AU2008226639B2 - Compounds for the treatment of hepatitis C - Google Patents
Compounds for the treatment of hepatitis C Download PDFInfo
- Publication number
- AU2008226639B2 AU2008226639B2 AU2008226639A AU2008226639A AU2008226639B2 AU 2008226639 B2 AU2008226639 B2 AU 2008226639B2 AU 2008226639 A AU2008226639 A AU 2008226639A AU 2008226639 A AU2008226639 A AU 2008226639A AU 2008226639 B2 AU2008226639 B2 AU 2008226639B2
- Authority
- AU
- Australia
- Prior art keywords
- pct
- cyclohexyl
- methoxy
- benzazepine
- indolo
- 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.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 113
- 208000005176 Hepatitis C Diseases 0.000 title claims 2
- 238000000034 method Methods 0.000 claims abstract description 114
- 239000000203 mixture Substances 0.000 claims abstract description 91
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 104
- -1 hydroxy, benzyloxy Chemical group 0.000 claims description 74
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 74
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 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
- 125000006254 cycloalkyl carbonyl group Chemical group 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
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- RFIPHXRWMOZWAD-UHFFFAOYSA-N NNNSN Chemical compound NNNSN RFIPHXRWMOZWAD-UHFFFAOYSA-N 0.000 claims 1
- 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 abstract description 69
- 230000000694 effects Effects 0.000 abstract description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 240
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- 239000007787 solid Substances 0.000 description 124
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 106
- 239000000047 product Substances 0.000 description 90
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 230000014759 maintenance of location Effects 0.000 description 75
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 71
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- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 45
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- DEJWXFOYYYLRBU-UHFFFAOYSA-N 12-azapentacyclo[10.7.0.02,7.08,10.013,18]nonadeca-1(19),2(7),8,10,13,15,17-heptaene-9-carboxamide Chemical compound NC(=O)C1=C2C1=CN1C3=CC=CC=C3C=C1C1=C2CCCC1 DEJWXFOYYYLRBU-UHFFFAOYSA-N 0.000 description 41
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- JAOINXWEFKZYIL-UHFFFAOYSA-N 4-(1-methyl-2-oxoquinolin-4-yl)oxy-n-(4-methylpyridin-2-yl)butanamide;2,2,2-trifluoroacetic acid Chemical group OC(=O)C(F)(F)F.CC1=CC=NC(NC(=O)CCCOC=2C3=CC=CC=C3N(C)C(=O)C=2)=C1 JAOINXWEFKZYIL-UHFFFAOYSA-N 0.000 description 22
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
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- Virology (AREA)
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
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| US89488707P | 2007-03-14 | 2007-03-14 | |
| US60/894,887 | 2007-03-14 | ||
| US98947407P | 2007-11-21 | 2007-11-21 | |
| US60/989,474 | 2007-11-21 | ||
| PCT/US2008/055893 WO2008112473A1 (en) | 2007-03-14 | 2008-03-05 | Compounds for the treatment of hepatitis c |
Publications (2)
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| AU2008226639A1 AU2008226639A1 (en) | 2008-09-18 |
| AU2008226639B2 true AU2008226639B2 (en) | 2012-07-19 |
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| BR (1) | BRPI0808763A2 (enExample) |
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| TW (1) | TW200848058A (enExample) |
| WO (1) | WO2008112473A1 (enExample) |
| ZA (1) | ZA200906129B (enExample) |
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| EP1688420A4 (en) * | 2003-11-19 | 2008-10-22 | Japan Tobacco Inc | 5-5 LOW-CONDENSED HETEROCYCLIC COMPOUND AND THEIR USE AS HCV POLYMERASE INHIBITOR |
| 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 |
| US7521443B2 (en) * | 2006-05-17 | 2009-04-21 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US7652004B2 (en) * | 2007-08-09 | 2010-01-26 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8143243B2 (en) * | 2007-08-09 | 2012-03-27 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7642251B2 (en) * | 2007-08-09 | 2010-01-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| PL2209789T3 (pl) * | 2007-11-20 | 2012-04-30 | Bristol Myers Squibb Co | Skondensowane z cyklopropylem indolobenzoazepinowe inhibitory NS5B HCV |
