N,N'-[2,5,8,11,14-pentaoxapentadecane-1,15-diylbis[(2-methoxy-4,1-phenylene)piperazine-4,1-diylbutane-4,1-diyl]]dibenzamide | 1355460-64-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N,N'-[2,5,8,11,14-pentaoxapentadecane-1,15-diylbis[(2-methoxy-4,1-phenylene)piperazine-4,1-diylbutane-4,1-diyl]]dibenzamide
• 英文别名: N-[4-[4-[4-[2-[2-[2-[2-[[4-[4-(4-benzamidobutyl)piperazin-1-yl]-3-methoxyphenyl]methoxy]ethoxy]ethoxy]ethoxy]ethoxymethyl]-2-methoxyphenyl]piperazin-1-yl]butyl]benzamide
• CAS: 1355460-64-8
• 化学式: C₅₄H₇₆N₆O₉
• 分子量: 953.232
• InChiKey: BGMQCQHMPBHOMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  69
• 可旋转键数：
  32
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  四乙二醇二对甲苯磺酸酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hydride 、 potassium carbonate 、 sodium iodide 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲苯 、 乙腈 、 paraffin oil 为溶剂， 反应 34.25h， 生成 N,N'-[2,5,8,11,14-pentaoxapentadecane-1,15-diylbis[(2-methoxy-4,1-phenylene)piperazine-4,1-diylbutane-4,1-diyl]]dibenzamide
  参考文献：
  名称：

  Bivalent molecular probes for dopamine D2-like receptors

  摘要：

  Merging two arylamidoalkyl substituted phenylpiperazines as prototypical recognition elements for dopamine D-2-like receptors by oligoethylene glycol linkers led to a series of bivalent ligands. These dimers were investigated in comparison to their monomeric analogues for their dopamine D-2long, D-2short, D-3 and D-4 receptor binding. Radioligand binding experiments revealed strong bivalent effects for some para-substituted benzamide derivatives. For the D-3 subtype, the target compounds 32, 34 and 36 showed an up to 70-fold increase of affinity and a substantial enhancement of subtype selectivity when compared to the monovalent analogue 24. Analysis of the binding curves displayed Hill slopes very close to one indicating that the bivalent ligands displace 1 equiv of radioligand. Obviously, the two pharmacophores occupy an orthosteric and an allosteric binding site rather than adopting a receptor-bridging binding mode. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.063

文献信息

• Bivalent molecular probes for dopamine D2-like receptors
  作者：Daniela Huber、Stefan Löber、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.bmc.2011.10.063

  日期：2012.1

  Merging two arylamidoalkyl substituted phenylpiperazines as prototypical recognition elements for dopamine D-2-like receptors by oligoethylene glycol linkers led to a series of bivalent ligands. These dimers were investigated in comparison to their monomeric analogues for their dopamine D-2long, D-2short, D-3 and D-4 receptor binding. Radioligand binding experiments revealed strong bivalent effects for some para-substituted benzamide derivatives. For the D-3 subtype, the target compounds 32, 34 and 36 showed an up to 70-fold increase of affinity and a substantial enhancement of subtype selectivity when compared to the monovalent analogue 24. Analysis of the binding curves displayed Hill slopes very close to one indicating that the bivalent ligands displace 1 equiv of radioligand. Obviously, the two pharmacophores occupy an orthosteric and an allosteric binding site rather than adopting a receptor-bridging binding mode. (C) 2011 Elsevier Ltd. All rights reserved.