CN106038556A - 1‑(5,6‑二氯‑1h‑苯并[d]咪唑‑2‑基)‑1h‑吡唑‑4‑羧酸的葡甲胺盐制剂 - Google Patents
1‑(5,6‑二氯‑1h‑苯并[d]咪唑‑2‑基)‑1h‑吡唑‑4‑羧酸的葡甲胺盐制剂 Download PDFInfo
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| CN201280052789.4A Active CN104053439B (zh) | 2011-10-25 | 2012-10-25 | 1-(5,6-二氯-1h-苯并[d]咪唑-2-基)-1h-吡唑-4-羧酸的葡甲胺盐制剂 |
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Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2523720T3 (es) | 2008-04-28 | 2014-12-01 | Janssen Pharmaceutica, N.V. | Benzoimidazoles como inhibidores de prolilhidroxilasa |
| JP6093768B2 (ja) | 2011-09-14 | 2017-03-08 | ニューファーマ， インコーポレイテッド | 特定の化学的実体、組成物、および方法 |
| EP2776023B1 (en) * | 2011-10-25 | 2016-03-09 | Janssen Pharmaceutica, N.V. | Meglumine salt formulations of 1-(5,6-dichloro-1h-benzo[d]imidazol-2-yl)-1h-pyrazole-4-carboxylic acid |
| US9670180B2 (en) | 2012-01-25 | 2017-06-06 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| CN104812389B (zh) | 2012-09-24 | 2020-07-17 | 润新生物公司 | 某些化学实体、组合物及方法 |
| EP2916838B1 (en) | 2012-11-12 | 2019-03-13 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| CN104610153B (zh) * | 2015-01-19 | 2017-02-22 | 沈阳中海生物技术开发有限公司 | 奥扎格雷葡甲胺盐及其组合物、制备方法和用途 |
| AU2019319448B2 (en) | 2018-08-07 | 2022-06-02 | Metagone Biotech Inc. | Ammonium salts of 3-(3,5-dibromo-4-hydroxybenzyliden)-5-indo-1,3-dihydroindol-2-one and uses thereof |
| WO2021107110A1 (ja) | 2019-11-28 | 2021-06-03 | 日本農薬株式会社 | ベンゾイミダゾール化合物又はその塩類及び該化合物を含有する農園芸用殺虫殺ダニ剤並びにその使用方法 |
| TW202200134A (zh) | 2020-04-20 | 2022-01-01 | 美商阿克比治療有限公司 | 治療病毒感染、器官損傷及相關症狀之方法 |
| WO2022150623A1 (en) | 2021-01-08 | 2022-07-14 | Akebia Therapeutics, Inc. | Compounds and composition for the treatment of anemia |
| EP4347022A1 (en) | 2021-05-27 | 2024-04-10 | Keryx Biopharmaceuticals, Inc. | Pediatric formulations of ferric citrate |
| WO2025049599A1 (en) | 2023-08-29 | 2025-03-06 | President And Fellows Of Harvard College | Methods for treating muscle-related disorders by modulating prolyl hydroxylase 3 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001042238A1 (en) * | 1999-12-08 | 2001-06-14 | Glaxosmithkline Spa | Heterocyclic derivatives |
| CN102076680A (zh) * | 2008-04-28 | 2011-05-25 | 詹森药业有限公司 | 作为脯氨酰羟化酶抑制剂的苯并咪唑 |
| CN104053439B (zh) * | 2011-10-25 | 2016-08-24 | 詹森药业有限公司 | 1-(5,6-二氯-1h-苯并[d]咪唑-2-基)-1h-吡唑-4-羧酸的葡甲胺盐制剂 |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1207994B (it) * | 1986-01-03 | 1989-06-01 | Therapicon Srl | Sali idrosulubili di composti adattivita' antiinfiammatoria ed analgesica, loro preparazione ed utilizzo in composizioni farmaceutiche. |
| DE3783122T2 (de) | 1986-10-22 | 1993-04-22 | Schering Corp | Verwendung von rekombiniertem menschlichem alpha-interferon zur herstellung eines arzneimittels zur behandlung des aids-virus. |
| DE3824658A1 (de) | 1988-07-15 | 1990-01-18 | Schering Ag | N-hetaryl-imidazolderivate |
| US5258362A (en) | 1991-06-11 | 1993-11-02 | Abbott Laboratories | Renin inhibiting compounds |
| DK0650960T3 (da) | 1993-11-02 | 1997-09-01 | Hoechst Ag | Substituerede heterocykliske carboxylsyreamid-estere, deres fremstilling og deres anvendelse som lægemidler. |
