7,8-dimethoxy-5-methyl-2-(2-phenylpropyn-2y-l)-1H-benzo[e]isoindole-1,3(2H)-dione | 1187745-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 7,8-dimethoxy-5-methyl-2-(2-phenylpropyn-2y-l)-1H-benzo[e]isoindole-1,3(2H)-dione
• 英文别名: 7,8-Dimethoxy-5-methyl-2-(2-phenylpropan-2-yl)benzo[e]isoindole-1,3-dione
• CAS: 1187745-67-0
• 化学式: C₂₄H₂₃NO₄
• 分子量: 389.451
• InChiKey: HBQVCVORKNETLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7,8-dimethoxy-5-methyl-2-(2-phenylpropyn-2y-l)-1H-benzo[e]isoindole-1,3(2H)-dione 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到
  参考文献：
  名称：

  Structure-based design of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3β inhibitors to activate Wnt/β-catenin pathway

  摘要：

  Deregulation of Wnt/beta-catenin pathway is closely related to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), and glycogen synthase kinase 3 beta (GSK-3 beta), the central negative regulator of Wnt pathway, is regarded as an important target for these diseases. Here, we report a series of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3 beta inhibitors by rational-design and synthesis, which show high selectivity against GSK-3 beta over Cyclin-dependent kinase 2 (CDK2), and significantly activate the cellular Wnt/beta-catenin pathway. The structure-activity relationship of these GSK-3 beta inhibitors was also explored by in silico molecular docking. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2015.05.009
• 作为产物：
  描述：

  3-hydroxy-5-methyl-7,8-dimethoxy-2-(2-phenylpropyn-2-yl)-2,3-dihydro-1H-benzo[e]isoindol-1-one 在 重铬酸吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以85%的产率得到7,8-dimethoxy-5-methyl-2-(2-phenylpropyn-2y-l)-1H-benzo[e]isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Benzo[e]isoindole-1,3-diones as Potential Inhibitors of Glycogen Synthase Kinase-3 (GSK-3). Synthesis, Kinase Inhibitory Activity, Zebrafish Phenotype, and Modeling of Binding Mode

  摘要：

  Benzo[e]isoindole-1,3-dione derivatives were synthesized, and the effects on GSK-3 beta activity and zebrafish embryo growth were evaluated. A series of derivatives show obvious inhibitory activity against GSK-3 beta. The most potent inhibitor, 7,8-dimethoxy-5-methylbenzo[e]isoindole-1,3-dione (8a), shows nanomolar IC50 and obvious phenotype on zebrafish embryo growth associated with the inhibition of GSK-3 beta at low micromolar concentration. The interaction mode between 8a and GSK-3 beta was characterized by computational modeling.

  DOI：

  10.1021/jm9013373