6-(3-Azidopropyl)-5,11-dioxo-3-nitro-11H-indeno[1,2-c]isoquinoline | 744229-18-3

• 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)-5,11-dioxo-3-nitro-11H-indeno[1,2-c]isoquinoline
• 英文别名: 6-(3-azidopropyl)-3-nitroindeno[1,2-c]isoquinoline-5,11-dione
• CAS: 744229-18-3
• 化学式: C₁₉H₁₃N₅O₄
• 分子量: 375.343
• InChiKey: LXCKTBKQPKICDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  97.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(3-Azidopropyl)-5,11-dioxo-3-nitro-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， 以86%的产率得到6-(3-aminopropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione hydrochloride
  参考文献：
  名称：

  Synthesis of indenoisoquinolines

  摘要：

  描述了Indenoisoquinolines和dihydroindenoisoquinolines。特别是，描述了具有一个或多个电子提取取代基的这类化合物。描述了这些分子在国家癌症研究所对55种细胞系进行的体外抗癌活性测试。描述了对这些化合物进行的拓扑异构酶I（top1）抑制测试。

  公开号：

  US20060025595A1
• 作为产物：
  描述：

  在 三氯化铝 、 sodium azide 作用下， 以 二甲基亚砜 、 硝基苯 为溶剂， 反应 2.0h， 生成 6-(3-Azidopropyl)-5,11-dioxo-3-nitro-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Optimization of the Indenone Ring of Indenoisoquinoline Topoisomerase I Inhibitors

  摘要：

  Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary biological evaluation, a more focused series of inhibitors was prepared utilizing a 2,3-dimethoxy-substituted isoquinoline ring. The results of the two series indicate the existence of superior functional groups such as methoxy, fluorine, and cyano for the indenoisoquinoline 9-position. Interestingly, these functional groups coincide with established structure-activity relationships for the 11-position of camptothecin.

  DOI：

  10.1021/jm070307+

文献信息

• Synthesis of nitrated indenoisoquinolines as topoisomerase I inhibitors
  作者：Andrew Morrell、Smitha Antony、Glenda Kohlhagen、Yves Pommier、Mark Cushman

  DOI：10.1016/j.bmcl.2004.05.022

  日期：2004.7

  Indenoisoquinolines and dihydroindenoisoquinolines have been synthesized possessing a nitro-substituted isoquinoline ring in an effort to explore the effects of electron-withdrawing substituents on biological activity. The in vitro anticancer activities of these molecules have been tested in the National Cancer Institute's screen of 55 cell lines. The compounds have also been tested for topoisomerase I (topI) inhibition. The results indicate that these substances are a potent class of topI inhibitors with sub-micromolar cytotoxicity mean graph midpoints (MGM) and topI inhibition equal to camptothecin. (C) 2004 Elsevier Ltd. All rights reserved.
• US7495100B2
  申请人：——

  公开号：US7495100B2

  公开（公告）日：2009-02-24
• Synthesis of indenoisoquinolines
  申请人：Cushman S. Mark

  公开号：US20060025595A1

  公开（公告）日：2006-02-02

  Indenoisoquinolines and dihydroindenoisoquinolines are described. In particular, such compounds possessing one or more electron withdrawing substituents are described. The in vitro anticancer activities of these molecules tested in the National Cancer Institute's screen of 55 cell lines is described. The compounds tested for topoisomerase I (top1) inhibition is described.

  描述了Indenoisoquinolines和dihydroindenoisoquinolines。特别是，描述了具有一个或多个电子提取取代基的这类化合物。描述了这些分子在国家癌症研究所对55种细胞系进行的体外抗癌活性测试。描述了对这些化合物进行的拓扑异构酶I（top1）抑制测试。
• Optimization of the Indenone Ring of Indenoisoquinoline Topoisomerase I Inhibitors
  作者：Andrew Morrell、Michael Placzek、Seth Parmley、Brian Grella、Smitha Antony、Yves Pommier、Mark Cushman

  DOI：10.1021/jm070307+

  日期：2007.9.1

  Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary biological evaluation, a more focused series of inhibitors was prepared utilizing a 2,3-dimethoxy-substituted isoquinoline ring. The results of the two series indicate the existence of superior functional groups such as methoxy, fluorine, and cyano for the indenoisoquinoline 9-position. Interestingly, these functional groups coincide with established structure-activity relationships for the 11-position of camptothecin.