| JP3314938B2 (ja) | 1995-06-06 | 2002-08-19 | ファイザー・インコーポレーテッド | グリコーゲンホスホリラーゼ抑制剤としての置換されたｎ−（インドール−２−カルボニル）−グリシンアミド類および誘導体 |
| WO1998039343A1 (en) | 1997-03-07 | 1998-09-11 | Metabasis Therapeutics, Inc. | Novel benzimidazole inhibitors of fructose-1,6-bisphosphatase |
| DE19746287A1 (de) | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| ATE286034T1 (de) | 1998-02-27 | 2005-01-15 | Pfizer Prod Inc | N-((substitutierte fünfgliedrige di- oder triaza- doppeltungesättigter ring)carbonyl)guanidinderivate zur behandlung von ischemie |
| EP1231857B1 (en) | 1999-11-22 | 2005-01-19 | Mallinckrodt Inc. | Pulse oximeter sensor with widened metal strip |
| AR038658A1 (es) | 2001-06-15 | 2005-01-26 | Novartis Ag | Derivados de 4-aril-2(1h) quinazolinona y 4-aril-quinazolina 2-sustituidas, un proceso para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la preparacion de un medicamento |
| US8124582B2 (en) | 2002-12-06 | 2012-02-28 | Fibrogen, Inc. | Treatment of diabetes |
| US7618940B2 (en) | 2002-12-06 | 2009-11-17 | Fibrogen, Inc. | Fat regulation |
| EP1644336B1 (en) | 2003-06-06 | 2011-01-19 | Fibrogen, Inc. | Nitrogen-containing heteroaryl compounds and their use in increasing endogeneous erythropoietin |
| AU2004261628B2 (en) | 2003-07-28 | 2011-05-12 | Janssen Pharmaceutica N.V. | Benzimidazole, benzthiazole and benzoxazole derivatives and their use as LTA4H modulators |
| EP1702919B1 (en) | 2003-12-29 | 2012-05-30 | Msd K.K. | Novel 2-heteroaryl-substituted benzimidazole derivative |
| ATE513833T1 (de) | 2005-03-02 | 2011-07-15 | Fibrogen Inc | Thienopyridinverbindungen und verfahren zu ihrer verwendung |
| EP1893186A2 (en) | 2005-06-06 | 2008-03-05 | Fibrogen, Inc. | Improved treatment for anemia using a hif-alpha stabilising agent |
| WO2007038571A2 (en) | 2005-09-26 | 2007-04-05 | Smithkline Beecham Corporation | Prolyl hydroxylase antagonists |
| ES2274712B1 (es) | 2005-10-06 | 2008-03-01 | Laboratorios Almirall S.A. | Nuevos derivados imidazopiridina. |
| US7728130B2 (en) | 2005-12-09 | 2010-06-01 | Amgen Inc. | Quinolone based compounds exhibiting prolyl hydroxylase inhibitory activity |
| BRPI0707302B8 (pt) | 2006-01-27 | 2021-05-25 | Fibrogen Inc | compostos de cianoisoquinolina que atuam no dano tecidual associado com isquemia, hipóxia e anemia, bem como composição farmacêutica que os compreende |
| AR059733A1 (es) | 2006-03-07 | 2008-04-23 | Smithkline Beecham Corp | Compuesto derivado de glicina n- sustituida con heteroaromaticos bicicicos, composicion farmaceutica que lo comprende, uso para preparar un medicamento para tratar la anemia y proceso para su preparacion |
| WO2007136990A2 (en) | 2006-05-16 | 2007-11-29 | Smithkline Beecham Corporation | Prolyl hydroxylase inhibitors |
| TWI394747B (zh) | 2006-06-23 | 2013-05-01 | Smithkline Beecham Corp | 脯胺醯基羥化酶抑制劑 |
| SI3357911T1 (sl) | 2006-06-26 | 2022-10-28 | Akebia Therapeutics Inc. | Inhibitorji prolil hidroksilaze in postopki uporabe |
| WO2008033739A2 (en) | 2006-09-12 | 2008-03-20 | Neurogen Corporation | Benzimidazole carboxamide derivatives |
| DE102006050513A1 (de) | 2006-10-26 | 2008-04-30 | Bayer Healthcare Ag | Substitiuierte Dihydropyrazolone und ihre Verwendung |
