CA2594340C - Aminophenyl derivatives as selective androgen receptor modulators - Google Patents
Aminophenyl derivatives as selective androgen receptor modulators Download PDFInfo
- Publication number
- CA2594340C CA2594340C CA2594340A CA2594340A CA2594340C CA 2594340 C CA2594340 C CA 2594340C CA 2594340 A CA2594340 A CA 2594340A CA 2594340 A CA2594340 A CA 2594340A CA 2594340 C CA2594340 C CA 2594340C
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- Prior art keywords
- substituted
- alkyl
- compound
- stereoisomer
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- -1 Aminophenyl Chemical class 0.000 title claims abstract description 125
- 239000000849 selective androgen receptor modulator Substances 0.000 title description 7
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- 108010080146 androgen receptors Proteins 0.000 claims abstract description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 34
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
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- 125000005843 halogen group Chemical group 0.000 claims description 38
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Reproductive Health (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Pregnancy & Childbirth (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64284105P | 2005-01-10 | 2005-01-10 | |
| 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 (2)
| Publication Number | Publication Date |
|---|---|
| CA2594340A1 CA2594340A1 (en) | 2006-07-20 |
| CA2594340C true CA2594340C (en) | 2015-11-10 |
Family
ID=36591321
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2594340A Expired - Fee Related CA2594340C (en) | 2005-01-10 | 2006-01-09 | Aminophenyl derivatives as selective androgen receptor modulators |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7585877B2 (enExample) |
| EP (1) | EP1836202B1 (enExample) |
| JP (1) | JP5203712B2 (enExample) |
| KR (1) | KR20070112775A (enExample) |
| CN (1) | CN101119993B (enExample) |
| AU (1) | AU2006205066B2 (enExample) |
| CA (1) | CA2594340C (enExample) |
| MX (1) | MX2007008334A (enExample) |
| NZ (1) | NZ555974A (enExample) |
| RU (1) | RU2007130558A (enExample) |
| WO (1) | WO2006076317A2 (enExample) |
| ZA (1) | ZA200705458B (enExample) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20070004679A1 (en) * | 2004-05-17 | 2007-01-04 | Nathalie Schlienger | Androgen receptor modulators and methods of treating disease using the same |
| MX2007008334A (es) | 2005-01-10 | 2007-09-11 | Acadia Pharm Inc | Derivados aminofenilo como moduladores de receptor de androgeno selectivos. |
| US20060173037A1 (en) * | 2005-01-10 | 2006-08-03 | Nathalie Schlienger | Aminophenyl derivatives as selective androgen receptor modulators |
| WO2007015567A1 (ja) * | 2005-08-01 | 2007-02-08 | Takeda Pharmaceutical Company Limited | 環状アミン化合物 |
| MX2008014672A (es) | 2006-05-19 | 2009-03-09 | Abbott Lab | Derivados de alcano azabiciclico sustituidos con bicicloheterociclo fusionado activos en el sistema nervioso central. |
| US8013008B2 (en) | 2006-11-30 | 2011-09-06 | Takeda Pharmaceutical Company Limited | Cyclic amine compound |
| AR067823A1 (es) | 2007-08-07 | 2009-10-21 | Takeda Pharmaceutical | Compuestos de amina ciclica |
| MX2010009162A (es) | 2008-02-22 | 2010-12-21 | Radius Health Inc | Moduladores selectivos del receptor de androgeno. |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| MX338831B (es) | 2010-02-04 | 2016-05-03 | Radius Health Inc | Moduladores selectivos de receptores de androgenos. |
