JP5203712B2 - 選択的アンドロゲン受容体モジュレータとしてのアミノフェニル誘導体 - Google Patents
選択的アンドロゲン受容体モジュレータとしてのアミノフェニル誘導体 Download PDFInfo
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- JP5203712B2 JP5203712B2 JP2007550547A JP2007550547A JP5203712B2 JP 5203712 B2 JP5203712 B2 JP 5203712B2 JP 2007550547 A JP2007550547 A JP 2007550547A JP 2007550547 A JP2007550547 A JP 2007550547A JP 5203712 B2 JP5203712 B2 JP 5203712B2
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- substituted
- alkyl
- group
- optionally substituted
- azabicyclo
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
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| US60/642,841 | 2005-01-10 | ||
| PCT/US2006/000733 WO2006076317A2 (en) | 2005-01-10 | 2006-01-09 | Aminophenyl derivatives as selective androgen receptor modulators |
Publications (3)
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| JP2008526888A JP2008526888A (ja) | 2008-07-24 |
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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070004679A1 (en) * | 2004-05-17 | 2007-01-04 | Nathalie Schlienger | Androgen receptor modulators and methods of treating disease using the same |
| US20060173037A1 (en) * | 2005-01-10 | 2006-08-03 | Nathalie Schlienger | Aminophenyl derivatives as selective androgen receptor modulators |
| KR20070112775A (ko) * | 2005-01-10 | 2007-11-27 | 아카디아 파마슈티칼스 인코포레이티드 | 선택적인 안드로겐 수용체 조절자로서의 아미노페닐 유도체 |
| CA2617256C (en) * | 2005-08-01 | 2014-07-15 | Takeda Pharmaceutical Company Limited | Cyclic amine compound |
| NZ573735A (en) | 2006-05-19 | 2011-10-28 | Abbott Lab | Cns active fused bicycloheterocycle substituted azabicyclic alkane derivatives |
| WO2008066117A1 (en) | 2006-11-30 | 2008-06-05 | Takeda Pharmaceutical Company Limited | Cyclic amine compound |
| EA017429B1 (ru) | 2007-08-07 | 2012-12-28 | Такеда Фармасьютикал Компани Лимитед | Циклические аминные соединения |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| MX2010009162A (es) | 2008-02-22 | 2010-12-21 | Radius Health Inc | Moduladores selectivos del receptor de androgeno. |
| EP2531029B1 (en) | 2010-02-04 | 2016-10-19 | Radius Health, Inc. | Selective androgen receptor modulators |
| WO2011143469A1 (en) | 2010-05-12 | 2011-11-17 | Radius Health,Inc | Therapeutic regimens |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| BR112013007685B1 (pt) | 2010-09-28 | 2021-11-09 | Radius Pharmaceuticals, Inc | Compostos moduladores de receptor andrógeno seletivos, composição farmacêutica compreendendo os referidos compostos, método de identificação de um composto capaz de modular um receptor andrógeno, usos de um composto ou da composição e processo para a preparação de um composto |
| BR112014001751A2 (pt) | 2011-07-27 | 2017-02-14 | Novartis Ag | derivados de pirazolina e seu uso como moduladores seletivos do receptor de estrogênio |
| WO2014125121A1 (en) | 2013-02-18 | 2014-08-21 | Acadia Pharmaceuticals Inc. | Compounds and compositions for treating neurodegenerative diseases |
| US20140274985A1 (en) * | 2013-03-15 | 2014-09-18 | Raman Malhotra | Systemic administration of androgen in treating dry eye syndrome |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| FI3834824T3 (fi) | 2014-03-28 | 2025-12-05 | Univ Duke | Estrogeenireseptoripositiivisen rintasyövän hoito selektiivisellä estrogeenireseptorin modulaattorilla |
| ES2703168T3 (es) | 2014-05-29 | 2019-03-07 | Taiho Pharmaceutical Co Ltd | Nuevo compuesto de tetrahidropiridopirimidina o sal del mismo |
| US10441570B2 (en) | 2015-04-21 | 2019-10-15 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) Ligands and methods of use thereof |
