3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
• 英文别名: 3-(1,2,4-triazolo[4,3-a]pyridin-3-yl)-4-(1-methyl-1H-indol-3-yl)maleimide；3-(1-Methylindol-3-yl)-4-([1,2,4]triazolo[4,3-a]pyridin-3-yl)pyrrole-2,5-dione；3-(1-methylindol-3-yl)-4-([1,2,4]triazolo[4,3-a]pyridin-3-yl)pyrrole-2,5-dione
• 化学式: C₁₉H₁₃N₅O₂
• 分子量: 343.345
• InChiKey: JZMZMJWZUCNYNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  81.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)acetate 在 potassium tert-butylate 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 叔丁醇 为溶剂， 反应 8.0h， 生成 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3β inhibitors and neuroprotective agents

  摘要：

  A series of novel 3-([1,2,4] triazolo[4,3-a] pyridin-3-yl)-4-(indol-3-yl)-maleimides were designed, prepared and evaluated for their GSK-3 beta inhibitory activities. Most compounds showed high potency to GSK-3 beta inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3 beta substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3 beta. In the in vitro neuronal injury models, compounds 7c, 7f, 7h, 7l and 7m prevented neuronal death against glutamate, oxygen-glucose deprivation and nutrient serum deprivation which are associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 7f reduced infarct size by 15% and improved the neurological deficit following focal cerebral ischemia. These findings may provide new insights into the development of novel GSK-3b inhibitors with potential neuroprotective activity. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.12.026

文献信息

• Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3β inhibitors and neuroprotective agents
  作者：Qing Ye、Weili Mao、Yubo Zhou、Lei Xu、Qiu Li、Yuanxue Gao、Jing Wang、Chenhui Li、Yazhou Xu、Yuan Xu、Hong Liao、Luyong Zhang、Jianrong Gao、Jia Li、Tao Pang

  DOI：10.1016/j.bmc.2014.12.026

  日期：2015.3

  A series of novel 3-([1,2,4] triazolo[4,3-a] pyridin-3-yl)-4-(indol-3-yl)-maleimides were designed, prepared and evaluated for their GSK-3 beta inhibitory activities. Most compounds showed high potency to GSK-3 beta inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3 beta substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3 beta. In the in vitro neuronal injury models, compounds 7c, 7f, 7h, 7l and 7m prevented neuronal death against glutamate, oxygen-glucose deprivation and nutrient serum deprivation which are associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 7f reduced infarct size by 15% and improved the neurological deficit following focal cerebral ischemia. These findings may provide new insights into the development of novel GSK-3b inhibitors with potential neuroprotective activity. (C) 2015 Published by Elsevier Ltd.