ZA200301641B - Peptidomimetic protease inhibitors. - Google Patents
Peptidomimetic protease inhibitors. Download PDFInfo
- Publication number
- ZA200301641B ZA200301641B ZA200301641A ZA200301641A ZA200301641B ZA 200301641 B ZA200301641 B ZA 200301641B ZA 200301641 A ZA200301641 A ZA 200301641A ZA 200301641 A ZA200301641 A ZA 200301641A ZA 200301641 B ZA200301641 B ZA 200301641B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- optionally substituted
- hepatitis
- group
- interferon
- Prior art date
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
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- 230000017613 viral reproduction Effects 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
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Classifications
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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
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Applications Claiming Priority (2)
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|---|---|---|---|
| US22939800P | 2000-08-31 | 2000-08-31 | |
| US27764101P | 2001-03-21 | 2001-03-21 |
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| ZA200301641B true ZA200301641B (en) | 2004-06-21 |
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| ZA200301641A ZA200301641B (en) | 2000-08-31 | 2003-02-27 | Peptidomimetic protease inhibitors. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU227742B1 (en) * | 1996-10-18 | 2012-02-28 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| US6608027B1 (en) | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
| EP1268519B1 (en) * | 2000-04-03 | 2005-06-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| YU92202A (sh) | 2000-05-26 | 2006-01-16 | Idenix (Cayman) Limited | Metode i smeše za lečenje flavi virusa i pesti virusa |
| RU2355700C9 (ru) | 2000-07-21 | 2010-03-20 | Шеринг Корпорейшн | Новые пептиды как ингибиторы ns3-серинпротеазы вируса гепатита с |
| NZ523781A (en) | 2000-07-21 | 2004-10-29 | Corvas Int Inc | Novel peptides as NS3-serine protease inhibitors of hepatitis C virus |
| 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 |
| GB2368339B (en) | 2000-10-26 | 2002-09-18 | Yissum Res Dev Co | Complex incorporating a plurality of antioxidants |
| EP1441720B8 (en) * | 2001-10-24 | 2012-03-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine protease, particularly hepatitis c virus ns3-ns4a protease, incorporating a fused ring system |
| US7119072B2 (en) | 2002-01-30 | 2006-10-10 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis C virus |
| US6642204B2 (en) | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| US7091184B2 (en) | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| MXPA04009938A (es) * | 2002-04-11 | 2004-12-13 | Vertex Pharma | Inhibidores de serina proteasas, en particular la proteasa ns3-ns4a del hcv. |
| ES2361011T3 (es) * | 2002-05-20 | 2011-06-13 | Bristol-Myers Squibb Company | Inhibidores del virus de la hepatitis c. |
| PT1523489E (pt) | 2002-06-28 | 2014-06-24 | Centre Nat Rech Scient | Profármacos de nucleósido modificado em 2' e 3' para tratamento de infecções por flaviridae |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| WO2004026896A2 (en) * | 2002-09-23 | 2004-04-01 | Medivir Ab | Hcv ns-3 serine protease inhibitors |
| US20050075279A1 (en) | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| JP2006516548A (ja) | 2002-12-30 | 2006-07-06 | アンジオテック インターナショナル アクツィエン ゲゼルシャフト | 迅速ゲル化ポリマー組成物からの薬物送達法 |
| AU2011203054B2 (en) * | 2003-04-11 | 2012-04-26 | Vertex Pharmaceuticals, Incorporated | Inhibitors of Serine Proteases, Particularly HCV NS3-NS4A Protease |
| CA2521678A1 (en) * | 2003-04-11 | 2004-10-28 | Vertex Pharmaceuticals, Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| EP1613620A1 (en) * | 2003-04-11 | 2006-01-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| CL2004001161A1 (es) | 2003-05-21 | 2005-04-08 | Boehringer Ingelheim Int | Compuestos describe compuestos derivados de quinolina; composicion farmaceutica; y su uso para tratar una enfermedad causada por el virus de la hepatitis c. |
| SI2604620T2 (sl) | 2003-05-30 | 2024-10-30 | Gilead Pharmasset Llc | Modificirani fluorirani nukleozidni analogi |
| CN102020700A (zh) | 2003-07-18 | 2011-04-20 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶抑制剂、特别是hcv ns3-ns4a蛋白酶抑制剂 |
| PE20050374A1 (es) * | 2003-09-05 | 2005-05-30 | Vertex Pharma | Inhibidores de proteasas de serina, en particular proteasa ns3-ns4a del vhc |
| CA2538843A1 (en) * | 2003-09-12 | 2005-03-24 | Vertex Pharmaceuticals Incorporated | Animal model for protease activity and liver damage |
| TW200526686A (en) | 2003-09-18 | 2005-08-16 | Vertex Pharma | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
| US7642235B2 (en) | 2003-09-22 | 2010-01-05 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| CN1906208B (zh) * | 2003-10-10 | 2011-03-30 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂 |
| EP1692157B1 (en) | 2003-10-10 | 2013-04-17 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| US7491794B2 (en) | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| US8187874B2 (en) | 2003-10-27 | 2012-05-29 | Vertex Pharmaceuticals Incorporated | Drug discovery method |
| EP1677827B1 (en) * | 2003-10-27 | 2008-12-10 | Vertex Pharmaceuticals Incorporated | Combinations for hcv treatment |
| EP1944042A1 (en) | 2003-10-27 | 2008-07-16 | Vertex Pharmceuticals Incorporated | Combinations for HCV treatment |
| CN1894276B (zh) | 2003-10-27 | 2010-06-16 | 威特克斯医药股份有限公司 | Hcv ns3-ns4a蛋白酶抗药性突变体 |
| PE20050940A1 (es) | 2003-12-11 | 2005-11-08 | Schering Corp | Nuevos inhibidores de la ns3/ns4a serina proteasa del virus de la hepatitis c |
| CA2549851C (en) | 2004-01-21 | 2012-09-11 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis c virus |
| CN1938332B (zh) | 2004-02-04 | 2011-10-19 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂 |
| TW200536528A (en) * | 2004-02-27 | 2005-11-16 | Schering Corp | Novel inhibitors of hepatitis C virus NS3 protease |
| CN1946718A (zh) * | 2004-02-27 | 2007-04-11 | 先灵公司 | 用作丙型肝炎病毒ns3丝氨酸蛋白酶抑制剂的具有环p4′s的新型酮酰胺 |
