5-(2-bromopyridin-4-yl)-4-(naphthalen-2-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one | 1268247-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(2-bromopyridin-4-yl)-4-(naphthalen-2-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one
• CAS: 1268247-41-1
• 化学式: C₁₇H₁₁BrN₄O
• 分子量: 367.205
• InChiKey: KWLMBONWJSSIBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.57
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  环丁基胺 、 5-(2-bromopyridin-4-yl)-4-(naphthalen-2-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 作用下， 以 甲苯 为溶剂， 生成 3-(2-(cyclobutylamino)pyridin-4-yl)-4-(naphthalen-2-yl)-1H-1,2,4-triazol-5(4H)-one
  参考文献：
  名称：

  Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration

  摘要：

  In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38α and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-π stacking interaction. Compound 38 ameliorates neurotoxicity induced by amyloid-β in human cortical neurons. Lastly, we demonstrate how to install propitious in vitro CNS-like properties into these selective inhibitors.

  DOI：

  10.1016/j.bmcl.2010.11.010
• 作为产物：
  描述：

  在 potassium hexacyanoferrate(III) 作用下， 以 水 为溶剂， 生成 5-(2-bromopyridin-4-yl)-4-(naphthalen-2-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration

  摘要：

  In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38α and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-π stacking interaction. Compound 38 ameliorates neurotoxicity induced by amyloid-β in human cortical neurons. Lastly, we demonstrate how to install propitious in vitro CNS-like properties into these selective inhibitors.

  DOI：

  10.1016/j.bmcl.2010.11.010