| US8124601B2 (en) | 2007-11-21 | 2012-02-28 | 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 |
| AU2008339917B2 (en) | 2007-12-24 | 2013-02-07 | Tibotec Pharmaceuticals | Macrocyclic indoles as hepatitis C virus inhibitors |
| EP2280978B1 (en) * | 2008-03-27 | 2013-04-24 | Bristol-Myers Squibb Company | Pyrrolidine fused indolobenzadiazepine hcv ns5b inhibitors |
| US8178523B2 (en) * | 2008-03-27 | 2012-05-15 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8138171B2 (en) * | 2008-03-27 | 2012-03-20 | Bristol-Myers Squibb Company | Dioxolane and dioxolanone fused indolobenzadiazepine HCV NS5B inhibitors |
| US8133884B2 (en) * | 2008-05-06 | 2012-03-13 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8143244B2 (en) * | 2009-02-26 | 2012-03-27 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| BR112012013765A2 (pt) | 2009-12-07 | 2016-04-26 | Targacept Inc | 3,6-diazabiciclo[3.1.1] heptanos como ligantes de receptor nicotínico neuronal de acetilcolina |
| US8716275B2 (en) * | 2011-10-20 | 2014-05-06 | Bristol-Myers Squibb Company | Compound for the treatment of hepatitis C |
| WO2014011863A1 (en) * | 2012-07-12 | 2014-01-16 | Targacept, Inc. | Method of treatment with 3-cyclopropylcarbonyl-3,6-diazabicyclo[3.1.1]heptane |
| AU2013290402A1 (en) * | 2012-07-18 | 2015-03-05 | Bristol-Myers Squibb Holdings Ireland | Novel methods and intermediates for the preparation of (4bs,5ar)-12-cyclohexyl-n-(n,n-dimethylsulfamoyl)-3-methoxy-5a-((1 r,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 |
| JP2019510020A (ja) | 2016-03-15 | 2019-04-11 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 害虫を防除するための置換スルホニルアミド類 |
| TW201822637A (zh) | 2016-11-07 | 2018-07-01 | 德商拜耳廠股份有限公司 | 用於控制動物害蟲的經取代磺醯胺類 |
| CN110028510A (zh) * | 2019-05-22 | 2019-07-19 | 南京合巨药业有限公司 | 一种3-甲基-3,6-二氮杂-双环[3,1,1]庚烷二盐酸盐的制备方法 |
| KR20220098170A (ko) | 2019-11-07 | 2022-07-11 | 바이엘 악티엔게젤샤프트 | 동물 해충 방제를 위한 치환된 술포닐 아미드 |
| US12274700B1 (en) | 2020-10-30 | 2025-04-15 | Accencio LLC | Methods of treating symptoms of coronavirus infection with RNA polymerase inhibitors |
Citations (1)
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| WO2007136982A1 (en) * | 2006-05-17 | 2007-11-29 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors |
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| DE602005013922D1 (de) | 2004-02-24 | 2009-05-28 | Japan Tobacco Inc | Kondensierte heterotetracyclische verbindungen und deren verwendung als hcv-polymerase-inhibitor |
| US7348425B2 (en) | 2004-08-09 | 2008-03-25 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| US7153848B2 (en) * | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| AU2005298403A1 (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 |
| US7521441B2 (en) | 2006-05-22 | 2009-04-21 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US7521442B2 (en) | 2006-05-25 | 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 |
| US7452876B2 (en) | 2006-06-08 | 2008-11-18 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
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2008
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007136982A1 (en) * | 2006-05-17 | 2007-11-29 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| EA200901241A1 (ru) | 2010-02-26 |
| KR20100015304A (ko) | 2010-02-12 |
| ZA200906129B (en) | 2010-11-24 |
| CN101657455B (zh) | 2013-02-06 |
| TW200848058A (en) | 2008-12-16 |
| EP2118109B1 (en) | 2014-11-26 |
| CN101657455A (zh) | 2010-02-24 |
| AR065772A1 (es) | 2009-07-01 |
| BRPI0808763A2 (pt) | 2014-09-16 |
| JP2010521476A (ja) | 2010-06-24 |
| WO2008112473A1 (en) | 2008-09-18 |
| EA016614B1 (ru) | 2012-06-29 |
| PE20090648A1 (es) | 2009-05-29 |
| US7547690B2 (en) | 2009-06-16 |
| IL200905A0 (en) | 2010-05-17 |
| JP5232178B2 (ja) | 2013-07-10 |
| EP2118109A1 (en) | 2009-11-18 |
| CL2008000751A1 (es) | 2008-07-25 |
| MX2009009473A (es) | 2009-09-15 |
| CO6180426A2 (es) | 2010-07-19 |
| AU2008226639A1 (en) | 2008-09-18 |
| US20080227769A1 (en) | 2008-09-18 |
| CA2681093A1 (en) | 2008-09-18 |
| NZ579342A (en) | 2011-07-29 |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |