6-(3-chloropropyl)-3-nitro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | 744229-10-5

• 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-chloropropyl)-3-nitro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
• 英文别名: 6-(3-Chloropropyl)-5,9-methylenedioxy-5,11-dioxo-3-nitro-11H-indeno[1,2-c]isoquinoline；20-(3-chloropropyl)-16-nitro-5,7-dioxa-20-azapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13(18),14,16-heptaene-11,19-dione
• CAS: 744229-10-5
• 化学式: C₂₀H₁₃ClN₂O₆
• 分子量: 412.786
• InChiKey: SDOYHGOHOXTXFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(3-chloropropyl)-3-nitro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione 在 甲酸 、 镍 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 16-Amino-20-(3-chloropropyl)-5,7-dioxa-20-azapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13(18),14,16-heptaene-11,19-dione
  参考文献：
  名称：

  Synthesis of nitrated indenoisoquinolines as topoisomerase I inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.05.022
• 作为产物：
  描述：

  2-乙酸基-4-硝基苯甲酸 在 氯化亚砜 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 6.5h， 生成 6-(3-chloropropyl)-3-nitro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
  参考文献：
  名称：

  设计，合成和生物学评估作为拓扑异构酶I抑制剂的3-取代的茚并异喹啉衍生物

  摘要：

  设计并合成了一系列新的茚并异喹啉衍生物。在HepG2，A549和HCT-116细胞系中评估了这些新型化合物的体外抗增殖活性。化合物9a，9b，10a，10c，10e，18a和18b表现出对三种测试癌细胞系的有效抑制活性。还测试了19种化合物在50μM下对Top I的抑制作用。在该浓度下，几乎所有测试的化合物都显示出有效的Top I抑制活性。最有效的化合物9a和10a 与HCPT和TPT相比，它具有更高的细胞毒性，并且在我们的生物学分析中，对Top I的抑制活性可与CPT相媲美。

  DOI：

  10.1016/j.bmcl.2015.12.014

文献信息

• 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。
• US7495100B2
  申请人：——

  公开号：US7495100B2

  公开（公告）日：2009-02-24
• 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.
• Design, synthesis and biological evaluation of 3-substituted indenoisoquinoline derivatives as topoisomerase I inhibitors
  作者：Qian Zhao、Xi Xu、Zhouling Xie、Xiao Liu、Qidong You、Qinglong Guo、Yi Zhong、Zhiyu Li

  DOI：10.1016/j.bmcl.2015.12.014

  日期：2016.2

  new series of indenoisoquinoline derivatives was designed and synthesized. The in vitro anti-proliferative activity of these novel compounds was evaluated in HepG2, A549 and HCT-116 cell lines. Compounds 9a, 9b, 10a, 10c, 10e, 18a and 18b manifested potent inhibitory activity against the three tested cancer cell lines. Nineteen compounds were also tested for Top I inhibition at 50 μM. Almost all the

  设计并合成了一系列新的茚并异喹啉衍生物。在HepG2，A549和HCT-116细胞系中评估了这些新型化合物的体外抗增殖活性。化合物9a，9b，10a，10c，10e，18a和18b表现出对三种测试癌细胞系的有效抑制活性。还测试了19种化合物在50μM下对Top I的抑制作用。在该浓度下，几乎所有测试的化合物都显示出有效的Top I抑制活性。最有效的化合物9a和10a 与HCPT和TPT相比，它具有更高的细胞毒性，并且在我们的生物学分析中，对Top I的抑制活性可与CPT相媲美。