KR20140053836A - 조합물 - Google Patents
조합물 Download PDFInfo
- Publication number
- KR20140053836A KR20140053836A KR1020137021098A KR20137021098A KR20140053836A KR 20140053836 A KR20140053836 A KR 20140053836A KR 1020137021098 A KR1020137021098 A KR 1020137021098A KR 20137021098 A KR20137021098 A KR 20137021098A KR 20140053836 A KR20140053836 A KR 20140053836A
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- South Korea
- Prior art keywords
- cancer
- administered
- compound
- days
- methyl
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- 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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| WO2015069266A1 (en) * | 2013-11-07 | 2015-05-14 | Flynn Daniel L | Methods for inhibiting tie2 kinase useful in the treatment of cancer |
| AU2019216351B2 (en) | 2018-01-31 | 2024-07-25 | Deciphera Pharmaceuticals, Llc | Combination therapy for the treatment of mastocytosis |
| CN111818915B (zh) | 2018-01-31 | 2024-05-24 | 德西费拉制药有限责任公司 | 治疗胃肠道间质瘤的组合疗法 |
| NZ784949A (en) | 2019-08-12 | 2025-09-26 | Deciphera Pharmaceuticals Llc | Ripretinib for treating gastrointestinal stromal tumors |
| TWI878335B (zh) | 2019-08-12 | 2025-04-01 | 美商迪賽孚爾製藥有限公司 | 治療胃腸道基質瘤方法 |
| AU2020419197B2 (en) | 2019-12-30 | 2023-08-31 | Deciphera Pharmaceuticals, Llc | Amorphous kinase inhibitor formulations and methods of use thereof |
| KR20250057151A (ko) | 2019-12-30 | 2025-04-28 | 데시페라 파마슈티칼스, 엘엘씨 | 1-(4-브로모-5-(1-에틸-7-(메틸아미노)-2-옥소-1,2-디히드로-1,6-나프티리딘-3-일)-2-플루오로페닐)-3-페닐우레아의조성물 |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090131367A1 (en) * | 2007-11-19 | 2009-05-21 | The Regents Of The University Of Colorado | Combinations of HDAC Inhibitors and Proteasome Inhibitors |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5604213A (en) | 1992-03-31 | 1997-02-18 | British Technology Group Limited | 17-substituted steroids useful in cancer treatment |
| US5681835A (en) | 1994-04-25 | 1997-10-28 | Glaxo Wellcome Inc. | Non-steroidal ligands for the estrogen receptor |
| GB9716557D0 (en) | 1997-08-06 | 1997-10-08 | Glaxo Group Ltd | Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity |
| US6328590B1 (en) | 2000-07-20 | 2001-12-11 | Emc Corporation | Methods and apparatus for controlling attachment of an electronic module with a circuit board connector |
| ES2551293T3 (es) * | 2004-03-24 | 2015-11-17 | Abbvie Inc. | Inhibidores de quinasas de pirazol tricíclicos |
| US8324230B2 (en) | 2004-10-13 | 2012-12-04 | Pfizer Inc. | Crystalline forms of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-Yl]-N-(2-hydroxyethyl)-4-methylbenzamide |
| US7709517B2 (en) | 2005-05-13 | 2010-05-04 | The Regents Of The University Of California | Diarylhydantoin compounds |
| AU2006282896A1 (en) * | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP1840114A1 (en) | 2006-03-30 | 2007-10-03 | LTB4 Sweden AB | Crystalline Leukotriene B4 |
| WO2007115286A2 (en) | 2006-04-05 | 2007-10-11 | Novartis Ag. | Combinations of therapeutic agents for treating cancer |
| WO2007122686A1 (ja) | 2006-04-14 | 2007-11-01 | Eisai R & D Management Co., Ltd. | ベンズイミダゾール化合物 |
| NZ597830A (en) | 2006-08-25 | 2013-02-22 | Cougar Biotechnology Inc | Methods and compositions for treating cancer comprising abiraterone acetate and prednisone |
| US20080051380A1 (en) | 2006-08-25 | 2008-02-28 | Auerbach Alan H | Methods and compositions for treating cancer |
| JP4299327B2 (ja) | 2006-08-31 | 2009-07-22 | トヨタ自動車株式会社 | 可変バルブタイミング装置 |
| WO2008094321A2 (en) | 2006-10-04 | 2008-08-07 | Universtiy Of South Florida | Akt sensitization of cancer cells |
| EP2079714B1 (de) | 2006-10-13 | 2012-09-26 | Basf Se | Hydrate des 2-chlor-5-ý3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluormethyl)-1-(2h)-pyrimidinyl¨-4-fluor-n-ýýmethyl-(1-methylethyl)amino¨sulfonyl¨benzamids |
| AR064010A1 (es) | 2006-12-06 | 2009-03-04 | Merck & Co Inc | Inhibidores de la actividad de la akt |
| UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| ES2522365T3 (es) | 2007-10-11 | 2014-11-14 | Astrazeneca Ab | Derivados de pirrolo [2,3-D] pirimidina como inhibidores de proteína quinasas B |
| DE102008044901A1 (de) | 2008-08-29 | 2010-03-04 | Siemens Aktiengesellschaft | Verfahren und Vorrichtung zur Auswahl eines Bestrahlungsplans sowie Bestrahlungsanlage |
| UA106740C2 (uk) | 2009-01-30 | 2014-10-10 | Глаксосмітклайн Ллс | Кристалічний гідрохлорид n-{(1s)-2-аміно-1-[(3-фторфеніл)метил]етил}-5-хлор-4-(4-хлор-1-метил-1h-піразол-5-іл)-2-тіофенкарбоксаміду |
| WO2010149755A1 (en) | 2009-06-26 | 2010-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
| BR112012008274A2 (pt) | 2009-10-08 | 2015-09-22 | Glaxosmithkline Llc | combinação |
| SG10201504303SA (en) | 2011-04-01 | 2015-07-30 | Genentech Inc | Combinations Of AKT Inhibitor Compounds And Chemotherapeutic Agents, And Methods Of Use |
| EP2704699A1 (en) | 2011-05-03 | 2014-03-12 | University of Rochester | Methods for treating prostate cancer |
| AU2012283775A1 (en) | 2011-07-13 | 2014-01-23 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| HRP20161256T1 (hr) | 2011-10-10 | 2016-11-18 | Zach System | Postupak priprave 17-supstituiranih steroida |
| US20140329786A1 (en) | 2011-11-30 | 2014-11-06 | Astrazeneca Ab | Combination treatment of cancer |
| CA3218491A1 (en) | 2012-06-04 | 2013-12-12 | Pharmacyclics Llc | Crystalline forms of a bruton's tyrosine kinase inhibitor |
| JP6355724B2 (ja) | 2013-10-01 | 2018-07-11 | ノバルティス アーゲー | がんを治療するためのアフレセルチブと組み合わせたエンザルタミド |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090131367A1 (en) * | 2007-11-19 | 2009-05-21 | The Regents Of The University Of Colorado | Combinations of HDAC Inhibitors and Proteasome Inhibitors |
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| EP2663189B1 (en) | 2018-07-04 |
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| AU2012205601B2 (en) | 2016-03-24 |
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