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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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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- 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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
- 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
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- 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)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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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)
| Publication Number | Publication Date |
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| AU2008226639A1 AU2008226639A1 (en) | 2008-09-18 |
| AU2008226639B2 true AU2008226639B2 (en) | 2012-07-19 |
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| AU2008226639A Ceased AU2008226639B2 (en) | 2007-03-14 | 2008-03-05 | Compounds for the treatment of hepatitis C |
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| US (1) | US7547690B2 (OSRAM) |
| EP (1) | EP2118109B1 (OSRAM) |
| JP (1) | JP5232178B2 (OSRAM) |
| KR (1) | KR20100015304A (OSRAM) |
| CN (1) | CN101657455B (OSRAM) |
| AR (1) | AR065772A1 (OSRAM) |
| AU (1) | AU2008226639B2 (OSRAM) |
| BR (1) | BRPI0808763A2 (OSRAM) |
| CA (1) | CA2681093A1 (OSRAM) |
| CL (1) | CL2008000751A1 (OSRAM) |
| CO (1) | CO6180426A2 (OSRAM) |
| EA (1) | EA016614B1 (OSRAM) |
| IL (1) | IL200905A0 (OSRAM) |
| MX (1) | MX2009009473A (OSRAM) |
| NZ (1) | NZ579342A (OSRAM) |
| PE (1) | PE20090648A1 (OSRAM) |
| TW (1) | TW200848058A (OSRAM) |
| WO (1) | WO2008112473A1 (OSRAM) |
| ZA (1) | ZA200906129B (OSRAM) |
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| JPWO2005049622A1 (ja) * | 2003-11-19 | 2007-06-07 | 日本たばこ産業株式会社 | ５−５員縮合複素環化合物及びそのｈｃｖポリメラーゼ阻害剤としての用途 |
| US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
| US7659263B2 (en) | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
| US7521443B2 (en) * | 2006-05-17 | 2009-04-21 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US8143243B2 (en) * | 2007-08-09 | 2012-03-27 | 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 |
| US7642251B2 (en) * | 2007-08-09 | 2010-01-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| DK2209789T3 (da) * | 2007-11-20 | 2012-03-05 | Bristol Myers Squibb Co | Cyclopropyl-kondenserede indolobenzazepin HCV NS5B-hæmmere |
| 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 |
| CA2710644C (en) | 2007-12-24 | 2016-03-29 | Tibotec Pharmaceuticals | Macrocyclic indoles as hepatitis c virus inhibitors |
| JP2011515496A (ja) * | 2008-03-27 | 2011-05-19 | ブリストル−マイヤーズ スクイブ カンパニー | ジオキソランおよびジオキソラノン縮合インドロベンザジアゼピンｈｃｖｎｓ５ｂ阻害剤 |
| CN101977914A (zh) * | 2008-03-27 | 2011-02-16 | 百时美施贵宝公司 | 用于治疗丙型肝炎的化合物 |
| WO2009120733A1 (en) * | 2008-03-27 | 2009-10-01 | Bristol-Myers Squibb Company | Pyrrolidine 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 |
| SG181109A1 (en) * | 2009-12-07 | 2012-07-30 | Targacept Inc | 3,6-diazabicyclo[3.1.1]heptanes as neuronal nicotinic acetylcholine receptor ligands |
| 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 |
| 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 |
| US20200288710A1 (en) | 2016-03-15 | 2020-09-17 | Bayer Cropscience Aktiengesellschaft | Substituted sulphonamides for controlling animal pests |
| 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 |
| JP2023501978A (ja) | 2019-11-07 | 2023-01-20 | バイエル・アクチエンゲゼルシヤフト | 動物害虫駆除用の置換スルホニルアミド |
| 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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| 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 |
| US7348425B2 (en) | 2004-08-09 | 2008-03-25 | 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 |
| 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 |
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2008
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- 2008-03-05 CN CN200880008369XA patent/CN101657455B/zh not_active Expired - Fee Related
- 2008-03-05 MX MX2009009473A patent/MX2009009473A/es not_active Application Discontinuation
- 2008-03-05 JP JP2009553689A patent/JP5232178B2/ja not_active Expired - Fee Related
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- 2008-03-05 WO PCT/US2008/055893 patent/WO2008112473A1/en not_active Ceased
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- 2008-03-05 EP EP08743684.6A patent/EP2118109B1/en not_active Not-in-force
- 2008-03-05 KR KR1020097019018A patent/KR20100015304A/ko not_active Ceased
- 2008-03-13 TW TW097108906A patent/TW200848058A/zh unknown
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2009
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- 2009-09-13 IL IL200905A patent/IL200905A0/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
|---|---|
| BRPI0808763A2 (pt) | 2014-09-16 |
| PE20090648A1 (es) | 2009-05-29 |
| US7547690B2 (en) | 2009-06-16 |
| AR065772A1 (es) | 2009-07-01 |
| ZA200906129B (en) | 2010-11-24 |
| EP2118109A1 (en) | 2009-11-18 |
| NZ579342A (en) | 2011-07-29 |
| JP2010521476A (ja) | 2010-06-24 |
| EP2118109B1 (en) | 2014-11-26 |
| CN101657455A (zh) | 2010-02-24 |
| JP5232178B2 (ja) | 2013-07-10 |
| KR20100015304A (ko) | 2010-02-12 |
| US20080227769A1 (en) | 2008-09-18 |
| IL200905A0 (en) | 2010-05-17 |
| CN101657455B (zh) | 2013-02-06 |
| MX2009009473A (es) | 2009-09-15 |
| AU2008226639A1 (en) | 2008-09-18 |
| EA200901241A1 (ru) | 2010-02-26 |
| CL2008000751A1 (es) | 2008-07-25 |
| CA2681093A1 (en) | 2008-09-18 |
| TW200848058A (en) | 2008-12-16 |
| WO2008112473A1 (en) | 2008-09-18 |
| CO6180426A2 (es) | 2010-07-19 |
| EA016614B1 (ru) | 2012-06-29 |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |