N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide | 1365645-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide
• CAS: 1365645-64-2
• 化学式: C₂₂H₂₆BrN₅O₂
• 分子量: 472.385
• InChiKey: JUWVGQDRIAVTIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  91.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide 在 ammonium sulfide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 N-[3-[[6-carbamothioyl-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide
  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
• 作为产物：
  描述：

  大茴香酸 在 碳酸氢钠 、 三氯氧磷 作用下， 以 二氯甲烷 、 水 、 乙腈 、 正丁醇 为溶剂， 反应 4.0h， 生成 N-[3-[[6-bromo-2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-7-yl]amino]propyl]cyclopentanecarboxamide
  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 azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKKε kinases
  作者：Tao Wang、Michael A. Block、Scott Cowen、Audrey M. Davies、Erik Devereaux、Lakshmaiah Gingipalli、Jeffrey Johannes、Nicholas A. Larsen、Qibin Su、Julie A. Tucker、David Whitston、Jiaquan Wu、Hai-Jun Zhang、Michael Zinda、Claudio Chuaqui

  DOI：10.1016/j.bmcl.2012.01.018

  日期：2012.3

  The design, synthesis and biological evaluation of a series of azabenzimidazole derivatives as TBK1/IKK epsilon kinase inhibitors are described. Starting from a lead compound 1a, iterative design and SAR exploitation of the scaffold led to analogues with nM enzyme potencies against TBK1/IKK epsilon. These compounds also exhibited excellent cellular activity against TBK1. Further structure-based design to improve selectivity over CDK2 and Aurora B resulted in compounds such as 5b-e. These probe compounds will facilitate study of the complex cancer biology of TBK1 and IKK epsilon. (C) 2012 Elsevier Ltd. All rights reserved.