3-chloro-1-methyl-5-[1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-imidazol-5-yl]indole hydrochloride | 1345962-04-0

• 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-methyl-5-[1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-imidazol-5-yl]indole hydrochloride
• 英文别名: 1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-5-(N-methyl-3-chloroindol-5-yl)imidazole hydrochloride；3-Chloro-5-[5-(3-chloro-4,5-dimethoxyphenyl)-3-methylimidazol-4-yl]-1-methylindole;hydrochloride；3-chloro-5-[5-(3-chloro-4,5-dimethoxyphenyl)-3-methylimidazol-4-yl]-1-methylindole;hydrochloride
• CAS: 1345962-04-0
• 化学式: C₂₁H₁₉Cl₂N₃O₂*ClH
• 分子量: 452.768
• InChiKey: UYDAHYPKYHKKTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.99
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 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-chloro-1-methyl-5-[1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-imidazol-5-yl]indole 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.17h， 以51%的产率得到3-chloro-1-methyl-5-[1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-imidazol-5-yl]indole hydrochloride
  参考文献：
  名称：

  [EN] COMBRETASTATIN ANALOGS FOR USE IN THE TREATMENT OF CANCER
  [FR] ANALOGUES DE LA COMBRÉTASTATINE POUR UTILISATION DANS LE TRAITEMENT DU CANCER

  摘要：

  本发明涉及康柏替斯汀的特定类似物，特别是本文所描述和定义的式(I)化合物，以及包含这些化合物的药物组合物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药癌症方面。

  公开号：

  WO2011138409A1

文献信息

• [EN] COMBRETASTATIN ANALOGS FOR USE IN THE TREATMENT OF CANCER<br/>[FR] ANALOGUES DE LA COMBRÉTASTATINE POUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：UNIV BAYREUTH

  公开号：WO2011138409A1

  公开（公告）日：2011-11-10

  The present invention relates to specific analogs of combretastatin, in particular the compounds of formula (I) as described and defined herein, and pharmaceutical compositions comprising the compounds, as well as their medical use, in particular in the treatment or prevention of cancer, including multidrug-resistant cancer.

  本发明涉及康柏替斯汀的特定类似物，特别是本文所描述和定义的式(I)化合物，以及包含这些化合物的药物组合物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药癌症方面。
• 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
  作者：Katharina Mahal、Bernhard Biersack、Sebastian Schruefer、Marcus Resch、Ralf Ficner、Rainer Schobert、Thomas Mueller

  DOI：10.1016/j.ejmech.2016.04.045

  日期：2016.8

  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.