| BR112017022860A2 (pt) * | 2015-04-21 | 2018-07-17 | Gtx Inc | ligantes de decompostos receptores de andrógeno seletivos (sard) e métodos de utilização dos mesmos |
| US10093613B2 (en) | 2015-04-21 | 2018-10-09 | Gtx, Inc. | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| US10865184B2 (en) | 2015-04-21 | 2020-12-15 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| US10806720B2 (en) | 2015-04-21 | 2020-10-20 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| US10654809B2 (en) | 2016-06-10 | 2020-05-19 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| WO2017090719A1 (ja) * | 2015-11-27 | 2017-06-01 | 大鵬薬品工業株式会社 | 縮環ピリミジン化合物又はその塩 |
| TWI726969B (zh) | 2016-01-11 | 2021-05-11 | 比利時商健生藥品公司 | 用作雄性激素受體拮抗劑之經取代之硫尿囊素衍生物 |
| JP7221699B2 (ja) | 2016-06-22 | 2023-02-14 | エリプセス ファーマ エルティーディー | Ar+乳癌の治療方法 |
| KR102881465B1 (ko) | 2017-01-05 | 2025-11-04 | 래디어스 파마슈티컬스, 인코포레이티드 | Rad1901-2hcl의 다형 형태 |
| EA202092436A1 (ru) | 2018-05-14 | 2021-05-04 | Нувейшн Био Инк. | Противораковые соединения, нацеливающие на ядерные гормональные рецепторы |
| SG11202013177WA (en) | 2018-07-04 | 2021-01-28 | Radius Pharmaceuticals Inc | Polymorphic forms of rad 1901-2hcl |
| US12202815B2 (en) | 2018-09-05 | 2025-01-21 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| KR20210127961A (ko) | 2019-02-12 | 2021-10-25 | 래디어스 파마슈티컬스, 인코포레이티드 | 방법 및 화합물 |
| CA3138197A1 (en) | 2019-05-14 | 2020-11-19 | Nuvation Bio Inc. | Anti-cancer nuclear hormone receptor-targeting compounds |
| US11952349B2 (en) | 2019-11-13 | 2024-04-09 | Nuvation Bio Inc. | Anti-cancer nuclear hormone receptor-targeting compounds |
| IL306010A (en) | 2021-03-23 | 2023-11-01 | Nuvation Bio Inc | Anticancer compounds against the nuclear hormone receptor |
| WO2022212631A1 (en) * | 2021-03-31 | 2022-10-06 | Taiho Pharmaceutical Co., Ltd. | Treatment of patients metastatic castration-resistant prostate cancer with an androgen receptor antagonist |
| JP2024516024A (ja) | 2021-05-03 | 2024-04-11 | ニューベイション・バイオ・インコーポレイテッド | 抗がん核内ホルモン受容体標的化化合物 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL140992B (nl) | 1963-07-06 | 1974-01-15 | Kalle Ag | Kopieermateriaal, dat een lichtgevoelig diazoniumzout bevat en werkwijze voor het bereiden van dat zout. |
| DE3100535A1 (de) | 1981-01-10 | 1982-08-12 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue carbonsaeure-derivate, ihre herstellung und ihre verwendung als arzneimittel" |
| US4933447A (en) | 1987-09-24 | 1990-06-12 | Ss Pharmaceutical Co., Ltd. | Quinoline derivatives |
| US5707798A (en) | 1993-07-13 | 1998-01-13 | Novo Nordisk A/S | Identification of ligands by selective amplification of cells transfected with receptors |
| DE4404198A1 (de) | 1994-02-10 | 1995-08-17 | Henkel Kgaa | 2-Fluor-6-nitroaniline |
| US5507798A (en) * | 1994-09-14 | 1996-04-16 | United States Surgical Corporation | Surgical needle-suture attachment for controlled suture release |
| KR100392216B1 (ko) | 1994-11-15 | 2003-10-17 | 파마시아 앤드 업존 캄파니 | 이환상옥사진및티아진옥사졸리디논항세균물질 |
| GB9510459D0 (en) * | 1995-05-24 | 1995-07-19 | Zeneca Ltd | Bicyclic amines |
| AT403803B (de) * | 1996-04-19 | 1998-05-25 | Sanochemia Ltd | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| US6818453B1 (en) | 1998-05-26 | 2004-11-16 | Koninklijke Philips Electronics N.V. | Label for making a charge-transfer fluorescent probe |
| CA2333332A1 (en) * | 1998-06-05 | 1999-12-16 | Astrazeneca Ab | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| AU754529B2 (en) | 1998-09-22 | 2002-11-21 | Yamanouchi Pharmaceutical Co., Ltd. | Cyanophenyl derivatives |
| WO2000032600A1 (en) * | 1998-11-27 | 2000-06-08 | Neurosearch A/S | 8-azabicyclo[3.2.1]oct-2-ene and -octane derivatives |
