EA024201B1 - Ингибиторы вируса гепатита с - Google Patents
Ингибиторы вируса гепатита с Download PDFInfo
- Publication number
- EA024201B1 EA024201B1 EA201391685A EA201391685A EA024201B1 EA 024201 B1 EA024201 B1 EA 024201B1 EA 201391685 A EA201391685 A EA 201391685A EA 201391685 A EA201391685 A EA 201391685A EA 024201 B1 EA024201 B1 EA 024201B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- diyl
- mmol
- dimethyl
- imidazole
- oxo
- Prior art date
Links
- 241000711549 Hepacivirus C Species 0.000 title abstract description 6
- 239000003112 inhibitor Substances 0.000 title description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 238000000034 method Methods 0.000 claims abstract description 40
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- -1 1H-imidazole-4,2-diyl Chemical group 0.000 claims description 351
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 100
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
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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
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- XHVSCKNABCCCAC-UHFFFAOYSA-N trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound C[Si](C)(C)OC(=O)C(F)(F)S(F)(=O)=O XHVSCKNABCCCAC-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
-
- 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
- A61K31/41—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
-
- 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
- A61K31/41—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
-
- 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
- A61K31/535—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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- 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)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- 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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161485224P | 2011-05-12 | 2011-05-12 | |
| 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201391685A1 EA201391685A1 (ru) | 2014-03-31 |
| EA024201B1 true EA024201B1 (ru) | 2016-08-31 |
Family
ID=46147738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201391685A EA024201B1 (ru) | 2011-05-12 | 2012-05-09 | Ингибиторы вируса гепатита с |
Country Status (22)
| Country | Link |
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Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US9775831B2 (en) | 2013-07-17 | 2017-10-03 | Bristol-Myers Squibb Company | Combinations comprising biphenyl derivatives for use in the treatment of HCV |
| WO2015088817A1 (en) * | 2013-12-11 | 2015-06-18 | 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 |
| WO2017023631A1 (en) | 2015-08-06 | 2017-02-09 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| 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 |
| IL309666A (en) | 2021-07-09 | 2024-02-01 | Plexium Inc | Aryl compounds and pharmaceutical compositions that modulate ikzf2 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008021936A2 (en) * | 2006-08-11 | 2008-02-21 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2009102633A1 (en) * | 2008-02-13 | 2009-08-20 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010091413A1 (en) * | 2009-02-09 | 2010-08-12 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| WO2010096302A1 (en) * | 2009-02-17 | 2010-08-26 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010117635A1 (en) * | 2009-03-30 | 2010-10-14 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010117704A1 (en) * | 2009-03-30 | 2010-10-14 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010132601A1 (en) * | 2009-05-13 | 2010-11-18 | Gilead Sciences, Inc. | Antiviral compounds |
