bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} 3,3’-[octane-1,8-diylbis(1H-1,2,3-triazole-1,4-diyl)]dipropanoate | 1622913-97-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} 3,3’-[octane-1,8-diylbis(1H-1,2,3-triazole-1,4-diyl)]dipropanoate
• 英文别名: [4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-[1-[8-[4-[3-[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]oxy-3-oxopropyl]triazol-1-yl]octyl]triazol-4-yl]propanoate；[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-[1-[8-[4-[3-[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]oxy-3-oxopropyl]triazol-1-yl]octyl]triazol-4-yl]propanoate
• CAS: 1622913-97-6
• 化学式: C₆₀H₇₀Cl₂F₂N₈O₆
• 分子量: 1108.17
• InChiKey: WUVVNDIQBGLCOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.3
• 重原子数：
  78
• 可旋转键数：
  31
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  155
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  4-pentynoic chloride 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} 3,3’-[octane-1,8-diylbis(1H-1,2,3-triazole-1,4-diyl)]dipropanoate
  参考文献：
  名称：

  Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors

  摘要：

  Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.

  DOI：

  10.1016/j.bmcl.2014.06.079

文献信息

• Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors
  作者：Ismail Salama、Stefan Löber、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.bmcl.2014.06.079

  日期：2014.8

  Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.