JP5026259B2 - 増殖性障害の治療に有用な２−置換−４−ヘテロアリール−ピリミジン - Google Patents
増殖性障害の治療に有用な２−置換−４−ヘテロアリール−ピリミジン Download PDFInfo
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- JP5026259B2 JP5026259B2 JP2007514117A JP2007514117A JP5026259B2 JP 5026259 B2 JP5026259 B2 JP 5026259B2 JP 2007514117 A JP2007514117 A JP 2007514117A JP 2007514117 A JP2007514117 A JP 2007514117A JP 5026259 B2 JP5026259 B2 JP 5026259B2
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- thiazol
- methyl
- pyrimidinyl
- phenyl
- pyrimidin
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Classifications
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
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- Vascular Medicine (AREA)
- Biotechnology (AREA)
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- Hospice & Palliative Care (AREA)
- Immunology (AREA)
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| GBGB0411791.7A GB0411791D0 (en) | 2004-05-26 | 2004-05-26 | Compounds |
| GB0411791.7 | 2004-05-26 | ||
| PCT/GB2005/002134 WO2005116025A2 (en) | 2004-05-26 | 2005-05-26 | 2-substituted-4-heteroaryl-pyrimidines useful for the treatment of proliferative disorders |
Publications (3)
| Publication Number | Publication Date |
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| JP2008500320A JP2008500320A (ja) | 2008-01-10 |
| JP2008500320A5 JP2008500320A5 (enExample) | 2008-06-19 |
| JP5026259B2 true JP5026259B2 (ja) | 2012-09-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| US (1) | US20090137572A1 (enExample) |
| EP (1) | EP1756098A2 (enExample) |
| JP (1) | JP5026259B2 (enExample) |
| CN (1) | CN1989138A (enExample) |
| AU (1) | AU2005247682A1 (enExample) |
| BR (1) | BRPI0511616A (enExample) |
| CA (1) | CA2566051A1 (enExample) |
| GB (1) | GB0411791D0 (enExample) |
| IL (1) | IL179508A0 (enExample) |
| MX (1) | MXPA06013632A (enExample) |
| WO (1) | WO2005116025A2 (enExample) |
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| GB0205690D0 (en) | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| GB0205688D0 (en) | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| GB0205693D0 (en) | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| JP2005524672A (ja) | 2002-03-09 | 2005-08-18 | アストラゼネカ アクチボラグ | Ｃｄｋ阻害活性を有するイミダゾリル置換ピリミジン誘導体 |
| GB0311276D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| GB0311274D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| MX2007005125A (es) * | 2004-10-28 | 2007-07-04 | Irm Llc | Compuestos y composiciones como moduladores de la senda de hedgehog. |
| CN101203500B (zh) * | 2005-01-25 | 2013-08-21 | 格利尼公司 | 取代的芳胺化合物和它们作为5-ht6调节剂的用途 |
| AU2006209216A1 (en) * | 2005-01-25 | 2006-08-03 | Galenea Corp | Substituted arylamine compounds and their use as 5-HT6 modulators |
| CN101421265A (zh) | 2006-01-18 | 2009-04-29 | 安姆根有限公司 | 作为蛋白激酶b(pkb)抑制剂的噻唑化合物 |
| WO2007132220A1 (en) * | 2006-05-12 | 2007-11-22 | Cyclacel Limited | Combination of a 2-substituted-4-heter0aryl-pyrimidine amine with a cytotoxic drug and use thereof in the treatment of a proliferative disorder |
| GB0609530D0 (en) * | 2006-05-12 | 2006-06-21 | Cyclacel Ltd | Combination |
| WO2007132221A1 (en) * | 2006-05-12 | 2007-11-22 | Cyclacel Limited | Combined anticancer pyrimidine-thiazole aurora kinase inhibitors |
| WO2009011871A2 (en) | 2007-07-17 | 2009-01-22 | Amgen Inc. | Thiadiazole modulators of pkb |
| AU2008276521B2 (en) | 2007-07-17 | 2011-11-03 | Amgen Inc. | Heterocyclic modulators of PKB |
| US20110190280A1 (en) * | 2007-08-29 | 2011-08-04 | George Adjabeng | Thiazole And Oxazole Kinase Inhibitors |
