3-chloro-1-ethyl-5-[1-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-imidazol-5-yl]indole hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-chloro-1-ethyl-5-[1-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-imidazol-5-yl]indole hydrochloride
• 英文别名: 5-[5-(3-Bromo-4,5-dimethoxyphenyl)-3-methylimidazol-4-yl]-3-chloro-1-ethylindole;hydrochloride；5-[5-(3-bromo-4,5-dimethoxyphenyl)-3-methylimidazol-4-yl]-3-chloro-1-ethylindole;hydrochloride
• 化学式: C₂₂H₂₁BrClN₃O₂*ClH
• 分子量: 511.246
• InChiKey: BFLPDEOCAMOLDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.58
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  41.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-bromo-4,5-dimethoxyphenyl(tosyl)methyl isocyanide 、 在 potassium carbonate 、 盐酸 作用下， 以 乙醇 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 3.17h， 以110 mg的产率得到3-chloro-1-ethyl-5-[1-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-imidazol-5-yl]indole hydrochloride
  参考文献：
  名称：

  Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors

  摘要：

  5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vb1 cervix and MCF-7/Topo mamma carcinoma cells, and also against CA-4-resistant HT-29 colon carcinoma cells. While not interfering markedly with the polymerization of tubulin in vitro, indole 5c completely disrupted the microtubule cytoskeleton of cancer cells at low concentrations. It also destroyed real blood vessels, both in the chorioallantoic membrane (CAM) of fertilized chicken eggs and within tumor xenografts in mice, without harming embryo or mouse, respectively. Indole 5c was less toxic than CA-4 to endothelial cells, fibroblasts, and cardiomyocytes. In highly vascularized xenograft tumors 5c induced distinct discolorations and histological features typical of vascular-disrupting agents, such as disrupted vessel structures, hemorrhages, and extensive necrosis. In a first preliminary therapy trial, indole 5c retarded the growth of resistant xenograft tumors in mice. (C) 2016 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.045