| ATE470660T1 (de) * | 2004-02-27 | 2010-06-15 | Schering Corp | Schwefelverbindungen als inhibitoren der ns3- serinprotease des hepatitis-c-virus |
| CN1946692A (zh) * | 2004-02-27 | 2007-04-11 | 先灵公司 | 作为丙型肝炎病毒ns3丝氨酸蛋白酶抑制剂的3,4－(环戊基)－稠合的脯氨酸化合物 |
| AR049297A1 (es) * | 2004-06-08 | 2006-07-12 | Vertex Pharma | Una composicion farmaceutica y dispersiones solidas de vx-950 (inhibidor de la proteasa de hcv ns3/4a) y proceso de obtencion |
| UY29016A1 (es) | 2004-07-20 | 2006-02-24 | Boehringer Ingelheim Int | Analogos de dipeptidos inhibidores de la hepatitis c |
| WO2006007708A1 (en) | 2004-07-20 | 2006-01-26 | Boehringer Engelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
| CN102160891A (zh) * | 2004-10-01 | 2011-08-24 | 威特克斯医药股份有限公司 | Hcv ns3-ns4a蛋白酶抑制 |
| TWI437990B (zh) * | 2004-10-29 | 2014-05-21 | Vertex Pharma | Vx-950之醫藥用途 |
| CA2602175C (en) | 2005-03-21 | 2012-11-27 | Applera Corporation | Alpha ketoamide compounds as cysteine protease inhibitors |
| WO2006110814A2 (en) * | 2005-04-12 | 2006-10-19 | Romark Laboratories, L.C. | Methods for treating diseases through inhibition the function of molecular chaperones such as protein disulfide isomerases, pharmaceutical compositions comprising them, and screening methods for identifying therapeutic agents |
| MX2007014117A (es) | 2005-05-13 | 2008-02-05 | Virochem Pharma Inc | Compuestos y metodos para el tratamiento o prevencion de infecciones de flavivirus. |
| US20060276404A1 (en) * | 2005-06-02 | 2006-12-07 | Anima Ghosal | Medicaments and methods combining a HCV protease inhibitor and an AKR competitor |
| WO2006130553A2 (en) * | 2005-06-02 | 2006-12-07 | Schering Corporation | Hcv protease inhibitors |
| EP1891089B1 (en) | 2005-06-02 | 2014-11-05 | Merck Sharp & Dohme Corp. | HCV protease inhibitors in combination with food |
| JP5160415B2 (ja) | 2005-06-02 | 2013-03-13 | メルク・シャープ・アンド・ドーム・コーポレーション | 医薬処方物およびそれを用いる治療方法 |
| US7608592B2 (en) | 2005-06-30 | 2009-10-27 | Virobay, Inc. | HCV inhibitors |
| MY141245A (en) | 2005-07-29 | 2010-03-31 | Tibotec Pharm Ltd | Macrocylic inhibitors of hepatitis c virus |
| DE602006019883D1 (de) | 2005-07-29 | 2011-03-10 | Medivir Ab | Makrocyclische inhibitoren des hepatitis-c-virus |
| CN101273030B (zh) | 2005-07-29 | 2012-07-18 | 泰博特克药品有限公司 | 丙型肝炎病毒的大环抑制剂 |
| PE20070210A1 (es) | 2005-07-29 | 2007-04-16 | Tibotec Pharm Ltd | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
| AR055361A1 (es) | 2005-07-29 | 2007-08-22 | Medivir Ab | Inhibidores macrociclicos del virus de la hepatitis c |
| BRPI0614696A2 (pt) | 2005-07-29 | 2011-04-12 | Tibotec Pharm Ltd | inibidores macrocìclicos de vìrus da hepatite c |
| JO2768B1 (en) | 2005-07-29 | 2014-03-15 | تيبوتيك فارماسيوتيكالز ليمتد | Large cyclic inhibitors of hepatitis C virus |
| PE20070211A1 (es) | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
| RU2441020C2 (ru) | 2005-08-02 | 2012-01-27 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы серинпротеазы |
| PT1934179E (pt) * | 2005-08-19 | 2010-07-12 | Vertex Pharma | PROCESSOS E INTERMEDIáRIOS |
| US8399615B2 (en) | 2005-08-19 | 2013-03-19 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
| US7964624B1 (en) | 2005-08-26 | 2011-06-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
| 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 |
| US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
| JP5409008B2 (ja) | 2005-11-11 | 2014-02-05 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｃ型肝炎ウイルス改変体 |
| JP4047365B2 (ja) * | 2006-01-11 | 2008-02-13 | 生化学工業株式会社 | シクロアルカンカルボキサミド誘導体及びその製造方法 |
| AU2007205578B2 (en) * | 2006-01-11 | 2012-06-28 | Seikagaku Corporation | Cycloalkylcarbonylamino acid ester derivative and process for producing the same |
| JP3975226B2 (ja) * | 2006-01-11 | 2007-09-12 | 生化学工業株式会社 | シクロアルキルカルボニルアミノ酸誘導体及びその製造方法 |
| WO2007083620A1 (ja) * | 2006-01-20 | 2007-07-26 | Kaneka Corporation | β－アミノ－α－ヒドロキシ酸アミド誘導体の製造法 |
| EP1991229A2 (en) | 2006-02-27 | 2008-11-19 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical compositions comprising the same |
| CN101460166B (zh) | 2006-03-06 | 2014-11-19 | Abbvie公司 | 用于治疗c型肝炎病毒的利托那韦组合物及其用途 |
| EP2194039A1 (en) * | 2006-03-16 | 2010-06-09 | Vertex Pharmceuticals Incorporated | Process for preparing optically enriched compounds |
| MX2008011869A (es) | 2006-03-16 | 2008-12-03 | Vertex Pharma | Procedimientos e intermediarios para preparar compuestos estericos. |
| NZ571934A (en) | 2006-03-20 | 2012-05-25 | Vertex Pharma | Methods of spray drying formulations of vx-950 (telaprevir) |
| EP1998759A2 (en) * | 2006-03-23 | 2008-12-10 | Schering Corporation | Combinations of hcv protease inhibitor(s) and cyp3a4 inhibitor(s), and methods of treatment related thereto |
| WO2007120595A2 (en) * | 2006-04-11 | 2007-10-25 | Novartis Ag | Amines for the treatment of hcv |
| WO2007133865A2 (en) | 2006-04-11 | 2007-11-22 | Novartis Ag | Hcv/hiv inhibitors an their uses |
| EP2027143A2 (en) | 2006-05-23 | 2009-02-25 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| DE102006059317A1 (de) * | 2006-07-04 | 2008-01-10 | Evonik Degussa Gmbh | Verfahren zur Herstellung von β-Amino-α-hydroxy-carbonsäureamiden |
| EP1886685A1 (en) | 2006-08-11 | 2008-02-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods, uses and compositions for modulating replication of hcv through the farnesoid x receptor (fxr) activation or inhibition |
| US20120220520A1 (en) * | 2006-10-17 | 2012-08-30 | Van T Klooster Gerben Albert Eleutherius | Bioavailable combinations for hcv treatment |
| AP2579A (en) | 2006-11-15 | 2013-01-29 | Virochem Pharma Inc | Thiophene analogues for the treatment or prevention of flavivirus infections |
| ES2470568T3 (es) | 2006-11-17 | 2014-06-24 | Janssen R&D Ireland | Inhibidores macroc�clicos del virus de la hepatitis C |
| WO2008073282A2 (en) | 2006-12-07 | 2008-06-19 | Schering Corporation | Ph sensitive matrix formulation |
| WO2008074035A1 (en) | 2006-12-27 | 2008-06-19 | Abbott Laboratories | Hcv protease inhibitors and uses thereof |
| US20080207528A1 (en) * | 2007-02-01 | 2008-08-28 | Syaulan Yang | Hcv protease inhibitors |
| KR20090110314A (ko) | 2007-02-08 | 2009-10-21 | 티보텍 파마슈티칼즈 리미티드 | 피리미딘 치환된 마크로사이클릭 ｈｃｖ 억제제 |
