UA78029C2 - Fluorinated derivatives of 4-azasteroid as modulators of androgen receptor - Google Patents
Fluorinated derivatives of 4-azasteroid as modulators of androgen receptor Download PDFInfo
- Publication number
- UA78029C2 UA78029C2 UA20041008266A UA20041008266A UA78029C2 UA 78029 C2 UA78029 C2 UA 78029C2 UA 20041008266 A UA20041008266 A UA 20041008266A UA 20041008266 A UA20041008266 A UA 20041008266A UA 78029 C2 UA78029 C2 UA 78029C2
- Authority
- UA
- Ukraine
- Prior art keywords
- fluoro
- methyl
- oxo
- carboxamide
- aza
- Prior art date
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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Reproductive Health (AREA)
- Virology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Gynecology & Obstetrics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Nutrition Science (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Tropical Medicine & Parasitology (AREA)
- Dermatology (AREA)
- AIDS & HIV (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36382202P | 2002-03-13 | 2002-03-13 | |
| PCT/US2003/008277 WO2003077919A1 (en) | 2002-03-13 | 2003-03-07 | Fluorinated 4-azasteroid derivatives as androgen receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA78029C2 true UA78029C2 (en) | 2007-02-15 |
Family
ID=28041817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20041008266A UA78029C2 (en) | 2002-03-13 | 2003-07-03 | Fluorinated derivatives of 4-azasteroid as modulators of androgen receptor |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US7186838B2 (no) |
| EP (1) | EP1485095A4 (no) |
| JP (2) | JP4516316B2 (no) |
| KR (1) | KR100938136B1 (no) |
| CN (1) | CN1652786A (no) |
| AU (1) | AU2003218235B2 (no) |
| BR (1) | BR0308355A (no) |
| CA (1) | CA2478186C (no) |
| EC (1) | ECSP045287A (no) |
| HR (1) | HRP20040822A2 (no) |
| IL (2) | IL163825A0 (no) |
| IS (1) | IS7425A (no) |
| MA (1) | MA27112A1 (no) |
| MX (1) | MXPA04008800A (no) |
| NO (1) | NO20044312L (no) |
| NZ (1) | NZ534946A (no) |
| PL (1) | PL372920A1 (no) |
| RU (1) | RU2320670C2 (no) |
| UA (1) | UA78029C2 (no) |
| WO (1) | WO2003077919A1 (no) |
| ZA (1) | ZA200406843B (no) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8853266B2 (en) | 2001-12-06 | 2014-10-07 | University Of Tennessee Research Foundation | Selective androgen receptor modulators for treating diabetes |
| US7772433B2 (en) | 2002-02-28 | 2010-08-10 | University Of Tennessee Research Foundation | SARMS and method of use thereof |
| CA2478186C (en) * | 2002-03-13 | 2011-08-23 | Merck & Co., Inc. | Fluorinated 4-azasteroid derivatives as androgen receptor modulators |
| KR20120065435A (ko) * | 2002-05-10 | 2012-06-20 | 에프. 호프만-라 로슈 아게 | 골다공증 치료 및 예방용 비스포스폰산 |
| US8309603B2 (en) | 2004-06-07 | 2012-11-13 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| US20070088042A1 (en) * | 2004-09-09 | 2007-04-19 | Meissner Robert S | Fluorinated 4-azasteroid derivatives as androgen receptor modulators |
| CA2537660A1 (en) * | 2003-09-10 | 2005-03-24 | Merck & Co., Inc. | 17-heterocyclic-4-azasteroid derivatives as androgen receptor modulators |
| CN101721402B (zh) * | 2003-10-14 | 2013-03-13 | 田纳西大学研究基金会 | 用选择性雄激素受体调节剂治疗骨相关病症 |
| JP2007509962A (ja) * | 2003-10-31 | 2007-04-19 | メルク エンド カムパニー インコーポレーテッド | アンドロゲン受容体調節剤としての２１−複素環−４−アザステロイド誘導体 |
| CA2551737C (en) | 2004-01-07 | 2009-11-10 | Endorecherche, Inc. | Helix 12 directed steroidal pharmaceutical products |
| WO2005097127A2 (en) * | 2004-04-02 | 2005-10-20 | Merck & Co., Inc. | Method of treating men with metabolic and anthropometric disorders |
| CN1950086A (zh) * | 2004-04-28 | 2007-04-18 | 默克公司 | 作为雄激素受体调节剂的氟化的4－氮杂甾族化合物 |
| US9889110B2 (en) | 2004-06-07 | 2018-02-13 | University Of Tennessee Research Foundation | Selective androgen receptor modulator for treating hormone-related conditions |
| US9884038B2 (en) | 2004-06-07 | 2018-02-06 | University Of Tennessee Research Foundation | Selective androgen receptor modulator and methods of use thereof |
| CA2576988A1 (en) * | 2004-08-25 | 2006-03-09 | Merck & Co., Inc. | Androgen receptor modulators |
