ethyl 4-amino-2-(4-biphenylyl)-5-methoxy-1-methylindole-3-carboxylate | 219325-63-0

• 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-2-(4-biphenylyl)-5-methoxy-1-methylindole-3-carboxylate
• 英文别名: Ethyl 4-amino-2-(biphenyl-4-yl)-5-methoxy-1-methylindole-3-carboxylate；Ethyl 4-amino-5-methoxy-1-methyl-2-(4-phenylphenyl)indole-3-carboxylate
• CAS: 219325-63-0
• 化学式: C₂₅H₂₄N₂O₃
• 分子量: 400.477
• InChiKey: YMLMZZOTLJUSLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-amino-2-(4-biphenylyl)-5-methoxy-1-methylindole-3-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 (4-Amino-2-biphenyl-4-yl-5-methoxy-1-methyl-1H-indol-3-yl)-methanol
  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
• 作为产物：
  描述：

  ethyl 2-(4-biphenylyl)-5-methoxy-1-methylindole-3-carboxylate 在 盐酸 、 tin 、 硝酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 ethyl 4-amino-2-(4-biphenylyl)-5-methoxy-1-methylindole-3-carboxylate
  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

• Indium metal as a reducing agent in organic synthesis
  作者：Michael R. Pitts、Justin R. Harrison、Christopher J. Moody

  DOI：10.1039/b101712h

  日期：——

  aromatic nitro compounds under similar conditions results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected. Likewise indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters. Indium is also an effective reducing agent under non-aqueous conditions and α-oximino carbonyl compounds can

  铟的低第一电离能（5.8 eV）及其对空气和水的稳定性表明，这种金属元素应是有机基材的有用还原剂。使用铟金属还原C描述了肟，硝基化合物和共轭烯烃的亚胺中的N键，苯并稠合的氮杂环中的杂环以及4-硝基苄基保护基的去除。因此，使用乙醇氯化铵水溶液中的铟金属选择性地还原喹啉，异喹啉和喹喔啉中的杂环。在相似条件下处理一系列芳香族硝基化合物会导致硝基的选择性还原；酯，腈，酰胺和卤化物取代基不受影响。同样地，乙醇乙醇铵水溶液中的铟是使4-硝基苄基醚和酯脱保护的有效方法。铟在非水条件下也是有效的还原剂，α-肟基羰基化合物可以选择性地还原为相应的N-在乙酸酐或二碳酸二叔丁酯存在下，用铟粉，乙酸在THF中的叔胺保护。在THF-乙酸中的铟也会还原共轭烯烃。
• 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.