| EA016327B1 (ru) | 2007-02-09 | 2012-04-30 | Айрм Ллк | Соединения и композиции в качестве ингибиторов протеазы, активирующей каналы |
| BRPI0807907A2 (pt) * | 2007-02-27 | 2017-05-16 | Vertex Pharma | co-cristais e composições farmacêuticas compreendendo os mesmos. |
| CN101903392A (zh) | 2007-02-27 | 2010-12-01 | 弗特克斯药品有限公司 | 丝氨酸蛋白酶的抑制剂 |
| WO2008127613A1 (en) * | 2007-04-11 | 2008-10-23 | Scynexis, Inc. | New pharmaceutical compositions |
| CN102872461A (zh) | 2007-05-04 | 2013-01-16 | 弗特克斯药品有限公司 | 用于治疗hcv感染的组合治疗 |
| CN101827589B (zh) * | 2007-08-03 | 2016-08-17 | 拜伊特朗有限公司 | 抗丙型肝炎病毒的组合物及方法 |
| TW200922933A (en) | 2007-08-30 | 2009-06-01 | Vertex Pharma | Co-crystals and pharmaceutical compositions comprising the same |
| CA2699280A1 (en) | 2007-09-14 | 2009-03-26 | Schering Corporation | Method of treating hepatitis c patients |
| US20090082366A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched telaprevir |
| AU2008309589B2 (en) | 2007-10-10 | 2012-07-05 | Novartis Ag | Spiropyrrolidines and their use against HCV and HIV infection |
| EP2215076A4 (en) * | 2007-10-24 | 2012-05-02 | Virobay Inc | COMPOUNDS CAPABLE OF INHIBITING CATHEPSIN S PROTEASE AND HCV REPLICATION |
| US20090111757A1 (en) * | 2007-10-25 | 2009-04-30 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
| PL2238142T3 (pl) | 2007-12-24 | 2012-11-30 | Janssen R&D Ireland | Makrocykliczne indole jako inhibitory wirusa zapalenia wątroby typu C |
| DE102008009761A1 (de) | 2008-02-19 | 2009-08-27 | Bayer Materialscience Ag | Verfahren zur Herstellung von Isocyanaten |
| EP2101173A1 (en) | 2008-03-14 | 2009-09-16 | Vivalis | In vitro method to determine whether a drug candidate active against a target protein is active against a variant of said protein |
| 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 |
| MX2010014500A (es) | 2008-06-24 | 2011-05-30 | Codexis Inc | Procedimientos biocataliticos para la preparacion de compuestos de prolina biciclica fusionada sustancialmente estereomericamente puros. |
| US8569337B2 (en) | 2008-07-23 | 2013-10-29 | Vertex Pharmaceuticals Incorporated | Tri-cyclic pyrazolopyridine kinase inhibitors |
| WO2010014744A1 (en) * | 2008-07-29 | 2010-02-04 | The Scripps Research Institute | Inhibitors of hepatitis c virus infection |
| US8188137B2 (en) | 2008-08-15 | 2012-05-29 | Avila Therapeutics, Inc. | HCV protease inhibitors and uses thereof |
| JP2012510523A (ja) | 2008-12-03 | 2012-05-10 | プレシディオ ファーマシューティカルズ インコーポレイテッド | Ｈｃｖｎｓ５ａの阻害剤 |
| HK1203929A1 (en) | 2008-12-03 | 2015-11-06 | 普雷西迪奥制药公司 | Inhibitors of hcv ns5a |
| GB0900914D0 (en) | 2009-01-20 | 2009-03-04 | Angeletti P Ist Richerche Bio | Antiviral agents |
| WO2010093843A2 (en) | 2009-02-12 | 2010-08-19 | Vertex Pharmaceuticals Incorporated | Hcv combination therapies |
| CA2755658A1 (en) | 2009-03-27 | 2010-09-30 | Presidio Pharmaceuticals, Inc. | Fused ring inhibitors of hepatitis c |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| US20100324059A1 (en) | 2009-06-23 | 2010-12-23 | Gilead Sciences, Inc. | Pharmaceutical compositions useful for treating hcv |
| HUE030402T2 (en) | 2009-09-15 | 2017-05-29 | Taigen Biotechnology Co Ltd | HCV protease inhibitors |
| TWI404269B (zh) * | 2009-09-18 | 2013-08-01 | Advanced Connectek Inc | High speed plug connector |
| UA108211C2 (uk) | 2009-11-04 | 2015-04-10 | Янссен Рід Айрленд | Бензімідазолімідазольні похідні |
| EP2504329A1 (en) | 2009-11-25 | 2012-10-03 | Vertex Pharmaceuticals Incorporated | 5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections |
| US8362068B2 (en) * | 2009-12-18 | 2013-01-29 | Idenix Pharmaceuticals, Inc. | 5,5-fused arylene or heteroarylene hepatitis C virus inhibitors |
| KR20120130173A (ko) | 2009-12-24 | 2012-11-29 | 버텍스 파마슈티칼스 인코포레이티드 | 플라비바이러스 감염을 치료 또는 예방하기 위한 유사체들 |
| US20110178107A1 (en) * | 2010-01-20 | 2011-07-21 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
| CN102140100B (zh) | 2010-01-27 | 2014-06-11 | 爱博新药研发(上海)有限公司 | 高效抑制丙型肝炎病毒的多环化合物及其制备方法和用途 |
| EP2528605A1 (en) | 2010-01-29 | 2012-12-05 | Vertex Pharmaceuticals Incorporated | Therapies for treating hepatitis c virus infection |
| WO2011112516A1 (en) | 2010-03-08 | 2011-09-15 | Ico Therapeutics Inc. | Treating and preventing hepatitis c virus infection using c-raf kinase antisense oligonucleotides |
| CA2794145A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| TW201139438A (en) | 2010-03-24 | 2011-11-16 | Vertex Pharma | 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 |
| WO2011119870A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| WO2011123586A1 (en) | 2010-04-01 | 2011-10-06 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| EP2575866A4 (en) | 2010-05-24 | 2013-10-16 | Presidio Pharmaceuticals Inc | HCV NS5A INHIBITORS |
| KR20130082137A (ko) | 2010-06-03 | 2013-07-18 | 버텍스 파마슈티칼스 인코포레이티드 | 방법 및 중간체 |
| WO2011156545A1 (en) | 2010-06-09 | 2011-12-15 | Vertex Pharmaceuticals Incorporated | Viral dynamic model for hcv combination therapy |
| EP2582717A2 (en) | 2010-06-15 | 2013-04-24 | Vertex Pharmaceuticals Incorporated | Hcv ns5b polymerase mutants |
| WO2012006070A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| CA2803248A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| JP2013531011A (ja) | 2010-06-28 | 2013-08-01 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス感染の処置または予防のための化合物および方法 |
| AR082215A1 (es) | 2010-07-14 | 2012-11-21 | Vertex Pharma | Composicion farmaceutica agradable al paladar |
| WO2012020036A1 (en) | 2010-08-13 | 2012-02-16 | F. Hoffmann-La Roche Ag | Hepatitis c virus inhibitors |
| WO2012024363A2 (en) | 2010-08-17 | 2012-02-23 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flaviviridae viral infections |
| US8871737B2 (en) | 2010-09-22 | 2014-10-28 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| JP5909495B2 (ja) | 2010-10-08 | 2016-04-26 | ノバルティス アーゲー | スルファミドｎｓ３阻害剤のビタミンｅ製剤 |
| CA2815416A1 (en) | 2010-10-21 | 2012-04-26 | Vertex Pharmaceuticals Incorporated | Biomarkers for hcv infected patients |
| CN103269586B (zh) | 2010-10-26 | 2015-07-15 | 普雷西迪奥制药公司 | 丙型肝炎病毒抑制剂 |
| WO2012107589A1 (en) | 2011-02-11 | 2012-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment and prevention of hcv infections |
