ZA200604638B - Inhibitors of hepatitis C virus NS3/NS4A serine protease - Google Patents
Inhibitors of hepatitis C virus NS3/NS4A serine protease Download PDFInfo
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- ZA200604638B ZA200604638B ZA200604638A ZA200604638A ZA200604638B ZA 200604638 B ZA200604638 B ZA 200604638B ZA 200604638 A ZA200604638 A ZA 200604638A ZA 200604638 A ZA200604638 A ZA 200604638A ZA 200604638 B ZA200604638 B ZA 200604638B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- 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
- 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
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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- C07D403/02—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 two hetero rings
- C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
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Families Citing this family (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1133649C (zh) | 1996-10-18 | 2004-01-07 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是丙型肝炎病毒ns3蛋白酶的抑制剂 |
| US7491794B2 (en) * | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| US8119602B2 (en) | 2005-06-02 | 2012-02-21 | Schering Corporation | Administration of HCV protease inhibitors in combination with food to improve bioavailability |
| ES2572980T3 (es) * | 2005-06-02 | 2016-06-03 | Merck Sharp & Dohme Corp. | Combinación de inhibidores de la proteasa del VHC con un tensioactivo |
| US20070237818A1 (en) * | 2005-06-02 | 2007-10-11 | Malcolm Bruce A | Controlled-release formulation of HCV protease inhibitor and methods using the same |
| WO2006130666A2 (en) * | 2005-06-02 | 2006-12-07 | Schering Corporation | Medicaments and methods combining a hcv protease inhibitor and an akr competitor |
| CA2615626A1 (en) * | 2005-07-18 | 2007-01-25 | Novartis Ag | Small animal model for hcv replication |
| GEP20105124B (en) | 2005-07-25 | 2010-11-25 | Array Biopharma Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
| AR055395A1 (es) | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
| BRPI0617274A2 (pt) * | 2005-10-11 | 2011-07-19 | Intermune Inc | compostos e métodos para a inibição de replicação viral de hepatite c |
| US7772183B2 (en) * | 2005-10-12 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| KR20140098867A (ko) | 2005-11-11 | 2014-08-08 | 버텍스 파마슈티칼스 인코포레이티드 | Ｃ형 간염 바이러스 변이체 |
| US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
| US8183413B2 (en) | 2006-01-20 | 2012-05-22 | Kaneka Corporation | Process for production of β-amino-α-hydroxy carboxamide derivative |
| US7816348B2 (en) | 2006-02-03 | 2010-10-19 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| WO2007120595A2 (en) * | 2006-04-11 | 2007-10-25 | Novartis Ag | Amines for the treatment of hcv |
| KR101059593B1 (ko) | 2006-04-11 | 2011-08-25 | 노파르티스 아게 | Ｈｃｖ/ｈｉｖ 억제제 및 이들의 용도 |
| WO2007137080A2 (en) | 2006-05-23 | 2007-11-29 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| US7834190B2 (en) * | 2006-05-26 | 2010-11-16 | Kaneka Corporation | Process for production of optically active-3-amino-2-hydroxypropionic cyclopropylamide derivatives and salts thereof |
| US9526769B2 (en) * | 2006-06-06 | 2016-12-27 | Enanta Pharmaceuticals, Inc. | Macrocylic oximyl hepatitis C protease inhibitors |
| AR061629A1 (es) * | 2006-06-26 | 2008-09-10 | Enanta Pharm Inc | Quinoxalinil macrociclicos inhibidores de serina proteasa del virus de la hepatitis c. proceso de obtencion y composiciones farmaceuticas |
| DE102006059317A1 (de) | 2006-07-04 | 2008-01-10 | Evonik Degussa Gmbh | Verfahren zur Herstellung von β-Amino-α-hydroxy-carbonsäureamiden |
| RU2008152171A (ru) * | 2006-07-05 | 2010-08-10 | Интермьюн, Инк. (Us) | Новые ингибиторы вирусной репликации гепатита с |
