(S)-5-(3-(methoxymethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol | 1374671-83-6

• 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: (S)-5-(3-(methoxymethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol
• 英文别名: 5-[(3S)-3-(methoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-3H-1,3,4-oxadiazole-2-thione
• CAS: 1374671-83-6
• 化学式: C₁₂H₁₂N₂O₄S
• 分子量: 280.304
• InChiKey: WJIZKXPWULCRCL-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-5-(3-(methoxymethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol 、 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84%的产率得到(S)-4'-((5-(3-(methoxymethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile
  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：

  原儿茶酸 在 氯化亚砜 、 sodium hydride 、 potassium carbonate 、 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 114.0h， 生成 (S)-5-(3-(methoxymethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol
  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

• Identification of Glycogen Synthase Kinase-3 Inhibitors with a Selective Sting for Glycogen Synthase Kinase-3α
  作者：Fabio Lo Monte、Thomas Kramer、Jiamin Gu、Upendra Rao Anumala、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Bénédicte Franco、David Demedts、Fred Van Leuven、Ana Fuertes、Juan Manuel Dominguez、Batya Plotkin、Hagit Eldar-Finkelman、Boris Schmidt

  DOI：10.1021/jm300309a

  日期：2012.5.10

  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.