| WO2011009084A2 (en) * | 2009-07-16 | 2011-01-20 | Vertex Pharmaceuticals Incorporated | Benzimidazole analogues for the treatment or prevention of flavivirus infections |
Family Cites Families (132)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0679153A4 (en) | 1993-01-14 | 1996-05-15 | Magainin Pharma | FINALLY MODIFIED AMINO ACIDS AND PEPTIDES. |
| US5654451B1 (en) | 1993-01-14 | 2000-02-22 | Magainin Pharma | Amino acids and peptides having modified c-terminals and modified n-terminals |
| WO2004005264A2 (en) | 2002-07-05 | 2004-01-15 | Axxima Pharmaceuticals Ag | Imidazole compounds for the treatment of hepatitis c virus infections |
| WO2004014852A2 (en) | 2002-08-12 | 2004-02-19 | Bristol-Myers Squibb Company | Iminothiazolidinones as inhibitors of hcv replication |
| WO2006022442A1 (ja) | 2004-08-24 | 2006-03-02 | Santen Pharmaceutical Co., Ltd. | ジヒドロオロテートデヒドロゲナーゼ阻害活性を有する新規複素環アミド誘導体 |
| WO2006093867A1 (en) | 2005-02-28 | 2006-09-08 | The Rockefeller University | Structure of the hepatitits c virus ns5a protein |
| US8143288B2 (en) | 2005-06-06 | 2012-03-27 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| ES2348332T3 (es) | 2005-09-16 | 2010-12-02 | Arrow Therapeutics Limited | Derivados de bifenilo y su uso en el tratamiento de la hepatitis 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 |
| EP1971611B1 (en) | 2005-12-21 | 2012-10-10 | Abbott Laboratories | Anti-viral compounds |
| NZ569817A (en) | 2005-12-21 | 2011-10-28 | Abbott Lab | Anti-viral compounds |
| SG133452A1 (en) | 2005-12-30 | 2007-07-30 | Novartis Ag | Peptide deformylase inhibitors for treatment of mycobacterial and other parasitic diseases |
| CA2653924A1 (en) | 2006-05-30 | 2007-12-06 | Arrow Therapeutics Limited | Biphenyl derivatives and their use in treating hepatitis c |
| CN101558059B (zh) * | 2006-08-11 | 2014-12-03 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
| US7659270B2 (en) | 2006-08-11 | 2010-02-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8329159B2 (en) | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US20100158862A1 (en) | 2006-08-11 | 2010-06-24 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US8303944B2 (en) | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7745636B2 (en) | 2006-08-11 | 2010-06-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TW200831084A (en) | 2006-11-21 | 2008-08-01 | Genelabs Tech Inc | Anti-viral compounds |
| US8236950B2 (en) | 2006-12-20 | 2012-08-07 | Abbott Laboratories | Anti-viral compounds |
| US7741347B2 (en) | 2007-05-17 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| 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 |
| BRPI0907733A2 (pt) | 2008-02-12 | 2015-07-14 | Bristol Myers Squibb Co | Inibidores do vírus da hepatite c |
| US7704992B2 (en) | 2008-02-13 | 2010-04-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7906655B2 (en) | 2008-08-07 | 2011-03-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8383094B2 (en) | 2008-10-01 | 2013-02-26 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8729077B2 (en) | 2008-11-28 | 2014-05-20 | Glaxosmithkline Llc | Anti-viral compounds, compositions, and methods of use |
| KR20110098779A (ko) | 2008-12-03 | 2011-09-01 | 프레시디오 파마슈티칼스, 인코포레이티드 | Ｈｃｖ ｎｓ5ａ의 억제제 |
| EA024853B1 (ru) | 2008-12-03 | 2016-10-31 | Пресидио Фармасьютикалс, Инк. | Ингибиторы ns5a вгс |
| RU2505540C2 (ru) | 2008-12-23 | 2014-01-27 | Эббви Инк. | Антивирусные соединения |
| WO2010096462A1 (en) | 2009-02-17 | 2010-08-26 | Enanta Pharmaceuticals, Inc | Linked diimidazole derivatives |
