4'-methoxycinnamoyl 8-O-[4-[(tert-butoxycarbonyl)aminomethyl]benzoyl]-A-ring pyrrole-duocarmycin B2 | 267899-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4'-methoxycinnamoyl 8-O-[4-[(tert-butoxycarbonyl)aminomethyl]benzoyl]-A-ring pyrrole-duocarmycin B2
• CAS: 267899-52-5
• 化学式: C₃₇H₃₈BrN₃O₈
• 分子量: 732.628
• InChiKey: DLVAUSMHEIALAR-XAJMEMKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.05
• 重原子数：
  49.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  136.26
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4'-methoxycinnamoyl 8-O-[4-[(tert-butoxycarbonyl)aminomethyl]benzoyl]-A-ring pyrrole-duocarmycin B2 在 甲醇 、 氢溴酸 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.75h， 以15 mg的产率得到
  参考文献：
  名称：

  Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups

  摘要：

  A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups 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 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substituted A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs from KW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-21S9. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00293-x
• 作为产物：
  描述：

  3-methoxycarbonyl-2-methylduocarmycin A 在 4-二甲氨基吡啶 、 氢溴酸 、 sodium hydride 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 19.17h， 生成 4'-methoxycinnamoyl 8-O-[4-[(tert-butoxycarbonyl)aminomethyl]benzoyl]-A-ring pyrrole-duocarmycin B2
  参考文献：
  名称：

  Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups

  摘要：

  A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups 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 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substituted A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs from KW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-21S9. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00293-x