2-[7-[3-(cyclopentanecarbonylamino)propylamino]-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]-N-(2-methylpropyl)-1,3-thiazole-4-carboxamide | 1562498-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[7-[3-(cyclopentanecarbonylamino)propylamino]-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]-N-(2-methylpropyl)-1,3-thiazole-4-carboxamide
• CAS: 1562498-45-6
• 化学式: C₃₀H₃₇N₇O₃S
• 分子量: 575.735
• InChiKey: YSDVXKUGVXDCHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide 在 ammonium sulfide 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 乙醇 、 二甲胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 2-[7-[3-(cyclopentanecarbonylamino)propylamino]-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]-N-(2-methylpropyl)-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Discovery of 6-aryl-azabenzimidaoles that inhibit the TBK1/IKK-ε kinases

  摘要：

  The discovery and optimization of a series of 6-aryl-azabenzimidazole inhibitors of TBK1 and IKK-epsilon is described. Various internal azabenzimidazole leads and reported TBK1/IKK-epsilon inhibitors were docked into a TBK1 homology model. The resulting overlays inspired a focused screen of 6-substituted azabenzimidazoles against TBK1/IKK-epsilon. This screen resulted in initial hit compound 3. The TBK1/IKK-epsilon enzyme and cell potency of this compound was further improved using structure guided drug design. Systematic exploration of the C6 aryl group led to compound 19, a potent inhibitor of TBK1 with selectivity against cell cycle kinases CDK2 and Aurora B. Further elaboration and optimization gave compound 25, a single digit nM inhibitor of TBK1. These compounds may serve as in vitro probes to evaluate TBK1/IKK-epsilon as an oncology target. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.123

文献信息

• Discovery of 6-aryl-azabenzimidaoles that inhibit the TBK1/IKK-ε kinases
  作者：Jeffrey W. Johannes、Claudio Chuaqui、Scott Cowen、Erik Devereaux、Lakshmaiah Gingipalli、Audrey Molina、Tao Wang、David Whitston、Xiaoyun Wu、Hai-Jun Zhang、Michael Zinda

  DOI：10.1016/j.bmcl.2013.12.123

  日期：2014.2

  The discovery and optimization of a series of 6-aryl-azabenzimidazole inhibitors of TBK1 and IKK-epsilon is described. Various internal azabenzimidazole leads and reported TBK1/IKK-epsilon inhibitors were docked into a TBK1 homology model. The resulting overlays inspired a focused screen of 6-substituted azabenzimidazoles against TBK1/IKK-epsilon. This screen resulted in initial hit compound 3. The TBK1/IKK-epsilon enzyme and cell potency of this compound was further improved using structure guided drug design. Systematic exploration of the C6 aryl group led to compound 19, a potent inhibitor of TBK1 with selectivity against cell cycle kinases CDK2 and Aurora B. Further elaboration and optimization gave compound 25, a single digit nM inhibitor of TBK1. These compounds may serve as in vitro probes to evaluate TBK1/IKK-epsilon as an oncology target. (C) 2014 Elsevier Ltd. All rights reserved.