| CN101146535A (zh) * | 2005-03-25 | 2008-03-19 | 默克公司 | 用睾酮补充剂和5α-还原酶抑制剂治疗男性病人的方法 |
| US7301026B2 (en) * | 2005-05-05 | 2007-11-27 | Merck & Co., Inc | Process for making fluorinated 4-azasteroid derivatives |
| TW200730505A (en) | 2005-12-07 | 2007-08-16 | Merck & Co Inc | Polymorphs of an androgen receptor modulator |
| US9730908B2 (en) | 2006-08-24 | 2017-08-15 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| US10010521B2 (en) | 2006-08-24 | 2018-07-03 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| US9844528B2 (en) | 2006-08-24 | 2017-12-19 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| EP2269611B1 (en) | 2006-11-16 | 2016-03-23 | Gemmus Pharma Inc. | EP2 and EP4 agonists as agents for the treatment of influenza A viral infection |
| US7968603B2 (en) | 2007-09-11 | 2011-06-28 | University Of Tennessee Research Foundation | Solid forms of selective androgen receptor modulators |
| WO2009082437A2 (en) | 2007-12-21 | 2009-07-02 | Ligand Pharmaceuticals Incorporated | Selective androgen receptor modulators (sarms) and uses thereof |
| WO2009100171A1 (en) * | 2008-02-07 | 2009-08-13 | Bristol-Myers Squibb Company | Fused heteroaryl modulators of glucocorticoid receptor, ap-1, and/or nf-kb activity and use thereof |
| EP2149551A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | N-(Indol-3-ylalkyl)-(hetero)arylamidderivate als Modulatoren des EP2-Rezeptors |
| EP2149554A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma Aktiengesellschaft | Indolylamide als Modulatoren des EP2-Rezeptors |
| EP2149552A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | 5,6 substituierte Benzamid-Derivate als Modulatoren des EP2-Rezeptors |
| RS56042B1 (sr) | 2010-06-10 | 2017-09-29 | Seragon Pharmaceuticals Inc | Modulatori estrogenih receptora i njihove upotrebe |
| DE102010027016A1 (de) | 2010-07-09 | 2012-01-12 | Universitätsklinikum Jena | Steroid-Styrylfarbstoff-Konjugate zur Simulation und direkten lichtoptischen Detektion des Verhaltens von Steroiden im lebenden biologischen Gewebe und in Gegenwart von steroidbindenden Proteinen |
| US9193714B2 (en) | 2011-12-14 | 2015-11-24 | Seragon Pharmaceuticals, Inc. | Fluorinated estrogen receptor modulators and uses thereof |
| US10314807B2 (en) | 2012-07-13 | 2019-06-11 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
| US10987334B2 (en) | 2012-07-13 | 2021-04-27 | University Of Tennessee Research Foundation | Method of treating ER mutant expressing breast cancers with selective androgen receptor modulators (SARMs) |
| US9744149B2 (en) | 2012-07-13 | 2017-08-29 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
| US9969683B2 (en) | 2012-07-13 | 2018-05-15 | Gtx, Inc. | Method of treating estrogen receptor (ER)-positive breast cancers with selective androgen receptor modulator (SARMS) |
| US9622992B2 (en) | 2012-07-13 | 2017-04-18 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
| US10258596B2 (en) | 2012-07-13 | 2019-04-16 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
| EP3733170A1 (en) | 2012-07-13 | 2020-11-04 | Oncternal Therapeutics, Inc. | A method of treating androgen receptor (ar) -positive breast cancers with selective androgen receptor modulator (sarms) |
| US9566310B2 (en) | 2012-09-10 | 2017-02-14 | Board Of Regents Of The Nevada System Of Higher Education On Behalf Of The University Of Nevada, Reno | Methods of treating muscular dystrophy |
| EP2968273A4 (en) | 2013-03-15 | 2016-08-31 | Univ Nevada | METHOD FOR THE TREATMENT OF MUSCLE DYSTROPHIES |
| EP3094323A4 (en) | 2014-01-17 | 2017-10-11 | Ligand Pharmaceuticals Incorporated | Methods and compositions for modulating hormone levels |
| KR101586345B1 (ko) * | 2014-08-06 | 2016-01-18 | 한국생명공학연구원 | 에스트라디올 벤조에이트(Estradiol benzoate) 또는 이의 약학적으로 허용 가능한 염을 포함하는 근력약화 관련 질환의 예방 또는 치료용 약학적 조성물 |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| WO2019071144A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | USE OF P38 INHIBITORS TO REDUCE DUX4 EXPRESSION |
| CA3090724A1 (en) | 2018-02-11 | 2019-08-15 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Steroid derivative regulators, method for preparing the same, and uses thereof |
