1-(2′,4′-dichlorophenyl)-3-methylpyrazolo[3,4-e]pyrrolo[3,4-g]-indolizine-4,6(1H,5H)-dione | 1510825-76-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2′,4′-dichlorophenyl)-3-methylpyrazolo[3,4-e]pyrrolo[3,4-g]-indolizine-4,6(1H,5H)-dione
• 英文别名: 3-(2,4-Dichlorophenyl)-5-methyl-1,3,4,9-tetrazatetracyclo[10.3.0.02,6.07,11]pentadeca-2(6),4,7(11),12,14-pentaene-8,10-dione；3-(2,4-dichlorophenyl)-5-methyl-1,3,4,9-tetrazatetracyclo[10.3.0.02,6.07,11]pentadeca-2(6),4,7(11),12,14-pentaene-8,10-dione
• CAS: 1510825-76-9
• 化学式: C₁₈H₁₀Cl₂N₄O₂
• 分子量: 385.209
• InChiKey: KJKOBDWTGMVEHK-UHFFFAOYSA-N

物化性质

• 密度：
  1.72±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  sodium 3,4-dicyanobut-2-en-2-olate 在 硫酸 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 14.5h， 生成 1-(2′,4′-dichlorophenyl)-3-methylpyrazolo[3,4-e]pyrrolo[3,4-g]-indolizine-4,6(1H,5H)-dione
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1-Phenylpyrazolo[3,4-e]pyrrolo[3,4-g]indolizine-4,6(1H,5H)-diones as New Glycogen Synthase Kinase-3β Inhibitors

  摘要：

  Compound 5 was selected from our in-house library as a suitable starting point for the rational design of new GSK-3 beta inhibitors. MC/FEP calculations of 5 led to the identication of a structural class of new GSK-3 beta inhibitors. Compound 18 inhibited GSK-3 beta with an IC50 of 0.24 mu M and inhibited tau phosphorylation in a cell-based assay. It proved to be a selective inhibitor of GSK-3 against a panel of 17 kinases and showed >10-fold selectivity against CDK2. Calculated physicochemical properties and Volsurf predictions suggested that compound 18 has the potential to diffuse passively across the blood brain barrier.

  DOI：

  10.1021/jm401466v

文献信息

• Design, Synthesis, and Biological Evaluation of 1-Phenylpyrazolo[3,4-<i>e</i>]pyrrolo[3,4-<i>g</i>]indolizine-4,6(1<i>H</i>,5<i>H</i>)-diones as New Glycogen Synthase Kinase-3β Inhibitors
  作者：Valeria La Pietra、Giuseppe La Regina、Antonio Coluccia、Valeria Famiglini、Sveva Pelliccia、Batya Plotkin、Hagit Eldar-Finkelman、Andrea Brancale、Carlo Ballatore、Alex Crowe、Kurt R. Brunden、Luciana Marinelli、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm401466v

  日期：2013.12.27

  Compound 5 was selected from our in-house library as a suitable starting point for the rational design of new GSK-3 beta inhibitors. MC/FEP calculations of 5 led to the identication of a structural class of new GSK-3 beta inhibitors. Compound 18 inhibited GSK-3 beta with an IC50 of 0.24 mu M and inhibited tau phosphorylation in a cell-based assay. It proved to be a selective inhibitor of GSK-3 against a panel of 17 kinases and showed >10-fold selectivity against CDK2. Calculated physicochemical properties and Volsurf predictions suggested that compound 18 has the potential to diffuse passively across the blood brain barrier.