| DE102006050516A1 (de) | 2006-10-26 | 2008-04-30 | Bayer Healthcare Ag | Substituierte Dihydropyrazolone und ihre Verwendung |
| CN101611007A (zh) | 2006-12-20 | 2009-12-23 | 先灵公司 | 新颖的jnk抑制剂 |
| TW200845994A (en) | 2007-01-12 | 2008-12-01 | Smithkline Beecham Corp | N-substituted glycine derivatives: prolyl hydroxylase inhibitors |
| TW200845991A (en) | 2007-01-12 | 2008-12-01 | Smithkline Beecham Corp | N-substituted glycine derivatives: hydroxylase inhibitors |
| WO2008130600A2 (en) | 2007-04-18 | 2008-10-30 | Amgen Inc. | Quinolones and azaquinolones that inhibit prolyl hydroxylase |
| CN101663037A (zh) | 2007-04-18 | 2010-03-03 | 默克公司 | 新的1,8-二氮杂萘化合物 |
| AU2008248165B2 (en) | 2007-05-04 | 2011-12-08 | Amgen Inc. | Diazaquinolones that inhibit prolyl hydroxylase activity |
| ES2389063T3 (es) | 2007-05-04 | 2012-10-22 | Amgen, Inc | Derivados de tienopiridina y tiazolopiridina que inhiben la actividad prolil hidroxilasa |
| WO2009024190A1 (en) * | 2007-08-22 | 2009-02-26 | 4Sc Ag | Indolopyridines as inhibitors of the kinesin spindle protein (eg5 ) |
| DE102007048447A1 (de) | 2007-10-10 | 2009-04-16 | Bayer Healthcare Ag | Substituierte Dihydropyrazolthione und ihre Verwendung |
| DE102007049157A1 (de) | 2007-10-13 | 2009-04-16 | Bayer Healthcare Ag | Substituierte Dihydrotriazolone und ihre Verwendung |
| EP2227475B1 (en) | 2007-12-03 | 2014-02-19 | Fibrogen, Inc. | Isoxazolopyridine derivatives for use in the treatment of hif-mediated conditions |
| JP2011507894A (ja) | 2007-12-19 | 2011-03-10 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | プロリルヒドロキシラーゼ阻害剤 |
| US20110003013A1 (en) | 2008-01-04 | 2011-01-06 | Garvan Institute Of Medical Research | Method of increasing metabolism |
| EP2252619B1 (en) | 2008-01-11 | 2013-10-09 | Fibrogen, Inc. | Isothiazole-pyridine derivatives as modulators of hif (hypoxia inducible factor) activity |
| EP2257171B1 (en) | 2008-02-25 | 2016-02-10 | Merck Sharp & Dohme Corp. | Tetrahydro-1h-pyrrolo-fused pyridones |
| US8471024B2 (en) | 2008-02-25 | 2013-06-25 | Merck Sharp & Dohme, Corp. | Tetrahydrofuropyridones |
| EP2257169B1 (en) | 2008-02-25 | 2013-06-05 | Merck Sharp & Dohme Corp. | Tetrahydrothieno pyridines |
| AU2009225869B2 (en) | 2008-03-18 | 2014-01-23 | Merck Sharp & Dohme Llc | Substituted 4-hydroxypyrimidine-5-carboxamides |
| BRPI1008376B1 (pt) | 2009-02-10 | 2021-08-31 | Janssen Pharmaceutica Nv | Quinazolinonas como inibidores de prolil hidroxilase |
| WO2012021830A1 (en) | 2010-08-13 | 2012-02-16 | Janssen Pharmaceutica Nv | 4 - aminoquinazolin- 2 - yl - 1 - pyrrazole - 4 - carboxylic acid compounds as prolyl hydroxylase inhibitors |
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2012
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001042238A1 (en) * | 1999-12-08 | 2001-06-14 | Glaxosmithkline Spa | Heterocyclic derivatives |
| CN102076680A (zh) * | 2008-04-28 | 2011-05-25 | 詹森药业有限公司 | 作为脯氨酰羟化酶抑制剂的苯并咪唑 |
| CN104053439B (zh) * | 2011-10-25 | 2016-08-24 | 詹森药业有限公司 | 1-(5,6-二氯-1h-苯并[d]咪唑-2-基)-1h-吡唑-4-羧酸的葡甲胺盐制剂 |
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