| CN112638928B (zh) | 2019-08-07 | 2023-12-22 | 上海翰森生物医药科技有限公司 | 一种甾族类衍生物调节剂的盐及其晶型 |
| US11904006B2 (en) | 2019-12-11 | 2024-02-20 | University Of Iowa Research Foundation | Poly(diaminosulfide) particle-based vaccine |
| CN112851745B (zh) * | 2021-01-25 | 2021-11-16 | 广西民族大学 | 氮杂甾体吡啶类化合物及其合成与应用 |
| WO2022271951A1 (en) | 2021-06-23 | 2022-12-29 | University Of Iowa Research Foundation | Sustained release formulations comprising a selective androgen receptor modulator |
| CN115558013A (zh) * | 2021-07-02 | 2023-01-03 | 石家庄迪斯凯威医药科技有限公司 | 一种甾体磷酸酯化合物及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5187278A (en) | 1990-08-27 | 1993-02-16 | Merck & Co., Inc. | Trialkylsilyl trifluoromethanesulfonate mediated α-methylenic carbon functionalization of 4-aza-5α-androstan-3-one steroids |
| GB9216284D0 (en) * | 1992-07-31 | 1992-09-16 | Erba Carlo Spa | Fluorinated 17beta-substituted 4-aza-5alpha-androstane-3-one derivatives |
| TW408127B (en) * | 1993-09-17 | 2000-10-11 | Glaxo Inc | Androstenones |
| AU707324B2 (en) * | 1995-09-15 | 1999-07-08 | Merck & Co., Inc. | 4-azasteroids for treatment of hyperandrogenic conditions |
| AU5594398A (en) * | 1996-12-09 | 1998-07-03 | Merck & Co., Inc. | Methods and compositions for preventing and treating bone loss |
| CA2478186C (en) * | 2002-03-13 | 2011-08-23 | Merck & Co., Inc. | Fluorinated 4-azasteroid derivatives as androgen receptor modulators |
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2003
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- 2003-03-07 CN CNA038104857A patent/CN1652786A/zh active Pending
- 2003-03-07 PL PL03372920A patent/PL372920A1/xx not_active Application Discontinuation
- 2003-03-07 EP EP03714228A patent/EP1485095A4/en not_active Withdrawn
- 2003-03-07 NZ NZ534946A patent/NZ534946A/en not_active IP Right Cessation
- 2003-03-07 RU RU2004130452/04A patent/RU2320670C2/ru not_active IP Right Cessation
- 2003-03-07 AU AU2003218235A patent/AU2003218235B2/en not_active Ceased
- 2003-03-07 MX MXPA04008800A patent/MXPA04008800A/es active IP Right Grant
- 2003-03-07 WO PCT/US2003/008277 patent/WO2003077919A1/en active Application Filing
- 2003-03-07 BR BR0308355-1A patent/BR0308355A/pt not_active IP Right Cessation
- 2003-03-07 IL IL16382503A patent/IL163825A0/xx unknown
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- 2003-03-07 KR KR1020047014281A patent/KR100938136B1/ko not_active IP Right Cessation
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2004
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- 2004-08-27 ZA ZA200406843A patent/ZA200406843B/en unknown
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- 2004-09-10 EC EC2004005287A patent/ECSP045287A/es unknown
- 2004-10-07 MA MA27893A patent/MA27112A1/fr unknown
- 2004-10-12 NO NO20044312A patent/NO20044312L/no unknown
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2010
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2478186C (en) | 2011-08-23 |
| US7186838B2 (en) | 2007-03-06 |
| MXPA04008800A (es) | 2004-11-26 |
| KR20040097167A (ko) | 2004-11-17 |
| NO20044312L (no) | 2004-10-12 |
| IL163825A0 (en) | 2005-12-18 |
| US20050165039A1 (en) | 2005-07-28 |
| ECSP045287A (es) | 2004-10-26 |
| JP4516316B2 (ja) | 2010-08-04 |
| AU2003218235B2 (en) | 2008-05-15 |
| IS7425A (is) | 2004-08-26 |
| PL372920A1 (en) | 2005-08-08 |
| BR0308355A (pt) | 2005-01-25 |
| CN1652786A (zh) | 2005-08-10 |
| KR100938136B1 (ko) | 2010-01-22 |
| HRP20040822A2 (en) | 2005-06-30 |
| EP1485095A1 (en) | 2004-12-15 |
| ZA200406843B (en) | 2007-06-27 |
| AU2003218235A1 (en) | 2003-09-29 |
| RU2004130452A (ru) | 2005-04-10 |
| CA2478186A1 (en) | 2003-09-25 |
| MA27112A1 (fr) | 2004-12-20 |
| JP2010168391A (ja) | 2010-08-05 |
| JP2005526082A (ja) | 2005-09-02 |
| IL163825A (en) | 2010-12-30 |
| JP5268975B2 (ja) | 2013-08-21 |
| RU2320670C2 (ru) | 2008-03-27 |
| WO2003077919A1 (en) | 2003-09-25 |
| EP1485095A4 (en) | 2009-11-18 |
| NZ534946A (en) | 2007-05-31 |
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