3-methoxycarbonyl-1,2-dimethylduocarmycin A | 182360-51-6

• 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-methoxycarbonyl-1,2-dimethylduocarmycin A
• 英文别名: methyl (1R,12S)-4,5-dimethyl-7-oxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-3-carboxylate
• CAS: 182360-51-6
• 化学式: C₂₇H₂₇N₃O₇
• 分子量: 505.527
• InChiKey: RLECHHDAAFHPTG-ASHKIFAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-methoxycarbonyl-1,2-dimethylduocarmycin A 在 氢溴酸 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.5h， 生成
  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：

  8-O-tert-butyldimethylsilyl-3-methoxycarbonyl-2-methylduocarmycin B2 在 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-methoxycarbonyl-1,2-dimethylduocarmycin A
  参考文献：
  名称：

  Antitumor antibiotics: Duocarmycins

  摘要：

  DOI：

  10.1007/bf02317808

文献信息

• Studies on the active metabolite (DU-86) of KW-2189, a novel derivative of duocarmycin
  作者：Satoru Nagamura、Eiji Kobayashi、Katsushige Gomi、Hiromitsu Saito

  DOI：10.1016/0960-894x(96)00388-5

  日期：1996.9

  Some derivatives of DU-86 as an active metabolite of KW-2189, which is a novel duocarmycin derivative, have been synthesized and evaluated for the biological activity. The results suggested that the methylation of aromatic NH moiety showed extremely decreased anticellular and antitumor activity, demonstrating that the free NH moiety play an important role in the biological activity. Copyright (C) 1996 Elsevier Science Ltd
• Antitumor antibiotics: Duocarmycins
  作者：Satoru Nagamura、Hiromitsu Saito

  DOI：10.1007/bf02317808

  日期：1998.12
• Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole analogues of duocarmycin B2
  作者：Satoru Nagamura、Eiji Kobayashi、Katsushige Gomi、Hiromitsu Saito

  DOI：10.1016/0968-0896(96)00132-0

  日期：1996.8

  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