3-(2-(cyclohexylamino)pyridin-4-yl)-4-(naphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-1,2,4-triazol-5(4H)-one | 1268247-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-(cyclohexylamino)pyridin-4-yl)-4-(naphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-1,2,4-triazol-5(4H)-one
• 英文别名: 5-[2-(cyclohexylamino)pyridin-4-yl]-4-naphthalen-2-yl-2-(oxan-4-ylmethyl)-1,2,4-triazol-3-one
• CAS: 1268247-63-7
• 化学式: C₂₉H₃₃N₅O₂
• 分子量: 483.613
• InChiKey: DXTYYUXUIQZDHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  、 环己胺 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 生成 3-(2-(cyclohexylamino)pyridin-4-yl)-4-(naphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-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