4-[2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]thiophene-2-carboxylic acid | 1562497-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]thiophene-2-carboxylic acid
• CAS: 1562497-89-5
• 化学式: C₁₈H₁₃N₃O₃S
• 分子量: 351.386
• InChiKey: PDMRUTWXKCFDFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]thiophene-2-carboxylic acid 、 异丁胺 在 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 二甲胺 为溶剂， 生成 4-[2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]-N-(2-methylpropyl)thiophene-2-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
• 作为产物：
  描述：

  2,3-二氨基-5-溴吡啶 在 trisodium tris-(3-sulfonatophenyl)phosphine trihydrate 、 palladium diacetate 、 caesium carbonate 、 三氯氧磷 作用下， 以 水 、 乙腈 为溶剂， 反应 1.08h， 生成 4-[2-(4-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-6-yl]thiophene-2-carboxylic acid
  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