| WO2012109646A1 (en) | 2011-02-11 | 2012-08-16 | Vertex Pharmaceuticals Incorporated | Treatment of hcv in hiv infection patients |
| WO2012123298A1 (en) | 2011-03-11 | 2012-09-20 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| EP2691409B1 (en) | 2011-03-31 | 2018-02-21 | Idenix Pharmaceuticals LLC. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| US8680152B2 (en) | 2011-05-02 | 2014-03-25 | Virobay, Inc. | Cathepsin inhibitors for the treatment of bone cancer and bone cancer pain |
| CN103814001A (zh) | 2011-05-13 | 2014-05-21 | 弗特克斯药品有限公司 | 方法和中间体 |
| WO2012171332A1 (zh) | 2011-06-16 | 2012-12-20 | 爱博新药研发(上海)有限公司 | 抑制丙型肝炎病毒的大环状杂环化合物及其制备和应用 |
| RU2014102102A (ru) | 2011-06-23 | 2015-07-27 | Дигна Байотек, С.Л. | КОМПОЗИЦИЯ И КОМБИНИРОВАННЫЙ ПРЕПАРАТ ИНТЕРФЕРОНА-а5 С ИНТЕРФЕРОНОМ-а2 И СПОСОБ ЛЕЧЕНИЯ ХРОНИЧЕСКОГО ГЕПАТИТА С |
| US20120328565A1 (en) | 2011-06-24 | 2012-12-27 | Brinkman John A | Antiviral compounds |
| TW201317223A (zh) | 2011-07-26 | 2013-05-01 | Vertex Pharma | 噻吩化合物 |
| WO2013016499A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Methods for preparation of thiophene compounds |
| AU2012308900A1 (en) | 2011-09-12 | 2013-05-09 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| US9474759B2 (en) | 2011-09-27 | 2016-10-25 | Kansas State University Research Foundation | Broad-spectrum antivirals against 3C or 3C-like proteases of picornavirus-like supercluster: picornaviruses, caliciviruses and coronaviruses |
| US9180193B2 (en) | 2011-10-10 | 2015-11-10 | Hoffmann-La Roche Inc. | Antiviral compounds |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP3309148A1 (en) | 2011-10-14 | 2018-04-18 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2899183B1 (en) | 2011-10-14 | 2018-09-19 | Bristol-Myers Squibb Company | Substituted Tetrahydroisoquinoline Compounds as Factor Xia Inhibitors |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| EP2583680A3 (en) | 2011-10-21 | 2013-06-12 | Abbvie Inc. | Mono (PSI-7977) or combination treatment of DAAs for use in treating HCV |
| AU2013201406B2 (en) | 2011-10-21 | 2014-10-02 | Abbvie Ireland Unlimited Company | Methods for treating HCV |
| MX2014006745A (es) | 2011-12-16 | 2014-10-15 | Hoffmann La Roche | Inhibidores de hcv ns5a. |
| LT2794628T (lt) | 2011-12-20 | 2017-07-10 | Riboscience Llc | 4`-azido-3`-fluoro pakeistieji nukleozido dariniai kaip hcv replikacijos inhibitoriai |
| PE20141423A1 (es) | 2011-12-20 | 2014-10-16 | Hoffmann La Roche | Derivados nucleosidos con sustitucion 2',4'-difluoro-2'-metilo como inhibidores de la replicacion del arn del vhc |
| WO2013098313A1 (en) | 2011-12-28 | 2013-07-04 | Janssen R&D Ireland | Hetero-bicyclic derivatives as hcv inhibitors |
| US20130195797A1 (en) | 2012-01-31 | 2013-08-01 | Vertex Pharmaceuticals Incorporated | High potency formulations of vx-950 |
| ITMI20120192A1 (it) | 2012-02-13 | 2013-08-14 | Dipharma Francis Srl | Procedimento per la preparazione di un inibitore delle proteasi virali e suoi intermedi |
| CN104254518A (zh) * | 2012-02-16 | 2014-12-31 | 阿奇克斯制药公司 | 线性肽抗生素 |
| BR112014015582A8 (pt) | 2012-02-24 | 2017-07-04 | Hoffmann La Roche | compostos antivirais |
| ITMI20120359A1 (it) | 2012-03-07 | 2013-09-08 | Dipharma Francis Srl | Procedimento per la preparazione di intermedi utili nella preparazione di un inibitore delle proteasi virali |
| WO2013136265A1 (en) | 2012-03-13 | 2013-09-19 | Dipharma Francis S.R.L. | Synthesis of an intermediate of an antiviral compound |
| ITMI20120391A1 (it) * | 2012-03-13 | 2013-09-14 | Dipharma Francis Srl | Procedimento per la sintesi di un intermedio ciclopropilammidico utile nella preparazione di un inibitore delle proteasi virali |
| CN104321333A (zh) | 2012-03-21 | 2015-01-28 | 沃泰克斯药物股份有限公司 | 硫代氨基磷酸酯核苷酸前药的固体形式 |
| EP2827876A4 (en) | 2012-03-22 | 2015-10-28 | Alios Biopharma Inc | PHARMACEUTICAL COMBINATIONS WITH A THIONUCLEOTIDE ANALOG |
| EP2844249A4 (en) | 2012-05-02 | 2016-03-09 | Univ Kansas State | MACROCYCLIC AND PEPTIDOMIMETIC COMPOUNDS AS VIRUZIDES AGAINST 3C OR 3C LIKE PROTEASES OF PICORNIVERS, CALICIVIRES AND CORONA VIRUSES |
| ITMI20120800A1 (it) * | 2012-05-10 | 2013-11-11 | Dipharma Francis Srl | Procedimento per la preparazione di un intermedio utile nella preparazione di un inibitore delle proteasi virali |
| AR091192A1 (es) | 2012-05-30 | 2015-01-21 | Chemo Iberica Sa | Procedimiento multicomponente para la preparacion de compuestos biciclicos |
| CN103450066B (zh) * | 2012-05-30 | 2017-03-15 | 博瑞生物医药（苏州）股份有限公司 | 特拉匹韦中间体的制备方法 |
| US20140010783A1 (en) | 2012-07-06 | 2014-01-09 | Hoffmann-La Roche Inc. | Antiviral compounds |
| WO2014015217A1 (en) | 2012-07-19 | 2014-01-23 | Vertex Pharmaceuticals Incorporated | Biomarkers for hcv infected patients |
| WO2014033667A1 (en) | 2012-08-30 | 2014-03-06 | Ranbaxy Laboratories Limited | Process for the preparation of telaprevir |
| WO2014045263A2 (en) * | 2012-09-24 | 2014-03-27 | Dr. Reddy's Laboratories Limited | Process for preparation of intermediates of telaprevir |
| WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| DK2906551T3 (en) | 2012-10-12 | 2018-05-22 | Bristol Myers Squibb Co | CRYSTALLIC FORMS OF A FACTOR XIA INHIBITOR |
| EP2906541B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| CA2889903C (en) | 2012-10-29 | 2021-03-09 | Manjinder Singh Phull | Antiviral phosphonate analogues and process for preparation thereof |
| ITMI20122036A1 (it) | 2012-11-29 | 2014-05-30 | Dipharma Francis Srl | Sintesi di un intermedio di un composto antivirale |
| WO2014096374A1 (en) | 2012-12-21 | 2014-06-26 | Sandoz Ag | Process for the synthesis of pyrrolidines and pyrroles |
| CN105073726B (zh) | 2013-01-23 | 2017-05-31 | 弗·哈夫曼-拉罗切有限公司 | 抗病毒三唑衍生物 |
| CN103113288B (zh) * | 2013-02-04 | 2015-05-20 | 苏州永健生物医药有限公司 | 一种八氢环戊烯并[c]吡咯羧酸衍生物的合成方法 |
| US20150065439A1 (en) | 2013-02-28 | 2015-03-05 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
| CA2900319A1 (en) | 2013-03-05 | 2014-09-12 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| US9738655B2 (en) | 2013-03-25 | 2017-08-22 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor XIa inhibitors |