| CA2753313A1 (en) | 2009-02-23 | 2010-08-26 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| UY32462A (es) | 2009-02-23 | 2010-09-30 | Arrow Therapeutics Ltd | Derivados de bifenilo novedosos para el tratamiento de infección por virus de hepatitis c 644 |
| RU2544010C2 (ru) | 2009-02-27 | 2015-03-10 | Энанта Фармасьютикалс, Инк. | Ингибиторы вируса гепатита с |
| MX2011010084A (es) | 2009-03-27 | 2011-10-14 | Merck Sharp & Dohme | Inhibidores de la replicacion del virus de la hepatitis c. |
| US8709999B2 (en) | 2009-03-27 | 2014-04-29 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic HCV inhibitors |
| KR20110131312A (ko) | 2009-03-27 | 2011-12-06 | 프레시디오 파마슈티칼스, 인코포레이티드 | 융합된 고리 ｃ형 간염 억제제 |
| US20110237636A1 (en) | 2009-03-30 | 2011-09-29 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| TW201038559A (en) | 2009-04-09 | 2010-11-01 | Bristol Myers Squibb Co | Hepatitis C virus inhibitors |
| US8143414B2 (en) | 2009-04-13 | 2012-03-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CA2758484A1 (en) | 2009-04-15 | 2010-10-21 | David A. Degoey | Anti-viral compounds |
| JP2012524761A (ja) | 2009-04-24 | 2012-10-18 | テイボテク・フアーマシユーチカルズ | ジアリールエーテル類 |
| CA2760205A1 (en) | 2009-05-12 | 2010-11-18 | Schering Corporation | Fused tricyclic aryl compounds useful for the treatment of viral diseases |
| US8980920B2 (en) | 2009-05-29 | 2015-03-17 | Merck Sharp & Dohme Corp. | Antiviral compounds of three linked aryl moieties to treat diseases such as hepatitis C |
| US8772505B2 (en) | 2009-05-29 | 2014-07-08 | Merck Sharp & Dohme Corp. | Antiviral compounds composed of three aligned aryl moieties to treat diseases such as hepatitis C |
| US8211928B2 (en) | 2009-05-29 | 2012-07-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8138215B2 (en) | 2009-05-29 | 2012-03-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US9394279B2 (en) | 2009-06-11 | 2016-07-19 | Abbvie Inc. | Anti-viral compounds |
| PL2628481T3 (pl) | 2009-06-11 | 2016-08-31 | Abbvie Bahamas Ltd | Tripodstawione heterocykle jako inhibitory replikacji wirusa HCV zapalenia wątroby typu C |
| US8937150B2 (en) | 2009-06-11 | 2015-01-20 | Abbvie Inc. | Anti-viral compounds |
| WO2010148006A1 (en) | 2009-06-16 | 2010-12-23 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| WO2011004276A1 (en) | 2009-07-06 | 2011-01-13 | Pfizer Limited | Hepatitis c virus inhibitors |
| RU2540897C2 (ru) | 2009-08-07 | 2015-02-10 | Тиботек Фармасьютикалз | Производные бис-бензимидазола в качестве ингибиторов вируса гепатита с |
| WO2011015657A1 (en) | 2009-08-07 | 2011-02-10 | Tibotec Pharmaceuticals | Phenyl ethynyl derivatives as hepatitis c virus inhibitors |
| RU2012112824A (ru) | 2009-09-03 | 2013-10-10 | Тиботек Фармасьютикалз | Производные бис-бензимидазола |
| SG178952A1 (en) | 2009-09-04 | 2012-04-27 | Glaxosmithkline Llc | Chemical compounds |
| US9156818B2 (en) | 2009-09-11 | 2015-10-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| WO2011031934A1 (en) | 2009-09-11 | 2011-03-17 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| US8415374B2 (en) | 2009-10-12 | 2013-04-09 | Bristol-Myers Squibb Company | Combinations of hepatitis C virus inhibitors |
| WO2011050146A1 (en) | 2009-10-23 | 2011-04-28 | Glaxosmithkline Llc | Chemical compounds |
| UA108211C2 (uk) | 2009-11-04 | 2015-04-10 | Янссен Рід Айрленд | Бензімідазолімідазольні похідні |
