6-(3-(Nα,Nω,Nω'-tri-Boc-L-arginylamino)propyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione | 1259521-07-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 6-(3-(Nα,Nω,Nω'-tri-Boc-L-arginylamino)propyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione
• CAS: 1259521-07-7
• 化学式: C₄₀H₅₂N₆O₉
• 分子量: 760.888
• InChiKey: FZDCCYBYAYQGSN-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  55.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  195.52
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  6-(3-(Nα,Nω,Nω'-tri-Boc-L-arginylamino)propyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione 在 四氯化锡 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 以15%的产率得到6-(3-(L-arginylamino)propyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione dihydrochloride
  参考文献：
  名称：

  Indeno[1,2-c]isoquinolin-5,11-diones conjugated to amino acids: Synthesis, cytotoxicity, DNA interaction, and topoisomerase II inhibition properties

  摘要：

  Three series of indeno[1,2-c]isoquinolin-5,11-dione-amino acid conjugates were designed and synthesized. Amino acids were connected to the tetracycle through linkers with lengths of n = 2 and 3 atoms using ester (series I), amide (series II), and secondary amine (series III) functions. DNA binding was evaluated by thermal denaturation and fluorescence measurements. Lysine and arginine substituted derivatives with n = 3 provided the highest DNA binding. Arginine derivative 32 (n = 2, series II) and glycine derivative 34 (n = 2, series III) displayed high topoisomerase II inhibition. Incrementing the length of the N-6 side chain from two to three methylene units provided a significant increase in DNA affinity but a substantial loss in topoisomerase II inhibition. The most cytotoxic compounds toward HL60 leukemia cells were 19, 33, and 34 displaying micromolar IC50 values. When tested with the topoisomerase II-mutated HL60/MX2 cell line, little variation of IC50 values was found, suggesting that topoisomerase II might not be the main target of these compounds and that additional targets could be involved. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.025
• 作为产物：
  描述：

  Boc-Arg(Boc)2OH 、 5,6-dihydro-5,11-dioxo-5-(3-aminopropyl)-11H-indeno(1,2-c)isoquinoline hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.25h， 以89%的产率得到6-(3-(Nα,Nω,Nω'-tri-Boc-L-arginylamino)propyl)-6H-indeno[1,2-c]isoquinoline-5,11-dione
  参考文献：
  名称：

  Indeno[1,2-c]isoquinolin-5,11-diones conjugated to amino acids: Synthesis, cytotoxicity, DNA interaction, and topoisomerase II inhibition properties

  摘要：

  Three series of indeno[1,2-c]isoquinolin-5,11-dione-amino acid conjugates were designed and synthesized. Amino acids were connected to the tetracycle through linkers with lengths of n = 2 and 3 atoms using ester (series I), amide (series II), and secondary amine (series III) functions. DNA binding was evaluated by thermal denaturation and fluorescence measurements. Lysine and arginine substituted derivatives with n = 3 provided the highest DNA binding. Arginine derivative 32 (n = 2, series II) and glycine derivative 34 (n = 2, series III) displayed high topoisomerase II inhibition. Incrementing the length of the N-6 side chain from two to three methylene units provided a significant increase in DNA affinity but a substantial loss in topoisomerase II inhibition. The most cytotoxic compounds toward HL60 leukemia cells were 19, 33, and 34 displaying micromolar IC50 values. When tested with the topoisomerase II-mutated HL60/MX2 cell line, little variation of IC50 values was found, suggesting that topoisomerase II might not be the main target of these compounds and that additional targets could be involved. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.025