| 1466558-64-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• CAS: 1466558-64-4
• 化学式: C₂₁H₂₅N₃O₂Si
• 分子量: 379.534
• InChiKey: LTULVAZSFCMUKW-CSKARUKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  57.01
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2-乙烯基吡啶 、 3-碘吲唑-6-羧醛 、 2-(三甲基硅烷基)乙氧甲基氯 在 四丁基溴化铵 、 potassium hydroxide 、 palladium diacetate 、 N,N-二异丙基乙胺 、 三(邻甲基苯基)磷 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 、
  参考文献：
  名称：

  The Discovery of PLK4 Inhibitors: (E)-3-((1H-Indazol-6-yl)methylene)indolin-2-ones as Novel Antiproliferative Agents

  摘要：

  The family of Polo-like kinases is important in the regulation of mitotic progression; this work keys on one member, namely Polo-like kinase 4 (PLK4). PLK4 has been identified as a candidate anticancer target which prompted a search for potent and selective inhibitors of PLK4. The body of the paper describes lead generation and optimization work which yielded nanomolar PLK4 inhibitors. Lead generation began with directed virtual screening, using a ligand-based focused library and a PLK4 homology model. Validated hits were used as starting points for the design and discovery of PLK4 inhibitors of novel structure, namely (E)-3-((1H-indazol-6-yl)methylene)indolin-2-ones. Computational models, based on a published X-ray structure (PLK4 kinase domain), were used to understand and optimize the in vitro activity of the series; potent antiproliferative activity was obtained. The kinase selectivity profile and cell cycle analysis of selected inhibitors are described. The results of a xenograft study with an optimized compound 50 (designated CFI-400437) support the potential of these novel PLK4 inhibitors for cancer therapy.

  DOI：

  10.1021/jm400380m