| US20110274648A1 (en) | 2009-11-11 | 2011-11-10 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110269956A1 (en) | 2009-11-11 | 2011-11-03 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110281910A1 (en) | 2009-11-12 | 2011-11-17 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| EP2503881B1 (en) | 2009-11-25 | 2015-05-13 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds and derivatives thereof useful for the treatment of viral diseases |
| US8415482B2 (en) | 2009-12-04 | 2013-04-09 | National Health Research Institutes | Proline derivatives |
| US8653070B2 (en) | 2009-12-14 | 2014-02-18 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8377980B2 (en) | 2009-12-16 | 2013-02-19 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN104530079B (zh) | 2009-12-18 | 2017-10-20 | 北京凯因科技股份有限公司 | C型肝炎病毒复制的新型抑制剂 |
| MX2012006877A (es) | 2009-12-18 | 2012-08-31 | Idenix Pharmaceuticals Inc | Inhibidores de virus de hepatitis c de arileno o heteroarileno 5, 5 - fusionado. |
| CA2785488A1 (en) | 2009-12-22 | 2011-07-21 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseases |
| CA2784036A1 (en) | 2009-12-24 | 2011-06-30 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2011091446A1 (en) | 2010-01-22 | 2011-07-28 | Glaxosmithkline Llc | Chemical compounds |
| WO2011091417A1 (en) | 2010-01-25 | 2011-07-28 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| WO2011091532A1 (en) | 2010-01-28 | 2011-08-04 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor compounds |
| US8623814B2 (en) | 2010-02-23 | 2014-01-07 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| US8178531B2 (en) | 2010-02-23 | 2012-05-15 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| KR20120124495A (ko) | 2010-03-04 | 2012-11-13 | 이난타 파마슈티칼스, 인코포레이티드 | Ｈｃｖ 복제의 억제제로서의 조합 제약 작용제 |
| CN102918049A (zh) * | 2010-03-09 | 2013-02-06 | 默沙东公司 | 稠合三环甲硅烷基化合物及其用于治疗病毒性疾病的方法 |
| AU2011232348A1 (en) | 2010-03-24 | 2012-10-11 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of Flavivirus infections |
| TW201141857A (en) | 2010-03-24 | 2011-12-01 | Vertex Pharma | Analogues for the treatment or prevention of flavivirus infections |
| WO2011119853A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| EP2555622A4 (en) | 2010-04-09 | 2013-09-18 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| US20110312996A1 (en) | 2010-05-17 | 2011-12-22 | Intermune, Inc. | Novel inhibitors of hepatitis c virus replication |
| EP2575866A4 (en) | 2010-05-24 | 2013-10-16 | Presidio Pharmaceuticals Inc | HCV NS5A INHIBITORS |
| US20130296311A1 (en) | 2010-05-28 | 2013-11-07 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| US8778938B2 (en) | 2010-06-04 | 2014-07-15 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| TW201201801A (en) | 2010-06-09 | 2012-01-16 | Presidio Pharmaceuticals Inc | Inhibitors of HCV NS5A protein |
| NZ605440A (en) | 2010-06-10 | 2014-05-30 | Abbvie Bahamas Ltd | Solid compositions comprising an hcv inhibitor |
| WO2011154871A1 (en) | 2010-06-10 | 2011-12-15 | Pfizer Limited | Hepatitis c virus inhibitors |
| WO2012003642A1 (en) | 2010-07-09 | 2012-01-12 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds and use thereof for treating viral diseases |
| US20140377223A1 (en) | 2010-07-26 | 2014-12-25 | Joseph A. Kozlowski | Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases |
| US8815849B2 (en) | 2010-07-26 | 2014-08-26 | Janssen R&D Ireland | Hetero-bicyclic derivatives as HCV inhibitors |
| JP5596861B2 (ja) | 2010-08-04 | 2014-09-24 | ブリストル−マイヤーズ スクイブ カンパニー | Ｃ型肝炎ウイルス阻害剤 |
| US20120196794A1 (en) | 2010-08-06 | 2012-08-02 | Bristol-Myers Squibb Company | Combinations of Hepatitis C Virus Inhibitors |
| WO2012021704A1 (en) | 2010-08-12 | 2012-02-16 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| US20120195857A1 (en) | 2010-08-12 | 2012-08-02 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| WO2012020036A1 (en) | 2010-08-13 | 2012-02-16 | F. Hoffmann-La Roche Ag | Hepatitis c virus inhibitors |
