EA015978B1 - Соединения для лечения гепатита с - Google Patents
Соединения для лечения гепатита с Download PDFInfo
- Publication number
- EA015978B1 EA015978B1 EA201000277A EA201000277A EA015978B1 EA 015978 B1 EA015978 B1 EA 015978B1 EA 201000277 A EA201000277 A EA 201000277A EA 201000277 A EA201000277 A EA 201000277A EA 015978 B1 EA015978 B1 EA 015978B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- cyclohexyl
- indolo
- methoxy
- benzazepine
- methyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 156
- 208000006454 hepatitis Diseases 0.000 title 1
- 231100000283 hepatitis Toxicity 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 65
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 316
- -1 hydroxy, benzyloxy Chemical group 0.000 claims description 311
- HJHICYAWGPPIND-UHFFFAOYSA-N 7h-indolo[2,1-a][2]benzazepine-10-carboxamide Chemical compound C1=CCN2C3=CC(C(=O)N)=CC=C3C=C2C2=CC=CC=C21 HJHICYAWGPPIND-UHFFFAOYSA-N 0.000 claims description 276
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 182
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 157
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 114
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- 229910052739 hydrogen Inorganic materials 0.000 claims description 98
- FRUWAONHRDGSAL-UHFFFAOYSA-N 7h-indolo[2,1-a][2]benzazepine-10-carboxylic acid Chemical compound C1=CCN2C3=CC(C(=O)O)=CC=C3C=C2C2=CC=CC=C21 FRUWAONHRDGSAL-UHFFFAOYSA-N 0.000 claims description 92
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 claims description 87
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 64
- 239000001257 hydrogen Substances 0.000 claims description 58
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 claims description 43
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 22
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 21
- 125000004193 piperazinyl group Chemical group 0.000 claims description 19
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 17
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- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- CPDUOSJMCFQXID-UHFFFAOYSA-N 3-(4-chlorophenyl)-1-(3-methylpyridin-2-yl)pyrrolidine-2,5-dione Chemical compound CC1=CC=CN=C1N1C(=O)C(C=2C=CC(Cl)=CC=2)CC1=O CPDUOSJMCFQXID-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
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- 239000010802 sludge Substances 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 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 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 34
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 6
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Chemical compound OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 claims 6
- IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 claims 2
- QRKIDYBDEVJLFN-UHFFFAOYSA-N 5h-indolo[2,1-a][2]benzazepine-10-carboxamide Chemical compound C1C=CN2C3=CC(C(=O)N)=CC=C3C=C2C2=CC=CC=C21 QRKIDYBDEVJLFN-UHFFFAOYSA-N 0.000 claims 2
- NRQHBNNTBIDSRK-YRNVUSSQSA-N (4e)-4-[(4-methoxyphenyl)methylidene]-2-methyl-1,3-oxazol-5-one Chemical compound C1=CC(OC)=CC=C1\C=C\1C(=O)OC(C)=N/1 NRQHBNNTBIDSRK-YRNVUSSQSA-N 0.000 claims 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
- 125000001401 1,2,4-triazol-4-yl group Chemical group N=1N=C([H])N([*])C=1[H] 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 208000005176 Hepatitis C Diseases 0.000 claims 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 190
- 241000711549 Hepacivirus C Species 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 769
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
