2-(biphenyl-4-yl)-3-hydroxymethyl-5-methoxy-1-methylindole-4,7-dione | 219325-75-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(biphenyl-4-yl)-3-hydroxymethyl-5-methoxy-1-methylindole-4,7-dione
• 英文别名: 3-(Hydroxymethyl)-5-methoxy-1-methyl-2-(4-phenylphenyl)indole-4,7-dione
• CAS: 219325-75-4
• 化学式: C₂₃H₁₉NO₄
• 分子量: 373.408
• InChiKey: LDCCFNWAEWOVQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(biphenyl-4-yl)-3-hydroxymethyl-5-methoxy-1-methylindole-4,7-dione 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 生成 2-Biphenyl-4-yl-3-chloromethyl-5-methoxy-1-methyl-1H-indole-4,7-dione
  参考文献：
  名称：

  Controlling the rates of reductively-activated elimination from the (indol-3-yl)methyl position of indolequinones

  摘要：

  合成了一系列取代的3-(4-硝基苯氧基)甲基吲哚-4,7-二酮（Q）。研究了取代模式对吲哚核心在4-硝基苯酚释放速率上的影响，作为药物释放的模型，药物释放是通过酚醚连接链的断裂发生的。在还原为自由基阴离子（Q˙−）或氢醌（QH2）后，4-硝基苯酚从（吲哚-3-基）甲基位置释放。Q˙−自由基在[O2] ≈ 5 µmol dm−3（典型的肿瘤缺氧环境）下的半衰期为t½ ≈ 0.3–1.8毫秒，较高的半衰期值与较高的还原电位相关。在相同的氧浓度下，QH2的自氧化半衰期明显更长（t½ ≈ 8–102分钟），在存在4 µmol dm−3超氧化物歧化酶的情况下更长（t½ ≈ 8–19小时）。尽管吲哚醌能够以高效率释放4-硝基苯酚，但仅有3-羧基取代的Q˙−自由基具有足够短的半衰期（t½ ≈ 41–2毫秒）以与氧的电子转移竞争，因此具有将离去基团靶向缺氧组织的潜力。即使在正常组织中预期的氧浓度下，氢醌的氧敏感性不足以阻止4-硝基苯酚的释放（t½ ≈ 1.5–3.5秒）。通过在吲哚基甲基位置引入富电子取代基，可以控制还原性碎裂的速率。这可能成为设计基于吲哚醌的生物还原药物递送系统的重要因素。

  DOI：

  10.1039/b009652k
• 作为产物：
  描述：

  (4-Amino-2-biphenyl-4-yl-5-methoxy-1-methyl-1H-indol-3-yl)-methanol 在 potassium nitrososulfonate 、 sodium dihydrogen phosphate buffer 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 2-(biphenyl-4-yl)-3-hydroxymethyl-5-methoxy-1-methylindole-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