4-[(4-methyl-1H-indol-5-yl)amino]-5-[(1E)-4-piperazin-1-ylbut-1-en-1-yl]nicotinonitrile trifluoroaceate | 1202920-68-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(1E)-4-piperazin-1-ylbut-1-en-1-yl]nicotinonitrile trifluoroaceate
• CAS: 1202920-68-0
• 化学式: C₂HF₃O₂*C₂₃H₂₆N₆
• 分子量: 500.524
• InChiKey: GKAOVRFXHVGRSW-VEELZWTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  117.07
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  异丙基磺酰氯 、 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(1E)-4-piperazin-1-ylbut-1-en-1-yl]nicotinonitrile trifluoroaceate 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 5-{(1E)-4-[4-(isopropylsulfonyl)piperazin-1-yl]but-1-en-1-yl}-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile
  参考文献：
  名称：

  5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCθ: Optimization of enzymatic and functional activity

  摘要：

  PKC theta is a serine/threonine kinase involved in the regulation of IL2 production in T cells. It has recently become an attractive therapeutic target for a variety of immunological disorders. We describe the optimization of the enzymatic and cellular potency of a series of 5-vinyl-3-pyridinecarbonitrile inhibitors of PKC theta. A binding model was developed that explains much of the SAR observed for this series, including the enzymatic potency observed for 19. An analysis of functional potency against various physiochemical parameters suggests that cellular potency is correlated with Log D(7.4), but not with c Log P, PAMPA permeability, or TPSA. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.020
• 作为产物：
  描述：

  tert-butyl 4-[(3E)-4-{5-cyano-4-[(4-methyl-1H-indol-5-yl)amino]pyridin-3-yl}but-3-en-1-yl]piperazine-1-carboxylate trifluoroacetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以41%的产率得到4-[(4-methyl-1H-indol-5-yl)amino]-5-[(1E)-4-piperazin-1-ylbut-1-en-1-yl]nicotinonitrile trifluoroaceate
  参考文献：
  名称：

  5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCθ: Optimization of enzymatic and functional activity

  摘要：

  PKC theta is a serine/threonine kinase involved in the regulation of IL2 production in T cells. It has recently become an attractive therapeutic target for a variety of immunological disorders. We describe the optimization of the enzymatic and cellular potency of a series of 5-vinyl-3-pyridinecarbonitrile inhibitors of PKC theta. A binding model was developed that explains much of the SAR observed for this series, including the enzymatic potency observed for 19. An analysis of functional potency against various physiochemical parameters suggests that cellular potency is correlated with Log D(7.4), but not with c Log P, PAMPA permeability, or TPSA. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.020