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- MFICNRISVWOURZ-UHFFFAOYSA-N ethyl 2-[13-cyclohexyl-10-(dimethylsulfamoylcarbamoyl)-3-methoxy-7h-indolo[2,1-a][2]benzazepin-6-yl]-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(C=2CN3C4=CC(=CC=C4C(C4CCCCC4)=C3C3=CC=C(OC)C=C3C=2)C(=O)NS(=O)(=O)N(C)C)=N1 MFICNRISVWOURZ-UHFFFAOYSA-N 0.000 description 3
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- 239000000872 buffer Substances 0.000 description 1
- FCWGIFCVCCHGTK-UHFFFAOYSA-N butane-2-sulfonamide Chemical compound CCC(C)S(N)(=O)=O FCWGIFCVCCHGTK-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
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- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
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- WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- MUJOVVKDDICVMS-UHFFFAOYSA-N diazaphosphinine Chemical compound C1=CN=NP=C1 MUJOVVKDDICVMS-UHFFFAOYSA-N 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- UJTPZISIAWDGFF-UHFFFAOYSA-N ethenylsulfonylbenzene Chemical compound C=CS(=O)(=O)C1=CC=CC=C1 UJTPZISIAWDGFF-UHFFFAOYSA-N 0.000 description 1
- SYWQOPRAPDMWMC-UHFFFAOYSA-N ethyl 2-chloro-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(Cl)=N1 SYWQOPRAPDMWMC-UHFFFAOYSA-N 0.000 description 1
- 239000002038 ethyl acetate fraction Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- WHRIKZCFRVTHJH-UHFFFAOYSA-N ethylhydrazine Chemical compound CCNN WHRIKZCFRVTHJH-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- XKJFZAQHRQDNIF-UHFFFAOYSA-N methyl 1,3-dimethylpyrazole-4-carboxylate Chemical compound COC(=O)C1=CN(C)N=C1C XKJFZAQHRQDNIF-UHFFFAOYSA-N 0.000 description 1
- CRXFROMHHBMNAB-UHFFFAOYSA-N methyl 2-isocyanoacetate Chemical compound COC(=O)C[N+]#[C-] CRXFROMHHBMNAB-UHFFFAOYSA-N 0.000 description 1
- PEGSJNCGPSIJOX-UHFFFAOYSA-N methyl 3-bromothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1Br PEGSJNCGPSIJOX-UHFFFAOYSA-N 0.000 description 1
- UVEAHNBLCXALID-UHFFFAOYSA-N methyl 5-iodo-1,3-dimethylpyrazole-4-carboxylate Chemical compound COC(=O)C=1C(C)=NN(C)C=1I UVEAHNBLCXALID-UHFFFAOYSA-N 0.000 description 1
- ABRWGCJZYNWGMT-UHFFFAOYSA-N methyl 5-iodo-3-methyl-1-propan-2-ylpyrazole-4-carboxylate Chemical compound COC(=O)C=1C(C)=NN(C(C)C)C=1I ABRWGCJZYNWGMT-UHFFFAOYSA-N 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- PELLLKANMONICH-UHFFFAOYSA-N n-(oxolan-2-ylmethyl)propan-2-amine Chemical compound CC(C)NCC1CCCO1 PELLLKANMONICH-UHFFFAOYSA-N 0.000 description 1
- BLKXOFBWIOCFOQ-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.COC1=CC=CC=C1CNC(C)C BLKXOFBWIOCFOQ-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- VWNFFIGQDGOCIA-UHFFFAOYSA-N propylaminoazanium;chloride Chemical compound [Cl-].CCCN[NH3+] VWNFFIGQDGOCIA-UHFFFAOYSA-N 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000012882 sequential analysis Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- GVGQTAOPSVVRMJ-UHFFFAOYSA-N tert-butyl 13-cyclohexyl-3-methoxy-6-[4-(morpholine-4-carbonyl)-1,3-oxazol-5-yl]-7h-indolo[2,1-a][2]benzazepine-10-carboxylate Chemical compound C12=CC=C(C(=O)OC(C)(C)C)C=C2N2CC(C3=C(N=CO3)C(=O)N3CCOCC3)=CC3=CC(OC)=CC=C3C2=C1C1CCCCC1 GVGQTAOPSVVRMJ-UHFFFAOYSA-N 0.000 description 1
- DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US95481407P | 2007-08-09 | 2007-08-09 | |
| US4994408P | 2008-05-02 | 2008-05-02 | |
| US12/180,994 US7652004B2 (en) | 2007-08-09 | 2008-07-28 | Compounds for the treatment of hepatitis C |
| PCT/US2008/071881 WO2009029384A2 (en) | 2007-08-09 | 2008-08-01 | Compounds for the treatment of hepatitis c |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201000277A1 EA201000277A1 (ru) | 2010-06-30 |
| EA015978B1 true EA015978B1 (ru) | 2012-01-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201000277A EA015978B1 (ru) | 2007-08-09 | 2008-08-01 | Соединения для лечения гепатита с |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US7652004B2 (enExample) |
