(Z)-5-((1-methyl-1H-indol-3-yl)methylene)-4-thioxothiazolidin-2-one | 1401235-34-4

• 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: (Z)-5-((1-methyl-1H-indol-3-yl)methylene)-4-thioxothiazolidin-2-one
• 英文别名: 5-[(1-methyl-1H-indol-3-yl)methylene]-4-thioxo-1,3-thiazolidin-2-one；(5Z)-5-[(1-methylindol-3-yl)methylidene]-4-sulfanylidene-1,3-thiazolidin-2-one
• CAS: 1401235-34-4
• 化学式: C₁₃H₁₀N₂OS₂
• 分子量: 274.367
• InChiKey: MHNWGCUMEYITOR-WDZFZDKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  91.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-甲基吲哚-3-甲醛 、 4-硫代噻唑烷-2-酮 在 sodium acetate 、 溶剂黄146 作用下， 反应 2.0h， 以59%的产率得到(Z)-5-((1-methyl-1H-indol-3-yl)methylene)-4-thioxothiazolidin-2-one
  参考文献：
  名称：

  5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

  摘要：

  Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 mu M). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.

  DOI：

  10.1021/jm3008773

文献信息

• 5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I
  作者：Venkata Ramana Sirivolu、Sanjeev Kumar V. Vernekar、Christophe Marchand、Alena Naumova、Adel Chergui、Amelie Renaud、Andrew G. Stephen、Feng Chen、Yuk Y. Sham、Yves Pommier、Zhengqiang Wang

  DOI：10.1021/jm3008773

  日期：2012.10.25

  Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 mu M). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.