| WO2009047359A1 (en) * | 2007-10-12 | 2009-04-16 | Ingenium Pharmaceuticals Gmbh | Inhibitors of protein kinases |
| WO2009076140A1 (en) * | 2007-12-13 | 2009-06-18 | Smithkline Beecham Corporation | Thiazole and oxazole kinase inhibitors |
| HUE030912T2 (en) | 2008-02-15 | 2017-06-28 | Rigel Pharmaceuticals Inc | Pyrimidine-2-amine compounds and their use as inhibitors of yak kinases |
| GB0805477D0 (en) * | 2008-03-26 | 2008-04-30 | Univ Nottingham | Pyrimidines triazines and their use as pharmaceutical agents |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| EP2440058A4 (en) | 2009-06-12 | 2012-11-21 | Dana Farber Cancer Inst Inc | MELTED HETEROCYCLIC COMPOUNDS AND APPLICATIONS THEREOF |
| KR20120082906A (ko) | 2009-09-30 | 2012-07-24 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 자가포식현상-향상 유전자 생성물의 조절을 통한 자가포식현상의 조절 방법 |
| WO2011059610A1 (en) * | 2009-11-10 | 2011-05-19 | Glaxosmithkline Llc | Benzene sulfonamide thiazole and oxazole compounds |
| EP2937345B1 (en) | 2009-12-29 | 2018-03-21 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
| WO2012113774A1 (en) * | 2011-02-24 | 2012-08-30 | Nerviano Medical Sciences S.R.L. | Thiazolylphenyl-benzenesulfonamido derivatives as kinase inhibitors |
| WO2013059634A1 (en) | 2011-10-20 | 2013-04-25 | The Regents Of The University Of California | Use of cdk9 inhibitors to reduce cartilage degradation |
| WO2013074986A1 (en) * | 2011-11-17 | 2013-05-23 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-jun-n-terminal kinase (jnk) |
| US10112927B2 (en) | 2012-10-18 | 2018-10-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
| US10000483B2 (en) | 2012-10-19 | 2018-06-19 | Dana-Farber Cancer Institute, Inc. | Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof |
| US9758522B2 (en) | 2012-10-19 | 2017-09-12 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
| WO2015058140A1 (en) | 2013-10-18 | 2015-04-23 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
| WO2015058126A1 (en) | 2013-10-18 | 2015-04-23 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of prolferative diseases |
| RU2016141934A (ru) | 2014-04-04 | 2018-05-07 | Сирос Фармасьютикалз, Инк. | Ингибиторы циклин-зависимой киназы 7 (cdk7) |
| US10017477B2 (en) | 2014-04-23 | 2018-07-10 | Dana-Farber Cancer Institute, Inc. | Janus kinase inhibitors and uses thereof |
| WO2015164604A1 (en) | 2014-04-23 | 2015-10-29 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged janus kinase inhibitors and uses thereof |
| US10300073B2 (en) | 2014-10-14 | 2019-05-28 | The Regents Of The University Of California | Use of CDK9 and BRD4 inhibitors to inhibit inflammation |
| AU2015371251B2 (en) | 2014-12-23 | 2020-06-11 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
| CN107427521B (zh) | 2015-03-27 | 2021-08-03 | 达纳-法伯癌症研究所股份有限公司 | 细胞周期蛋白依赖性激酶的抑制剂 |
| EP3307728A4 (en) | 2015-06-12 | 2019-07-17 | Dana Farber Cancer Institute, Inc. | COMBINATION THERAPY OF TRANSCRIPTION INHIBITORS AND CHINESE INHIBITORS |
| USRE49850E1 (en) * | 2015-08-04 | 2024-02-27 | Aucentra Therapeutics Pty Ltd | N-(pyridin-2-yl)-4-(thiazol-5-yl)pyrimidin-2-amine derivatives as therapeutic compounds |
| JP7028766B2 (ja) | 2015-09-09 | 2022-03-02 | ダナ－ファーバー キャンサー インスティテュート， インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
| AU2019207517A1 (en) * | 2018-01-15 | 2020-08-27 | Aucentra Therapeutics Pty Ltd | 5-(pyrimidin-4-yl)thiazol-2-yl urea derivatives as therapeutic agents |
| JP7590185B2 (ja) | 2018-06-25 | 2024-11-26 | ダナ－ファーバー キャンサー インスティテュート， インコーポレイテッド | Ｔａｉｒｅファミリーキナーゼインヒビターおよびそれらの使用 |
