ethyl 3-cyano-2-hydroxy-3-[3-methyl-1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazol-4-yl]acrylate | 1510826-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-cyano-2-hydroxy-3-[3-methyl-1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazol-4-yl]acrylate
• CAS: 1510826-06-8
• 化学式: C₂₀H₁₈N₄O₃
• 分子量: 362.388
• InChiKey: DHLOBNLOARPXNL-UHFFFAOYSA-N

物化性质

• 沸点：
  561.3±50.0 °C(predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.33
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  93.07
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-cyano-2-hydroxy-3-[3-methyl-1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazol-4-yl]acrylate 在 polyphosphoric acid 作用下， 反应 1.0h， 以52%的产率得到3-methyl-1-phenylpyrazolo[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
• 作为产物：
  描述：

  2-[5-amino-3-methyl-1-(phenyl)-1H-pyrazol-4-yl]acetonitrile 在 sodium ethanolate 、 溶剂黄146 作用下， 反应 5.5h， 生成 ethyl 3-cyano-2-hydroxy-3-[3-methyl-1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazol-4-yl]acrylate
  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