JP2009531280A - 代謝障害を処置するための化合物 - Google Patents
代謝障害を処置するための化合物 Download PDFInfo
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- JP2009531280A JP2009531280A JP2008552536A JP2008552536A JP2009531280A JP 2009531280 A JP2009531280 A JP 2009531280A JP 2008552536 A JP2008552536 A JP 2008552536A JP 2008552536 A JP2008552536 A JP 2008552536A JP 2009531280 A JP2009531280 A JP 2009531280A
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- alkyl
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- C07C43/02—Ethers
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Landscapes
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
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| US76209106P | 2006-01-25 | 2006-01-25 | |
| PCT/US2007/060832 WO2007087505A2 (en) | 2006-01-25 | 2007-01-22 | Compounds for the treatment of metabolic disorders |
Publications (2)
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| JP2009531280A true JP2009531280A (ja) | 2009-09-03 |
| JP2009531280A5 JP2009531280A5 (enExample) | 2011-01-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2008552536A Withdrawn JP2009531280A (ja) | 2006-01-25 | 2007-01-22 | 代謝障害を処置するための化合物 |
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| US (1) | US7820721B2 (enExample) |
| EP (1) | EP1976377A4 (enExample) |
| JP (1) | JP2009531280A (enExample) |
| CA (1) | CA2637375A1 (enExample) |
| WO (1) | WO2007087505A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013510090A (ja) * | 2009-11-03 | 2013-03-21 | アクセルロン ファーマ， インコーポレイテッド | 脂肪肝疾患を処置するための方法 |
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| EP2266946A3 (en) * | 2003-02-13 | 2012-12-12 | Wellstat Therapeutics Corporation | Compound For The Treatment Of Metabolic Disorders |
| DE602004030004D1 (de) * | 2003-04-15 | 2010-12-23 | Wellstat Therapeutics Corp | Verbindungen zur behandlung von stoffwechselstörungen |
| EP1617835B1 (en) * | 2003-04-30 | 2011-09-28 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| EP3059245B1 (en) | 2004-07-23 | 2018-11-07 | Acceleron Pharma Inc. | Actrii receptor antagonistic antibodies |
| MX2008006626A (es) | 2005-11-23 | 2008-09-24 | Acceleron Pharma Inc | Antagonistas de activin-actriia y usos para promover el crecimiento de huesos. |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| EP1978948A4 (en) * | 2006-02-02 | 2010-06-16 | Wellstat Therapeutics Corp | COMPOUNDS FOR THE TREATMENT OF METABOLISM DISORDER |
| AU2007235145B2 (en) * | 2006-03-31 | 2011-09-22 | Wellstat Therapeutics Corporation | Combination treatment of metabolic disorders |
| WO2007137008A2 (en) * | 2006-05-18 | 2007-11-29 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| US20100234464A1 (en) * | 2006-06-09 | 2010-09-16 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| EP2056673A4 (en) * | 2006-08-17 | 2010-06-16 | Wellstat Therapeutics Corp | COMBINATION TREATMENT FOR METABOLISM DISEASES |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| WO2008094708A2 (en) | 2007-02-01 | 2008-08-07 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for treating or preventing breast cancer |
| TWI782836B (zh) | 2007-02-02 | 2022-11-01 | 美商艾瑟勒朗法瑪公司 | 衍生自ActRIIB的變體與其用途 |
| TWI606062B (zh) | 2007-02-09 | 2017-11-21 | 艾瑟勒朗法瑪公司 | 包含ＡｃｔＲＩＩａ-Ｆｃ融合蛋白的醫藥組合物；ＡｃｔＲＩＩａ-Ｆｃ融合蛋白於治療或預防與癌症相關的骨質流失之用途；ＡｃｔＲＩＩａ-Ｆｃ融合蛋白於治療或預防多發性骨髓瘤之用途 |
| WO2009038745A1 (en) | 2007-09-18 | 2009-03-26 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for decreasing or inhibiting fsh secretion |
