2-[5-amino-1-(2-methoxyphenyl)-1H-pyrazol-4-yl]acetonitrile | 1510825-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[5-amino-1-(2-methoxyphenyl)-1H-pyrazol-4-yl]acetonitrile
• 英文别名: 2-[5-Amino-1-(2-methoxyphenyl)pyrazol-4-yl]acetonitrile；2-[5-amino-1-(2-methoxyphenyl)pyrazol-4-yl]acetonitrile
• CAS: 1510825-82-7
• 化学式: C₁₂H₁₂N₄O
• 分子量: 228.253
• InChiKey: QZUFQLPQMIQKAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  76.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[5-amino-1-(2-methoxyphenyl)-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-[1-(2-methoxyphenyl)-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
• 作为产物：
  描述：

  sodium 2,3-dicyanoprop-1-en-1-olate 、 2-甲氧基苯肼盐酸盐 以 乙醇 为溶剂， 反应 2.0h， 以10%的产率得到2-[5-amino-1-(2-methoxyphenyl)-1H-pyrazol-4-yl]acetonitrile
  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.