CA2723683A1 - 7h-indolo[2,1-a] [2] benzazepine-10-carboxylic acid derivatives for the treatment of hepatitis c - Google Patents
7h-indolo[2,1-a] [2] benzazepine-10-carboxylic acid derivatives for the treatment of hepatitis c Download PDFInfo
- Publication number
- CA2723683A1 CA2723683A1 CA2723683A CA2723683A CA2723683A1 CA 2723683 A1 CA2723683 A1 CA 2723683A1 CA 2723683 A CA2723683 A CA 2723683A CA 2723683 A CA2723683 A CA 2723683A CA 2723683 A1 CA2723683 A1 CA 2723683A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- mmol
- solvent
- methoxy
- cyclohexyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- FRUWAONHRDGSAL-UHFFFAOYSA-N 7h-indolo[2,1-a][2]benzazepine-10-carboxylic acid Chemical class C1=CCN2C3=CC(C(=O)O)=CC=C3C=C2C2=CC=CC=C21 FRUWAONHRDGSAL-UHFFFAOYSA-N 0.000 title description 37
- 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 172
- 238000000034 method Methods 0.000 claims abstract description 44
- 239000000203 mixture Substances 0.000 claims abstract description 22
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 192
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 178
- -1 pyridinonyl Chemical group 0.000 claims description 178
- 229910052739 hydrogen Inorganic materials 0.000 claims description 154
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 153
- 125000000217 alkyl group Chemical group 0.000 claims description 127
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 101
- 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 100
- 239000001257 hydrogen Substances 0.000 claims description 66
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 66
- 229910052757 nitrogen Inorganic materials 0.000 claims description 54
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
- 125000001424 substituent group Chemical group 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000003282 alkyl amino group Chemical group 0.000 claims description 24
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 24
- 125000003386 piperidinyl group Chemical group 0.000 claims description 18
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 16
- 125000004193 piperazinyl group Chemical group 0.000 claims description 16
- 125000002393 azetidinyl group Chemical group 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000001475 halogen functional group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 claims description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 230000008901 benefit Effects 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 229910003844 NSO2 Inorganic materials 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
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([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 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 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
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl 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
- 208000005176 Hepatitis C Diseases 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 6
- 239000012268 protein inhibitor Substances 0.000 claims 6
- 229940121649 protein inhibitor Drugs 0.000 claims 6
- 108010036941 Cyclosporins Proteins 0.000 claims 2
- 229940122750 HCV entry inhibitor Drugs 0.000 claims 2
- 229940124683 HCV polymerase inhibitor Drugs 0.000 claims 2
- 102000014150 Interferons Human genes 0.000 claims 2
- 108010050904 Interferons Proteins 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
- 239000003001 serine protease inhibitor Substances 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 abstract description 29
- 230000000694 effects Effects 0.000 abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 546
- 239000002904 solvent Substances 0.000 description 508
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 307
- 238000006243 chemical reaction Methods 0.000 description 218
- 229910001868 water Inorganic materials 0.000 description 188
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 175
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 161
- 239000000047 product Substances 0.000 description 156
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 153
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 153
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 145
- 239000007787 solid Substances 0.000 description 140
- 239000000243 solution Substances 0.000 description 124
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 114
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 104
- 239000005695 Ammonium acetate Substances 0.000 description 104
- 235000019257 ammonium acetate Nutrition 0.000 description 104
- 229940043376 ammonium acetate Drugs 0.000 description 104
- 230000014759 maintenance of location Effects 0.000 description 101
