(3-(benzyloxy)-4-methoxyphenyl)(5,6,7-trimethoxy-1H-indol-3-yl)methanone | 1422373-16-7

• 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: (3-(benzyloxy)-4-methoxyphenyl)(5,6,7-trimethoxy-1H-indol-3-yl)methanone
• 英文别名: (4-methoxy-3-phenylmethoxyphenyl)-(5,6,7-trimethoxy-1H-indol-3-yl)methanone
• CAS: 1422373-16-7
• 化学式: C₂₆H₂₅NO₆
• 分子量: 447.488
• InChiKey: BNHGOBBAVUBMDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3-(benzyloxy)-4-methoxyphenyl)(5,6,7-trimethoxy-1H-indol-3-yl)methanone 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 甲酸铵 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (3-Hydroxy-4-methoxyphenyl)-(5,6,7-trimethoxy-1-methylindol-3-yl)methanone
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents

  摘要：

  Several new series of 5,6,7-trimethoxyindole derivatives were synthesized and their structure-activity relationships (SARs) were studied. Some of these compounds exhibited strong antiproliferative activities in the submicromolar range. N-Methyl-5,6,7-trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities, with IC50 values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells (HUVECs). In addition to vascular disrupting activity verified by in vitro assays, compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA-4. The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2/M phase after treatment with 21 and 31. It was showed that 21 disrupted tumor vasculature by use of in vivo assay. Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents.

  DOI：

  10.1021/jm3014663
• 作为产物：
  描述：

  5,6,7-trimethoxy-1H-indole 、 4-甲氧基-3-苯基甲氧基苯甲酰氯 在 乙基溴化镁 、 zinc(II) chloride 、 aluminum (III) chloride 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以57%的产率得到(3-(benzyloxy)-4-methoxyphenyl)(5,6,7-trimethoxy-1H-indol-3-yl)methanone
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents

  摘要：

  Several new series of 5,6,7-trimethoxyindole derivatives were synthesized and their structure-activity relationships (SARs) were studied. Some of these compounds exhibited strong antiproliferative activities in the submicromolar range. N-Methyl-5,6,7-trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities, with IC50 values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells (HUVECs). In addition to vascular disrupting activity verified by in vitro assays, compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA-4. The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2/M phase after treatment with 21 and 31. It was showed that 21 disrupted tumor vasculature by use of in vivo assay. Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents.

  DOI：

  10.1021/jm3014663

文献信息

• Synthesis and Structure–Activity Relationships of <i>N</i>-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents
  作者：Deng-Gao Zhao、JianJun Chen、Ya-Rong Du、Yan-Yan Ma、Ya-Xiong Chen、Kun Gao、Bu-Rong Hu

  DOI：10.1021/jm3014663

  日期：2013.2.28

  Several new series of 5,6,7-trimethoxyindole derivatives were synthesized and their structure-activity relationships (SARs) were studied. Some of these compounds exhibited strong antiproliferative activities in the submicromolar range. N-Methyl-5,6,7-trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities, with IC50 values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells (HUVECs). In addition to vascular disrupting activity verified by in vitro assays, compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA-4. The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2/M phase after treatment with 21 and 31. It was showed that 21 disrupted tumor vasculature by use of in vivo assay. Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents.