(S)-4-Benzyloxycarbonylmethylcarbamoyloxy-8-bromomethyl-2-methyl-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydro-pyrrolo[3,2-e]indole-1-carboxylic acid methyl ester | 182360-49-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (S)-4-Benzyloxycarbonylmethylcarbamoyloxy-8-bromomethyl-2-methyl-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydro-pyrrolo[3,2-e]indole-1-carboxylic acid methyl ester
• CAS: 182360-49-2
• 化学式: C₃₆H₃₅BrN₄O₁₀
• 分子量: 763.599
• InChiKey: LKYXIXYLGNNJBR-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  51.0
• 可旋转键数：
  11.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  170.51
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (S)-4-Benzyloxycarbonylmethylcarbamoyloxy-8-bromomethyl-2-methyl-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydro-pyrrolo[3,2-e]indole-1-carboxylic acid methyl ester 在 palladium on activated charcoal 氢溴酸 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 2.0h， 以89%的产率得到
  参考文献：
  名称：

  Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole analogues of duocarmycin B2

  摘要：

  A series of the eight-substituted A-ring pyrrole derivatives of duocarmycin B2 were synthesized, and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the analogues in aqueous solution was examined. The 8-H and the 8-CN compounds which cannot structurally release the cyclopropane compound (DU-86), exhibited extremely diminished anticellular activity compared with duocarmycin A (1a) or DU-86. The ethers and the sulfonates which were not converted to DU-86 under usual conditions (35 degrees C, pH 7), showed almost equal in vivo activities to that of 1a. However, their optimal doses were significantly higher than that for 1a. Most of the A-ring pyrrole analogues which can be chemically or enzymatically converted to DU-86, displayed remarkably superior in vivo antitumor activity to 1a. These results suggest that the A-ring pyrrole analogues need to chemically or enzymatically release DU-86 as an active metabolite to exhibit potent in vivo antitumor activity. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00132-0
• 作为产物：
  描述：

  3-methoxycarbonyl-2-methylduocarmycin A 在 氢溴酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (S)-4-Benzyloxycarbonylmethylcarbamoyloxy-8-bromomethyl-2-methyl-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydro-pyrrolo[3,2-e]indole-1-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole analogues of duocarmycin B2

  摘要：

  A series of the eight-substituted A-ring pyrrole derivatives of duocarmycin B2 were synthesized, and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the analogues in aqueous solution was examined. The 8-H and the 8-CN compounds which cannot structurally release the cyclopropane compound (DU-86), exhibited extremely diminished anticellular activity compared with duocarmycin A (1a) or DU-86. The ethers and the sulfonates which were not converted to DU-86 under usual conditions (35 degrees C, pH 7), showed almost equal in vivo activities to that of 1a. However, their optimal doses were significantly higher than that for 1a. Most of the A-ring pyrrole analogues which can be chemically or enzymatically converted to DU-86, displayed remarkably superior in vivo antitumor activity to 1a. These results suggest that the A-ring pyrrole analogues need to chemically or enzymatically release DU-86 as an active metabolite to exhibit potent in vivo antitumor activity. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00132-0