- 238000004128 high performance liquid chromatography Methods 0.000 description 96
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 92
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 88
- 238000010828 elution Methods 0.000 description 78
- 239000012299 nitrogen atmosphere Substances 0.000 description 74
- 239000011541 reaction mixture Substances 0.000 description 70
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 67
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 66
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 64
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
- 238000005481 NMR spectroscopy Methods 0.000 description 62
- 239000012317 TBTU Substances 0.000 description 57
- 238000004458 analytical method Methods 0.000 description 56
- 239000003039 volatile agent Substances 0.000 description 56
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 239000012267 brine Substances 0.000 description 53
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000007788 liquid Substances 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 44
- 235000019341 magnesium sulphate Nutrition 0.000 description 44
- 239000000741 silica gel Substances 0.000 description 44
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- 239000003643 water by type Substances 0.000 description 42
- 238000004809 thin layer chromatography Methods 0.000 description 38
- 239000000843 powder Substances 0.000 description 37
- 239000006260 foam Substances 0.000 description 36
- 239000006188 syrup Substances 0.000 description 36
- 235000020357 syrup Nutrition 0.000 description 36
- 238000003756 stirring Methods 0.000 description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000002360 preparation method Methods 0.000 description 27
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000003153 chemical reaction reagent Substances 0.000 description 22
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 21
- 239000007821 HATU Substances 0.000 description 21
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- 150000001412 amines Chemical class 0.000 description 18
- 239000012043 crude product Substances 0.000 description 17
- 229910052717 sulfur Inorganic materials 0.000 description 17
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- 125000004494 ethyl ester group Chemical group 0.000 description 16
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 15
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- 239000012074 organic phase Substances 0.000 description 15
- 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 13
- 238000003556 assay Methods 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
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- HNVIQLPOGUDBSU-OLQVQODUSA-N (2s,6r)-2,6-dimethylmorpholine Chemical compound C[C@H]1CNC[C@@H](C)O1 HNVIQLPOGUDBSU-OLQVQODUSA-N 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 11
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- 239000007858 starting material Substances 0.000 description 7
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- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 6
- 229910000162 sodium phosphate Inorganic materials 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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- CYWVAQCQWSJFMV-UHFFFAOYSA-N 3,7-dioxa-9-azabicyclo[3.3.1]nonane;hydrochloride Chemical compound Cl.C1OCC2COCC1N2 CYWVAQCQWSJFMV-UHFFFAOYSA-N 0.000 description 3
- AJPSDOLVFRJEID-UHFFFAOYSA-N 3-methyl-8-azabicyclo[3.2.1]octan-3-ol Chemical compound C1C(C)(O)CC2CCC1N2 AJPSDOLVFRJEID-UHFFFAOYSA-N 0.000 description 3
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- 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
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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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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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
- C07D471/08—Bridged systems
-
- 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
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5074308P | 2008-05-06 | 2008-05-06 | |
| US61/050,743 | 2008-05-06 | ||
| PCT/US2009/042805 WO2009137454A1 (en) | 2008-05-06 | 2009-05-05 | 7h-indolo[2,1-a] [2] benzazepine-10-carboxylic acid derivatives for the treatment of hepatitis c |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2723683A1 true CA2723683A1 (en) | 2009-11-12 |
Family
ID=40786514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2723683A Abandoned CA2723683A1 (en) | 2008-05-06 | 2009-05-05 | 7h-indolo[2,1-a] [2] benzazepine-10-carboxylic acid derivatives for the treatment of hepatitis c |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US8133884B2 (enExample) |
