N4-((1R,2R)-2-(dimethylamino)cyclopentyl)-N2-(pyridin-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine | 1095647-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N4-((1R,2R)-2-(dimethylamino)cyclopentyl)-N2-(pyridin-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
• 英文别名: 4-N-[(1R,2R)-2-(dimethylamino)cyclopentyl]-2-N-pyridin-4-yl-5-(trifluoromethyl)pyrimidine-2,4-diamine
• CAS: 1095647-99-6
• 化学式: C₁₇H₂₁F₃N₆
• 分子量: 366.389
• InChiKey: CACAHNPUHHBBQA-ZIAGYGMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-溴吡啶 、 4-N-[(1R,2R)-2-(dimethylamino)cyclopentyl]-5-(trifluoromethyl)pyrimidine-2,4-diamine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以52%的产率得到N4-((1R,2R)-2-(dimethylamino)cyclopentyl)-N2-(pyridin-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
  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