methyl 4-(5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl benzoate | 875456-04-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-(5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl benzoate
• 英文别名: Methyl 4-[[5-(1,3-benzodioxol-5-yl)-1,3,4-oxadiazol-2-yl]sulfanylmethyl]benzoate
• CAS: 875456-04-5
• 化学式: C₁₈H₁₄N₂O₅S
• 分子量: 370.386
• InChiKey: XQZMFILAQGRCMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 4-(5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl benzoate 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以83%的产率得到4-((5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl)benzoic acid
  参考文献：
  名称：

  Identification of Glycogen Synthase Kinase-3 Inhibitors with a Selective Sting for Glycogen Synthase Kinase-3α

  摘要：

  The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-3 alpha and GSK-3 beta to AD pathology and AML is ongoing. Thus, the identification of potent GSK-3 alpha-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-3 alpha inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-3 alpha selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.

  DOI：

  10.1021/jm300309a
• 作为产物：
  描述：

  胡椒酸 在 一水合肼 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.0h， 生成 methyl 4-(5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl benzoate
  参考文献：
  名称：

  Identification of Glycogen Synthase Kinase-3 Inhibitors with a Selective Sting for Glycogen Synthase Kinase-3α

  摘要：

  The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-3 alpha and GSK-3 beta to AD pathology and AML is ongoing. Thus, the identification of potent GSK-3 alpha-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-3 alpha inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-3 alpha selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.

  DOI：

  10.1021/jm300309a