RU2322971C2 - Фармацевтическая композиция, содержащая ингибитор гистондеацетилазы - Google Patents
Фармацевтическая композиция, содержащая ингибитор гистондеацетилазы Download PDFInfo
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- RU2322971C2 RU2322971C2 RU2005140570/15A RU2005140570A RU2322971C2 RU 2322971 C2 RU2322971 C2 RU 2322971C2 RU 2005140570/15 A RU2005140570/15 A RU 2005140570/15A RU 2005140570 A RU2005140570 A RU 2005140570A RU 2322971 C2 RU2322971 C2 RU 2322971C2
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- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Landscapes
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| WO2025041160A1 (en) * | 2023-08-19 | 2025-02-27 | Birla Institute Of Technology And Science (Bits), Pilani | Bifunctional conjugate molecules for cancer treatment and process of making the same |
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| US6777217B1 (en) | 1996-03-26 | 2004-08-17 | President And Fellows Of Harvard College | Histone deacetylases, and uses related thereto |
| US20030129724A1 (en) | 2000-03-03 | 2003-07-10 | Grozinger Christina M. | Class II human histone deacetylases, and uses related thereto |
| US7244853B2 (en) | 2001-05-09 | 2007-07-17 | President And Fellows Of Harvard College | Dioxanes and uses thereof |
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| KR20050122210A (ko) | 2003-03-17 | 2005-12-28 | 다케다 샌디에고, 인코포레이티드 | 히스톤 탈아세틸화 효소 억제제 |
| CA2540108A1 (en) * | 2003-09-25 | 2005-04-07 | Astellas Pharma Inc. | Antitumor agent_comprising a histone deacetylase inhibitor and a topoisomerase ii inhibitor |
| EP1712552A1 (en) * | 2005-04-11 | 2006-10-18 | INDENA S.p.A. | Semisynthesis process for the preparation of 10-deacetyl-n-debenzoyl-paclitaxel |
| US7446126B2 (en) * | 2004-10-08 | 2008-11-04 | Indena S.P.A. | Semisynthesis process for the preparation of 10-deacetyl-N-debenzoyl-paclitaxel |
| JP2008524246A (ja) | 2004-12-16 | 2008-07-10 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
| KR20080003334A (ko) * | 2005-03-11 | 2008-01-07 | 더 리젠트스 오브 더 유니버시티 오브 콜로라도 | 암 세포를 표피 성장 인자 억제제에 대해 감작화시키는히스톤 데아세틸라제 억제제 |
| US8999289B2 (en) | 2005-03-22 | 2015-04-07 | President And Fellows Of Harvard College | Treatment of protein degradation disorders |
| WO2006122319A2 (en) | 2005-05-11 | 2006-11-16 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| ZA200800901B (en) | 2005-07-14 | 2010-05-26 | Takeda San Diego Inc | Histone deacetylase inhibitors |
| US8222423B2 (en) | 2006-02-14 | 2012-07-17 | Dana-Farber Cancer Institute, Inc. | Bifunctional histone deacetylase inhibitors |
| JP5409015B2 (ja) | 2006-02-14 | 2014-02-05 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | ヒストンデアセチラーゼ阻害剤 |
| AU2007248656B2 (en) | 2006-05-03 | 2013-04-04 | Dana-Farber Cancer Institute, Inc. | Histone deacetylase and tubulin deacetylase inhibitors |
| GB0625283D0 (en) * | 2006-12-19 | 2007-01-24 | Cyclacel Ltd | Combination |
| PT2099442E (pt) | 2006-12-26 | 2015-02-10 | Pharmacyclics Inc | Métodos de utilização de inibidores de histona desacetilase e monitorização de biomarcadores em terapia de combinação |
| WO2009067453A1 (en) * | 2007-11-19 | 2009-05-28 | Syndax Pharmaceuticals, Inc. | Combinations of hdac inhibitors and proteasome inhibitors |
| US8293513B2 (en) * | 2007-12-14 | 2012-10-23 | Georgetown University | Histone deacetylase inhibitors |
| US8440716B2 (en) | 2008-07-23 | 2013-05-14 | President And Fellows Of Harvard College | Deacetylase inhibitors and uses thereof |
| SI2350005T1 (sl) * | 2008-08-29 | 2012-03-30 | Bayer Pharma AG | Polimorf B N aminofenil N piridin il metoksikarbonilaminometil benzamida MS |
| GB2462893B (en) * | 2008-08-29 | 2010-10-13 | Bayer Schering Pharma Ag | N-(2-aminophenyl)-4-[N-(pyridine-3-yl)-methoxycarbonyl-aminomethyl]-benzamide (MS-275) polymorph B |
| BRPI0924084B1 (pt) | 2008-12-19 | 2021-12-21 | Vertex Pharmaceuticals Incorporated | Derivados de pirazina e composição farmacêutica que os compreende |
| EP2395972A4 (en) * | 2009-02-11 | 2014-02-12 | Liangping Yu | PARTICULATE COMPOSITION AND METHOD FOR PRODUCING THE SAME |