| EP (1) | EP2183252B1 (enExample) |
| JP (1) | JP5465670B2 (enExample) |
| KR (1) | KR20100066492A (enExample) |
| CN (1) | CN101821267B (enExample) |
| AR (1) | AR067897A1 (enExample) |
| AU (1) | AU2008293845B2 (enExample) |
| BR (1) | BRPI0814931A2 (enExample) |
| CA (1) | CA2695781A1 (enExample) |
| CL (1) | CL2008002353A1 (enExample) |
| CO (1) | CO6251359A2 (enExample) |
| EA (1) | EA015978B1 (enExample) |
| MX (1) | MX2010001416A (enExample) |
| NZ (1) | NZ583149A (enExample) |
| PE (1) | PE20090618A1 (enExample) |
| TW (1) | TW200906418A (enExample) |
| WO (1) | WO2009029384A2 (enExample) |
| ZA (1) | ZA201000923B (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2005049622A1 (ja) * | 2003-11-19 | 2007-06-07 | 日本たばこ産業株式会社 | ５−５員縮合複素環化合物及びそのｈｃｖポリメラーゼ阻害剤としての用途 |
| US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
| US7659263B2 (en) | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
| US8143243B2 (en) * | 2007-08-09 | 2012-03-27 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| JP5416710B2 (ja) * | 2007-11-20 | 2014-02-12 | ブリストル−マイヤーズ スクイブ カンパニー | シクロプロピル縮合インドロベンズアゼピンｈｃｖｎｓ５ｂ阻害剤 |
| US8129367B2 (en) * | 2007-11-21 | 2012-03-06 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
| AU2009228451A1 (en) | 2008-03-27 | 2009-10-01 | Bristol-Myers Squibb Company | Aromatic heterocyclic fused indolobenzadiazepine HCV NS5B inhibitors |
| US8133884B2 (en) * | 2008-05-06 | 2012-03-13 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| CN102388045A (zh) * | 2009-02-11 | 2012-03-21 | 百时美施贵宝公司 | 用于治疗丙型肝炎的化合物 |
| JP5918264B2 (ja) | 2010-12-22 | 2016-05-18 | アッヴィ・インコーポレイテッド | Ｃ型肝炎阻害剤およびその使用 |
| JP5915004B2 (ja) * | 2011-06-22 | 2016-05-11 | セントラル硝子株式会社 | ピラゾール化合物の製造方法 |
| DE112012002522T5 (de) | 2011-06-22 | 2014-03-13 | Central Glass Co., Ltd. | Verfahren zur Herstellung einer Pyrazol-Verbindung |
| EP3091022A3 (en) * | 2012-07-18 | 2016-12-14 | Bristol-Myers Squibb Holdings Ireland | Methods and intermediates for the preparation of (4bs,5ar)-12-cyclohexyl-n-(n,n-dimethylsulfamoyl)-3- methoxy-5a-((1r,5s)-3-methyl-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-4b,5,5a,6-tetrahydrobenzo [3,4]cyclopropa[5,6]azepino[1,2-a]indole-9-carboxamide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007033032A1 (en) * | 2005-09-12 | 2007-03-22 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors |
| WO2007092888A2 (en) * | 2006-02-08 | 2007-08-16 | Bristol-Myers Squibb Company | Hcv ns5b inhibitors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE428714T1 (de) | 2004-02-24 | 2009-05-15 | Japan Tobacco Inc | Kondensierte heterotetracyclische verbindungen und deren verwendung als hcv-polymerase-inhibitor |
| US7153848B2 (en) * | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| CA2585084A1 (en) | 2004-10-26 | 2006-05-04 | Immacolata Conte | Tetracyclic indole derivatives as antiviral agents |
| GB0518390D0 (en) | 2005-09-09 | 2005-10-19 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US7473688B2 (en) | 2005-09-13 | 2009-01-06 | Bristol-Myers Squibb Company | Indolobenzazepine HCV NS5B inhibitors |
| GB0608928D0 (en) | 2006-05-08 | 2006-06-14 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| US7456166B2 (en) | 2006-05-17 | 2008-11-25 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US7521441B2 (en) | 2006-05-22 | 2009-04-21 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| CN101490054B (zh) | 2006-05-25 | 2012-05-16 | 百时美施贵宝公司 | 环丙基稠合的吲哚并苯并氮杂*hcv ns5b抑制剂 |
| WO2007140200A2 (en) | 2006-05-25 | 2007-12-06 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors |
| US7452876B2 (en) | 2006-06-08 | 2008-11-18 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US7541351B2 (en) | 2007-01-11 | 2009-06-02 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7517872B2 (en) | 2007-02-22 | 2009-04-14 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7541353B2 (en) | 2007-03-14 | 2009-06-02 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7521444B2 (en) | 2007-03-14 | 2009-04-21 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7538102B2 (en) | 2007-03-14 | 2009-05-26 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
| US7547690B2 (en) | 2007-03-14 | 2009-06-16 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
| US7538103B2 (en) | 2007-03-15 | 2009-05-26 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
-
2008
- 2008-07-28 US US12/180,994 patent/US7652004B2/en active Active
- 2008-08-01 EA EA201000277A patent/EA015978B1/ru not_active IP Right Cessation
- 2008-08-01 AU AU2008293845A patent/AU2008293845B2/en not_active Ceased
- 2008-08-01 CA CA2695781A patent/CA2695781A1/en not_active Abandoned
- 2008-08-01 BR BRPI0814931-3A2A patent/BRPI0814931A2/pt not_active IP Right Cessation
- 2008-08-01 NZ NZ583149A patent/NZ583149A/en not_active IP Right Cessation
- 2008-08-01 KR KR1020107005086A patent/KR20100066492A/ko not_active Withdrawn
- 2008-08-01 MX MX2010001416A patent/MX2010001416A/es active IP Right Grant
- 2008-08-01 EP EP08828571.3A patent/EP2183252B1/en not_active Not-in-force
- 2008-08-01 WO PCT/US2008/071881 patent/WO2009029384A2/en not_active Ceased
- 2008-08-01 JP JP2010520215A patent/JP5465670B2/ja not_active Expired - Fee Related
- 2008-08-01 CN CN2008801108622A patent/CN101821267B/zh not_active Expired - Fee Related
- 2008-08-08 CL CL200802353A patent/CL2008002353A1/es unknown
- 2008-08-08 TW TW097130410A patent/TW200906418A/zh unknown
- 2008-08-08 PE PE2008001327A patent/PE20090618A1/es not_active Application Discontinuation
- 2008-08-08 AR ARP080103488A patent/AR067897A1/es unknown
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2010
- 2010-02-03 CO CO10011252A patent/CO6251359A2/es not_active Application Discontinuation
- 2010-02-08 ZA ZA2010/00923A patent/ZA201000923B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007033032A1 (en) * | 2005-09-12 | 2007-03-22 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors |
| WO2007092888A2 (en) * | 2006-02-08 | 2007-08-16 | Bristol-Myers Squibb Company | Hcv ns5b inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| IKEGASHIRA K. ET AL.: "Discovery of Conformationally Constrained Tetracyclic Compounds as Potent Hepatitis S Virus NS5B RNA Polymerase Inhibitors" JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON., US, vol. 49, no. 24, 1 January 2006 (2006-01-01), pages 6950-6953, XP002505121 ISSN: 0022-2623 [retrieved on 2006-11-02] * |
Also Published As
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|---|---|
| AR067897A1 (es) | 2009-10-28 |
| MX2010001416A (es) | 2010-03-01 |
| NZ583149A (en) | 2011-07-29 |
| EA201000277A1 (ru) | 2010-06-30 |
| AU2008293845A1 (en) | 2009-03-05 |
| CL2008002353A1 (es) | 2008-10-24 |
| AU2008293845B2 (en) | 2013-02-14 |
| EP2183252B1 (en) | 2015-01-14 |
| TW200906418A (en) | 2009-02-16 |
| WO2009029384A2 (en) | 2009-03-05 |
| EP2183252A2 (en) | 2010-05-12 |
| US7652004B2 (en) | 2010-01-26 |
| KR20100066492A (ko) | 2010-06-17 |
| PE20090618A1 (es) | 2009-05-16 |
| CN101821267B (zh) | 2013-07-10 |
| WO2009029384A3 (en) | 2009-05-28 |
| CA2695781A1 (en) | 2009-03-05 |
| ZA201000923B (en) | 2011-04-28 |
| US20090074715A1 (en) | 2009-03-19 |
| CN101821267A (zh) | 2010-09-01 |
| JP5465670B2 (ja) | 2014-04-09 |
| BRPI0814931A2 (pt) | 2015-02-03 |
| JP2010535787A (ja) | 2010-11-25 |
| CO6251359A2 (es) | 2011-02-21 |
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