2-[5-amino-1-(4-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]acetonitrile | 1510825-87-2

• 英文名称: 2-[5-amino-1-(4-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]acetonitrile
• CAS: 1510825-87-2
• 化学式: C₁₃H₁₃ClN₄
• 分子量: 260.726
• InChiKey: XUHWYXTWVMZCBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-[5-amino-1-(4-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]acetonitrile 在 硫酸 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 8.5h， 生成 1-(4 ′-chloro-2′-methylphenyl)-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
• 作为产物：
  描述：

  sodium 3,4-dicyanobut-2-en-2-olate 、 4-氯邻甲苯肼盐酸盐 以 乙醇 为溶剂， 反应 2.0h， 以28%的产率得到2-[5-amino-1-(4-chloro-2-methylphenyl)-3-methyl-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