6-(3-Azidopropyl)-5,9,10-trimethoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline | 918336-18-2

• 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-Azidopropyl)-5,9,10-trimethoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
• 英文别名: 6-(3-azidopropyl)-8,9,10-trimethoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione
• CAS: 918336-18-2
• 化学式: C₂₂H₁₉N₅O₇
• 分子量: 465.422
• InChiKey: NVMQERCTMIMUDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-(3-Azidopropyl)-5,9,10-trimethoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 亚磷酸三乙酯 、 盐酸 作用下， 以 苯 、 甲醇 为溶剂， 反应 18.0h， 以86%的产率得到6-(3-Aminopropyl)-5,9,10-trimethoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline Hydrochloride
  参考文献：
  名称：

  A Systematic Study of Nitrated Indenoisoquinolines Reveals a Potent Topoisomerase I Inhibitor

  摘要：

  The biological activity of indenoisoquinoline topoisomerase I inhibitors is significantly enhanced by nitration of the isoquinoline ring. In the present study, nitrated analogues were synthesized with the indenone ring substituted with methoxy groups to further explore a previously identified structure-activity relationship between the nitrated isoquinoline ring and a methylenedioxy-substituted indenone ring. The results indicate that a single methoxy group at the 9-position of an indenoisoquinoline affords superior biological activity. Hypothetical binding models have been developed to rationalize these results, and they indicate that pi-stacking between the indenoisoquinolines and the DNA base pairs, as visualized by electrostatic complementarity, is important for the intercalation and biological activity of the indenoisoquinoline analogues. Collectively, the analysis of methoxy groups on the indenone ring also illustrates a strict steric requirement for substituents extending toward the nonscissile DNA backbone and emphasizes a need for planarity to afford potent biological activity.

  DOI：

  10.1021/jm060974n
• 作为产物：
  描述：

  4-硝基邻苯二价酸酐 在 sodium azide 、 phosphorus pentoxide 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 34.0h， 生成 6-(3-Azidopropyl)-5,9,10-trimethoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  A Systematic Study of Nitrated Indenoisoquinolines Reveals a Potent Topoisomerase I Inhibitor

  摘要：

  The biological activity of indenoisoquinoline topoisomerase I inhibitors is significantly enhanced by nitration of the isoquinoline ring. In the present study, nitrated analogues were synthesized with the indenone ring substituted with methoxy groups to further explore a previously identified structure-activity relationship between the nitrated isoquinoline ring and a methylenedioxy-substituted indenone ring. The results indicate that a single methoxy group at the 9-position of an indenoisoquinoline affords superior biological activity. Hypothetical binding models have been developed to rationalize these results, and they indicate that pi-stacking between the indenoisoquinolines and the DNA base pairs, as visualized by electrostatic complementarity, is important for the intercalation and biological activity of the indenoisoquinoline analogues. Collectively, the analysis of methoxy groups on the indenone ring also illustrates a strict steric requirement for substituents extending toward the nonscissile DNA backbone and emphasizes a need for planarity to afford potent biological activity.

  DOI：

  10.1021/jm060974n

文献信息

• A Systematic Study of Nitrated Indenoisoquinolines Reveals a Potent Topoisomerase I Inhibitor
  作者：Andrew Morrell、Smitha Antony、Glenda Kohlhagen、Yves Pommier、Mark Cushman

  DOI：10.1021/jm060974n

  日期：2006.12.1

  The biological activity of indenoisoquinoline topoisomerase I inhibitors is significantly enhanced by nitration of the isoquinoline ring. In the present study, nitrated analogues were synthesized with the indenone ring substituted with methoxy groups to further explore a previously identified structure-activity relationship between the nitrated isoquinoline ring and a methylenedioxy-substituted indenone ring. The results indicate that a single methoxy group at the 9-position of an indenoisoquinoline affords superior biological activity. Hypothetical binding models have been developed to rationalize these results, and they indicate that pi-stacking between the indenoisoquinolines and the DNA base pairs, as visualized by electrostatic complementarity, is important for the intercalation and biological activity of the indenoisoquinoline analogues. Collectively, the analysis of methoxy groups on the indenone ring also illustrates a strict steric requirement for substituents extending toward the nonscissile DNA backbone and emphasizes a need for planarity to afford potent biological activity.