| ES2321933T3 (es) | 2000-08-24 | 2009-06-15 | University Of Tennessee Research Foundation | Moduladores selectivos del receptor de androgeno y metodos de uso de los mismos. |
| JP2002088073A (ja) * | 2000-09-08 | 2002-03-27 | Yamanouchi Pharmaceut Co Ltd | 抗アンドロゲン剤 |
| US7214690B2 (en) | 2001-02-23 | 2007-05-08 | Ligand Pharmaceuticals Incorporated | Tricyclic quinolinone and tricyclic quinoline androgen receptor modulator compounds and methods |
| US20040087548A1 (en) * | 2001-02-27 | 2004-05-06 | Salvati Mark E. | Fused cyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
| US6670386B2 (en) | 2001-07-31 | 2003-12-30 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| EP1433771B1 (en) | 2001-08-16 | 2009-12-30 | Ube Industries, Ltd. | Process for preparation of cyclododecanone |
| US7405234B2 (en) | 2002-05-17 | 2008-07-29 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| TW200407324A (en) | 2002-05-17 | 2004-05-16 | Bristol Myers Squibb Co | Bicyclic modulators of androgen receptor function |
| KR20050044902A (ko) | 2002-08-12 | 2005-05-13 | 다케다 야쿠힌 고교 가부시키가이샤 | 축합 벤젠 유도체 및 용도 |
| US6933311B2 (en) * | 2003-02-11 | 2005-08-23 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| DE10322108B4 (de) * | 2003-05-09 | 2008-12-11 | Bayer Schering Pharma Aktiengesellschaft | Antiandrogene Pyrrolidine mit tumorhemmender Wirksamkeit |
| JP2007500245A (ja) | 2003-06-10 | 2007-01-11 | スミスクライン ビーチャム コーポレーション | 化合物 |
| US20050113576A1 (en) * | 2003-08-05 | 2005-05-26 | Chih-Hung Lee | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| GB0324551D0 (en) | 2003-10-21 | 2003-11-26 | Karobio Ab | Novel compounds |
| GB0324790D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Amide derivatives |
| US7256208B2 (en) | 2003-11-13 | 2007-08-14 | Bristol-Myers Squibb Company | Monocyclic N-Aryl hydantoin modulators of androgen receptor function |
| EP1687274A1 (en) | 2003-11-20 | 2006-08-09 | Warner-Lambert Company LLC | Androgen receptor modulators |
| US8519158B2 (en) | 2004-03-12 | 2013-08-27 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
| CN101248069A (zh) | 2004-05-17 | 2008-08-20 | 阿卡蒂亚药品公司 | 雄激素受体调节剂及用其治疗疾病的方法 |
| ATE503746T1 (de) | 2004-08-03 | 2011-04-15 | Chugai Pharmaceutical Co Ltd | Neue imidazolidinderivate |
| US20060173037A1 (en) * | 2005-01-10 | 2006-08-03 | Nathalie Schlienger | Aminophenyl derivatives as selective androgen receptor modulators |
| KR20070112775A (ko) | 2005-01-10 | 2007-11-27 | 아카디아 파마슈티칼스 인코포레이티드 | 선택적인 안드로겐 수용체 조절자로서의 아미노페닐 유도체 |
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- 2006-01-09 JP JP2007550547A patent/JP5203712B2/ja not_active Expired - Fee Related
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2009
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Also Published As
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|---|---|
| MX2007008334A (es) | 2007-09-11 |
| CA2594340A1 (en) | 2006-07-20 |
| EP1836202B1 (en) | 2016-12-21 |
| NZ555974A (en) | 2010-11-26 |
| AU2006205066B2 (en) | 2012-05-17 |
| CN101119993A (zh) | 2008-02-06 |
| CA2594340C (en) | 2015-11-10 |
| EP1836202A2 (en) | 2007-09-26 |
| WO2006076317A9 (en) | 2007-09-27 |
| US7585877B2 (en) | 2009-09-08 |
| CN101119993B (zh) | 2015-03-04 |
| JP2008526888A (ja) | 2008-07-24 |
| US20090270449A1 (en) | 2009-10-29 |
| KR20070112775A (ko) | 2007-11-27 |
| ZA200705458B (en) | 2008-12-31 |
| AU2006205066A1 (en) | 2006-07-20 |
| WO2006076317A3 (en) | 2006-11-23 |
| US20060160845A1 (en) | 2006-07-20 |
| RU2007130558A (ru) | 2009-02-20 |
| WO2006076317A2 (en) | 2006-07-20 |
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