| EP2424516A4 (en) * | 2009-05-01 | 2014-04-02 | Oncozyme Pharma Inc | PENTAMIDINE COMBINATIONS FOR THE TREATMENT OF CANCER |
| KR20120031170A (ko) * | 2009-06-08 | 2012-03-30 | 길리애드 사이언시즈, 인코포레이티드 | 알카노일아미노 벤즈아미드 아닐린 ｈｄａｃ 저해제 화합물 |
| US8716344B2 (en) | 2009-08-11 | 2014-05-06 | President And Fellows Of Harvard College | Class- and isoform-specific HDAC inhibitors and uses thereof |
| JP2013503174A (ja) * | 2009-08-25 | 2013-01-31 | アブラクシス バイオサイエンス， エルエルシー | タキサンおよびヘッジホッグ阻害剤のナノ粒子組成物を使用する併用療法 |
| AU2011253025A1 (en) | 2010-05-12 | 2012-11-29 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| NZ621221A (en) | 2011-09-13 | 2016-07-29 | Pharmacyclics Llc | Formulations of histone deacetylase inhibitor in combination with bendamustine and uses thereof |
| IN2014CN02501A (enExample) * | 2011-09-30 | 2015-06-26 | Vertex Pharma | |
| SG10201606774UA (en) | 2011-09-30 | 2016-10-28 | Vertex Pharma | Processes for making compounds useful as inhibitors of atr kinase |
| WO2013085902A1 (en) * | 2011-12-05 | 2013-06-13 | The University Of Texas M.D. | Combination therapy methods for treating an inflammatory breast cancer |
| US20140044802A1 (en) | 2012-04-05 | 2014-02-13 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase and combination therapies thereof |
| DK2904406T3 (en) | 2012-10-04 | 2018-06-18 | Vertex Pharma | METHOD OF DETERMINING THE ATR INHIBITION, INCREASED DNA DAMAGE |
| US9738637B2 (en) | 2013-03-12 | 2017-08-22 | Celgene Quantical Research, Inc. | Histone demethylase inhibitors |
| WO2014141129A2 (en) * | 2013-03-14 | 2014-09-18 | Grueneberg Dorre A | Novel methods, compounds, and compositions for inhibition of ros |
| EA201592012A8 (ru) * | 2014-02-21 | 2018-10-31 | Общество С Ограниченной Ответственностью "Биолаб 612" | Применение флагеллина для улучшенной химиотерапии |
| EA201790604A1 (ru) | 2014-09-17 | 2017-09-29 | Селджен Квонтисел Рисёрч, Инк. | Ингибиторы гистондеметилазы |
| KR102678021B1 (ko) | 2015-09-30 | 2024-06-26 | 버텍스 파마슈티칼스 인코포레이티드 | Dna 손상제와 병용되는, atr 저해제를 포함하는 암 치료용 약제학적 조성물 |
| TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
| US11596612B1 (en) | 2022-03-08 | 2023-03-07 | PTC Innovations, LLC | Topical anesthetics |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2131250C1 (ru) * | 1992-11-10 | 1999-06-10 | Рон-Пуленк Роре С.А. | Противоопухолевая композиция, содержащая производные таксана |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6174905B1 (en) * | 1996-09-30 | 2001-01-16 | Mitsui Chemicals, Inc. | Cell differentiation inducer |
| JP3354090B2 (ja) * | 1996-09-30 | 2002-12-09 | シエーリング アクチエンゲゼルシャフト | 分化誘導剤 |
| US6794392B1 (en) * | 1996-09-30 | 2004-09-21 | Schering Aktiengesellschaft | Cell differentiation inducer |
| US5753637A (en) * | 1996-10-09 | 1998-05-19 | Ideal Ideas, Inc. | Method of treating acne conditions |
| YU22401A (sh) * | 1998-09-25 | 2004-03-12 | Warner-Lambert Company | Kombinacija acetildinalina sa gemcitabinom, capecitabinom i cisplatinom |
| EP1177796B1 (en) * | 1999-04-27 | 2011-04-27 | Mitsubishi Tanabe Pharma Corporation | Medicament for prevention or therapeutic treatment of liver disease |
| NZ518668A (en) * | 1999-11-10 | 2004-04-30 | Warner Lambert Co | Combination chemotherapy comprising acetyldinaline and paclitaxal and/or carboplatin |
| US6905669B2 (en) * | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
| CZ20022216A3 (cs) * | 2001-07-02 | 2003-05-14 | Warner-Lambert Company | Kombinační chemoterapie |
| JP2003137866A (ja) * | 2001-11-01 | 2003-05-14 | Sankyo Co Ltd | フェニレンジアミン誘導体 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2131250C1 (ru) * | 1992-11-10 | 1999-06-10 | Рон-Пуленк Роре С.А. | Противоопухолевая композиция, содержащая производные таксана |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2025041160A1 (en) * | 2023-08-19 | 2025-02-27 | Birla Institute Of Technology And Science (Bits), Pilani | Bifunctional conjugate molecules for cancer treatment and process of making the same |
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