1-[(3-chlorophenyl)methyl]-1H-indole-3-carbonitrile

• 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: 1-[(3-chlorophenyl)methyl]-1H-indole-3-carbonitrile
• 英文别名: 1-(3-chlorobenzyl)-1H-indole-3-carbonitrile；1-[(3-chlorophenyl)methyl]indole-3-carbonitrile
• 化学式: C₁₆H₁₁ClN₂
• 分子量: 266.73
• InChiKey: PDFYGPOATKAPDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  28.7
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3-氰基吲哚 、 间氯氯苄 在 sodium hydride 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 1.0h， 生成 1-[(3-chlorophenyl)methyl]-1H-indole-3-carbonitrile
  参考文献：
  名称：

  Analogues and Derivatives of Oncrasin-1, a Novel Inhibitor of the C-Terminal Domain of RNA Polymerase II and Their Antitumor Activities

  摘要：

  To optimize the antitumor activity of oncrasin-1, a small molecule RNA polymerase II inhibitor, We evaluated 69 oncrasin-1 analogues for their cytotoxic activity against normal human epithelial cells and K-Ras mutant tumor cells. About 40 of those compounds were as potent as or more potent than oncrasin-1 in tumor cells and had a minimal cytotoxic effect on normal cells. Structure activity relationship analysis revealed that most of the active compounds contained either a hydroxymethyl group or an aldehyde group as a substitute at the 3-position of the indole. Both electron-donating and electron-withdrawing groups in the benzene ring were well tolerated. The hydroxymethyl compounds ranged from equipotent with to 100 times as potent as the corresponding aldehyde compounds. We tested three active analogues' effect on RNA, polymerase phosphorylation and found that they all inhibited phosphorylation of the C-terminal domain of RNA polymerase suggesting that the active compounds might act through the same mechanisms as oncrasin-1.

  DOI：

  10.1021/jm101417n

文献信息

• Analogues and Derivatives of Oncrasin-1, a Novel Inhibitor of the C-Terminal Domain of RNA Polymerase II and Their Antitumor Activities
  作者：Shuhong Wu、Li Wang、Wei Guo、Xiaoying Liu、Jinsong Liu、Xiaoli Wei、Bingliang Fang

  DOI：10.1021/jm101417n

  日期：2011.4.28

  To optimize the antitumor activity of oncrasin-1, a small molecule RNA polymerase II inhibitor, We evaluated 69 oncrasin-1 analogues for their cytotoxic activity against normal human epithelial cells and K-Ras mutant tumor cells. About 40 of those compounds were as potent as or more potent than oncrasin-1 in tumor cells and had a minimal cytotoxic effect on normal cells. Structure activity relationship analysis revealed that most of the active compounds contained either a hydroxymethyl group or an aldehyde group as a substitute at the 3-position of the indole. Both electron-donating and electron-withdrawing groups in the benzene ring were well tolerated. The hydroxymethyl compounds ranged from equipotent with to 100 times as potent as the corresponding aldehyde compounds. We tested three active analogues' effect on RNA, polymerase phosphorylation and found that they all inhibited phosphorylation of the C-terminal domain of RNA polymerase suggesting that the active compounds might act through the same mechanisms as oncrasin-1.