NZ588556A - 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 CInfo
- Publication number
- NZ588556A NZ588556A NZ588556A NZ58855609A NZ588556A NZ 588556 A NZ588556 A NZ 588556A NZ 588556 A NZ588556 A NZ 588556A NZ 58855609 A NZ58855609 A NZ 58855609A NZ 588556 A NZ588556 A NZ 588556A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- mmol
- solvent
- indolo
- cyclohexyl
- Prior art date
Links
- 208000005176 Hepatitis C Diseases 0.000 title claims description 5
- 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 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 206
- 239000000203 mixture Substances 0.000 claims abstract description 39
- -1 tetrahydrofiiranyl Chemical group 0.000 claims description 205
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 181
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 175
- 229910052739 hydrogen Inorganic materials 0.000 claims description 152
- 125000000217 alkyl group Chemical group 0.000 claims description 128
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 98
- 239000001257 hydrogen Substances 0.000 claims description 66
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 66
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 65
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000003282 alkyl amino group Chemical group 0.000 claims description 24
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 21
- 125000003386 piperidinyl group Chemical group 0.000 claims description 20
- 125000004193 piperazinyl group Chemical group 0.000 claims description 19
- 239000003112 inhibitor Substances 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
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000002393 azetidinyl group Chemical group 0.000 claims description 14
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 claims description 12
- 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
- 108010026228 mRNA guanylyltransferase Proteins 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 229910003844 NSO2 Inorganic materials 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- 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
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 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
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 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
- 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
- 125000000325 methylidene group Chemical group [H]C([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
- 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
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 229940126656 GS-4224 Drugs 0.000 claims description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 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
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 abstract description 69
- 238000000034 method Methods 0.000 abstract description 55
- 230000000694 effects Effects 0.000 abstract description 23
- DNVWIMVPKQGQQL-UHFFFAOYSA-N 3,12-diazatetracyclo[9.7.0.02,8.013,18]octadeca-1,3,5,7,9,11,13,15,17-nonaene-4-carboxamide Chemical class N1=C(C=CC=C2C1=C1C(C=C2)=NC=2C=CC=CC=21)C(=O)N DNVWIMVPKQGQQL-UHFFFAOYSA-N 0.000 abstract 1
- 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 220
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 159
- 239000000047 product Substances 0.000 description 157
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 155
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 154
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 142
- 239000007787 solid Substances 0.000 description 141
- 239000000243 solution Substances 0.000 description 124
- 238000005481 NMR spectroscopy Methods 0.000 description 115
- 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 100
- 238000004128 high performance liquid chromatography Methods 0.000 description 94
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 86
- 238000010828 elution Methods 0.000 description 78
- 239000012299 nitrogen atmosphere Substances 0.000 description 74
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 68
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 66
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 61
- 238000004458 analytical method Methods 0.000 description 60
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- 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
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
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- 238000003756 stirring Methods 0.000 description 33
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- 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 description 15
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- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 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 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 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
- 229960003531 phenolsulfonphthalein Drugs 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
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229940038850 rebif Drugs 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000010512 small scale reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 1
- 229950006081 taribavirin Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ZNFZQJAVXBBTCJ-UHFFFAOYSA-N tert-butyl n-(cyclobutylideneamino)carbamate Chemical compound CC(C)(C)OC(=O)NN=C1CCC1 ZNFZQJAVXBBTCJ-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- 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
-
- 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
-
- 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
Landscapes
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5074308P | 2008-05-06 | 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 |
|---|---|
| NZ588556A true NZ588556A (en) | 2012-06-29 |
Family
ID=40786514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ588556A NZ588556A (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 |
| CA2723683A1 (en) | 2009-11-12 |
| 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 |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |
Free format text: PATENT RENEWED FOR 3 YEARS UNTIL 05 MAY 2016 BY CPA GLOBAL Effective date: 20130328 |
|
| LAPS | Patent lapsed |