| US7662779B2 (en) * | 2006-08-11 | 2010-02-16 | Enanta Pharmaceuticals, Inc. | Triazolyl macrocyclic hepatitis C serine protease inhibitors |
| CN101506167A (zh) | 2006-08-17 | 2009-08-12 | 贝林格尔.英格海姆国际有限公司 | 病毒聚合酶抑制剂 |
| US20100216161A1 (en) | 2009-02-26 | 2010-08-26 | Vertex Pharmaceuticals Incorporated | Method for identifying protease inhibitors |
| WO2008027397A2 (en) * | 2006-08-28 | 2008-03-06 | Vertex Pharmaceuticals Incorporated | Method for identifying protease inhibitors |
| DE102006042147A1 (de) * | 2006-09-06 | 2008-03-27 | Dynamit Nobel Gmbh Explosivstoff- Und Systemtechnik | Hydrochloride von 3-Amino-2-hydroxycarbonsäureamiden |
| US8003604B2 (en) * | 2006-11-16 | 2011-08-23 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CA2673111A1 (en) | 2006-12-07 | 2008-06-19 | Schering Corporation | Ph sensitive matrix formulation |
| BRPI0807483A2 (pt) | 2007-02-09 | 2014-05-13 | Irm Llc | Compostos e composições como inibidores de protease de ativação de canal |
| WO2008137779A2 (en) * | 2007-05-03 | 2008-11-13 | Intermune, Inc. | Novel macrocyclic inhibitors of hepatitis c virus replication |
| MX2009012093A (es) * | 2007-05-10 | 2010-01-25 | Intermune Inc | Nuevos peptidos inhibidores de la replicacion del virus de la hepatitis c. |
| US20090005387A1 (en) * | 2007-06-26 | 2009-01-01 | Deqiang Niu | Quinoxalinyl macrocyclic hepatitis c virus serine protease inhibitors |
| US8242140B2 (en) | 2007-08-03 | 2012-08-14 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| JP5095824B2 (ja) * | 2007-10-10 | 2012-12-12 | ノバルティス アーゲー | スピロピロリジン類およびｈｃｖおよびｈｉｖ感染に対するその使用 |
| US8419332B2 (en) * | 2007-10-19 | 2013-04-16 | Atlas Bolt & Screw Company Llc | Non-dimpling fastener |
| WO2009073713A1 (en) * | 2007-12-05 | 2009-06-11 | Enanta Pharmaceuticals, Inc. | Oximyl macrocyclic derivatives |
| BRPI0821342A2 (pt) | 2007-12-19 | 2019-09-24 | Boehringer Ingelheim Int | inibidores da polimerase viral |
| JP2011051896A (ja) * | 2007-12-21 | 2011-03-17 | Kaneka Corp | Ｎ−シクロプロピル−３−アミノ−２−ヒドロキシヘキサン酸アミド塩酸塩の製造方法 |
| CN102046622A (zh) | 2008-04-15 | 2011-05-04 | 因特蒙公司 | 丙型肝炎病毒复制的新颖大环抑制剂 |
| US20090285773A1 (en) * | 2008-05-15 | 2009-11-19 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| CN101580535B (zh) * | 2008-05-16 | 2012-10-03 | 太景生物科技股份有限公司 | 丙型肝炎病毒蛋白酶抑制剂 |
| US8044023B2 (en) * | 2008-05-29 | 2011-10-25 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
| US20100272674A1 (en) * | 2008-12-04 | 2010-10-28 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| CN102271699A (zh) | 2009-01-07 | 2011-12-07 | 西尼克斯公司 | 用于治疗hcv和hiv感染的环孢菌素衍生物 |
| AR075584A1 (es) | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| 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 |
| US8232246B2 (en) * | 2009-06-30 | 2012-07-31 | Abbott Laboratories | Anti-viral compounds |
| EP2477980B1 (en) * | 2009-09-15 | 2016-06-08 | Taigen Biotechnology Co., Ltd. | Hcv protease 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 |
| US20130156731A1 (en) | 2009-12-22 | 2013-06-20 | Kevin X. Chen | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseas |
| US20110178107A1 (en) * | 2010-01-20 | 2011-07-21 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
| EP2539334A1 (en) * | 2010-02-25 | 2013-01-02 | Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patiëntenzorg | Process for the preparation of -acyloxy -formamido amides |
| US8609635B2 (en) | 2010-03-09 | 2013-12-17 | Merck Sharp & Dohme Corp. | Fused tricyclic silyl compounds and methods of use thereof for the treatment of viral diseases |
| AU2011286276A1 (en) | 2010-07-26 | 2013-01-24 | Merck Sharp & Dohme Corp. | Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases |
