6-{4-[(pyridin-2-ylmethyl)amino]-5-trifluoromethylpyrimidin-2-ylamino}-3,4-dihydro-1H-quinolin-2-one | 869288-95-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-{4-[(pyridin-2-ylmethyl)amino]-5-trifluoromethylpyrimidin-2-ylamino}-3,4-dihydro-1H-quinolin-2-one
• 英文别名: 6-(4-(pyridin-2-ylmethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one；6-[[4-(pyridin-2-ylmethylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-3,4-dihydro-1H-quinolin-2-one
• CAS: 869288-95-9
• 化学式: C₂₀H₁₇F₃N₆O
• 分子量: 414.39
• InChiKey: HJHMZOIXHWLHQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  91.8
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氨甲基吡啶 、 6-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-{4-[(pyridin-2-ylmethyl)amino]-5-trifluoromethylpyrimidin-2-ylamino}-3,4-dihydro-1H-quinolin-2-one
  参考文献：
  名称：

  Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): Structure–activity relationships and strategies for the elimination of reactive metabolite formation

  摘要：

  The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.

  DOI：

  10.1016/j.bmcl.2008.10.030

文献信息

• Pyrimidine derivatives for the treatment of abnormal cell growth
  申请人：Kath Charles John

  公开号：US20050256111A1

  公开（公告）日：2005-11-17

  The present invention relates to a compound of the formula 1 wherein R 1 -R 4 and Ar are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及一种式子为1的化合物，其中R1-R4和Ar的定义如本文所述。这种新型嘧啶衍生物在哺乳动物中治疗异常细胞生长，如癌症方面具有用处。本发明还涉及一种使用这种化合物治疗哺乳动物，特别是人类异常细胞生长的方法，以及包含这种化合物的制药组合物。
• PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
  申请人：Pfizer Products Incorporated

  公开号：EP1758887A1

  公开（公告）日：2007-03-07
• US7235562B2
  申请人：——

  公开号：US7235562B2

  公开（公告）日：2007-06-26
• [EN] PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH<br/>[FR] DERIVES DE PYRIMIDINE POUR LE TRAITEMENT D'UNE CROISSANCE CELLULAIRE ANORMALE
  申请人：PFIZER PROD INC

  公开号：WO2005111016A1

  公开（公告）日：2005-11-24

  The present invention relates to a compound of the formula (1) wherein R1-R4 and Ar are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.