| US8481595B2 (en) * | 2008-01-15 | 2013-07-09 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| HRP20191109T1 (hr) | 2008-08-14 | 2019-09-20 | Acceleron Pharma Inc. | Gdf klopke za uporabu u liječenju anemije |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| AU2010258931B2 (en) | 2009-06-08 | 2015-04-23 | Acceleron Pharma Inc. | Methods for increasing thermogenic adipocytes |
| CN107267520A (zh) | 2009-06-12 | 2017-10-20 | 阿塞勒隆制药公司 | 截短的actriib‑fc融合蛋白 |
| CA2781152A1 (en) | 2009-11-17 | 2011-05-26 | Acceleron Pharma Inc. | Actriib proteins and variants and uses therefore relating to utrophin induction for muscular dystrophy therapy |
| JP2014502260A (ja) | 2010-11-08 | 2014-01-30 | アクセルロン ファーマ， インコーポレイテッド | Ａｃｔｒｉｉａ結合剤およびその使用 |
| ES2884095T3 (es) | 2012-11-02 | 2021-12-10 | Celgene Corp | Antagonistas de activina-actrii y usos para el tratamiento de trastornos óseos y otros trastornos |
| MA40008A (fr) | 2014-06-13 | 2021-05-05 | Acceleron Pharma Inc | Antagoniste actrii pour le traitement et la prevention d'un ulcere cutane chez un sujet ayant l'anemie |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| AU2015358469B2 (en) | 2014-12-03 | 2021-05-27 | Acceleron Pharma Inc. | Activin-ActRII antagonists and uses for treating anemia |
Family Cites Families (42)
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|---|---|---|---|---|
| FR2216999B1 (enExample) * | 1972-10-10 | 1977-04-15 | Serdex | |
| US4350822A (en) * | 1975-03-12 | 1982-09-21 | American Cyanamid Company | Antilipidemicpara-[aryl(alkyl or alkenyl)amino]benzoic acid derivatives |
| GB1561350A (en) | 1976-11-05 | 1980-02-20 | May & Baker Ltd | Benzamide derivatives |
| WO1985003701A1 (fr) | 1984-02-14 | 1985-08-29 | Hidefumi Hirai | PROCEDE DE PREPARATION DE DERIVES DE PHENOL p-SUBSTITUE |
| DE3884825D1 (de) | 1987-02-16 | 1993-11-18 | Konishiroku Photo Ind | Entwickler für lichtempfindliche lithographische Druckplatte, gemeinschaftlich verarbeitungsfähig für den Negativ-Typ und den Positiv-Typ und Entwicklerzusammensetzung für lichtempfindliches Material. |
| JPH0770025B2 (ja) | 1987-09-16 | 1995-07-31 | 富士通株式会社 | 薄膜磁気ヘッドの製造方法 |
| US4923501A (en) | 1987-11-04 | 1990-05-08 | Kumiai Chemical Industry Co., Ltd. | Pyrimidine derivatives, processes for their production, and herbicidal method and compositions |
| US5108363A (en) * | 1988-02-19 | 1992-04-28 | Gensia Pharmaceuticals, Inc. | Diagnosis, evaluation and treatment of coronary artery disease by exercise simulation using closed loop drug delivery of an exercise simulating agent beta agonist |
| NZ231735A (en) * | 1988-12-23 | 1992-04-28 | Ici Plc | Alcohol/ether derivatives, preparation and pharmaceutical compositions thereof |
| US5089514A (en) * | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
| JPH04154773A (ja) | 1990-10-15 | 1992-05-27 | Green Cross Corp:The | チアゾール誘導体 |
| JPH04282345A (ja) | 1991-03-11 | 1992-10-07 | Mitsubishi Petrochem Co Ltd | 光学活性化合物 |
| JPH08501100A (ja) | 1992-09-09 | 1996-02-06 | イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー | 除草性ベンゼン化合物 |
| US5484926A (en) | 1993-10-07 | 1996-01-16 | Agouron Pharmaceuticals, Inc. | HIV protease inhibitors |
| JPH06293700A (ja) | 1993-04-08 | 1994-10-21 | Nippon Soda Co Ltd | ６−クロロサリチル酸の製造法 |
| GB9315595D0 (en) | 1993-07-28 | 1993-09-08 | Res Inst Medicine Chem | New compounds |
| JPH07206658A (ja) | 1994-01-12 | 1995-08-08 | Shiseido Co Ltd | 尋常性座瘡治療剤 |
| JPH08119959A (ja) | 1994-10-20 | 1996-05-14 | Oyo Seikagaku Kenkyusho | キサントン誘導体及びこれを有効成分とするモノアミン酸化酵素阻害剤 |
