NZ583149A - Benzazepine compounds for the treatment of hepatitis c - Google Patents
Benzazepine compounds for the treatment of hepatitis cInfo
- Publication number
- NZ583149A NZ583149A NZ583149A NZ58314908A NZ583149A NZ 583149 A NZ583149 A NZ 583149A NZ 583149 A NZ583149 A NZ 583149A NZ 58314908 A NZ58314908 A NZ 58314908A NZ 583149 A NZ583149 A NZ 583149A
- Authority
- NZ
- New Zealand
- Prior art keywords
- methoxy
- indolo
- cyclohexyl
- benzazepine
- methyl
- Prior art date
Links
- 150000008038 benzoazepines Chemical class 0.000 title abstract 2
- 208000006454 hepatitis Diseases 0.000 title description 2
- 231100000283 hepatitis Toxicity 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 165
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 208000005176 Hepatitis C Diseases 0.000 claims abstract 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 335
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 199
- -1 hydroxy, benzyloxy Chemical group 0.000 claims description 183
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 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 117
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 113
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 80
- 229910052739 hydrogen Inorganic materials 0.000 claims description 70
- 239000001257 hydrogen Substances 0.000 claims description 59
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 54
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 39
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 27
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 27
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 125000004494 ethyl ester group Chemical group 0.000 claims description 25
- 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 23
- 125000004193 piperazinyl group Chemical group 0.000 claims description 23
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 18
- 125000002393 azetidinyl 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
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 150000004702 methyl esters Chemical class 0.000 claims description 11
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 claims description 10
- 108010026228 mRNA guanylyltransferase Proteins 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 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
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 229910003844 NSO2 Inorganic materials 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 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
- 102000014150 Interferons Human genes 0.000 claims description 4
- 108010050904 Interferons Proteins 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 108060004795 Methyltransferase Proteins 0.000 claims description 3
- 101800001019 Non-structural protein 4B Proteins 0.000 claims description 3
- 101800001014 Non-structural protein 5A Proteins 0.000 claims description 3
- 230000008901 benefit Effects 0.000 claims description 3
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 3
- 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
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 claims description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 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
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 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
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims 20
- 229940121649 protein inhibitor Drugs 0.000 claims 6
- 239000012268 protein inhibitor Substances 0.000 claims 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 5
- 239000003001 serine protease inhibitor Substances 0.000 claims 3
- IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 claims 2
- 108010036941 Cyclosporins Proteins 0.000 claims 2
- 229940126656 GS-4224 Drugs 0.000 claims 2
- 229940124683 HCV polymerase inhibitor Drugs 0.000 claims 2
- 102000015696 Interleukins Human genes 0.000 claims 2
- 108010063738 Interleukins Proteins 0.000 claims 2
- 229930182912 cyclosporin Natural products 0.000 claims 2
- 229940047124 interferons Drugs 0.000 claims 2
- 229940047122 interleukins Drugs 0.000 claims 2
- 239000003475 metalloproteinase inhibitor Substances 0.000 claims 2
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Chemical compound OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 claims 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- PASOFFRBGIVJET-YRKGHMEHSA-N (2r,3r,4r,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 PASOFFRBGIVJET-YRKGHMEHSA-N 0.000 claims 1
- 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
- 108010030583 (melle-4)cyclosporin Proteins 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- NYPIRLYMDJMKGW-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 NYPIRLYMDJMKGW-VPCXQMTMSA-N 0.000 claims 1
- WTDWVLJJJOTABN-UHFFFAOYSA-N 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-n-methyl-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC(N(CCO)S(C)(=O)=O)=C1C1CC1 WTDWVLJJJOTABN-UHFFFAOYSA-N 0.000 claims 1
- 101100273797 Caenorhabditis elegans pct-1 gene Proteins 0.000 claims 1
- 229940122806 Cyclophilin inhibitor Drugs 0.000 claims 1
- 229940122750 HCV entry inhibitor Drugs 0.000 claims 1
- 241000276498 Pollachius virens Species 0.000 claims 1
- 229940122055 Serine protease inhibitor Drugs 0.000 claims 1
- 101710102218 Serine protease inhibitor Proteins 0.000 claims 1
- 108010078233 Thymalfasin Proteins 0.000 claims 1
- 229960000517 boceprevir Drugs 0.000 claims 1
- LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 claims 1
- 239000000134 cyclophilin inhibitor Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 230000002584 immunomodulator Effects 0.000 claims 1
- 230000005923 long-lasting effect Effects 0.000 claims 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 claims 1
- 229960000907 methylthioninium chloride Drugs 0.000 claims 1
- RPJPZDVUUKWPGT-FOIHOXPVSA-N nim811 Chemical compound CC[C@H](C)[C@@H]1N(C)C(=O)CN(C)C(=O)[C@H](CC)NC(=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)NC1=O RPJPZDVUUKWPGT-FOIHOXPVSA-N 0.000 claims 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=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@@H](C)O)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@@H](C)O)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)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims 1
- 229960004231 thymalfasin Drugs 0.000 claims 1
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 705
- 239000002904 solvent Substances 0.000 description 486
- 238000006243 chemical reaction Methods 0.000 description 358
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 241
- 229910001868 water Inorganic materials 0.000 description 225
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 179
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 161
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 158
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 133