| ME02474B (me) | 2010-05-12 | 2017-02-20 | Radius Health Inc | Terapijski režimi |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| EP2621901B1 (en) | 2010-09-28 | 2015-07-29 | Radius Health, Inc | Selective androgen receptor modulators |
| MX2014001086A (es) | 2011-07-27 | 2014-02-27 | Novartis Ag | Derivados de pirazolina y su uso como moduladores selectivos de los receptores de androgenos. |
| 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 |
| SMT202300072T1 (it) | 2014-03-28 | 2023-05-12 | Univ Duke | Cancro della mammella mediante l'utilizzo di modulatori selettivi del recetiore degli estrogeni |
| TWI585087B (zh) * | 2014-05-29 | 2017-06-01 | Taiho Pharmaceutical Co Ltd | Novel tetrahydropyridine pyrimidine compounds or salts 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 |
| US10441570B2 (en) | 2015-04-21 | 2019-10-15 | University Of Tennessee Research Foundation | 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 |
| US10654809B2 (en) | 2016-06-10 | 2020-05-19 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| RU2019115778A (ru) * | 2015-04-21 | 2019-06-24 | Джи Ти Икс, ИНК. | Селективные лиганды - разрушители андрогенных рецепторов (sard) и способы их применения |
| US10093613B2 (en) | 2015-04-21 | 2018-10-09 | Gtx, Inc. | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| US10370372B2 (en) | 2015-11-27 | 2019-08-06 | Taiho Pharmaceutical Co., Ltd. | Fused pyrimidine compound or salt thereof |
| 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 |
| RU2022108295A (ru) | 2016-06-22 | 2022-04-06 | Эллипсес Фарма Лтд | Способы лечения ar+ рака молочной железы |
| CN117417263A (zh) | 2017-01-05 | 2024-01-19 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
| MX2020012066A (es) | 2018-05-14 | 2021-04-28 | Nuvation Bio Inc | Compuestos anticancerígenos dirigidos a los receptores hormonales nucleares. |
| CN112423844B (zh) | 2018-07-04 | 2024-08-13 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
| US12202815B2 (en) | 2018-09-05 | 2025-01-21 | University Of Tennessee Research Foundation | Selective androgen receptor degrader (SARD) ligands and methods of use thereof |
| MA54946A (fr) | 2019-02-12 | 2021-12-22 | Radius Pharmaceuticals Inc | Procédés et composés |
| MX2021013774A (es) | 2019-05-14 | 2021-12-10 | Nuvation Bio Inc | Compuestos anticancerigenos dirigidos a los receptores hormonales nucleares. |
| TW202131930A (zh) | 2019-11-13 | 2021-09-01 | 美商諾維雪碧歐公司 | 抗癌核荷爾蒙受體標靶化合物 |
| 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 |
| AU2022269568A1 (en) | 2021-05-03 | 2023-11-16 | Nuvation Bio Inc. | Anti-cancer nuclear hormone receptor-targeting compounds |
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 |
| IL110298A (en) | 1993-07-13 | 1999-04-11 | Brann Mark Robert | 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 |
| US5952324A (en) * | 1994-11-15 | 1999-09-14 | Pharmacia & Upjohn Company | Bicyclic oxazine and thiazine oxazolidinone antibacterials |
| 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 |
| JP2002516825A (ja) | 1998-05-26 | 2002-06-11 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 電荷移動蛍光プローブを作製するためのプローブ |
| IL140084A0 (en) * | 1998-06-05 | 2002-02-10 | Astra Ab | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| BR9914018A (pt) * | 1998-09-22 | 2001-07-03 | Yamanouchi Pharmaceuticals Co | Derivado de cianofenila |
| ATE259804T1 (de) * | 1998-11-27 | 2004-03-15 | Neurosearch As | 8-azabicyclo(3.2.1)okt-2-en- und -oktanderivate |
| CA2420279C (en) | 2000-08-24 | 2011-07-19 | The University Of Tennessee Research Corporation | Selective androgen receptor modulators and methods of use thereof |
