5-phenyl-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-phenyl-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
• 英文别名: 2-(2-dimethylaminoethyl)-5-phenylbenzo[de]isoquinoline-1,3-dione；2-[2-(Dimethylamino)ethyl]-5-phenylbenzo[de]isoquinoline-1,3-dione
• 化学式: C₂₂H₂₀N₂O₂
• 分子量: 344.413
• InChiKey: ZCKQGGIKNHFHOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  氨萘非特 在 四(三苯基膦)钯 、 硫酸 、 sodium carbonate 作用下， 以 乙醇 、 水 、 丙酮 、 甲苯 为溶剂， 反应 8.75h， 生成 5-phenyl-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides

  摘要：

  A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo. By performing all these assays we conclude that the 5-arylsubstituted naphthalimides not only keep but also improve amonafide's biological activities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.039

文献信息

• 5-Non-amino aromatic substituted naphthalimides as potential antitumor agents: Synthesis via Suzuki reaction, antiproliferative activity, and DNA-binding behavior
  作者：Lijuan Xie、Jingnan Cui、Xuhong Qian、Yufang Xu、Jianwen Liu、Ruian Xu

  DOI：10.1016/j.bmc.2010.11.055

  日期：2011.1

  enter clinical phase III, because of its high-variable and unpredictable toxicity. In order to develop selective, efficient, and safe drugs, applying the ‘nonfused’ aromatic system strategy, a series of 5-non-amino aromatic substituted naphthalimides as replacement for amonafide were designed and were synthesized from naphthalic anhydride by three steps including bromination, amination, and Pd(PPh3)4

  阿莫那肽是一种具有抗肿瘤活性的萘二甲酰亚胺衍生物，由于其多变且不可预测的毒性而未能进入临床III期。为了开发选择性，高效和安全的药物，应用“非融合”芳族体系策略，设计了一系列5-非氨基芳族取代萘二甲酰亚胺替代阿莫那肽，并通过包括溴化在内的三个步骤从萘酐中合成了这些化合物：胺化反应和Pd（PPh 3）4催化的Suzuki反应。这些新的萘二甲酰亚胺衍生物，4b除外，不仅在相同的实验条件下在体外对HeLa和P388D1细胞系表现出比阿莫那肽更好的活性，而且由于其结构（在5位缺少易乙酰化的芳胺），还可以避免阿莫那肽的副作用。还研究了萘二甲酰亚胺衍生物的DNA结合行为，结果表明它们通过插层与DNA结合，而4a和4g以不同方式插层到DNA中。
• Synthesis, Biological Activity, and Quantitative Structure−Activity Relationship Study of Azanaphthalimide and Arylnaphthalimide Derivatives
  作者：Miguel F. Braña、Ana Gradillas、Angel Gómez、Nuria Acero、Francisco Llinares、Dolores Muñoz-Mingarro、Cristina Abradelo、Fernanda Rey-Stolle、Mercedes Yuste、Joaquín Campos、Miguel Á. Gallo、Antonio Espinosa

  DOI：10.1021/jm0310784

  日期：2004.4.1

  A series of quinoline derivatives as aza analogues of the naphthalene chromophore and a series of "nonfused" tricyclic aromatic systems, in particular 5-arylquinolines and 5- or 6-aryl and heteroaryl naphthalene systems, were synthesized and evaluated for growth-inhibitory properties in several human cell lines. The analysis of quantitative structure-antitumor activity relationships for the growth-inhibitory properties is also reported. Findings suggest that these compounds may not express their cytotoxicity via interaction on DNA.
• Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides
  作者：Patricia Quintana-Espinoza、Jonay García-Luis、Ángel Amesty、Patricia Martín-Rodríguez、Isabel Lorenzo-Castrillejo、Angel G. Ravelo、Leandro Fernández-Pérez、Félix Machín、Ana Estévez-Braun

  DOI：10.1016/j.bmc.2013.08.039

  日期：2013.11

  A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo. By performing all these assays we conclude that the 5-arylsubstituted naphthalimides not only keep but also improve amonafide's biological activities. (C) 2013 Elsevier Ltd. All rights reserved.