MXPA03011452A - Compuestos y metodos para el tratamiento o prevencion de las infecciones por flavivirus. - Google Patents
Compuestos y metodos para el tratamiento o prevencion de las infecciones por flavivirus.Info
- Publication number
- MXPA03011452A MXPA03011452A MXPA03011452A MXPA03011452A MXPA03011452A MX PA03011452 A MXPA03011452 A MX PA03011452A MX PA03011452 A MXPA03011452 A MX PA03011452A MX PA03011452 A MXPA03011452 A MX PA03011452A MX PA03011452 A MXPA03011452 A MX PA03011452A
- Authority
- MX
- Mexico
- Prior art keywords
- acid
- phenyl
- amino
- compound
- carboxylic
- Prior art date
Links
- 239000003443 antiviral agent Substances 0.000 title claims description 27
- 206010054261 Flavivirus infection Diseases 0.000 title claims description 6
- 150000003577 thiophenes Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 1070
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 208000036142 Viral infection Diseases 0.000 claims abstract description 19
- 230000009385 viral infection Effects 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims description 1122
- -1 2-phenylethenyl Chemical group 0.000 claims description 730
- 125000000217 alkyl group Chemical group 0.000 claims description 273
- 125000000623 heterocyclic group Chemical group 0.000 claims description 272
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical class CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 256
- 125000003118 aryl group Chemical group 0.000 claims description 199
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 195
- 125000000304 alkynyl group Chemical group 0.000 claims description 185
- 125000003342 alkenyl group Chemical group 0.000 claims description 175
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 163
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 94
- 229910052736 halogen Inorganic materials 0.000 claims description 81
- 150000002367 halogens Chemical class 0.000 claims description 81
- 230000003612 virological effect Effects 0.000 claims description 75
- 239000000203 mixture Substances 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
- 239000003795 chemical substances by application Substances 0.000 claims description 50
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- QECVIPBZOPUTRD-UHFFFAOYSA-N N=S(=O)=O Chemical compound N=S(=O)=O QECVIPBZOPUTRD-UHFFFAOYSA-N 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 44
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 32
- 108060004795 Methyltransferase Proteins 0.000 claims description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 31
- 125000001544 thienyl group Chemical group 0.000 claims description 30
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
- 239000000460 chlorine Substances 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 23
- 229910052705 radium Inorganic materials 0.000 claims description 23
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 150000003536 tetrazoles Chemical class 0.000 claims description 21
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 241000710831 Flavivirus Species 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 16
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 229910052701 rubidium Inorganic materials 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 14
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 14
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 13
- 150000004702 methyl esters Chemical class 0.000 claims description 13
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 12
- 229940124530 sulfonamide Drugs 0.000 claims description 12
- 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 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 229960000329 ribavirin Drugs 0.000 claims description 11
- 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 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- KWWGBNRBZMJKPA-UHFFFAOYSA-N 3-phenylthiophene-2-carboxylic acid Chemical compound S1C=CC(C=2C=CC=CC=2)=C1C(=O)O KWWGBNRBZMJKPA-UHFFFAOYSA-N 0.000 claims description 10
- 102000014150 Interferons Human genes 0.000 claims description 10
- 108010050904 Interferons Proteins 0.000 claims description 10
- 229940079322 interferon Drugs 0.000 claims description 10
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical class [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
- 102000053642 Catalytic RNA Human genes 0.000 claims description 8
- 108090000994 Catalytic RNA Proteins 0.000 claims description 8
- 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 8
- 108010036949 Cyclosporine Proteins 0.000 claims description 8
- 102000013462 Interleukin-12 Human genes 0.000 claims description 8
- 108010065805 Interleukin-12 Proteins 0.000 claims description 8
- 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 8
- 244000272459 Silybum marianum Species 0.000 claims description 8
- 235000010841 Silybum marianum Nutrition 0.000 claims description 8
- 108010046075 Thymosin Proteins 0.000 claims description 8
- 102000007501 Thymosin Human genes 0.000 claims description 8
- 229960004308 acetylcysteine Drugs 0.000 claims description 8
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 8
- 229960003805 amantadine Drugs 0.000 claims description 8
- 239000003242 anti bacterial agent Substances 0.000 claims description 8
- 230000000692 anti-sense effect Effects 0.000 claims description 8
- 239000003963 antioxidant agent Substances 0.000 claims description 8
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 229960001265 ciclosporin Drugs 0.000 claims description 8
- 229930182912 cyclosporin Natural products 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- 229940117681 interleukin-12 Drugs 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 108091092562 ribozyme Proteins 0.000 claims description 8
- 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 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
