(S)-((7-(5-(2'-cyanobiphenyl-4-yl)methylthio)-1,3,4-oxadiazol-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methylmethanesulfonate | 1374671-86-9

• 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: (S)-((7-(5-(2'-cyanobiphenyl-4-yl)methylthio)-1,3,4-oxadiazol-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methylmethanesulfonate
• 英文别名: [(3S)-6-[5-[[4-(2-cyanophenyl)phenyl]methylsulfanyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1,4-benzodioxin-3-yl]methyl methanesulfonate
• CAS: 1374671-86-9
• 化学式: C₂₆H₂₁N₃O₆S₂
• 分子量: 535.601
• InChiKey: QIJADFOJWVECHX-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  158
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-((7-(5-(2'-cyanobiphenyl-4-yl)methylthio)-1,3,4-oxadiazol-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methylmethanesulfonate 、 氨基乙醛缩二甲醇 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 120.0h， 以83%的产率得到(R)-4'-((5-(3-((2,2-dimethoxyethylamino)methyl)-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 、 三溴化硼 、 sodium hydride 、 potassium carbonate 、 一水合肼 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 149.0h， 生成 (S)-((7-(5-(2'-cyanobiphenyl-4-yl)methylthio)-1,3,4-oxadiazol-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methylmethanesulfonate
  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