9-benzyloxy-6-3-(bromopropyl)-5,6-dihydro-2,3,8-trimethoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline | 1415806-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 9-benzyloxy-6-3-(bromopropyl)-5,6-dihydro-2,3,8-trimethoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
• 英文别名: 6-(3-Bromopropyl)-2,3,8-trimethoxy-9-phenylmethoxyindeno[1,2-c]isoquinoline-5,11-dione；6-(3-bromopropyl)-2,3,8-trimethoxy-9-phenylmethoxyindeno[1,2-c]isoquinoline-5,11-dione
• CAS: 1415806-42-6
• 化学式: C₂₉H₂₆BrNO₆
• 分子量: 564.433
• InChiKey: NJLDWUQBEJIRQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-benzyloxy-6-3-(bromopropyl)-5,6-dihydro-2,3,8-trimethoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 氢溴酸 、 溶剂黄146 、 sodium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 9-Hydroxy-6-(3-imidazol-1-ylpropyl)-2,3,8-trimethoxyindeno[1,2-c]isoquinoline-5,11-dione
  参考文献：
  名称：

  Identification, Synthesis, and Biological Evaluation of Metabolites of the Experimental Cancer Treatment Drugs Indotecan (LMP400) and Indimitecan (LMP776) and Investigation of Isomerically Hydroxylated Indenoisoquinoline Analogues as Topoisomerase I Poisons

  摘要：

  Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.

  DOI：

  10.1021/jm300519w
• 作为产物：
  描述：

  香草醛 在 氯化亚砜 、 potassium carbonate 、 sodium sulfate 、 三乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.6h， 生成 9-benzyloxy-6-3-(bromopropyl)-5,6-dihydro-2,3,8-trimethoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Identification, Synthesis, and Biological Evaluation of Metabolites of the Experimental Cancer Treatment Drugs Indotecan (LMP400) and Indimitecan (LMP776) and Investigation of Isomerically Hydroxylated Indenoisoquinoline Analogues as Topoisomerase I Poisons

  摘要：

  Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.

  DOI：

  10.1021/jm300519w