(5-Bromo-1-methylbenzimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanone | 1427690-99-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5-Bromo-1-methylbenzimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1427690-99-0
• 化学式: C₁₈H₁₇BrN₂O₄
• 分子量: 405.248
• InChiKey: RXWVJTRGPDFXPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (5-Bromo-1-methylbenzimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanol 在 重铬酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以69%的产率得到(5-Bromo-1-methylbenzimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanone
  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