1-Methyl-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]indole-3-carbaldehyde | 1427690-75-2

• 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: 1-Methyl-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]indole-3-carbaldehyde
• 英文别名: 1-methyl-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]indole-3-carbaldehyde
• CAS: 1427690-75-2
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: UCXHWLWZEXUQKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-Methyl-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]indole-3-carbaldehyde 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以83%的产率得到1,3-Dimethyl-5-[1-(3,4,5-trimethoxyphenyl)ethyl]indole
  参考文献：
  名称：

  Endowing Indole-Based Tubulin Inhibitors with an Anchor for Derivatization: Highly Potent 3-Substituted Indolephenstatins and Indoleisocombretastatins

  摘要：

  Colchicine site ligands with indole B rings are potent tubulin polymerization inhibitors. Structural modifications at the indole 3-position of 1-methyl-5-indolyl-based isocombretastatins (1,1-diarylethenes) and phenstatins endowed them with anchors for further derivatization and resulted in highly potent compounds. The substituted derivatives displayed potent cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies and promoted cell killing mediated by caspase-3 activation. Binding at the colchicine site was confirmed by means of fluorescence measurements of MTC displacement. Molecular modeling suggests that the tropolone-binding region of the colchicine site of tubulin can adapt to hosting small polar substituents. Isocombretastatins accepted substitutions better than phenstatins, and the highest potencies were achieved for the cyano and hydroxyiminomethyl substituents, with TPI values in the submicromolar range and cytotoxicities in the subnanomolar range. A 3,4,5-trimethoxyphenyl ring usually afforded more potent derivatives than a 2,3,4-trimethoxyphenyl ring.

  DOI：

  10.1021/jm3015603
• 作为产物：
  描述：

  5-溴-1-甲基吲哚 在 重铬酸吡啶 、 正丁基锂 、 三氯氧磷 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 77.0h， 生成 1-Methyl-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]indole-3-carbaldehyde 、 1-methyl-5-[(Z)-3-oxo-1-(3,4,5-trimethoxyphenyl)prop-1-enyl]indole-3-carbaldehyde
  参考文献：
  名称：

  Endowing Indole-Based Tubulin Inhibitors with an Anchor for Derivatization: Highly Potent 3-Substituted Indolephenstatins and Indoleisocombretastatins

  摘要：

  Colchicine site ligands with indole B rings are potent tubulin polymerization inhibitors. Structural modifications at the indole 3-position of 1-methyl-5-indolyl-based isocombretastatins (1,1-diarylethenes) and phenstatins endowed them with anchors for further derivatization and resulted in highly potent compounds. The substituted derivatives displayed potent cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies and promoted cell killing mediated by caspase-3 activation. Binding at the colchicine site was confirmed by means of fluorescence measurements of MTC displacement. Molecular modeling suggests that the tropolone-binding region of the colchicine site of tubulin can adapt to hosting small polar substituents. Isocombretastatins accepted substitutions better than phenstatins, and the highest potencies were achieved for the cyano and hydroxyiminomethyl substituents, with TPI values in the submicromolar range and cytotoxicities in the subnanomolar range. A 3,4,5-trimethoxyphenyl ring usually afforded more potent derivatives than a 2,3,4-trimethoxyphenyl ring.

  DOI：

  10.1021/jm3015603

文献信息

• Endowing Indole-Based Tubulin Inhibitors with an Anchor for Derivatization: Highly Potent 3-Substituted Indolephenstatins and Indoleisocombretastatins
  作者：Raquel Álvarez、Pilar Puebla、J. Fernando Díaz、Ana C. Bento、Rósula García-Navas、Janis de la Iglesia-Vicente、Faustino Mollinedo、José Manuel Andreu、Manuel Medarde、Rafael Peláez

  DOI：10.1021/jm3015603

  日期：2013.4.11

  Colchicine site ligands with indole B rings are potent tubulin polymerization inhibitors. Structural modifications at the indole 3-position of 1-methyl-5-indolyl-based isocombretastatins (1,1-diarylethenes) and phenstatins endowed them with anchors for further derivatization and resulted in highly potent compounds. The substituted derivatives displayed potent cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies and promoted cell killing mediated by caspase-3 activation. Binding at the colchicine site was confirmed by means of fluorescence measurements of MTC displacement. Molecular modeling suggests that the tropolone-binding region of the colchicine site of tubulin can adapt to hosting small polar substituents. Isocombretastatins accepted substitutions better than phenstatins, and the highest potencies were achieved for the cyano and hydroxyiminomethyl substituents, with TPI values in the submicromolar range and cytotoxicities in the subnanomolar range. A 3,4,5-trimethoxyphenyl ring usually afforded more potent derivatives than a 2,3,4-trimethoxyphenyl ring.