| CN111039941B (zh) * | 2018-10-12 | 2023-03-21 | 上海医药集团股份有限公司 | 一种含氮杂环化合物、其制备方法及应用 |
| WO2020140098A1 (en) | 2018-12-28 | 2020-07-02 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 and uses thereof |
| KR20260040130A (ko) * | 2023-06-14 | 2026-03-23 | 프로테나 바이오사이언시즈 리미티드 | 신경계 장애 치료를 위한 5-(신놀린-6-일)티아졸 화합물 |
| CN116903592B (zh) * | 2023-07-13 | 2025-08-01 | 特科罗生物科技(成都)有限公司 | 一种嘧啶胺类nuak抑制剂及其制备方法和用途 |
| WO2026024674A1 (en) | 2024-07-22 | 2026-01-29 | Genesis Therapeutics, Inc. | Methods of treating skp2-associated cancers |
Family Cites Families (22)
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| US5516775A (en) * | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
| CA2174080A1 (en) * | 1993-10-12 | 1995-04-20 | Paul Edward Aldrich | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
| GB9519275D0 (en) * | 1995-09-21 | 1995-11-22 | Univ Dundee | Substances and their therapeutic use |
| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| DE69736351T4 (de) * | 1996-05-08 | 2009-07-23 | Cyclacel Ltd. | Methoden und mittel zur hemmung der cdk4-aktivität |
| US6703395B2 (en) * | 1998-03-04 | 2004-03-09 | Institute Of Experimental Botany Of The Academy Of Sciences Of The Czech Republic | Cyclin dependent kinase inhibitor |
| AU753015B2 (en) * | 1998-03-04 | 2002-10-03 | Cyclacel Limited | Cyclin dependent kinase inhibitor |
| US6417185B1 (en) * | 1998-06-19 | 2002-07-09 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| US7045519B2 (en) * | 1998-06-19 | 2006-05-16 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| AU2001242629B2 (en) * | 2000-03-29 | 2005-08-11 | Cyclacel Limited | 2-substituted 4-heteroaryl-pyrimidines and their use in the treatment of proliferative disorders |
| GB0107901D0 (en) * | 2001-03-29 | 2001-05-23 | Cyclacel Ltd | Anti-cancer compounds |
| CA2446756C (en) * | 2001-06-01 | 2011-03-08 | Vertex Pharmaceuticals Incorporated | Thiazole compounds useful as inhibitors of protein kinase |
| US20040181066A1 (en) * | 2001-08-01 | 2004-09-16 | Fraley Mark E. | Tyrosine kinase inhibitors |
| ATE349443T1 (de) * | 2001-09-28 | 2007-01-15 | Cyclacel Ltd | N-(4-(4-methylthiazol-5-yl)pyrimidin-2-yl)-n- phenylamine als antiproliferative verbindungen |
| GB0226582D0 (en) * | 2002-11-14 | 2002-12-18 | Cyclacel Ltd | Anti-viral compounds |
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| WO2004087698A2 (en) * | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
| EP1648875A1 (en) * | 2003-07-30 | 2006-04-26 | Cyclacel Limited | 2-aminophenyl-4-phenylpyrimidines as kinase inhibitors |
| CA2533870A1 (en) * | 2003-07-30 | 2005-02-10 | Shudong Wang | Pyridinylamino-pyrimidine derivatives as protein kinase inhibitors |
| CA2542880A1 (en) * | 2003-10-21 | 2005-05-12 | Cyclacel Limited | Pyrimidin-4-yl-3, 4-thione compounds and their use in therapy |
| WO2005113550A1 (ja) * | 2004-05-20 | 2005-12-01 | Mitsubishi Pharma Corporation | アミノピリミジン誘導体及びその医薬としての用途 |
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Also Published As
| Publication number | Publication date |
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| JP2008500320A (ja) | 2008-01-10 |
| US20090137572A1 (en) | 2009-05-28 |
| GB0411791D0 (en) | 2004-06-30 |
| WO2005116025A3 (en) | 2006-02-23 |
| IL179508A0 (en) | 2007-05-15 |
| AU2005247682A1 (en) | 2005-12-08 |
| BRPI0511616A (pt) | 2008-01-02 |
| MXPA06013632A (es) | 2007-03-23 |
| CN1989138A (zh) | 2007-06-27 |
| EP1756098A2 (en) | 2007-02-28 |
| WO2005116025A2 (en) | 2005-12-08 |
| CA2566051A1 (en) | 2005-12-08 |
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