ethyl 2-(4-methoxyphenyl)-7H-pyrrolo[2,3-h]quinoline-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 2-(4-methoxyphenyl)-7H-pyrrolo[2,3-h]quinoline-4-carboxylate
• 化学式: C₂₁H₁₈N₂O₃
• 分子量: 346.386
• InChiKey: LIAUAUNLKQBFPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  64.21
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-methoxyphenyl)-7H-pyrrolo[2,3-h]quinoline-4-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以86.5%的产率得到(2-(4-methoxyphenyl)-7H-pyrrolo[2,3-h]quinolin-4-yl)methanol
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationships of Azolylmethylpyrroloquinolines as Nonsteroidal Aromatase Inhibitors

  摘要：

  A small library of both [2,3-h] and [3,2-f] novel pyrroloquinolines equipped with an azolylmethyl group was designed and synthesized as nonsteroidal CYP19 aromatase inhibitors. The results showed that azolylmethyl derivatives 11, 13, 14, 21, and 22 exhibited an inhibitory potency on aromatase comparable to that of letrozole chosen as a reference compound. When assayed on CYP11B1 (steroid-11 beta-hydroxylase) and CYPI7 (17 alpha-hydroxy/17,20-lyase), compound 22 was found to be the best and most selective CYP19 inhibitor of them all. In a panel of nine human cancer-cell lines, all compounds were either slightly cytotoxic or not at all. Docking simulations were carried out to inspect crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding, and heme iron coordination. This study, along with the prediction of the pharmacokinetics of compounds 11, 13, 14, 21, and 22, demonstrates that the pyrroloquinoline scaffold represents a starting point for the development of new pyrroloquinoline-based aromatase inhibitors.

  DOI：

  10.1021/jm400377z
• 作为产物：
  描述：

  丙酮酸乙酯 、 4-氨基吲哚 、 4-甲氧基苯甲醛 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以20%的产率得到ethyl 2-(4-methoxyphenyl)-7H-pyrrolo[2,3-h]quinoline-4-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationships of Azolylmethylpyrroloquinolines as Nonsteroidal Aromatase Inhibitors

  摘要：

  A small library of both [2,3-h] and [3,2-f] novel pyrroloquinolines equipped with an azolylmethyl group was designed and synthesized as nonsteroidal CYP19 aromatase inhibitors. The results showed that azolylmethyl derivatives 11, 13, 14, 21, and 22 exhibited an inhibitory potency on aromatase comparable to that of letrozole chosen as a reference compound. When assayed on CYP11B1 (steroid-11 beta-hydroxylase) and CYPI7 (17 alpha-hydroxy/17,20-lyase), compound 22 was found to be the best and most selective CYP19 inhibitor of them all. In a panel of nine human cancer-cell lines, all compounds were either slightly cytotoxic or not at all. Docking simulations were carried out to inspect crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding, and heme iron coordination. This study, along with the prediction of the pharmacokinetics of compounds 11, 13, 14, 21, and 22, demonstrates that the pyrroloquinoline scaffold represents a starting point for the development of new pyrroloquinoline-based aromatase inhibitors.

  DOI：

  10.1021/jm400377z