- 229930105110 Cyclosporin A Natural products 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
- 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 7
- 239000003814 drug Substances 0.000 claims description 7
- 230000002519 immonomodulatory effect Effects 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
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- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 6
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 6
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- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 6
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- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 238000004519 manufacturing process Methods 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
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- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 5
- 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 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
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- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- ORGXXKHNNJNAPB-UHFFFAOYSA-N 3-[(4-chlorobenzoyl)amino]-5-phenylthiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NC(=O)C1=CC=C(Cl)C=C1 ORGXXKHNNJNAPB-UHFFFAOYSA-N 0.000 claims description 4
- 208000005176 Hepatitis C Diseases 0.000 claims description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical class NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical class NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 3
- HJOOKKDLEJXVSI-UHFFFAOYSA-N 4-chloro-2,6-dimethylbenzenesulfonamide Chemical group CC1=CC(Cl)=CC(C)=C1S(N)(=O)=O HJOOKKDLEJXVSI-UHFFFAOYSA-N 0.000 claims description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
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- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- OIMWEHOYHJJPJD-UHFFFAOYSA-N pyridine;pyrimidine Chemical compound C1=CC=NC=C1.C1=CN=CN=C1 OIMWEHOYHJJPJD-UHFFFAOYSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- RADGOBKLTHEUQO-UHFFFAOYSA-N ruthenium(4+) Chemical compound [Ru+4] RADGOBKLTHEUQO-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
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- 159000000000 sodium salts Chemical class 0.000 description 1
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- APZLUNBSOZGIRE-UHFFFAOYSA-N tert-butyl 3-[(2,4-dichlorophenyl)-propan-2-ylcarbamoyl]-5-phenylthiophene-2-carboxylate Chemical compound C=1C=C(Cl)C=C(Cl)C=1N(C(C)C)C(=O)C(=C(S1)C(=O)OC(C)(C)C)C=C1C1=CC=CC=C1 APZLUNBSOZGIRE-UHFFFAOYSA-N 0.000 description 1
- LYIDOJMFDXEPEL-UHFFFAOYSA-N tert-butyl 4-[(2-methoxycarbonyl-5-phenylthiophen-3-yl)amino]piperidine-1-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=CC=1NC1CCN(C(=O)OC(C)(C)C)CC1 LYIDOJMFDXEPEL-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- XDIMYNGLNWJVMQ-UHFFFAOYSA-N tert-butyl 5-(4-methylphenyl)-3-[(2-methylphenyl)sulfonylamino]thiophene-2-carboxylate Chemical compound C1=CC(C)=CC=C1C1=CC(NS(=O)(=O)C=2C(=CC=CC=2)C)=C(C(=O)OC(C)(C)C)S1 XDIMYNGLNWJVMQ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 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
- 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
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
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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
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- 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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- A61K31/335—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
- A61K31/343—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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- A—HUMAN NECESSITIES
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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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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D409/06—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
-
- 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
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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
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- 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
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- 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
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- 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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- 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
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- C07D495/04—Ortho-condensed systems
Landscapes
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- Organic Chemistry (AREA)
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- Medicinal Chemistry (AREA)
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- Molecular Biology (AREA)
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29673101P | 2001-06-11 | 2001-06-11 | |
| PCT/CA2002/000876 WO2002100851A2 (en) | 2001-06-11 | 2002-06-11 | Thiophene derivatives as antiviral agents for flavivirus infection |
Publications (1)
| Publication Number | Publication Date |
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| MXPA03011452A true MXPA03011452A (es) | 2005-03-07 |
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| MXPA03011452A MXPA03011452A (es) | 2001-06-11 | 2002-06-11 | Compuestos y metodos para el tratamiento o prevencion de las infecciones por flavivirus. |
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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 |
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| 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 |
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| 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 |
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