EA019560B1 - Способ лечения простаты (варианты) - Google Patents
Способ лечения простаты (варианты) Download PDFInfo
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- EA019560B1 EA019560B1 EA200701872A EA200701872A EA019560B1 EA 019560 B1 EA019560 B1 EA 019560B1 EA 200701872 A EA200701872 A EA 200701872A EA 200701872 A EA200701872 A EA 200701872A EA 019560 B1 EA019560 B1 EA 019560B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- compounds
- mice
- cells
- prostate
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65739005P | 2005-03-02 | 2005-03-02 | |
| PCT/US2006/007143 WO2006093993A1 (en) | 2005-03-02 | 2006-03-02 | Novel c-17-heteroaryl steroidal cyp17 inhibitors/antiandrogens: synthesis, in vitro biological activities, pharmacokinetics and antitumor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200701872A1 EA200701872A1 (ru) | 2008-06-30 |
| EA019560B1 true EA019560B1 (ru) | 2014-04-30 |
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| EA200701872A EA019560B1 (ru) | 2005-03-02 | 2006-03-02 | Способ лечения простаты (варианты) |
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| BR (1) | BRPI0607523A2 (enExample) |
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| EA (1) | EA019560B1 (enExample) |
| ES (2) | ES2528055T3 (enExample) |
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| MX (1) | MX2007010593A (enExample) |
| NZ (1) | NZ561571A (enExample) |
| PL (2) | PL1853619T3 (enExample) |
| PT (2) | PT2206719E (enExample) |
| SI (2) | SI1853619T1 (enExample) |
| WO (1) | WO2006093993A1 (enExample) |
| ZA (1) | ZA200708106B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2749134C1 (ru) * | 2016-08-08 | 2021-06-04 | Индустриале Кимика С.Р.Л. | СПОСОБ ПОЛУЧЕНИЯ 3β-ГИДРОКСИ-17-(1Н-БЕНЗИМИДАЗОЛ-1-ИЛ)АНДРОСТА-5,16-ДИЕНА |
| RU2819604C1 (ru) * | 2023-10-31 | 2024-05-21 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | Малотоксичные 1,3,4-оксадиазольные производные дезоксихолевой кислоты с простатопротекторным и противовоспалительным действием |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8569275B2 (en) | 2002-08-28 | 2013-10-29 | Harbor Therapeutics, Inc. | Steroids having 7-oxgen and 17-heteroaryl substitution |
| PT2206719E (pt) * | 2005-03-02 | 2015-02-05 | Univ Maryland | Composição farmacêutica compreendendo 3-beta-hidroxi-17- (1-h-benzimidazol-1-il)androsta-5,16-dieno |
| CA2726734C (en) | 2007-06-06 | 2014-10-07 | University Of Maryland, Baltimore | Hdac inhibitor ms-275 and aromatase inhibitors for the treatment of cancer |
| US20110105445A1 (en) * | 2008-03-12 | 2011-05-05 | University Of Maryland, Baltimore | Androgen receptor inactivation contributes to antitumor efficacy of cyp17 inhibitors in prostate cancer |
| US20100048524A1 (en) * | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
| GB2470700B (en) | 2008-03-25 | 2012-08-08 | Univ Maryland | C-17 heteroaryl steroidal CYP17 inhibitors |
| US8785423B2 (en) * | 2008-04-14 | 2014-07-22 | University Of Maryland, Baltimore | Compositions and methods of inducing endoplasmic reticulum stress response for the treatment of cell proliferative diseases |
| US20110190323A1 (en) | 2008-08-28 | 2011-08-04 | President And Fellows Of Harvard College | Cortistatin analogues and syntheses thereof |
| WO2010062506A2 (en) * | 2008-10-28 | 2010-06-03 | Lead Therapeutics, Inc. | Decahydro-1h-indenoquinolinone and decahydro-3h-cyclopentaphenanthridinone cyp17 inhibitors |
| WO2010091306A1 (en) * | 2009-02-05 | 2010-08-12 | Tokai Pharmaceuticals | Novel prodrugs of steroidal cyp17 inhibitors/antiandrogens |
| US20110319369A1 (en) * | 2009-02-05 | 2011-12-29 | Tokai Pharmaceuticals, Inc. | Combination of a 17 alpha-hydroxylase/c17, 20-lyase inhibitor with an additional therapeutic agent |
| US8791095B2 (en) | 2009-02-05 | 2014-07-29 | Tokai Pharmaceuticals, Inc. | Steroidal CYP17 inhibitors/antiandrogens |
| MA33451B1 (fr) | 2009-06-26 | 2012-07-03 | Novartis Ag | Dérivés d'imidazolidin-2-one 1,3-disubstitués en tant qu'inhibiteurs de cyp 17 |
| BR112012002797A2 (pt) * | 2009-08-07 | 2019-09-24 | Tokai Pharmaceuticals Inc | tratamento de câncer de próstata |
| WO2011059969A2 (en) * | 2009-11-13 | 2011-05-19 | Tokai Pharmaceuticals, Inc. | Mammalian metabolites of steroids |
| EP2506855A4 (en) * | 2009-11-30 | 2014-07-30 | Harbor Biosciences Inc | ANTICARCINOMA COMPOUNDS AND SCREENING METHODS |
| JP2013537210A (ja) | 2010-09-16 | 2013-09-30 | ノバルティス アーゲー | １７α−ヒドロキシラーゼ／Ｃ１７，２０−リアーゼ阻害剤 |
