N,N'-(2-(3-(4-(3-chloropropanoyl)piperazin-1-yl)propyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-5,8-diyl)-bis(3-chloropropanamide) | 1346457-84-8

• 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: N,N'-(2-(3-(4-(3-chloropropanoyl)piperazin-1-yl)propyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-5,8-diyl)-bis(3-chloropropanamide)
• CAS: 1346457-84-8
• 化学式: C₂₈H₃₂Cl₃N₅O₅
• 分子量: 624.952
• InChiKey: UCLBDBBQRRGBBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.73
• 重原子数：
  41.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  119.13
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 N,N'-(2-(3-(4-(3-chloropropanoyl)piperazin-1-yl)propyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-5,8-diyl)-bis(3-chloropropanamide) 在 sodium iodide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以63%的产率得到N,N'-(1,3-dioxo-2-(3-(4-(3-(pyrrolidin-1-yl)propanoyl)piperazin-1-yl)propyl)-2,3-dihydro-1H-benzo[de]isoquinoline-5,8-diyl)bis(3-(pyrrolidin-1-yl)propanamide)
  参考文献：
  名称：

  Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands

  摘要：

  A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.062
• 作为产物：
  描述：

  3-硝基-1,8-萘二甲酸酐 在 硫酸 、 palladium 10% on activated carbon 、 硝酸 、 甲酸铵 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 N,N'-(2-(3-(4-(3-chloropropanoyl)piperazin-1-yl)propyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-5,8-diyl)-bis(3-chloropropanamide)
  参考文献：
  名称：

  Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands

  摘要：

  A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.062