ethyl 4-amino-5-methoxy-1-[(2-morpholin-4-yl)ethyl]-2,6-dimethylindole-3-carboxylate | 371193-06-5

• 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: ethyl 4-amino-5-methoxy-1-[(2-morpholin-4-yl)ethyl]-2,6-dimethylindole-3-carboxylate
• 英文别名: Ethyl 4-amino-5-methoxy-2,6-dimethyl-1-(2-morpholin-4-ylethyl)indole-3-carboxylate
• CAS: 371193-06-5
• 化学式: C₂₀H₂₉N₃O₄
• 分子量: 375.468
• InChiKey: MXUNNZNHACWGEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-amino-5-methoxy-1-[(2-morpholin-4-yl)ethyl]-2,6-dimethylindole-3-carboxylate 在 potassium nitrososulfonate 、 sodium dihydrogen phosphate buffer 作用下， 以 丙酮 为溶剂， 反应 1.0h， 以91%的产率得到5-Methoxy-2,6-dimethyl-1-(2-morpholin-4-yl-ethyl)-4,7-dioxo-4,7-dihydro-1H-indole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Indolequinone Antitumor Agents:  Correlation between Quinone Structure and Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase. Part 2

  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. Indolequinones were selected for study on the basis of the X-ray crystal structure of the human enzyme, and were designed to probe the effect of substituents particularly at N-1. 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, and that groups larger than methyl at N-1 are clearly tolerated. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward human colon carcinoma cells with either no detectable activity (BE-WT) or high NQO1 activity (BE-NQ) was also studied in representative quinones. The most toxic compounds were those with a leaving group at the C-3 position; these compounds were 1.1-5.3-fold more toxic. to the BE-NQ than the BE-WT cells.

  DOI：

  10.1021/jm010884c
• 作为产物：
  描述：

  甲基苯醌 在 盐酸 、 tin 、 硝酸 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 硝基甲烷 、 乙醇 为溶剂， 反应 52.75h， 生成 ethyl 4-amino-5-methoxy-1-[(2-morpholin-4-yl)ethyl]-2,6-dimethylindole-3-carboxylate
  参考文献：
  名称：

  Indolequinone Antitumor Agents:  Correlation between Quinone Structure and Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase. Part 2

  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. Indolequinones were selected for study on the basis of the X-ray crystal structure of the human enzyme, and were designed to probe the effect of substituents particularly at N-1. 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, and that groups larger than methyl at N-1 are clearly tolerated. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward human colon carcinoma cells with either no detectable activity (BE-WT) or high NQO1 activity (BE-NQ) was also studied in representative quinones. The most toxic compounds were those with a leaving group at the C-3 position; these compounds were 1.1-5.3-fold more toxic. to the BE-NQ than the BE-WT cells.

  DOI：

  10.1021/jm010884c

文献信息

• Indolequinone Antitumor Agents:  Correlation between Quinone Structure and Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase. Part 2
  作者：Elizabeth Swann、Paola Barraja、Ann M. Oberlander、Walter T. Gardipee、Anna R. Hudnott、Howard D. Beall、Christopher J. Moody

  DOI：10.1021/jm010884c

  日期：2001.9.1

  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. Indolequinones were selected for study on the basis of the X-ray crystal structure of the human enzyme, and were designed to probe the effect of substituents particularly at N-1. 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, and that groups larger than methyl at N-1 are clearly tolerated. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward human colon carcinoma cells with either no detectable activity (BE-WT) or high NQO1 activity (BE-NQ) was also studied in representative quinones. The most toxic compounds were those with a leaving group at the C-3 position; these compounds were 1.1-5.3-fold more toxic. to the BE-NQ than the BE-WT cells.