3-(hydroxymethyl)-1-methyl-5-(2-methylaziridin-1-yl)-2-phenyl-1H-indole-4,7-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-(hydroxymethyl)-1-methyl-5-(2-methylaziridin-1-yl)-2-phenyl-1H-indole-4,7-dione
• 英文别名: 3-Hydroxymethyl-5-(2-methylaziridin-1-yl)-1-methyl-2-phenylindole-4,7-dione；3-(hydroxymethyl)-1-methyl-5-(2-methylaziridin-1-yl)-2-phenylindole-4,7-dione
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: RQFCSAVLOHDQNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-甲基氮丙啶 、 3-hydroxymethyl-5-methoxy-1-methyl-2-phenylindole-4,7-dione 以 N,N-二甲基甲酰胺 为溶剂， 以79%的产率得到3-(hydroxymethyl)-1-methyl-5-(2-methylaziridin-1-yl)-2-phenyl-1H-indole-4,7-dione
  参考文献：
  名称：

  Indolequinone Antitumor Agents:  Correlation between Quinone Structure, Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase, and in Vitro Cytotoxicity

  摘要：

  A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H: quinone oxidoreductase (NQO1) were studied. Thus 5-methoxyindolequinones were prepared by the Nenitzescu reaction, followed by functional group interconversions. The methoxy group was subsequently displaced by amine nucleophiles to give a series of amine-substituted quinones. Metabolism of the quinones by NQO1 revealed that, in general, compounds with electron-withdrawing groups at the indole 3-position were among the best substrates, whereas those with amine groups at the 5-position were poor substrates. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward non-small-cell lung cancer cells with either high NQO1 activity (H460) or no detectable activity (H596) was also studied in representative quinones. Compounds which were good substrates for NQO1 showed the highest selectivity between the two cell lines.

  DOI：

  10.1021/jm980328r

文献信息

• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• Indolequinone Antitumor Agents:  Correlation between Quinone Structure, Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase, and in Vitro Cytotoxicity
  作者：Howard D. Beall、Shannon Winski、Elizabeth Swann、Anna R. Hudnott、Ann S. Cotterill、Noeleen O'Sullivan、Stephen J. Green、Richard Bien、David Siegel、David Ross、Christopher J. Moody

  DOI：10.1021/jm980328r

  日期：1998.11.1

  A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H: quinone oxidoreductase (NQO1) were studied. Thus 5-methoxyindolequinones were prepared by the Nenitzescu reaction, followed by functional group interconversions. The methoxy group was subsequently displaced by amine nucleophiles to give a series of amine-substituted quinones. Metabolism of the quinones by NQO1 revealed that, in general, compounds with electron-withdrawing groups at the indole 3-position were among the best substrates, whereas those with amine groups at the 5-position were poor substrates. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward non-small-cell lung cancer cells with either high NQO1 activity (H460) or no detectable activity (H596) was also studied in representative quinones. Compounds which were good substrates for NQO1 showed the highest selectivity between the two cell lines.