7-(3-(dimethylamino)propyl)benzo[a]phenazin-5(7H)-one | 30249-44-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-(3-(dimethylamino)propyl)benzo[a]phenazin-5(7H)-one
• 英文别名: 7-(3-dimethylamino-propyl)-7H-benzo[a]phenazin-5-one；7-[3-(Dimethylamino)propyl]benzo[a]phenazin-5-one；7-[3-(dimethylamino)propyl]benzo[a]phenazin-5-one
• CAS: 30249-44-6
• 化学式: C₂₁H₂₁N₃O
• 分子量: 331.417
• InChiKey: SVPHTHKPAZDJSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N,N-二甲基-1,3-二氨基丙烷 在 溶剂黄146 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 7-(3-(dimethylamino)propyl)benzo[a]phenazin-5(7H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors

  摘要：

  A novel series of benzo[a]phenazin derivatives bearing alkylamino side chains were designed, synthesized and evaluated for their topoisomerases inhibitory activity as well as cytotoxicity against four human cancer cell lines (HL-60, K-562, HeLa, and A549). These compounds were found to be dual inhibitors of topoisomerase (Topo) I and Topo II, and exhibited excellent antiproliferative activity, in particular against HL-60 cells with submicromolar IC50 values. Further mechanistic studies showed that this class of compounds acted as Topo I poisons by stabilizing the Topo I-DNA cleavage complexes and Topo II catalytic inhibitors by inhibiting the ATPase activity of hTopo II. Molecular docking studies revealed the binding modes of these compounds for Topo I and Topo II. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.024

文献信息

• 一种苯并吩嗪衍生物及其制备方法和应用
  申请人：中山大学

  公开号：CN103360327B

  公开（公告）日：2016-04-20

  本发明属于药物与化工领域，公开了一种苯并吩嗪类衍生物及其制备方法和作为抗癌药物的用途。该苯并吩嗪衍生物的如结构式（I）所示，其中R1、R2为H、卤素、-OCH3或-NO2；以及R1、R2=-O-CH2-O-；n=1或2；R表示各种脂肪胺，包括链状和环状脂肪胺。本发明同时公开了该苯并吩嗪衍生物的制备方法及其作为抗癌药物的用途，该苯并吩嗪衍生物对拓扑异构酶I和拓扑异构酶II有很强的抑制作用，对多种癌细胞株具有显著的抑制作用，在制备抗癌药物上有着广阔的应用空间。
• Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors
  作者：Bing-Lei Yao、Yan-Wen Mai、Shuo-Bin Chen、Hua-Ting Xie、Pei-Fen Yao、Tian-Miao Ou、Jia-Heng Tan、Hong-Gen Wang、Ding Li、Shi-Liang Huang、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.1016/j.ejmech.2015.01.024

  日期：2015.3

  A novel series of benzo[a]phenazin derivatives bearing alkylamino side chains were designed, synthesized and evaluated for their topoisomerases inhibitory activity as well as cytotoxicity against four human cancer cell lines (HL-60, K-562, HeLa, and A549). These compounds were found to be dual inhibitors of topoisomerase (Topo) I and Topo II, and exhibited excellent antiproliferative activity, in particular against HL-60 cells with submicromolar IC50 values. Further mechanistic studies showed that this class of compounds acted as Topo I poisons by stabilizing the Topo I-DNA cleavage complexes and Topo II catalytic inhibitors by inhibiting the ATPase activity of hTopo II. Molecular docking studies revealed the binding modes of these compounds for Topo I and Topo II. (C) 2015 Elsevier Masson SAS. All rights reserved.