(4-aminopiperidin-1-yl)(2-(butylamino)-4-((trans-4-hydroxycyclohexyl)amino)pyrimidin-5-yl)methanone

• 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: (4-aminopiperidin-1-yl)(2-(butylamino)-4-((trans-4-hydroxycyclohexyl)amino)pyrimidin-5-yl)methanone
• 化学式: C₂₀H₃₄N₆O₂
• 分子量: 390.529
• InChiKey: SOXQFVHZJHSFSW-WKILWMFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  116.4
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2,4-二氯-5-嘧啶甲酰氯 在 lithium hydroxide monohydrate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 9.5h， 生成 (4-aminopiperidin-1-yl)(2-(butylamino)-4-((trans-4-hydroxycyclohexyl)amino)pyrimidin-5-yl)methanone
  参考文献：
  名称：

  Discovery of Mer Specific Tyrosine Kinase Inhibitors for the Treatment and Prevention of Thrombosis

  摘要：

  The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug design and a pseudo ring replacement strategy. The cocrystal structure of Mer with two compounds (7 and 22) possessing distinct activity have been determined. Subsequent SAR studies identified compound 23 (UNC2881) as a lead compound for in vivo evaluation. When applied to live cells, 23 inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. Treatment with 23 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, 23 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis.

  DOI：

  10.1021/jm4013888