6-(3-Iodopropyl)-9-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione | 937367-14-1

• 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-Iodopropyl)-9-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione
• CAS: 937367-14-1
• 化学式: C₂₀H₁₅IN₂O₅
• 分子量: 490.254
• InChiKey: UUJPBZJHYIEZMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  咪唑 、 6-(3-Iodopropyl)-9-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以51%的产率得到AM-14–19
  参考文献：
  名称：

  Nitrated Indenoisoquinolines as Topoisomerase I Inhibitors:  A Systematic Study and Optimization

  摘要：

  The biological activity of indenoisoquinoline topoisomerase I (Topl) inhibitors can be greatly enhanced depending on the choice of substituents on the aromatic rings and lactam side chain. Previously, it was discovered that a 3-nitro group and a 9-methoxy group afforded enhanced biological activity. In the present investigation, indenoisoquinoline analogues were systematically prepared using combinations of nitro groups, methoxy groups, and hydrogen atoms in an effort to understand the contribution of each group toward cytotoxicity and Top I inhibition. Analysis of the biological results suggests that the nitro group is important for Top I inhibition and the methoxy group improves cytotoxicity. In addition, previously identified structure-activity relationships were utilized to select favorable lactam side chain functionalities for incorporation on the aromatic skeleton of analogues in this study. As a result, this investigation has provided optimal Topl inhibitors equipotent to camptothecin that demonstrate low nanomolar cytotoxicities toward cancer cells.

  DOI：

  10.1021/jm070361q
• 作为产物：
  描述：

  3-amino-6-(3-chloropropyl)-5,6-dihydro-9-methoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以37%的产率得到6-(3-Iodopropyl)-9-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione
  参考文献：
  名称：

  Nitrated Indenoisoquinolines as Topoisomerase I Inhibitors:  A Systematic Study and Optimization

  摘要：

  The biological activity of indenoisoquinoline topoisomerase I (Topl) inhibitors can be greatly enhanced depending on the choice of substituents on the aromatic rings and lactam side chain. Previously, it was discovered that a 3-nitro group and a 9-methoxy group afforded enhanced biological activity. In the present investigation, indenoisoquinoline analogues were systematically prepared using combinations of nitro groups, methoxy groups, and hydrogen atoms in an effort to understand the contribution of each group toward cytotoxicity and Top I inhibition. Analysis of the biological results suggests that the nitro group is important for Top I inhibition and the methoxy group improves cytotoxicity. In addition, previously identified structure-activity relationships were utilized to select favorable lactam side chain functionalities for incorporation on the aromatic skeleton of analogues in this study. As a result, this investigation has provided optimal Topl inhibitors equipotent to camptothecin that demonstrate low nanomolar cytotoxicities toward cancer cells.

  DOI：

  10.1021/jm070361q

文献信息

• Nitrated Indenoisoquinolines as Topoisomerase I Inhibitors:  A Systematic Study and Optimization
  作者：Andrew Morrell、Michael Placzek、Seth Parmley、Smitha Antony、Thomas S. Dexheimer、Yves Pommier、Mark Cushman

  DOI：10.1021/jm070361q

  日期：2007.9.1

  The biological activity of indenoisoquinoline topoisomerase I (Topl) inhibitors can be greatly enhanced depending on the choice of substituents on the aromatic rings and lactam side chain. Previously, it was discovered that a 3-nitro group and a 9-methoxy group afforded enhanced biological activity. In the present investigation, indenoisoquinoline analogues were systematically prepared using combinations of nitro groups, methoxy groups, and hydrogen atoms in an effort to understand the contribution of each group toward cytotoxicity and Top I inhibition. Analysis of the biological results suggests that the nitro group is important for Top I inhibition and the methoxy group improves cytotoxicity. In addition, previously identified structure-activity relationships were utilized to select favorable lactam side chain functionalities for incorporation on the aromatic skeleton of analogues in this study. As a result, this investigation has provided optimal Topl inhibitors equipotent to camptothecin that demonstrate low nanomolar cytotoxicities toward cancer cells.