| ITMI20130706A1 (it) | 2013-04-30 | 2014-10-31 | Dipharma Francis Srl | Procedimento per la preparazione di un inibitore delle proteasi virali e suoi intermedi |
| US20180200280A1 (en) | 2013-05-16 | 2018-07-19 | Riboscience Llc | 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication |
| CA2912682C (en) | 2013-05-16 | 2021-07-06 | Riboscience Llc | 4'-fluoro-2'-methyl substituted nucleoside derivatives |
| MA38678A1 (fr) | 2013-05-16 | 2017-07-31 | Riboscience Llc | Dérivés nucléosidiques 4'-azido, 3'désoxy-3'-fluoro substitués |
| CN104163851B (zh) * | 2013-05-20 | 2019-03-05 | 湘北威尔曼制药股份有限公司 | 氟代的α-羰基类HCV NS3/4A丝氨酸蛋白酶抑制剂 |
| CN103288671B (zh) * | 2013-06-20 | 2014-10-29 | 上海步越化工科技有限公司 | 一种(3s)-3-氨基-n-环丙基-2-羟基己酰胺盐酸盐的合成方法 |
| WO2014203224A1 (en) | 2013-06-21 | 2014-12-24 | Ranbaxy Laboratories Limited | Process for the preparation of telaprevir and its intermediates |
| WO2014203208A1 (en) | 2013-06-21 | 2014-12-24 | Ranbaxy Laboratories Limited | Process for the preparation of telaprevir and intermediates thereof |
| CN104292146B (zh) * | 2013-06-24 | 2017-04-26 | 上海医药工业研究院 | 特拉匹韦中间体及其制备方法 |
| CN104558106B (zh) * | 2013-10-19 | 2019-12-10 | 广东东阳光药业有限公司 | 一种治疗丙肝药物的制备方法 |
| 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 |
| EP2899207A1 (en) | 2014-01-28 | 2015-07-29 | Amikana.Biologics | New method for testing HCV protease inhibition |
| UY40230A (es) | 2014-01-31 | 2023-08-15 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Macrociclos con grupos P2’ heterocíclicos como inhibidores del factor XIa y composiciones farmacéuticas que los comprenden |
| NO2760821T3 (enExample) | 2014-01-31 | 2018-03-10 | ||
| CN104926831A (zh) * | 2014-03-20 | 2015-09-23 | 上海医药工业研究院 | 合成特拉匹韦的中间体及其制备方法 |
| CN104926712B (zh) * | 2014-03-20 | 2018-03-23 | 上海医药工业研究院 | 合成特拉匹韦的中间体及其制备方法 |
| WO2016007119A1 (en) | 2014-07-07 | 2016-01-14 | Halliburton Energy Services, Inc. | Downhole tools comprising aqueous-degradable sealing elements |
| ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| EP3423469A1 (en) | 2016-03-04 | 2019-01-09 | H. Hoffnabb-La Roche Ag | New trifluoromethylpropanamide derivatives as htra1 inhibitors |
| EP3423467B1 (en) | 2016-03-04 | 2021-04-28 | F. Hoffmann-La Roche AG | New difluoroketamide derivatives as htra1 inhibitors |
| WO2017189978A1 (en) | 2016-04-28 | 2017-11-02 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| EP3472151A4 (en) | 2016-06-21 | 2020-03-04 | Orion Ophthalmology LLC | CARBOCYCLIC PROLINAMIDE DERIVATIVES |
| ES2971784T3 (es) | 2016-06-21 | 2024-06-07 | Orion Ophthalmology LLC | Derivados heterocíclicos de prolinamida |
| WO2017222917A1 (en) | 2016-06-21 | 2017-12-28 | Inception 4, Inc. | Aliphatic prolinamide derivatives |
| JP2019526563A (ja) * | 2016-08-23 | 2019-09-19 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｈｔｒａ１阻害剤としての新規ジフルオロケタミド誘導体 |
| AU2018335411B2 (en) | 2017-09-21 | 2024-06-27 | Riboscience Llc | 4'-fluoro-2'-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication |
| CN109337537B (zh) * | 2018-09-26 | 2022-10-25 | 河北晨阳工贸集团有限公司 | 一种起重机专用单组分水性面漆及其制备方法 |
| CN110668538B (zh) * | 2019-09-20 | 2021-10-22 | 济南大学 | 一种聚合氯化钛的制备方法 |
| CN115960088B (zh) * | 2020-07-31 | 2024-07-26 | 四川大学 | 一种新型冠状病毒主蛋白酶的抑制剂及其制备方法和用途 |
| CN114057702B (zh) * | 2020-07-31 | 2022-09-30 | 四川大学 | 一种新型冠状病毒主蛋白酶的抑制剂及其制备方法和用途 |
| US12083099B2 (en) | 2020-10-28 | 2024-09-10 | Accencio LLC | Methods of treating symptoms of coronavirus infection with viral protease inhibitors |
| WO2023149981A1 (en) * | 2022-02-07 | 2023-08-10 | Purdue Research Foundation | Compounds for the treatment of sars |
| CN114703003B (zh) * | 2022-04-14 | 2023-04-28 | 上海绿晟环保科技有限公司 | 一种负载碳量子点的纳米材料润滑添加剂及其制备方法 |
| CN115417790A (zh) * | 2022-10-09 | 2022-12-02 | 山东大学 | 一类新型偶氮类发泡剂及合成方法 |
| KR102829944B1 (ko) | 2023-05-16 | 2025-07-03 | 최유성 | 하천 준설토 관리시스템 |
Family Cites Families (163)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719667A (en) | 1970-08-24 | 1973-03-06 | Lilly Co Eli | Epimerization of 6-acylamido and 6-imido penicillin sulfoxide esters |
| US3840556A (en) | 1971-05-28 | 1974-10-08 | Lilly Co Eli | Penicillin conversion by halogen electrophiles and anti-bacterials derived thereby |
| DE3226768A1 (de) | 1981-11-05 | 1983-05-26 | Hoechst Ag, 6230 Frankfurt | Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| DE3211676A1 (de) | 1982-03-30 | 1983-10-06 | Hoechst Ag | Neue derivate von cycloalka (c) pyrrol-carbonsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue cycloalka (c) pyrrol-carbonsaeuren als zwischenstufen und verfahren zu deren herstellung |
| US4499082A (en) | 1983-12-05 | 1985-02-12 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid peptides |
| FR2570695A1 (fr) * | 1984-09-27 | 1986-03-28 | Synthelabo | Diphenylazomethines a chaine ramifiee ou cyclique, leur preparation et leur application en therapeutique |
| FR2575753B1 (fr) | 1985-01-07 | 1987-02-20 | Adir | Nouveaux derives peptidiques a structure polycyclique azotee, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US5496927A (en) | 1985-02-04 | 1996-03-05 | Merrell Pharmaceuticals Inc. | Peptidase inhibitors |
| ATE71934T1 (de) * | 1985-06-07 | 1992-02-15 | Ici America Inc | Selektionierte difluorverbindungen. |
| US4835168A (en) | 1985-12-16 | 1989-05-30 | Eli Lilly And Company | Thiadiazole antiviral agents |
| US5231084A (en) | 1986-03-27 | 1993-07-27 | Hoechst Aktiengesellschaft | Compounds having a cognition adjuvant action, agents containing them, and the use thereof for the treatment and prophylaxis of cognitive dysfuncitons |
| US5736520A (en) | 1988-10-07 | 1998-04-07 | Merrell Pharmaceuticals Inc. | Peptidase inhibitors |
| NZ235155A (en) | 1989-09-11 | 1993-04-28 | Merrell Dow Pharma | Peptidase substrates in which the carboxy terminal group has been replaced by a tricarbonyl radical |
| US5371072A (en) * | 1992-10-16 | 1994-12-06 | Corvas International, Inc. | Asp-Pro-Arg α-keto-amide enzyme inhibitors |
| ES2150933T3 (es) | 1992-12-22 | 2000-12-16 | Lilly Co Eli | Inhibidores de la proteasa vih utiles para el tratamiento del sida. |
| EP1090914B1 (en) | 1992-12-29 | 2003-01-02 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| US5384410A (en) | 1993-03-24 | 1995-01-24 | The Du Pont Merck Pharmaceutical Company | Removal of boronic acid protecting groups by transesterification |