| WO2012027712A2 (en) | 2010-08-26 | 2012-03-01 | Rfs Pharma, Llc | Potent and selective inhibitors of hepatitis c virus |
| WO2012040389A2 (en) | 2010-09-22 | 2012-03-29 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic hcv inhibitors |
| EP2621279B1 (en) | 2010-09-29 | 2018-04-04 | Merck Sharp & Dohme Corp. | Fused tetracycle derivatives and methods of use thereof for the treatment of viral diseases |
| EP2621501A4 (en) | 2010-09-29 | 2014-04-09 | Merck Sharp & Dohme | POLYCYCLIC HETEROCYCLUS DERIVATIVES AND METHOD FOR THEIR USE FOR THE TREATMENT OF VIRUS DISEASES |
| JP2013538831A (ja) | 2010-09-29 | 2013-10-17 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｃ型肝炎ウィルス感染治療のための四環式インドール誘導体 |
| WO2012040924A1 (en) | 2010-09-29 | 2012-04-05 | Merck Sharp & Dohme Corp. | Fused tetracyclic heterocycle compounds and methods of use thereof for treatment of viral diseases |
| WO2012041227A1 (en) | 2010-09-29 | 2012-04-05 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds for treating hepatitis c viral infection |
| WO2012040923A1 (en) | 2010-09-29 | 2012-04-05 | Merck Sharp & Dohme Corp. | Tetracyclic indole derivatives and methods of use thereof for the treatment of viral diseases |
| WO2012050918A2 (en) | 2010-09-29 | 2012-04-19 | Presidio Pharmaceutical, Inc. | Tricyclic fused ring inhibitors of hepatitis c |
| WO2012048421A1 (en) | 2010-10-14 | 2012-04-19 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor compounds |
| CA2814534A1 (en) | 2010-11-04 | 2012-05-10 | Theravance, Inc. | Novel inhibitors of hepatitis c virus |
| AU2011328980B2 (en) | 2010-11-17 | 2015-07-30 | Gilead Sciences, Inc. | Antiviral compounds |
| RU2452735C1 (ru) | 2010-11-30 | 2012-06-10 | Александр Васильевич Иващенко | Замещенные азолы, противовирусный активный компонент, фармацевтическая композиция, способ получения и применения |
| WO2012083059A1 (en) | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| WO2012083053A2 (en) | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| WO2012083043A1 (en) | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| WO2012083048A2 (en) | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| WO2012083061A2 (en) | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| US20140343286A1 (en) | 2010-12-15 | 2014-11-20 | Allan C. Krueger | Anti-viral compounds |
| MX2013006951A (es) | 2010-12-16 | 2013-10-03 | Abbvie Inc | Compuestos antivirales. |
| EP2651924A1 (en) | 2010-12-16 | 2013-10-23 | Abbvie Inc. | Anti-viral compounds |
| WO2012087976A2 (en) | 2010-12-21 | 2012-06-28 | Intermune, Inc. | Novel inhibitors of hepatitis c virus replication |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2012123298A1 (en) | 2011-03-11 | 2012-09-20 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| WO2012122716A1 (en) | 2011-03-17 | 2012-09-20 | Merck Sharp & Dohme Corp. | Tetracyclic xanthene derivatives and methods of use thereof for treatment of viral diseases |
| US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
| US20150126747A1 (en) | 2011-05-26 | 2015-05-07 | Abbvie Inc. | Anti-viral compounds |
| US20150105548A1 (en) | 2011-05-26 | 2015-04-16 | Abbvie Inc | Anti-viral compounds |
| CN103561739B (zh) | 2011-05-27 | 2016-03-02 | 艾其林医药公司 | 可用于治疗hcv感染的经取代的脂肪芬、环芬、异芬、杂芬、杂-异芬以及金属茂 |
| US20120328565A1 (en) | 2011-06-24 | 2012-12-27 | Brinkman John A | Antiviral compounds |
| BR112014000563A2 (pt) | 2011-07-09 | 2019-12-10 | Sunshine Lake Pharma Co., Ltd | composto, composição farmacêutica, e, uso do composto |
