4-((5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-ylthio)methyl)benzonitrile | 1374671-54-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 4-((5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-ylthio)methyl)benzonitrile
• 英文别名: 4-[[5-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,3,4-oxadiazol-2-yl]sulfanylmethyl]benzonitrile
• CAS: 1374671-54-1
• 化学式: C₁₈H₁₃N₃O₃S
• 分子量: 351.386
• InChiKey: MYBZDSDFVPDTCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-((5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-ylthio)methyl)benzonitrile 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以79%的产率得到2-(4-(1H-tetrazol-5-yl)benzylthio)-5-(2,3-dihydrobenzo[d][1,4]dioxin-5-yl)-1,3,4-oxadiazole
  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：

  2,3-二氢-1,4-苯并二噁烷-6-羧酸 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 4-((5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-ylthio)methyl)benzonitrile
  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

文献信息

• [DE] DERIVATE VON 2-BENZYLSULFANYL[1,3,4]-OXADIAZOL UND DEREN MEDIZINISCHE VERWENDUNG<br/>[EN] 2-BENZYLSULFANYL[1,3,4]-OXADIAZOLE DERIVATIVES, AND MEDICAL USE THEREOF<br/>[FR] DÉRIVÉS DE 2-BENZYLSULFANYL[1,3,4]OXADIAZOLE ET UTILISATION DESDITS DÉRIVÉS EN MÉDECINE
  申请人：UNIV DARMSTADT TECH

  公开号：WO2013007663A1

  公开（公告）日：2013-01-17

  Die vorliegende Erfindung betrifft Verbindungen, die als selektive Liganden der Glykogen Synthase Kinase 3 (GSK-3) wirken und für die Behandlung von GSK-3-vermittelten Erkrankungen verwendet werden können. Die erfindungsgemäßen Verbindungen wirken als Inhibitoren der Glykogen Synthase Kinase 3 (GSK-3).