6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline | 915360-11-1

• 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: 6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
• 英文别名: 20-[3-(1,4-Diazepan-1-yl)propyl]-15,16-dimethoxy-5,7-dioxa-20-azapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13,15,17-heptaene-11,19-dione
• CAS: 915360-11-1
• 化学式: C₂₇H₂₉N₃O₆
• 分子量: 491.544
• InChiKey: UTQWGRHDYWXDRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  89.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 盐酸 作用下， 以 乙醚 、 氯仿 为溶剂， 以82%的产率得到6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
  参考文献：
  名称：

  WO2007/59008

  摘要：

  公开号：
• 作为产物：
  描述：

  高哌嗪 、 6-(3-bromo-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以69%的产率得到6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Synthesis and Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Substituted with Nitrogen Heterocycles

  摘要：

  In connection with an ongoing investigation of indenoisoquinoline topoisomerase I (Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing di(methoxy) and methylenedioxy substituents was held constant, and new derivatives were synthesized with nitrogen heterocycles appended to the lactam side chain. Compounds were evaluated for Top1 inhibition and for cytotoxicity in the National Cancer Institute's human cancer cell screen. Some of the more potent derivatives were also screened for in vivo activity in a hollow fiber assay. The results of these studies indicate that lactam substituents possessing nitrogen heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition. Molecular modeling of these compounds in complex with DNA and Top1 suggests that some of the lactam substituents are capable of interacting with the DNA base pairs above and below the site of intercalation and/or with Top1 amino acid residues, resulting in increased biological activity.

  DOI：

  10.1021/jm060564z

文献信息

• WO2007/59008
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Substituted with Nitrogen Heterocycles
  作者：Muthukaman Nagarajan、Andrew Morrell、Alexandra Ioanoviciu、Smitha Antony、Glenda Kohlhagen、Keli Agama、Melinda Hollingshead、Yves Pommier、Mark Cushman

  DOI：10.1021/jm060564z

  日期：2006.10.1

  In connection with an ongoing investigation of indenoisoquinoline topoisomerase I (Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing di(methoxy) and methylenedioxy substituents was held constant, and new derivatives were synthesized with nitrogen heterocycles appended to the lactam side chain. Compounds were evaluated for Top1 inhibition and for cytotoxicity in the National Cancer Institute's human cancer cell screen. Some of the more potent derivatives were also screened for in vivo activity in a hollow fiber assay. The results of these studies indicate that lactam substituents possessing nitrogen heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition. Molecular modeling of these compounds in complex with DNA and Top1 suggests that some of the lactam substituents are capable of interacting with the DNA base pairs above and below the site of intercalation and/or with Top1 amino acid residues, resulting in increased biological activity.