SG194846A1 - Hepatitis c virus inhibitors - Google Patents
Hepatitis c virus inhibitors Download PDFInfo
- Publication number
- SG194846A1 SG194846A1 SG2013082730A SG2013082730A SG194846A1 SG 194846 A1 SG194846 A1 SG 194846A1 SG 2013082730 A SG2013082730 A SG 2013082730A SG 2013082730 A SG2013082730 A SG 2013082730A SG 194846 A1 SG194846 A1 SG 194846A1
- Authority
- SG
- Singapore
- Prior art keywords
- diyl
- alkyl
- imidazole
- mmol
- cap
- Prior art date
Links
- 241000711549 Hepacivirus C Species 0.000 title abstract description 58
- 239000003112 inhibitor Substances 0.000 title description 35
- 239000000203 mixture Substances 0.000 claims abstract description 211
- 150000001875 compounds Chemical class 0.000 claims abstract description 126
- 238000000034 method Methods 0.000 claims abstract description 46
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 208000015181 infectious disease Diseases 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 162
- 229910052739 hydrogen Inorganic materials 0.000 claims description 125
- -1 -NR°R® Chemical group 0.000 claims description 86
- 125000003118 aryl group Chemical group 0.000 claims description 66
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
- 125000005843 halogen group Chemical group 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 44
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 43
- 125000001188 haloalkyl group Chemical group 0.000 claims description 36
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 29
- 229940079322 interferon Drugs 0.000 claims description 28
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
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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 claims description 18
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- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 18
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- SSERCMQZZYTNBY-UHFFFAOYSA-M sodium;3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylate Chemical compound [Na+].C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C([O-])=O)C1CCC(O)CC1 SSERCMQZZYTNBY-UHFFFAOYSA-M 0.000 description 1
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- TTZHDVOVKQGIBA-IQWMDFIBSA-N sofosbuvir Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IQWMDFIBSA-N 0.000 description 1
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- 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
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- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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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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- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US13/465,298 US9546160B2 (en) | 2011-05-12 | 2012-05-07 | Hepatitis C virus inhibitors |
| PCT/US2012/037012 WO2012154777A1 (en) | 2011-05-12 | 2012-05-09 | Hepatitis c virus inhibitors |
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| US8303944B2 (en) * | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US9326973B2 (en) | 2012-01-13 | 2016-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP6196678B2 (ja) * | 2012-10-24 | 2017-09-13 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｃ型肝炎ウイルス阻害剤 |
| US9717712B2 (en) | 2013-07-02 | 2017-08-01 | Bristol-Myers Squibb Company | Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus |
| US20150023913A1 (en) | 2013-07-02 | 2015-01-22 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| JP2016527232A (ja) | 2013-07-17 | 2016-09-08 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｈｃｖの治療に使用するためのビフェニル誘導体を含む組み合わせ |
| US20160311806A1 (en) * | 2013-12-11 | 2016-10-27 | Bristol-Myers Squibb Company | 4,4'-biphenyldiyl-bis-(1 h-imidazolyl) derivatives as hepatitis hcv inhibitors |
| CN104725365B (zh) * | 2013-12-23 | 2019-02-26 | 南京圣和药业股份有限公司 | 丙型肝炎病毒抑制剂及其应用 |
| CN104860931A (zh) * | 2014-02-21 | 2015-08-26 | 常州寅盛药业有限公司 | 丙肝病毒抑制剂及其制药用途 |
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| CN115073308A (zh) * | 2021-03-15 | 2022-09-20 | 苏州信礼发医药技术有限公司 | 1-氨甲基-1-环丙醇的合成方法 |
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| PL1940786T3 (pl) | 2005-09-16 | 2010-12-31 | Arrow Therapeutics Ltd | Pochodne bifenylowe i ich zastosowanie w leczeniu zapalenia wątroby typu C |
| WO2007058384A1 (en) | 2005-11-17 | 2007-05-24 | Osaka University | Method of suppressing replication of hepatitis c virus, inhibitor of replication of the virus and method of screening for the same |
| WO2007081517A2 (en) | 2005-12-21 | 2007-07-19 | Abbott Laboratories | Anti-viral compounds |
| ATE541844T1 (de) | 2005-12-21 | 2012-02-15 | Abbott Lab | Antivirale verbindungen |
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| US7759495B2 (en) | 2006-08-11 | 2010-07-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
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| EP2097405A2 (en) | 2006-11-21 | 2009-09-09 | Smithkline Beecham Corporation | Anti-viral compounds |
| EP2094276A4 (en) | 2006-12-20 | 2011-01-05 | Abbott Lab | ANTIVIRAL COMPOUNDS |
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| US7728027B2 (en) | 2007-08-08 | 2010-06-01 | Bristol-Myers Squibb Company | Process for synthesizing compounds useful for treating hepatitis C |
| US8629171B2 (en) | 2007-08-08 | 2014-01-14 | Bristol-Myers Squibb Company | Crystalline form of methyl ((1S)-1-((25)-2-(5-(4'-(2-((25)-1((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate dihydrochloride salt |
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- 2012-05-09 JP JP2014510419A patent/JP5977819B2/ja not_active Expired - Fee Related
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| ZA201309356B (en) | 2015-05-27 |
| EA024201B1 (ru) | 2016-08-31 |
| EA201391685A1 (ru) | 2014-03-31 |
| PE20150105A1 (es) | 2015-02-06 |
| KR20140037114A (ko) | 2014-03-26 |
| CA2835688A1 (en) | 2012-11-15 |
| CO6821952A2 (es) | 2013-12-31 |
| US20130121957A1 (en) | 2013-05-16 |
| CN103827108B (zh) | 2018-05-15 |
| CN103827108A (zh) | 2014-05-28 |
| WO2012154777A1 (en) | 2012-11-15 |
| PH12013502177A1 (en) | 2014-01-13 |
| US9546160B2 (en) | 2017-01-17 |
| AU2012253578A1 (en) | 2014-01-16 |
| CL2013003229A1 (es) | 2014-09-05 |
| EP2707365B1 (en) | 2018-10-17 |
| AR086389A1 (es) | 2013-12-11 |
| JP5977819B2 (ja) | 2016-08-24 |
| MX2013012870A (es) | 2014-02-20 |
| BR112013028679A2 (pt) | 2017-01-24 |
| UY34066A (es) | 2012-11-30 |
| IL229331A0 (en) | 2014-01-30 |
| EP2707365A1 (en) | 2014-03-19 |
| JP2014513690A (ja) | 2014-06-05 |
| MA35104B1 (fr) | 2014-05-02 |
| TW201249834A (en) | 2012-12-16 |
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