| US5656600A (en) * | 1993-03-25 | 1997-08-12 | Corvas International, Inc. | α-ketoamide derivatives as inhibitors of thrombosis |
| US5672582A (en) | 1993-04-30 | 1997-09-30 | Merck & Co., Inc. | Thrombin inhibitors |
| IL110752A (en) | 1993-09-13 | 2000-07-26 | Abbott Lab | Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor |
| US5559158A (en) | 1993-10-01 | 1996-09-24 | Abbott Laboratories | Pharmaceutical composition |
| US5468858A (en) | 1993-10-28 | 1995-11-21 | The Board Of Regents Of Oklahoma State University Physical Sciences | N-alkyl and n-acyl derivatives of 3,7-diazabicyclo-[3.3.1]nonanes and selected salts thereof as multi-class antiarrhythmic agents |
| IL111991A (en) | 1994-01-28 | 2000-07-26 | Abbott Lab | Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent |
| HUT72440A (en) | 1994-03-31 | 1996-04-29 | Bristol Myers Squibb Co | Imidazole-containing inhibitors of farnesyl protein transferase and pharmaceutical compositions containing them |
| US5756466A (en) | 1994-06-17 | 1998-05-26 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1β converting enzyme |
| US5847135A (en) | 1994-06-17 | 1998-12-08 | Vertex Pharmaceuticals, Incorporated | Inhibitors of interleukin-1β converting enzyme |
| US5716929A (en) | 1994-06-17 | 1998-02-10 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1β converting enzyme |
| US6420522B1 (en) | 1995-06-05 | 2002-07-16 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β converting enzyme |
| US5861267A (en) * | 1995-05-01 | 1999-01-19 | Vertex Pharmaceuticals Incorporated | Methods, nucleotide sequences and host cells for assaying exogenous and endogenous protease activity |
| US6037157A (en) | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| JPH09124691A (ja) * | 1995-08-25 | 1997-05-13 | Green Cross Corp:The | ペプチド化合物およびそれを含有する医薬組成物 |
| WO1997019084A1 (en) | 1995-11-23 | 1997-05-29 | Merck Sharp & Dohme Limited | Spiro-piperidine derivatives and their use as tachykinin antagonists |
| US6054472A (en) | 1996-04-23 | 2000-04-25 | Vertex Pharmaceuticals, Incorporated | Inhibitors of IMPDH enzyme |
| US5807876A (en) | 1996-04-23 | 1998-09-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of IMPDH enzyme |
| ZA972195B (en) | 1996-03-15 | 1998-09-14 | Du Pont Merck Pharma | Spirocycle integrin inhibitors |
| WO1997040028A1 (en) | 1996-04-23 | 1997-10-30 | Vertex Pharmaceuticals Incorporated | Urea derivatives as inhibitors of impdh enzyme |
| US6127422A (en) | 1996-05-06 | 2000-10-03 | Eli Lilly And Company | Anti-viral method |
| US5990276A (en) | 1996-05-10 | 1999-11-23 | Schering Corporation | Synthetic inhibitors of hepatitis C virus NS3 protease |
| EP0907659A1 (en) | 1996-05-10 | 1999-04-14 | Schering Corporation | Synthetic inhibitors of hepatitis c virus ns3 protease |
| JP3982638B2 (ja) | 1996-05-17 | 2007-09-26 | データカード コーポレーション | 硬化形トップコート組成およびその使用方法 |
| US6245919B1 (en) * | 1996-06-28 | 2001-06-12 | Haruhiko Shinozaki | Cyclopropylglycine derivatives and agonists for metabotronic L-glutamate receptors |
| EP0913389A4 (en) * | 1996-06-28 | 2000-02-02 | Nippon Chemiphar Co | CYCLOPROPYLGLYCINE DERIVATIVES AND AGONISTS OF THE L-GLUTAMATE RECEPTOR TYPE OF METABOLITE REGULATION |
| US6153579A (en) * | 1996-09-12 | 2000-11-28 | Vertex Pharmaceuticals, Incorporated | Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex |
| AU723414B2 (en) | 1996-09-25 | 2000-08-24 | Merck Sharp & Dohme Limited | Spiro-azacyclic derivatives, their preparation and their use as tachykinin antagonists |
| CA2268255A1 (en) | 1996-10-08 | 1998-04-16 | Colorado State University Research Foundation | Catalytic asymmetric epoxidation |
| HU227742B1 (en) * | 1996-10-18 | 2012-02-28 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| GB9623908D0 (en) | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| DE19648011A1 (de) | 1996-11-20 | 1998-05-28 | Bayer Ag | Cyclische Imine |
| CA2282398A1 (en) | 1997-03-14 | 1998-09-17 | Steven M. Ronkin | Inhibitors of impdh enzyme |
| GB9707659D0 (en) | 1997-04-16 | 1997-06-04 | Peptide Therapeutics Ltd | Hepatitis C NS3 Protease inhibitors |
| GB9708484D0 (en) | 1997-04-25 | 1997-06-18 | Merck Sharp & Dohme | Therapeutic agents |
| GB9711114D0 (en) | 1997-05-29 | 1997-07-23 | Merck Sharp & Dohme | Therapeutic agents |
| JP4354632B2 (ja) * | 1997-08-11 | 2009-10-28 | ベーリンガー インゲルハイム （カナダ） リミテッド | Ｃ型肝炎抑制剤ペプチド |
| NZ503263A (en) | 1997-08-11 | 2002-10-25 | Boehringer Ingelheim Ca Ltd | Hepatitis C NS3 protease inhibitor peptides and peptide analogues |
| US6767991B1 (en) | 1997-08-11 | 2004-07-27 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C inhibitor peptides |
| US6183121B1 (en) * | 1997-08-14 | 2001-02-06 | Vertex Pharmaceuticals Inc. | Hepatitis C virus helicase crystals and coordinates that define helicase binding pockets |
| US20040058982A1 (en) | 1999-02-17 | 2004-03-25 | Bioavailability System, Llc | Pharmaceutical compositions |
| US20020017295A1 (en) | 2000-07-07 | 2002-02-14 | Weers Jeffry G. | Phospholipid-based powders for inhalation |
| AU1416099A (en) | 1997-11-28 | 1999-06-16 | Schering Corporation | Single-chain recombinant complexes of hepatitis c virus ns3 protease and ns4a cofactor peptide |
| ES2281170T3 (es) * | 1998-03-31 | 2007-09-16 | Vertex Pharmaceuticals Incorporated | Inhibidores de serina proteasas, particularmente proteasa ns3 del virus de la hepatitis c. |
| US6518305B1 (en) * | 1998-04-23 | 2003-02-11 | Abbott Laboratories | Five-membered carbocyclic and heterocyclic inhibitors of neuraminidases |
| US6251583B1 (en) | 1998-04-27 | 2001-06-26 | Schering Corporation | Peptide substrates for HCV NS3 protease assays |
| GB9812523D0 (en) | 1998-06-10 | 1998-08-05 | Angeletti P Ist Richerche Bio | Peptide inhibitors of hepatitis c virus ns3 protease |
| US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| AR022061A1 (es) * | 1998-08-10 | 2002-09-04 | Boehringer Ingelheim Ca Ltd | Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos. |
| DE19836514A1 (de) | 1998-08-12 | 2000-02-17 | Univ Stuttgart | Modifikation von Engineeringpolymeren mit N-basischen Gruppe und mit Ionenaustauschergruppen in der Seitenkette |
| US6117639A (en) * | 1998-08-31 | 2000-09-12 | Vertex Pharmaceuticals Incorporated | Fusion proteins, DNA molecules, vectors, and host cells useful for measuring protease activity |
| US6025516A (en) | 1998-10-14 | 2000-02-15 | Chiragene, Inc. | Resolution of 2-hydroxy-3-amino-3-phenylpropionamide and its conversion to C-13 sidechain of taxanes |
| ES2306646T3 (es) | 1999-02-09 | 2008-11-16 | Pfizer Products Inc. | Composiciones de farmacos basicos con biodisponibilidad incrementada. |
| US20020042046A1 (en) | 1999-02-25 | 2002-04-11 | Vertex Pharmaceuticals, Incorporated | Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex |
| WO2000056331A1 (en) | 1999-03-19 | 2000-09-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of impdh enzyme |
| US6608027B1 (en) | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
| US7122627B2 (en) | 1999-07-26 | 2006-10-17 | Bristol-Myers Squibb Company | Lactam inhibitors of Hepatitis C virus NS3 protease |
| US20020183249A1 (en) | 1999-08-31 | 2002-12-05 | Taylor Neil R. | Method of identifying inhibitors of CDC25 |
| US6774212B2 (en) | 1999-12-03 | 2004-08-10 | Bristol-Myers Squibb Pharma Company | Alpha-ketoamide inhibitors of hepatitis C virus NS3 protease |
| US6365380B2 (en) * | 2000-02-23 | 2002-04-02 | Pcbu Services, Inc. | Method for stereoselectively inverting a chiral center of a chemical compound using an enzyme and a metal catalyst |
| US6699855B2 (en) | 2000-02-29 | 2004-03-02 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus NS3 protease |
| EP1268519B1 (en) * | 2000-04-03 | 2005-06-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| DE60137207D1 (de) | 2000-04-05 | 2009-02-12 | Schering Corp | Makrozyklische inhibitoren der ns3-serinprotease des hepatitis c-virus mit stickstoffhaltigen zyklischen p2-gruppen |
| SK14952002A3 (sk) | 2000-04-19 | 2003-03-04 | Schering Corporation | Makrocyklické zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie |
| WO2002002546A1 (en) | 2000-06-30 | 2002-01-10 | Seikagaku Corporation | EPOXYCARBOXYLIC ACID AMIDES, AZIDES AND AMINO ALCOHOLS AND PROCESSES FOR PREPARATION OF α-KETO AMIDES BY USING THEM |
| US7244721B2 (en) | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| RU2355700C9 (ru) | 2000-07-21 | 2010-03-20 | Шеринг Корпорейшн | Новые пептиды как ингибиторы ns3-серинпротеазы вируса гепатита с |
| AR034127A1 (es) | 2000-07-21 | 2004-02-04 | Schering Corp | Imidazolidinonas como inhibidores de ns3-serina proteasa del virus de hepatitis c, composicion farmaceutica, un metodo para su preparacion, y el uso de las mismas para la manufactura de un medicamento |
| NZ523781A (en) | 2000-07-21 | 2004-10-29 | Corvas Int Inc | Novel peptides as NS3-serine protease inhibitors of hepatitis C virus |
| AR029851A1 (es) | 2000-07-21 | 2003-07-16 | Dendreon Corp | Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c |
| EP1301527A2 (en) | 2000-07-21 | 2003-04-16 | Corvas International, Inc. | Peptides as ns3-serine protease inhibitors of hepatitis c virus |
| US6777400B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| US6939692B2 (en) | 2000-09-12 | 2005-09-06 | Degussa Ag | Nucleotide sequences coding for the pknB gene |
| US6846806B2 (en) | 2000-10-23 | 2005-01-25 | Bristol-Myers Squibb Company | Peptide inhibitors of Hepatitis C virus NS3 protein |
| AU2002248147B2 (en) | 2000-11-20 | 2006-04-06 | Bristol-Myers Squibb Company | Hepatitis C tripeptide inhibitors |
| HUP0303436A2 (hu) | 2000-12-12 | 2004-01-28 | Schering Corp. | Diaril-peptidek mint a hepatitis C vírus NS3-szerin proteáz inhibitorai, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk |
| WO2002048157A2 (en) | 2000-12-13 | 2002-06-20 | Bristol-Myers Squibb Pharma Company | Imidazolidinones and their related derivatives as hepatitis c virus ns3 protease inhibitors |
| US6653295B2 (en) | 2000-12-13 | 2003-11-25 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus NS3 protease |
| CN1267446C (zh) | 2001-01-22 | 2006-08-02 | 默克公司 | 作为依赖于rna的rna病毒聚合酶的抑制剂的核苷衍生物 |
| GB0102342D0 (en) | 2001-01-30 | 2001-03-14 | Smithkline Beecham Plc | Pharmaceutical formulation |
| CA2436518A1 (en) * | 2001-01-30 | 2002-08-08 | Vertex Pharmaceuticals Incorporated | A quantitative assay for nucleic acids |
| EP1381673B1 (en) * | 2001-03-27 | 2009-05-13 | Vertex Pharmaceuticals Incorporated | Compositions and methods useful for hcv infection |
| GB0107924D0 (en) | 2001-03-29 | 2001-05-23 | Angeletti P Ist Richerche Bio | Inhibitor of hepatitis C virus NS3 protease |
| CA2450545A1 (en) | 2001-07-03 | 2003-01-16 | Altana Pharma Ag | Process for the production of 3-phenylisoserine |
| KR100926244B1 (ko) * | 2001-07-11 | 2009-11-12 | 버텍스 파마슈티칼스 인코포레이티드 | 브릿지된 바이사이클릭 세린 프로테아제 억제제 |
| US7029561B2 (en) | 2001-07-25 | 2006-04-18 | The United States Of America As Represented By The Secretary Of Commerce | Fluidic temperature gradient focusing |
| JP2003055389A (ja) | 2001-08-09 | 2003-02-26 | Univ Tokyo | 錯体及びそれを用いたエポキシドの製法 |
| US6824769B2 (en) * | 2001-08-28 | 2004-11-30 | Vertex Pharmaceuticals Incorporated | Optimal compositions and methods thereof for treating HCV infections |
| EP1441720B8 (en) * | 2001-10-24 | 2012-03-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine protease, particularly hepatitis c virus ns3-ns4a protease, incorporating a fused ring system |
| AU2002360386A1 (en) | 2001-11-14 | 2003-06-17 | Teva Pharmaceutical Industries Ltd. | Amorphous and crystalline forms of losartan potassium and process for their preparation |
| CA2369711A1 (en) | 2002-01-30 | 2003-07-30 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis c virus |
| CA2369970A1 (en) | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
| AR038375A1 (es) | 2002-02-01 | 2005-01-12 | Pfizer Prod Inc | Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo |
| US6642204B2 (en) | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| US7091184B2 (en) | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| MXPA04009938A (es) * | 2002-04-11 | 2004-12-13 | Vertex Pharma | Inhibidores de serina proteasas, en particular la proteasa ns3-ns4a del hcv. |
| MXPA05001298A (es) | 2002-08-01 | 2005-11-04 | Pharmasset Inc | Compuestos con el sistema biciclo[4.2.1] nonano para el tratamiento de infecciones por flaviviridae. |
| US20050075279A1 (en) | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| CA2413705A1 (en) | 2002-12-06 | 2004-06-06 | Raul Altman | Use of meloxicam in combination with an antiplatelet agent for treatment of acute coronary syndrome and related conditions |
| US7601709B2 (en) | 2003-02-07 | 2009-10-13 | Enanta Pharmaceuticals, Inc. | Macrocyclic hepatitis C serine protease inhibitors |
| US7098231B2 (en) | 2003-01-22 | 2006-08-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US7223785B2 (en) | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US20040180815A1 (en) | 2003-03-07 | 2004-09-16 | Suanne Nakajima | Pyridazinonyl macrocyclic hepatitis C serine protease inhibitors |
| JP2006517960A (ja) | 2003-02-18 | 2006-08-03 | ファイザー インコーポレイテッド | Ｃ型肝炎ウイルスの阻害剤、それを使用する組成物および治療法 |
| WO2004101602A2 (en) | 2003-03-05 | 2004-11-25 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
| EP1601685A1 (en) | 2003-03-05 | 2005-12-07 | Boehringer Ingelheim International GmbH | Hepatitis c inhibiting compounds |
| EP1613620A1 (en) * | 2003-04-11 | 2006-01-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| CA2521678A1 (en) * | 2003-04-11 | 2004-10-28 | Vertex Pharmaceuticals, Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| CL2004001161A1 (es) | 2003-05-21 | 2005-04-08 | Boehringer Ingelheim Int | Compuestos describe compuestos derivados de quinolina; composicion farmaceutica; y su uso para tratar una enfermedad causada por el virus de la hepatitis c. |
| CN102020700A (zh) * | 2003-07-18 | 2011-04-20 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶抑制剂、特别是hcv ns3-ns4a蛋白酶抑制剂 |
| WO2005018330A1 (en) | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| PE20050374A1 (es) * | 2003-09-05 | 2005-05-30 | Vertex Pharma | Inhibidores de proteasas de serina, en particular proteasa ns3-ns4a del vhc |
| CA2538843A1 (en) * | 2003-09-12 | 2005-03-24 | Vertex Pharmaceuticals Incorporated | Animal model for protease activity and liver damage |
| TW200526686A (en) * | 2003-09-18 | 2005-08-16 | Vertex Pharma | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
| US6933760B2 (en) | 2003-09-19 | 2005-08-23 | Intel Corporation | Reference voltage generator for hysteresis circuit |
| US7642235B2 (en) | 2003-09-22 | 2010-01-05 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| EP1692157B1 (en) * | 2003-10-10 | 2013-04-17 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| AR045870A1 (es) * | 2003-10-11 | 2005-11-16 | Vertex Pharma | Terapia de combinacion para la infeccion de virus de hepatitis c |
| CN1894276B (zh) | 2003-10-27 | 2010-06-16 | 威特克斯医药股份有限公司 | Hcv ns3-ns4a蛋白酶抗药性突变体 |
| US8187874B2 (en) * | 2003-10-27 | 2012-05-29 | Vertex Pharmaceuticals Incorporated | Drug discovery method |
| EP1677827B1 (en) * | 2003-10-27 | 2008-12-10 | Vertex Pharmaceuticals Incorporated | Combinations for hcv treatment |
| AU2004285972A1 (en) * | 2003-10-28 | 2005-05-12 | Vertex Pharmaceuticals, Incorporated | Preparation of 4,5-dialkyl-3-acyl-pyrrole-2-carboxylic acid derivatives by Fischer-Fink type synthesis and subsequent acylation |
| US20050119318A1 (en) | 2003-10-31 | 2005-06-02 | Hudyma Thomas W. | Inhibitors of HCV replication |
| US7132504B2 (en) | 2003-11-12 | 2006-11-07 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| AU2004295702A1 (en) * | 2003-12-01 | 2005-06-16 | Vertex Pharmaceuticals Incorporated | Compositions comprising fetal liver cells and methods useful for HCV infection |
| CA2549851C (en) | 2004-01-21 | 2012-09-11 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis c virus |
| CN1938332B (zh) * | 2004-02-04 | 2011-10-19 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂 |
| US20050187192A1 (en) | 2004-02-20 | 2005-08-25 | Kucera Pharmaceutical Company | Phospholipids for the treatment of infection by togaviruses, herpes viruses and coronaviruses |
| KR20120091276A (ko) | 2004-02-20 | 2012-08-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이러스 폴리머라제 억제제 |
| CN1946692A (zh) | 2004-02-27 | 2007-04-11 | 先灵公司 | 作为丙型肝炎病毒ns3丝氨酸蛋白酶抑制剂的3,4－(环戊基)－稠合的脯氨酸化合物 |
| CA2768700C (en) * | 2004-03-12 | 2014-04-29 | Vertex Pharmaceuticals Incorporated | Processes and intermediates for the preparation of aspartic acetal caspase inhibitors |
| WO2005107745A1 (en) | 2004-05-06 | 2005-11-17 | Schering Corporation | An inhibitor of hepatitis c |
| AR049297A1 (es) * | 2004-06-08 | 2006-07-12 | Vertex Pharma | Una composicion farmaceutica y dispersiones solidas de vx-950 (inhibidor de la proteasa de hcv ns3/4a) y proceso de obtencion |
| ATE513844T1 (de) | 2004-08-27 | 2011-07-15 | Schering Corp | Acylsulfonamidverbindungen als inhibitoren der ns3-serinprotease des hepatitis-c-virus |
| US7863274B2 (en) | 2005-07-29 | 2011-01-04 | Concert Pharmaceuticals Inc. | Deuterium enriched analogues of tadalafil as PDE5 inhibitors |
| RU2441020C2 (ru) * | 2005-08-02 | 2012-01-27 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы серинпротеазы |
| PT1934179E (pt) * | 2005-08-19 | 2010-07-12 | Vertex Pharma | PROCESSOS E INTERMEDIáRIOS |
| 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 |
| US7705138B2 (en) * | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
| EP1991229A2 (en) * | 2006-02-27 | 2008-11-19 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical compositions comprising the same |
| MX2008011869A (es) * | 2006-03-16 | 2008-12-03 | Vertex Pharma | Procedimientos e intermediarios para preparar compuestos estericos. |
| EP2194039A1 (en) * | 2006-03-16 | 2010-06-09 | Vertex Pharmceuticals Incorporated | Process for preparing optically enriched compounds |
| NZ571934A (en) * | 2006-03-20 | 2012-05-25 | Vertex Pharma | Methods of spray drying formulations of vx-950 (telaprevir) |
| AU2007226983A1 (en) * | 2006-03-20 | 2007-09-27 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
| EP2037887B1 (en) * | 2006-05-31 | 2010-09-15 | Vertex Pharmaceuticals Incorporated | Oral controlled release formulations of an interleukin-1 beta converting enzyme inhibitor |
| CN101903392A (zh) | 2007-02-27 | 2010-12-01 | 弗特克斯药品有限公司 | 丝氨酸蛋白酶的抑制剂 |
-
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