| EP (1) | EP2280975B1 (enExample) |
| JP (1) | JP2011520810A (enExample) |
| KR (1) | KR20110015588A (enExample) |
| CN (1) | CN102083834A (enExample) |
| AR (1) | AR071684A1 (enExample) |
| AU (1) | AU2009244409A1 (enExample) |
| BR (1) | BRPI0915130A2 (enExample) |
| CA (1) | CA2723683A1 (enExample) |
| CL (1) | CL2009001089A1 (enExample) |
| CO (1) | CO6290645A2 (enExample) |
| EA (1) | EA201001748A1 (enExample) |
| IL (1) | IL208753A0 (enExample) |
| MX (1) | MX2010011921A (enExample) |
| NZ (1) | NZ588556A (enExample) |
| PE (1) | PE20091879A1 (enExample) |
| TW (1) | TW200951135A (enExample) |
| WO (1) | WO2009137454A1 (enExample) |
| ZA (1) | ZA201007649B (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
| KR20100124848A (ko) | 2008-03-27 | 2010-11-29 | 브리스톨-마이어스 스큅 컴퍼니 | 방향족 헤테로시클릭 융합된 인돌로벤자디아제핀 ｈｃｖ ｎｓ5ｂ 억제제 |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| CA2822357A1 (en) | 2010-12-22 | 2012-06-28 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
| WO2013030750A1 (en) | 2011-09-01 | 2013-03-07 | Lupin Limited | Antiviral compounds |
| AU2013217224B2 (en) | 2012-02-10 | 2017-04-06 | Lupin Limited | Antiviral compounds with a dibenzooxaheterocycle moiety |
| US9556204B2 (en) * | 2012-07-18 | 2017-01-31 | Bristol-Myers Squibb Company | 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 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1719773B1 (en) | 2004-02-24 | 2009-04-15 | Japan Tobacco, Inc. | Fused heterotetracyclic compounds and use tehreof as hcv polymerase inhibitor |
| US7153848B2 (en) | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| AU2005298412B2 (en) | 2004-10-26 | 2011-06-09 | 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 |
| ATE469155T1 (de) | 2006-05-25 | 2010-06-15 | Bristol Myers Squibb Co | Cyclopropyl-fusionierte indolbenzazepin-hcv-ns5b- hemmer |
| 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 |
| US7521444B2 (en) | 2007-03-14 | 2009-04-21 | 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 |
| 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 |
| US20090018163A1 (en) | 2007-07-11 | 2009-01-15 | Bristol-Myers Squibb Company | Substituted Heterocyclic Ethers and Their Use in CNS Disorders |
| US7642251B2 (en) | 2007-08-09 | 2010-01-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7652004B2 (en) | 2007-08-09 | 2010-01-26 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8129367B2 (en) | 2007-11-21 | 2012-03-06 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
| US8124601B2 (en) | 2007-11-21 | 2012-02-28 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
-
2009
- 2009-05-04 US US12/434,748 patent/US8133884B2/en active Active
- 2009-05-05 MX MX2010011921A patent/MX2010011921A/es active IP Right Grant
- 2009-05-05 CA CA2723683A patent/CA2723683A1/en not_active Abandoned
- 2009-05-05 BR BRPI0915130A patent/BRPI0915130A2/pt not_active IP Right Cessation
- 2009-05-05 EA EA201001748A patent/EA201001748A1/ru unknown
- 2009-05-05 NZ NZ588556A patent/NZ588556A/en not_active IP Right Cessation
- 2009-05-05 AU AU2009244409A patent/AU2009244409A1/en not_active Abandoned
- 2009-05-05 PE PE2009000605A patent/PE20091879A1/es not_active Application Discontinuation
- 2009-05-05 WO PCT/US2009/042805 patent/WO2009137454A1/en not_active Ceased
- 2009-05-05 KR KR1020107027222A patent/KR20110015588A/ko not_active Withdrawn
- 2009-05-05 CN CN2009801263266A patent/CN102083834A/zh active Pending
- 2009-05-05 JP JP2011508593A patent/JP2011520810A/ja not_active Withdrawn
- 2009-05-05 EP EP09743440.1A patent/EP2280975B1/en not_active Ceased
- 2009-05-06 AR ARP090101641A patent/AR071684A1/es not_active Application Discontinuation
- 2009-05-06 TW TW098115001A patent/TW200951135A/zh unknown
- 2009-05-06 CL CL2009001089A patent/CL2009001089A1/es unknown
-
2010
- 2010-10-14 IL IL208753A patent/IL208753A0/en unknown
- 2010-10-26 ZA ZA2010/07649A patent/ZA201007649B/en unknown
- 2010-10-28 CO CO10134256A patent/CO6290645A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009137454A1 (en) | 2009-11-12 |
| EP2280975A1 (en) | 2011-02-09 |
| KR20110015588A (ko) | 2011-02-16 |
| NZ588556A (en) | 2012-06-29 |
| CL2009001089A1 (es) | 2011-04-29 |
| EA201001748A1 (ru) | 2011-06-30 |
| TW200951135A (en) | 2009-12-16 |
| MX2010011921A (es) | 2010-11-30 |
| JP2011520810A (ja) | 2011-07-21 |
| AR071684A1 (es) | 2010-07-07 |
| EP2280975B1 (en) | 2014-01-01 |
| CN102083834A (zh) | 2011-06-01 |
| AU2009244409A1 (en) | 2009-11-12 |
| PE20091879A1 (es) | 2009-12-19 |
| BRPI0915130A2 (pt) | 2019-09-24 |
| CO6290645A2 (es) | 2011-06-20 |
| ZA201007649B (en) | 2012-04-25 |
| US20090280083A1 (en) | 2009-11-12 |
| US8133884B2 (en) | 2012-03-13 |
| IL208753A0 (en) | 2010-12-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20150505 |