-
2012
- 2012-05-07 US US13/465,298 patent/US9546160B2/en active Active
- 2012-05-09 BR BR112013028679A patent/BR112013028679A2/pt not_active IP Right Cessation
- 2012-05-09 CN CN201280034345.8A patent/CN103827108B/zh not_active Expired - Fee Related
- 2012-05-09 CA CA2835688A patent/CA2835688A1/en not_active Abandoned
- 2012-05-09 WO PCT/US2012/037012 patent/WO2012154777A1/en not_active Ceased
- 2012-05-09 KR KR1020137032604A patent/KR20140037114A/ko not_active Withdrawn
- 2012-05-09 JP JP2014510419A patent/JP5977819B2/ja not_active Expired - Fee Related
- 2012-05-09 PH PH1/2013/502177A patent/PH12013502177A1/en unknown
- 2012-05-09 EA EA201391685A patent/EA024201B1/ru not_active IP Right Cessation
- 2012-05-09 EP EP12723010.0A patent/EP2707365B1/en not_active Not-in-force
- 2012-05-09 PE PE2013002484A patent/PE20150105A1/es not_active Application Discontinuation
- 2012-05-09 AU AU2012253578A patent/AU2012253578A1/en not_active Abandoned
- 2012-05-09 MX MX2013012870A patent/MX2013012870A/es unknown
- 2012-05-09 SG SG2013082730A patent/SG194846A1/en unknown
- 2012-05-11 AR ARP120101698A patent/AR086389A1/es unknown
- 2012-05-11 UY UY0001034066A patent/UY34066A/es unknown
- 2012-05-11 TW TW101116982A patent/TW201249834A/zh unknown
-
2013
- 2013-11-07 MA MA36399A patent/MA35104B1/fr unknown
- 2013-11-07 IL IL229331A patent/IL229331A0/en unknown
- 2013-11-11 CL CL2013003229A patent/CL2013003229A1/es unknown
- 2013-12-09 CO CO13288206A patent/CO6821952A2/es not_active Application Discontinuation
- 2013-12-11 ZA ZA2013/09356A patent/ZA201309356B/en unknown
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008021936A2 (en) * | 2006-08-11 | 2008-02-21 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2009102633A1 (en) * | 2008-02-13 | 2009-08-20 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010091413A1 (en) * | 2009-02-09 | 2010-08-12 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| WO2010096302A1 (en) * | 2009-02-17 | 2010-08-26 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010117635A1 (en) * | 2009-03-30 | 2010-10-14 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010117704A1 (en) * | 2009-03-30 | 2010-10-14 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2010132601A1 (en) * | 2009-05-13 | 2010-11-18 | Gilead Sciences, Inc. | Antiviral compounds |
| WO2011009084A2 (en) * | 2009-07-16 | 2011-01-20 | Vertex Pharmaceuticals Incorporated | Benzimidazole analogues for the treatment or prevention of flavivirus infections |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014513690A (ja) | 2014-06-05 |
| ZA201309356B (en) | 2015-05-27 |
| MA35104B1 (fr) | 2014-05-02 |
| JP5977819B2 (ja) | 2016-08-24 |
| TW201249834A (en) | 2012-12-16 |
| PH12013502177A1 (en) | 2014-01-13 |
| EP2707365B1 (en) | 2018-10-17 |
| US9546160B2 (en) | 2017-01-17 |
| BR112013028679A2 (pt) | 2017-01-24 |
| IL229331A0 (en) | 2014-01-30 |
| KR20140037114A (ko) | 2014-03-26 |
| CN103827108B (zh) | 2018-05-15 |
| PE20150105A1 (es) | 2015-02-06 |
| CL2013003229A1 (es) | 2014-09-05 |
| SG194846A1 (en) | 2013-12-30 |
| AU2012253578A1 (en) | 2014-01-16 |
| MX2013012870A (es) | 2014-02-20 |
| UY34066A (es) | 2012-11-30 |
| EA201391685A1 (ru) | 2014-03-31 |
| EP2707365A1 (en) | 2014-03-19 |
| US20130121957A1 (en) | 2013-05-16 |
| CN103827108A (zh) | 2014-05-28 |
| CA2835688A1 (en) | 2012-11-15 |
| AR086389A1 (es) | 2013-12-11 |
| CO6821952A2 (es) | 2013-12-31 |
| WO2012154777A1 (en) | 2012-11-15 |
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| Date | Code | Title | Description |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG TJ TM RU |