=C1 IVEHHMJVVPJWPX-UHFFFAOYSA-N 0.000 claims description 4
- QIPDHDRHVPDMEH-UHFFFAOYSA-N 5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-chloro-2,5-dimethylphenyl)sulfonylamino]thiophene-2-carboxylic acid Chemical compound C1=C(Cl)C(C)=CC(S(=O)(=O)NC2=C(SC(=C2)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C(O)=O)=C1C QIPDHDRHVPDMEH-UHFFFAOYSA-N 0.000 claims description 4
- FCJOOCHSXUKBHV-UHFFFAOYSA-N 5-phenyl-3-(thiophen-2-ylsulfonylamino)thiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NS(=O)(=O)C1=CC=CS1 FCJOOCHSXUKBHV-UHFFFAOYSA-N 0.000 claims description 4
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- DDAXEOSVDTWWRD-UHFFFAOYSA-N 3-[(4-tert-butylbenzoyl)-methylamino]-5-phenylthiophene-2-carboxylic acid Chemical compound C1=C(C=2C=CC=CC=2)SC(C(O)=O)=C1N(C)C(=O)C1=CC=C(C(C)(C)C)C=C1 DDAXEOSVDTWWRD-UHFFFAOYSA-N 0.000 claims 2
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- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 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
- 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
- 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
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
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- 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
- 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
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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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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- 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
- C07D409/06—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 carbon chain containing only aliphatic carbon atoms
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- 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
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- 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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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
- C07D419/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D471/10—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
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- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
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| US29673101P | 2001-06-11 | 2001-06-11 |
Publications (1)
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| OA12622A true OA12622A (en) | 2006-06-12 |
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| EA007484B1 (ru) * | 2001-06-11 | 2006-10-27 | Вирокем Фарма Инк. | Соединения и способы лечения или предупреждения инфекций flavivirus |
| US8329924B2 (en) * | 2001-06-11 | 2012-12-11 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| SE0102616D0 (sv) * | 2001-07-25 | 2001-07-25 | Astrazeneca Ab | Novel compounds |
| US7166639B2 (en) * | 2001-10-04 | 2007-01-23 | Smithkline Beecham Corporation | NF-κB inhibitors |
| WO2003104218A1 (en) * | 2002-06-06 | 2003-12-18 | Smithkline Beecham Corporation | Nf-:b inhibitors |
| US7179836B2 (en) * | 2002-09-20 | 2007-02-20 | Smithkline Beecham Corporation | Chemical compounds |
| TW200418863A (en) * | 2002-10-17 | 2004-10-01 | Upjohn Co | Novel anthelmintic and insecticidal compositions |
| US20050075279A1 (en) | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| PT1569929E (pt) * | 2002-12-10 | 2010-06-18 | Virochem Pharma Inc | Compostos e métodos para o tratamento ou prevenção de infecções por flavivírus |
| US20040192707A1 (en) * | 2002-12-10 | 2004-09-30 | Laval Chan Chun Kong | Compounds and methods for the treatment or prevention of Flavivirus infections |
| WO2004052885A1 (en) * | 2002-12-10 | 2004-06-24 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of flavivirus infections |
| WO2004056746A1 (en) | 2002-12-23 | 2004-07-08 | 4Sc Ag | Cycloalkene dicarboxylic acid compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents |
| US7365094B2 (en) | 2002-12-23 | 2008-04-29 | 4Sc Ag | Compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents |
| US7247736B2 (en) | 2002-12-23 | 2007-07-24 | 4Sc Ag | Method of identifying inhibitors of DHODH |
| NZ541382A (en) * | 2002-12-23 | 2009-04-30 | 4Sc Ag | Aromatic compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents |
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| US7223785B2 (en) | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| EP2033654B1 (en) | 2003-04-16 | 2012-05-16 | Bristol-Myers Squibb Company | Process for resolving a mixture of alkyl ester enantiomers using an enzyme |
| US7112601B2 (en) | 2003-09-11 | 2006-09-26 | Bristol-Myers Squibb Company | Cycloalkyl heterocycles for treating hepatitis C virus |
| OA13315A (en) | 2003-10-14 | 2007-04-13 | Intermune Inc | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of HCV replication. |
| EP1944042A1 (en) * | 2003-10-27 | 2008-07-16 | Vertex Pharmceuticals Incorporated | Combinations for HCV treatment |
| EP1677827B1 (en) * | 2003-10-27 | 2008-12-10 | Vertex Pharmaceuticals Incorporated | Combinations for hcv treatment |
| DE10359791A1 (de) * | 2003-12-19 | 2005-07-21 | Bayer Healthcare Ag | Substituierte Thiophene |
| GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
| SG184700A1 (en) | 2004-02-20 | 2012-10-30 | Boehringer Ingelheim Int | Viral polymerase inhibitors |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| DE102004061746A1 (de) * | 2004-12-22 | 2006-07-06 | Bayer Healthcare Ag | Alkinyl-substituierte Thiophene |
| DE102005028077A1 (de) * | 2004-12-22 | 2006-07-13 | Aicuris Gmbh & Co. Kg | Alkinyl-substituierte Thiophene |
| HRP20150765T1 (hr) | 2004-12-30 | 2015-10-09 | Janssen Pharmaceutica N.V. | Amid derivati piperidin- i piperazin-1-karboksilne kiseline te povezani spojevi kao modulatori amid hidrolaze masnih kiselina (faah) za lijeäśenje tjeskobe, boli i drugih stanja |
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| AU2011205048B2 (en) * | 2005-05-13 | 2013-05-02 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of flavivirus infections |
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| DE602006003661D1 (de) | 2005-06-06 | 2008-12-24 | Lilly Co Eli | Ampa-rezeptoren-verstärker |
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