N-(4-chlorophenyl)-5-(4-(methylmercapto)phenyl)-1,3,4-oxadiazol-2-amine | 1257256-84-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-(4-chlorophenyl)-5-(4-(methylmercapto)phenyl)-1,3,4-oxadiazol-2-amine
• 英文别名: N-(4-chlorophenyl)-5-(4-methylsulfanylphenyl)-1,3,4-oxadiazol-2-amine
• CAS: 1257256-84-0
• 化学式: C₁₅H₁₂ClN₃OS
• 分子量: 317.799
• InChiKey: PUKKVPIASROPEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(4-氯苯)-3-氨基硫脲 、 4-甲硫基苯甲酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以34%的产率得到N-(4-chlorophenyl)-5-(4-(methylmercapto)phenyl)-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  Discovery of Novel GSK-3β Inhibitors with Potent in Vitro and in Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-Based Virtual Screening

  摘要：

  Dysregulation of glycogen synthase kinase (GSK-3 beta) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3 beta yielded, from among compounds in our in-house database and two commercial databases, new GSK-3 beta inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.

  DOI：

  10.1021/jm100941j

文献信息

• Discovery of Novel GSK-3β Inhibitors with Potent in Vitro and in Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-Based Virtual Screening
  作者：Mohammad A. Khanfar、Ronald A. Hill、Amal Kaddoumi、Khalid A. El Sayed

  DOI：10.1021/jm100941j

  日期：2010.12.23

  Dysregulation of glycogen synthase kinase (GSK-3 beta) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3 beta yielded, from among compounds in our in-house database and two commercial databases, new GSK-3 beta inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.