(2Z)-5-hydroxy-2-[2-oxo-5-(trifluoromethoxy)-1H-indol-3-ylidene]-1H-indol-3-one | 1223386-26-2

• 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: (2Z)-5-hydroxy-2-[2-oxo-5-(trifluoromethoxy)-1H-indol-3-ylidene]-1H-indol-3-one
• CAS: 1223386-26-2
• 化学式: C₁₇H₉F₃N₂O₄
• 分子量: 362.265
• InChiKey: FPRMXPPFAPYVFL-YPKPFQOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.26
• 重原子数：
  26.0
• 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：
  87.66
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1-acetyl-1H-indole-3, 5-diyl diacetate 、 5-三氟甲氧基吲哚-2,3-二酮 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成 (2Z)-5-hydroxy-2-[2-oxo-5-(trifluoromethoxy)-1H-indol-3-ylidene]-1H-indol-3-one
  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

文献信息

• INDIRUBIN-3'-OXIME DERIVATIVES AS POTENT CYCLIN DEPENDENT KINASE INHIBITORS
  申请人：Kim Yong-Chul

  公开号：US20120295948A1

  公开（公告）日：2012-11-22

  The present invention relates to an indirubin-3′-oxime derivative as potent cyclin dependent kinase inhibitor with anti-cancer activity. More particularly, this invention relates to an indirubin-3′-oxime derivative as potent cyclin dependent kinase inhibitor having excellent anti-cancer activity against human lung cancer cell, human fibro sarcoma cell, human colon cancer cell, human leukemia cell, human stomach cancer cell, human nasopharyngeal cancer cell and/or human breast cancer cell.

  本发明涉及一种indirubin-3'-oxime衍生物，作为强效的细胞周期蛋白依赖性激酶抑制剂，具有抗癌活性。更具体地说，本发明涉及一种indirubin-3'-oxime衍生物，作为强效的细胞周期蛋白依赖性激酶抑制剂，对人肺癌细胞、人纤维肉瘤细胞、人结肠癌细胞、人白血病细胞、人胃癌细胞、人鼻咽癌细胞和/或人乳腺癌细胞具有优异的抗癌活性。
• US8859783B2
  申请人：——

  公开号：US8859783B2

  公开（公告）日：2014-10-14
• [EN] INDIRUBIN-3'-OXIME DERIVATIVES AS POTENT CYCLIN DEPENDENT KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE L'INDIRUBIN-3'-OXIME EN TANT QU'INHIBITEURS PUISSANTS DE KINASES DÉPENDANTES DE CYCLINES
  申请人：ANYGEN CO LTD

  公开号：WO2011096676A2

  公开（公告）日：2011-08-11

  The present invention relates to an indirubin-3'-oxime derivative as potent cyclin dependent kinase inhibitor with anti-cancer activity. More particularly, this invention relates to an indirubin-3'-oxime derivative as potent cyclin dependent kinase inhibitor having excellent anti-cancer activity against human lung cancer cell, human fibro sarcoma cell, human colon cancer cell, human leukemia cell, human stomach cancer cell, human nasopharyngeal cancer cell and/or human breast cancer cell.