| US5728718A (en) | 1994-12-20 | 1998-03-17 | The United States Of America As Represented By The Department Of Health And Human Services | 2,5-diamino-3,4-disubstituted-1,6-diphenylhexane isosteres comprising benzamide, sulfonamide and anthranilamide subunits and methods of using same |
| FR2730731B1 (fr) | 1995-02-20 | 1997-04-04 | Rhone Poulenc Chimie | Procede de carboxylation d'un ether aromatique |
| WO1996028423A1 (en) | 1995-03-15 | 1996-09-19 | Sankyo Company, Limited | Dipeptide compounds having ahpba structure |
| FR2732017B1 (fr) * | 1995-03-21 | 2000-09-22 | Inst Nat Sante Rech Med | Nouveaux derives de l'imidazole antagonistes et/ou agonistes du recepteur h3 de l'histamine, leur preparation et leurs applications therapeutiques |
| US5519133A (en) | 1995-06-02 | 1996-05-21 | American Cyanamid Co. | 3-(3-aryloxyphenyl)-1-(substituted methyl)-s-triazine-2,4,6-oxo or thiotrione herbicidal agents |
| US6194406B1 (en) | 1995-12-20 | 2001-02-27 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic disease |
| US6423704B2 (en) | 1995-12-20 | 2002-07-23 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic diseases |
| AU1698997A (en) | 1996-01-16 | 1997-08-11 | Merck & Co., Inc. | Tocolytic oxytocin receptor antagonists |
| DE69716424T2 (de) | 1996-05-24 | 2003-02-20 | Neurosearch A/S, Ballerup | Saure gruppen enthaltende phenylderivate, ihre herstellung und ihre verwendung als chloridkanalblocker |
| JPH1087489A (ja) | 1996-09-13 | 1998-04-07 | Sankyo Co Ltd | Ａｈｐｂａ構造含有ジペプチド化合物を有効成分とする医薬 |
| EP0875562A4 (en) * | 1996-10-22 | 2004-11-17 | Daicel Chem | NEW SECONDARY ALCOHOLDEHYDROGENASE, PRODUCTION PROCESS FOR THE ENZYME AND FOR ALCOHOLS AND KETONES |
| CA2302009A1 (en) | 1997-09-09 | 1999-03-18 | Merck & Co., Inc. | 3-(iodophenoxymethyl) carbapenem antibacterials |
| DE69833036T2 (de) | 1997-09-30 | 2006-06-22 | Daiichi Pharmaceutical Co., Ltd. | Sulfonylderivate |
| GB9914371D0 (en) | 1999-06-18 | 1999-08-18 | Smithkline Beecham Plc | Novel compounds |
| EA005976B1 (ru) | 2000-06-28 | 2005-08-25 | Туларик Инк. | Хинолинил и бензотиазолил ppar-гамма модуляторы |
| AR031126A1 (es) | 2000-08-29 | 2003-09-10 | Abbott Lab | Acidos amino(oxo)aceticos inhibidores de la proteina tirosina fosfatasa |
| AR035216A1 (es) | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| CZ20033394A3 (cs) | 2001-06-12 | 2005-03-16 | Wellstat Therapeutics Corporation | Sloučeniny pro léčení metabolických poruch a způsob jejich přípravy |
| AU2003286728A1 (en) | 2002-11-01 | 2004-06-07 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| EP2266946A3 (en) | 2003-02-13 | 2012-12-12 | Wellstat Therapeutics Corporation | Compound For The Treatment Of Metabolic Disorders |
| DE602004030004D1 (de) | 2003-04-15 | 2010-12-23 | Wellstat Therapeutics Corp | Verbindungen zur behandlung von stoffwechselstörungen |
| US7361686B2 (en) | 2003-04-22 | 2008-04-22 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| EP1617835B1 (en) | 2003-04-30 | 2011-09-28 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| CN1835743A (zh) | 2003-08-20 | 2006-09-20 | 维尔斯达医疗公司 | 用于治疗代谢紊乱的化合物 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013510090A (ja) * | 2009-11-03 | 2013-03-21 | アクセルロン ファーマ， インコーポレイテッド | 脂肪肝疾患を処置するための方法 |
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| US20080306165A1 (en) | 2008-12-11 |
| EP1976377A4 (en) | 2010-06-23 |
| WO2007087505A3 (en) | 2007-12-13 |
| US7820721B2 (en) | 2010-10-26 |
| CA2637375A1 (en) | 2007-08-02 |
| WO2007087505A2 (en) | 2007-08-02 |
| EP1976377A2 (en) | 2008-10-08 |
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