(E,E)-N,N'-bis[[4-[[2-[[(4-amino-2-methylquinolin-6-yl)amino]carbonyl]phenyl]methoxy]phenyl]methylene]-1,7-heptanediamine | 1296209-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (E,E)-N,N'-bis[[4-[[2-[[(4-amino-2-methylquinolin-6-yl)amino]carbonyl]phenyl]methoxy]phenyl]methylene]-1,7-heptanediamine
• CAS: 1296209-86-3
• 化学式: C₅₇H₅₆N₈O₄
• 分子量: 917.123
• InChiKey: VUWVNEJHRRCJDJ-YIMDWRJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.72
• 重原子数：
  69.0
• 可旋转键数：
  20.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  179.2
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (E,E)-N,N'-bis[[4-[[2-[[(4-amino-2-methylquinolin-6-yl)amino]carbonyl]phenyl]methoxy]phenyl]methylene]-1,7-heptanediamine 在 甲醇 、 sodium tetrahydroborate 作用下， 反应 2.0h， 以92%的产率得到N,N'-bis[[4-[[2-[[(4-amino-2-methylquinolin-6-yl)amino]carbonyl]phenyl]methoxy]phenyl]methyl]-1,7-heptanediamine
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of bivalent antagonists of the nociceptin opioid receptor

  摘要：

  Bivalent ligands constituted by two identical pharmacophores structurally related to the Nociceptin Opioid Receptor (NOPr) antagonist JTC-801 were synthesized and their binding affinities for NOPr were evaluated. The novel ligands are formed by two modified JTC-801 units linked by di-iminic and di-aminic spacers with length ranging from three to ten methylene units. Moreover, the synthesis and the pharmacological characterization were extended to the corresponding univalent ligands. The latter compounds consisted in a single modified JTC-801 unit and an alkyl or alkylamino or alkylimino tail. The purpose of this study is to feature the location and surroundings of the allosteric binding site(s) of pharmacophores containing the 4-aminoquinoline structure. Most important, the bivalent ligands were exploited to reveal the eventual occurrence of a supramolecular receptorial architecture of the NOPr.All the bivalent derivatives 4 and 5 proved to be active in the nanomolar range with no outstanding dependence on the chain length. They showed potencies from three to ten times higher than the corresponding monomers. Consequently, results clearly indicated a positive role of the second pharmacophore in the ligand-protein interaction. The pharmacological profile of I he monomers 7 and 8 clarified the contribution of the linker chain to NOP receptor affinity and suggested the presence of a lipophilic acidic site neighbouring the binding site of the JTC-like ligands.Selectivity of saturated compounds 5, 7, and 8 was tested by binding experiments on delta, kappa and mu opioid receptors. Results indicated a general loss of selectivity as compared to JTC-801. In the [(35)S]GTP gamma S binding assay, all the compounds revealed antagonistic properties at the NOP Receptor.In conclusion the present study set the basis for a systematic investigation on the structural modifications that can be introduced into novel ligands for NOPr and helped to feature the surrounds of the allosteric site of NOPr. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.040
• 作为产物：
  描述：

  2-[(4-甲酰基苯氧基)甲基]苯甲酸甲酯 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 48.75h， 生成 (E,E)-N,N'-bis[[4-[[2-[[(4-amino-2-methylquinolin-6-yl)amino]carbonyl]phenyl]methoxy]phenyl]methylene]-1,7-heptanediamine
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of bivalent antagonists of the nociceptin opioid receptor

  摘要：

  Bivalent ligands constituted by two identical pharmacophores structurally related to the Nociceptin Opioid Receptor (NOPr) antagonist JTC-801 were synthesized and their binding affinities for NOPr were evaluated. The novel ligands are formed by two modified JTC-801 units linked by di-iminic and di-aminic spacers with length ranging from three to ten methylene units. Moreover, the synthesis and the pharmacological characterization were extended to the corresponding univalent ligands. The latter compounds consisted in a single modified JTC-801 unit and an alkyl or alkylamino or alkylimino tail. The purpose of this study is to feature the location and surroundings of the allosteric binding site(s) of pharmacophores containing the 4-aminoquinoline structure. Most important, the bivalent ligands were exploited to reveal the eventual occurrence of a supramolecular receptorial architecture of the NOPr.All the bivalent derivatives 4 and 5 proved to be active in the nanomolar range with no outstanding dependence on the chain length. They showed potencies from three to ten times higher than the corresponding monomers. Consequently, results clearly indicated a positive role of the second pharmacophore in the ligand-protein interaction. The pharmacological profile of I he monomers 7 and 8 clarified the contribution of the linker chain to NOP receptor affinity and suggested the presence of a lipophilic acidic site neighbouring the binding site of the JTC-like ligands.Selectivity of saturated compounds 5, 7, and 8 was tested by binding experiments on delta, kappa and mu opioid receptors. Results indicated a general loss of selectivity as compared to JTC-801. In the [(35)S]GTP gamma S binding assay, all the compounds revealed antagonistic properties at the NOP Receptor.In conclusion the present study set the basis for a systematic investigation on the structural modifications that can be introduced into novel ligands for NOPr and helped to feature the surrounds of the allosteric site of NOPr. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.040