| 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 |
| EP1414795A4 (en) | 2001-07-31 | 2006-03-01 | Bristol Myers Squibb Co | BICYCLIC MODULATORS OF THE FUNCTION OF THE ANDROGEN RECEPTOR |
| WO2003016251A1 (en) | 2001-08-16 | 2003-02-27 | Ube Industries, Ltd. | Process for preparation of cyclododecanone |
| TW200407324A (en) | 2002-05-17 | 2004-05-16 | Bristol Myers Squibb Co | Bicyclic modulators of androgen receptor function |
| US7405234B2 (en) * | 2002-05-17 | 2008-07-29 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| CA2495383A1 (en) | 2002-08-12 | 2004-02-26 | Takeda Pharmaceutical Company Limited | Fused benzene derivative and use |
| 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 |
| US20060148893A1 (en) | 2003-06-10 | 2006-07-06 | Blanc Jean-Baptiste E | Chemical compounds |
| 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 |
| US20070129409A1 (en) | 2003-11-20 | 2007-06-07 | Lain-Yen Hu | Androgen receptor modulators |
| US8519158B2 (en) | 2004-03-12 | 2013-08-27 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
| EP1756101A2 (en) * | 2004-05-17 | 2007-02-28 | Acadia Pharmaceuticals Inc. | Androgen receptor modulators and method of treating disease using the same |
| JP4912148B2 (ja) | 2004-08-03 | 2012-04-11 | 中外製薬株式会社 | 新規イミダゾリジン誘導体 |
| MX2007008334A (es) * | 2005-01-10 | 2007-09-11 | Acadia Pharm Inc | Derivados aminofenilo como moduladores de receptor de androgeno selectivos. |
| US20060173037A1 (en) * | 2005-01-10 | 2006-08-03 | Nathalie Schlienger | Aminophenyl derivatives as selective androgen receptor modulators |
-
2006
- 2006-01-09 MX MX2007008334A patent/MX2007008334A/es not_active Application Discontinuation
- 2006-01-09 US US11/329,267 patent/US7585877B2/en not_active Expired - Fee Related
- 2006-01-09 CN CN200680002003.2A patent/CN101119993B/zh not_active Expired - Fee Related
- 2006-01-09 KR KR1020077018305A patent/KR20070112775A/ko not_active Withdrawn
- 2006-01-09 AU AU2006205066A patent/AU2006205066B2/en not_active Ceased
- 2006-01-09 WO PCT/US2006/000733 patent/WO2006076317A2/en not_active Ceased
- 2006-01-09 NZ NZ555974A patent/NZ555974A/en not_active IP Right Cessation
- 2006-01-09 JP JP2007550547A patent/JP5203712B2/ja not_active Expired - Fee Related
- 2006-01-09 ZA ZA200705458A patent/ZA200705458B/xx unknown
- 2006-01-09 EP EP06733660.2A patent/EP1836202B1/en not_active Not-in-force
- 2006-01-09 CA CA2594340A patent/CA2594340C/en not_active Expired - Fee Related
- 2006-01-09 RU RU2007130558/04A patent/RU2007130558A/ru not_active Application Discontinuation
-
2009
- 2009-06-30 US US12/495,514 patent/US20090270449A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR20070112775A (ko) | 2007-11-27 |
| MX2007008334A (es) | 2007-09-11 |
| ZA200705458B (en) | 2008-12-31 |
| AU2006205066B2 (en) | 2012-05-17 |
| WO2006076317A2 (en) | 2006-07-20 |
| US7585877B2 (en) | 2009-09-08 |
| US20060160845A1 (en) | 2006-07-20 |
| JP2008526888A (ja) | 2008-07-24 |
| NZ555974A (en) | 2010-11-26 |
| EP1836202B1 (en) | 2016-12-21 |
| AU2006205066A1 (en) | 2006-07-20 |
| CA2594340A1 (en) | 2006-07-20 |
| EP1836202A2 (en) | 2007-09-26 |
| WO2006076317A9 (en) | 2007-09-27 |
| JP5203712B2 (ja) | 2013-06-05 |
| CN101119993B (zh) | 2015-03-04 |
| US20090270449A1 (en) | 2009-10-29 |
| RU2007130558A (ru) | 2009-02-20 |
| CN101119993A (zh) | 2008-02-06 |
| WO2006076317A3 (en) | 2006-11-23 |
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| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20190109 |