(2'Z,3'E)-5-trifluoromethoxy-5'-hydroxy-indirubin-3'-oxime | 1223385-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2'Z,3'E)-5-trifluoromethoxy-5'-hydroxy-indirubin-3'-oxime
• 英文别名: (2'Z,3'E)-5'-hydroxy-5-(trifluoromethoxy)indirubin-3'-oxime
• CAS: 1223385-99-6
• 化学式: C₁₇H₁₀F₃N₃O₄
• 分子量: 377.279
• InChiKey: IVZQQNNFEULKOJ-JHQIBEBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.26
• 重原子数：
  27.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  103.18
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  (2Z)-5-hydroxy-2-[2-oxo-5-(trifluoromethoxy)-1H-indol-3-ylidene]-1H-indol-3-one 在 盐酸羟胺 作用下， 以 吡啶 为溶剂， 反应 2.0h， 生成 (2'Z,3'E)-5-trifluoromethoxy-5'-hydroxy-indirubin-3'-oxime
  参考文献：
  名称：

  5,5′-Substituted Indirubin-3′-oxime Derivatives as Potent Cyclin-Dependent Kinase Inhibitors with Anticancer Activity

  摘要：

  To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3'-oxime derivatives with combined substitutions at the 5 and 5' positions. A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5' position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Among the synthesized derivatives, the 5-nitro-5'-hydroxy analogue 3a and the 5-nitro-5'-fluoro analogue Sa displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. These derivatives also showed antiproliferative activity against several human cancer cell lines, with IC(50) values of 0.2-3.3 mu M. A representative analogue, 3a, showed greater than 500-fold selectivity for CDK relative to selected kinase panel and potent in vivo anticancer activity.

  DOI：

  10.1021/jm100080z