3-chloro-1-methyl-5-[1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-imidazol-5-yl]indole | 1345962-03-9

• 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
• 英文别名: 1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-5-(N-methyl-3-chloroindol-5-yl)imidazole；3-Chloro-5-[5-(3-chloro-4,5-dimethoxyphenyl)-3-methylimidazol-4-yl]-1-methylindole
• CAS: 1345962-03-9
• 化学式: C₂₁H₁₉Cl₂N₃O₂
• 分子量: 416.307
• InChiKey: MJHVJPLOUFVGKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 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：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-chloro-4,5-dimethoxyphenyl(tosyl)methyl isocyanide 、 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 3-chloro-1-methyl-5-[1-methyl-4-(3-chloro-4,5-dimethoxyphenyl)-imidazol-5-yl]indole
  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

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 ANALOGS FOR USE IN THE TREATMENT OF CANCER
  申请人：Schobert Rainer

  公开号：US20130137740A1

  公开（公告）日：2013-05-30

  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.

  本发明涉及康布雷塔斯汀的特定类似物，特别是公式（I）中所描述和定义的化合物，以及包含这些化合物的药物组成物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药性癌症方面的应用。
• ENHANCING THE TARGETED IN VIVO DELIVERY OF CELLULAR THERAPIES
  申请人：Martin-Luther-Universität Halle-Wittenberg

  公开号：EP3366303A1

  公开（公告）日：2018-08-29

  The invention relates to a cell therapy product comprising mammalian therapeutic cells, preferably mesenchymal stem cell (MSCs) or T cells, for use as a medicament in the treatment of a medical condition, preferably for the treatment of a tumor and/or malignant disease or a disease associated with inflammation, wherein said treatment comprises administration of an endothelial damaging agent to the subject prior to or in combination with the cell therapy product.

  本发明涉及一种细胞治疗产品，该产品包含哺乳动物治疗细胞，最好是间充质干细胞（MSCs）或T细胞，用作治疗疾病的药物，最好用于治疗肿瘤和/或恶性疾病或与炎症相关的疾病，其中所述治疗包括在细胞治疗产品之前或与细胞治疗产品结合使用内皮损伤剂。
• Combretastatin analogs for use in the treatment of cancer
  申请人：Universität Bayreuth

  公开号：EP2566851B1

  公开（公告）日：2015-01-14
• US8980933B2
  申请人：——

  公开号：US8980933B2

  公开（公告）日：2015-03-17