4-(naphthalen-2-yl)-3-(2-(pyridin-2-ylamino)pyridin-4-yl)-1H-1,2,4-triazol-5(4H)-one | 1268247-50-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(naphthalen-2-yl)-3-(2-(pyridin-2-ylamino)pyridin-4-yl)-1H-1,2,4-triazol-5(4H)-one
• 英文别名: 4-naphthalen-2-yl-3-[2-(pyridin-2-ylamino)pyridin-4-yl]-1H-1,2,4-triazol-5-one
• CAS: 1268247-50-2
• 化学式: C₂₂H₁₆N₆O
• 分子量: 380.409
• InChiKey: PSUZEBSSYLZYCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基吡啶 、 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 4-(naphthalen-2-yl)-3-(2-(pyridin-2-ylamino)pyridin-4-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

文献信息

• SUBSTITUTED DIPYRIDYLAMINES AND USES THEREOF
  申请人：Genentech, Inc.

  公开号：US20150080367A1

  公开（公告）日：2015-03-19

  The present invention provides for compounds of Formula I and various embodiments thereof, and compositions comprising compounds of Formula I and various embodiments thereof. In compounds of Formula I, the groups R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , m, n and the C-linked Ring have the meaning as described herein. The present invention also provides for methods of using compounds of Formula I and compositions comprising compounds of Formula I as DLK inhibitors and for treating neurodegeneration diseases and disorders.

  本发明提供了公式I的化合物及其各种实施形式，以及包含公式I的化合物及其各种实施形式的组合物。在公式I的化合物中，基团R1，R2，R3，R4，R5，R6，m，n和C-连接环的含义如本文所述。本发明还提供了使用公式I的化合物和包含公式I的化合物作为DLK抑制剂和治疗神经退行性疾病和障碍的组合物的方法。
• US9399636B2
  申请人：——

  公开号：US9399636B2

  公开（公告）日：2016-07-26