7-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one | 1141374-90-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 7-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one
• CAS: 1141374-90-4
• 化学式: C₁₅H₁₂ClF₃N₄O
• 分子量: 356.735
• InChiKey: SCGUCANHHWVXAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.91
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  7-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one 、 环丁基胺 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-(4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-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
• 作为产物：
  描述：

  7-氨基-1,3,4,5-四氢-苯并[B]氮杂革-2-酮 、 2,4-二氯-5-三氟甲基嘧啶 在 zinc(II) chloride 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 1.0h， 生成 7-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-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