| CA2812779A1 (en) | 2010-09-29 | 2012-04-19 | Merck Sharp & Dohme Corp. | Fused tetracycle derivatives and methods of use thereof for the treatment of viral diseases |
| JP2014502620A (ja) | 2010-12-30 | 2014-02-03 | エナンタ ファーマシューティカルズ インコーポレイテッド | 大環状ｃ型肝炎セリンプロテアーゼ阻害剤 |
| WO2012092411A2 (en) | 2010-12-30 | 2012-07-05 | Enanta Pharmaceuticals, Inc. | Phenanthridine macrocyclic hepatitis c serine protease inhibitors |
| EA201391519A1 (ru) | 2011-04-13 | 2014-03-31 | Мерк Шарп И Доум Корп. | 2'-замещенные нуклеозидные производные и способы их применения для лечения вирусных заболеваний |
| WO2012142075A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| WO2013033899A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases |
| WO2013033901A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases |
| WO2013033900A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases |
| WO2013039876A1 (en) | 2011-09-14 | 2013-03-21 | Merck Sharp & Dohme Corp. | Silyl-containing heterocyclic compounds and methods of use thereof for the treatment of viral diseases |
| WO2013178682A2 (en) | 2012-05-30 | 2013-12-05 | Chemo Ibérica, S.A. | Multicomponent process for the preparation of bicyclic compounds |
| WO2013186248A1 (en) | 2012-06-13 | 2013-12-19 | Janssen Pharmaceutica Nv | A method for the preparation of 3-amino-n-cyclopropyl-2-hydroxyl-hexanamide |
| CN102875648B (zh) * | 2012-09-26 | 2014-02-19 | 深圳翰宇药业股份有限公司 | 一种制备特拉匹韦的方法 |
| CN102875649B (zh) * | 2012-09-26 | 2014-04-16 | 深圳翰宇药业股份有限公司 | 一种制备特拉匹韦及其中间体的方法及所述中间体 |
| EP3063140A4 (en) | 2013-10-30 | 2017-11-08 | Merck Sharp & Dohme Corp. | Pseudopolymorphs of an hcv ns5a inhibitor and uses thereof |
| CN104610272B (zh) * | 2013-11-05 | 2017-03-29 | 上海唐润医药科技有限公司 | 环状黄酮或异黄酮类化合物及其用途 |
| EP3089757A1 (en) | 2014-01-03 | 2016-11-09 | AbbVie Inc. | Solid antiviral dosage forms |
| JP2018131439A (ja) * | 2017-02-14 | 2018-08-23 | アッヴィ・インコーポレイテッド | Ｈｃｖを処置する方法 |
| US11124497B1 (en) | 2020-04-17 | 2021-09-21 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
| US11174231B1 (en) | 2020-06-09 | 2021-11-16 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3216325A (en) * | 1962-04-16 | 1965-11-09 | Dole Valve Co | Pneumatic control system |
| ATE297946T1 (de) | 2000-04-03 | 2005-07-15 | Vertex Pharma | Inhibitoren von serin proteasen, speziell der hepatitis-c-virus ns3-protease |
| SI1385870T1 (sl) * | 2000-07-21 | 2010-08-31 | Schering Corp | Peptidi kot NS3-serin proteazni inhibitorji virusa hepatitisa C |
| US7244721B2 (en) * | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| IL155842A0 (en) * | 2000-12-12 | 2003-12-23 | Schering Corp | Diaryl peptides as ns3-serine protease inhibitors of hepatitis c virus |
| US20040071656A1 (en) * | 2001-12-26 | 2004-04-15 | Felix Wieland | Modulation of heat-shock-protein-based immunotherapies |
| JP4301953B2 (ja) * | 2002-01-23 | 2009-07-22 | シェーリング コーポレイション | Ｃ型肝炎ウイルス感染の処置における使用のためのｎｓ３−セリンプロテアーゼ阻害剤としてのプロリン化合物 |
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| RU2006124594A (ru) | 2008-01-27 |
| BRPI0416902A (pt) | 2007-01-16 |
| PE20050940A1 (es) | 2005-11-08 |
| AU2004298498A1 (en) | 2005-06-30 |
| JP2007513971A (ja) | 2007-05-31 |
| TW200518746A (en) | 2005-06-16 |
| CN1890215A (zh) | 2007-01-03 |
| CO5700736A2 (es) | 2006-11-30 |
| KR20060118532A (ko) | 2006-11-23 |
| IL176237A0 (en) | 2006-10-05 |
| ECSP066626A (es) | 2006-10-25 |
| CN100509784C (zh) | 2009-07-08 |
| NO20063205L (no) | 2006-09-08 |
| WO2005058821A1 (en) | 2005-06-30 |
| EP1742913A1 (en) | 2007-01-17 |
| AR046758A1 (es) | 2005-12-21 |
| US7485625B2 (en) | 2009-02-03 |
| CA2549167A1 (en) | 2005-06-30 |
| US20050153900A1 (en) | 2005-07-14 |
| AU2004298498B2 (en) | 2008-09-11 |
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