- 239000000047 product Substances 0.000 description 133
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
- 239000007787 solid Substances 0.000 description 109
- 239000000243 solution Substances 0.000 description 108
- 230000014759 maintenance of location Effects 0.000 description 107
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 103
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
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- 235000019257 ammonium acetate Nutrition 0.000 description 100
- 229940043376 ammonium acetate Drugs 0.000 description 100
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- 239000003039 volatile agent Substances 0.000 description 86
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- 238000010828 elution Methods 0.000 description 79
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- 238000004458 analytical method Methods 0.000 description 57
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 54
- 238000002953 preparative HPLC Methods 0.000 description 51
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 41
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- 238000003756 stirring Methods 0.000 description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 23
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- 150000001412 amines Chemical class 0.000 description 18
- 229910000162 sodium phosphate Inorganic materials 0.000 description 18
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 17
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Classifications
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- 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
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- 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
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- 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
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- 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
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (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 (1)
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|---|---|
| NZ583149A true NZ583149A (en) | 2011-07-29 |
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|---|---|---|---|
| NZ583149A NZ583149A (en) | 2007-08-09 | 2008-08-01 | Benzazepine compounds for the treatment of hepatitis c |
Country Status (18)
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|---|---|
| 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 |
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| US8143243B2 (en) * | 2007-08-09 | 2012-03-27 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| MX2010005226A (es) * | 2007-11-20 | 2010-05-27 | Bristol Myers Squibb Co | Inhibidores de ns5b de hcv de indolobenzazepina fusionados a ciclopropilo. |
| US8129367B2 (en) * | 2007-11-21 | 2012-03-06 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
| US8431568B2 (en) | 2008-03-27 | 2013-04-30 | 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 |
| EP2396329B1 (en) * | 2009-02-11 | 2014-10-29 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis c |
| 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 |
| CH706864B1 (de) | 2011-06-22 | 2016-03-31 | Central Glass Co Ltd | Verfahren zur Herstellung einer Pyrazol-Verbindung. |
| 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 |
| BR112015000714A2 (pt) * | 2012-07-18 | 2017-06-27 | Bristol Myers Squibb Holdings Ireland | processos e intermediários para a preparação de (4bs,5ar)-12-ciclo-hexil-n-(n,n-dimetilsulfamoil)-3-metóxi-5a-((1r,5s)-3-metil-3,8-diazabiciclo[3.2.1]octano-8-carbonil)-4b,5,5a, 6-tetra-hidrobenzo [3,4]ciclopropa[5,6]azepino[1,2-a] indol-9-carboxamida |
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| PT1719773E (pt) | 2004-02-24 | 2009-06-03 | Japan Tobacco Inc | Compostos heterotetracíclicos fundidos e a sua utilização como inibidores da polimerase do hcv |
| US7153848B2 (en) | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| CA2585113A1 (en) | 2004-10-26 | 2006-05-04 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Tetracyclic indole derivatives as antiviral agents |
| GB0518390D0 (en) | 2005-09-09 | 2005-10-19 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US7399758B2 (en) | 2005-09-12 | 2008-07-15 | Meanwell Nicholas A | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US7473688B2 (en) | 2005-09-13 | 2009-01-06 | Bristol-Myers Squibb Company | Indolobenzazepine HCV NS5B inhibitors |
| US7456165B2 (en) | 2006-02-08 | 2008-11-25 | Bristol-Myers Squibb Company | 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 |
| US7547690B2 (en) | 2007-03-14 | 2009-06-16 | 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 |
| US7541353B2 (en) | 2007-03-14 | 2009-06-02 | 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 |
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2008
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- 2008-08-01 CA CA2695781A patent/CA2695781A1/en not_active Abandoned
- 2008-08-01 AU AU2008293845A patent/AU2008293845B2/en not_active Ceased
- 2008-08-01 WO PCT/US2008/071881 patent/WO2009029384A2/en not_active Ceased
- 2008-08-01 CN CN2008801108622A patent/CN101821267B/zh not_active Expired - Fee Related
- 2008-08-01 EA EA201000277A patent/EA015978B1/ru not_active IP Right Cessation
- 2008-08-01 JP JP2010520215A patent/JP5465670B2/ja not_active Expired - Fee Related
- 2008-08-01 NZ NZ583149A patent/NZ583149A/en not_active IP Right Cessation
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- 2008-08-01 MX MX2010001416A patent/MX2010001416A/es active IP Right Grant
- 2008-08-01 BR BRPI0814931-3A2A patent/BRPI0814931A2/pt not_active IP Right Cessation
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- 2008-08-08 CL CL200802353A patent/CL2008002353A1/es unknown
- 2008-08-08 PE PE2008001327A patent/PE20090618A1/es not_active Application Discontinuation
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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
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|---|---|
| MX2010001416A (es) | 2010-03-01 |
| AU2008293845A1 (en) | 2009-03-05 |
| BRPI0814931A2 (pt) | 2015-02-03 |
| JP2010535787A (ja) | 2010-11-25 |
| CA2695781A1 (en) | 2009-03-05 |
| CN101821267B (zh) | 2013-07-10 |
| US20090074715A1 (en) | 2009-03-19 |
| CN101821267A (zh) | 2010-09-01 |
| EA201000277A1 (ru) | 2010-06-30 |
| TW200906418A (en) | 2009-02-16 |
| EP2183252B1 (en) | 2015-01-14 |
| KR20100066492A (ko) | 2010-06-17 |
| US7652004B2 (en) | 2010-01-26 |
| WO2009029384A2 (en) | 2009-03-05 |
| EA015978B1 (ru) | 2012-01-30 |
| PE20090618A1 (es) | 2009-05-16 |
| CO6251359A2 (es) | 2011-02-21 |
| EP2183252A2 (en) | 2010-05-12 |
| AR067897A1 (es) | 2009-10-28 |
| JP5465670B2 (ja) | 2014-04-09 |
| CL2008002353A1 (es) | 2008-10-24 |
| WO2009029384A3 (en) | 2009-05-28 |
| AU2008293845B2 (en) | 2013-02-14 |
| ZA201000923B (en) | 2011-04-28 |
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