N-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)pyridin-2-yl)acetamide | 1417334-87-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)pyridin-2-yl)acetamide
• 英文别名: N-[4-(2-sulfanylidene-3H-1,3,4-oxadiazol-5-yl)pyridin-2-yl]acetamide
• CAS: 1417334-87-2
• 化学式: C₉H₈N₄O₂S
• 分子量: 236.254
• InChiKey: FMCIUUNYIBLWHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)pyridin-2-yl)acetamide 、 2-氰基-4'-溴甲基联苯 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以62%的产率得到N-[4-[5-[[4-(2-cyanophenyl)phenyl]methylsulfanyl]-1,3,4-oxadiazol-2-yl]pyridin-2-yl]acetamide
  参考文献：
  名称：

  Structure-based optimization of oxadiazole-based GSK-3 inhibitors

  摘要：

  Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases beta-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3 alpha and beta, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3 alpha and 17 nM for GSK-3 beta. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3 alpha over GSK-3 beta, with an IC50 of 35 nM for GSK-3 alpha. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.006
• 作为产物：
  描述：

  2-氨基异烟酸 在 氯化亚砜 、 一水合肼 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 67.0h， 生成 N-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)pyridin-2-yl)acetamide
  参考文献：
  名称：

  Structure-based optimization of oxadiazole-based GSK-3 inhibitors

  摘要：

  Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases beta-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3 alpha and beta, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3 alpha and 17 nM for GSK-3 beta. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3 alpha over GSK-3 beta, with an IC50 of 35 nM for GSK-3 alpha. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.006