| CA2819515A1 (en) * | 2010-12-16 | 2012-06-21 | Biomarin Pharmaceutical Inc. | Cyp11b, cyp17, and/or cyp21 inhibitors |
| EA023064B1 (ru) | 2011-04-28 | 2016-04-29 | Новартис Аг | ИНГИБИТОРЫ 17α-ГИДРОКСИЛАЗЫ/C-ЛИАЗЫ |
| CN103813794A (zh) * | 2011-07-18 | 2014-05-21 | 拓凯制药公司 | 用于治疗前列腺癌的新型组合物及方法 |
| AU2012358219A1 (en) * | 2011-12-22 | 2014-07-10 | Tokai Pharmaceuticals, Inc. | Methods and compositions for combination therapy using P13K/mTOR inhibitors |
| EP2968370A4 (en) | 2013-03-14 | 2016-09-21 | Univ Maryland | AGENT FOR ANDROGEN RECEPTOR DOWNWARD CONTROL AND USES THEREOF |
| US9694005B2 (en) | 2013-04-04 | 2017-07-04 | University Of Maryland, Baltimore | Nonsteroidal and steroidal compounds with potent androgen receptor down-regulation and anti prostate cancer activity |
| EP3033088A4 (en) | 2013-08-12 | 2017-03-08 | Tokai Pharmaceuticals, Inc. | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
| CA2934819A1 (en) | 2013-12-24 | 2015-07-02 | President And Fellows Of Harvard College | Cortistatin analogues and syntheses and uses thereof |
| CN103694299A (zh) * | 2014-01-13 | 2014-04-02 | 中国药科大学 | 甾体类雄激素受体抑制剂、其制备方法及其医药用途 |
| CN105732759A (zh) * | 2015-01-29 | 2016-07-06 | 苏州晶云药物科技有限公司 | (3β)-17-(1H-苯并咪唑-1-基)雄甾-5，16-二烯-3-醇的盐及其制备方法 |
| WO2016182932A1 (en) | 2015-05-08 | 2016-11-17 | President And Fellows Of Harvard College | Cortistatin analogues, syntheses, and uses thereof |
| WO2017004411A1 (en) | 2015-07-01 | 2017-01-05 | President And Fellows Of Harvard College | Cortistatin analogues and syntheses and uses thereof |
| US10682362B2 (en) | 2015-10-14 | 2020-06-16 | Wayne State University | Treatments and diagnostics for cancers |
| IT201600121375A1 (it) * | 2016-11-30 | 2018-05-30 | Ind Chimica Srl | PROCESSO PER LA PREPARAZIONE DI 3ß-IDROSSI-17-(1H-BENZIMIDAZOL-1-IL)ANDROSTA-5,16-DIENE |
| IT201600083406A1 (it) * | 2016-08-08 | 2018-02-08 | Ind Chimica Srl | PROCESSO PER LA PREPARAZIONE DI 3β-IDROSSI-17-(1H-BENZIMIDAZOL-1-IL)ANDROSTA-5,16-DIENE |
| AU2019222651B2 (en) * | 2018-02-13 | 2024-08-22 | Dana-Farber Cancer Institute, Inc. | Cyclin-dependent kinase inhibitors and methods of use |
| AU2019222652B2 (en) | 2018-02-13 | 2021-09-02 | Dana-Farber Cancer Institute, Inc. | Cyclin-dependent kinase degraders and methods of use |
| CA3159284A1 (en) | 2019-11-26 | 2021-06-03 | Dana-Farber Cancer Institute, Inc. | Potent and selective azaindole inhibitors of cdk8 and cdk19 |
Family Cites Families (6)
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|---|---|---|---|---|
| CA27440A (en) | 1887-08-16 | James T. Walsh | Art of making sheet metal cans, for packing meats, fruits, vegetables, etc. | |
| CH621803A5 (enExample) * | 1974-08-08 | 1981-02-27 | Siphar Sa | |
| US5604213A (en) * | 1992-03-31 | 1997-02-18 | British Technology Group Limited | 17-substituted steroids useful in cancer treatment |
| US5994335A (en) * | 1997-10-17 | 1999-11-30 | The University Of Maryland, Baltimore | 17-azolyl steroids useful as androgen synthesis inhibitors |
| WO2005014023A1 (en) | 2003-07-29 | 2005-02-17 | Dompe' Pha.R.Ma S.P.A. | Pharmaceutical combination of g-csf and plgf useful for blood stem cell |
| PT2206719E (pt) | 2005-03-02 | 2015-02-05 | Univ Maryland | Composição farmacêutica compreendendo 3-beta-hidroxi-17- (1-h-benzimidazol-1-il)androsta-5,16-dieno |
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2006
- 2006-03-02 PT PT101507630T patent/PT2206719E/pt unknown
- 2006-03-02 US US11/817,550 patent/US7875599B2/en active Active
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2007
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2011
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2012
- 2012-09-06 JP JP2012196525A patent/JP5613206B2/ja not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| RU et al., Syntheses and pharmacological activity of some 17-[(2'-substituted)-4'-pyrimidyl]androstene derivatives as inhibitors of human 17alpha-hydroxylase/C17,20-lyase. J. Chin. Pharm. Sci., June 2001, vol. 10, No. 1, pages 3-8, especially Abstract and page 4, compound #9. * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2749134C1 (ru) * | 2016-08-08 | 2021-06-04 | Индустриале Кимика С.Р.Л. | СПОСОБ ПОЛУЧЕНИЯ 3β-ГИДРОКСИ-17-(1Н-БЕНЗИМИДАЗОЛ-1-ИЛ)АНДРОСТА-5,16-ДИЕНА |
| RU2819604C1 (ru) * | 2023-10-31 | 2024-05-21 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | Малотоксичные 1,3,4-оксадиазольные производные дезоксихолевой кислоты с простатопротекторным и противовоспалительным действием |
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