1-[(1-(4-(3-(2-fluoroethoxy)propoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl]-4-(2-methoxyphenyl)piperazine

• 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: 1-[(1-(4-(3-(2-fluoroethoxy)propoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl]-4-(2-methoxyphenyl)piperazine
• 英文别名: 1-[[1-[4-[3-(2-Fluoroethoxy)propoxy]phenyl]triazol-4-yl]methyl]-4-(2-methoxyphenyl)piperazine；1-[[1-[4-[3-(2-fluoroethoxy)propoxy]phenyl]triazol-4-yl]methyl]-4-(2-methoxyphenyl)piperazine
• 化学式: C₂₅H₃₂FN₅O₃
• 分子量: 469.559
• InChiKey: GVZVJCKGJVWISH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(4-溴苯氧基)丙烷-1-醇 在 copper(l) iodide 、 sodium azide 、 双(三甲基硅烷基)氨基钾 、 copper(II) sulfate 、 sodium ascorbate 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 41.0h， 生成 1-[(1-(4-(3-(2-fluoroethoxy)propoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl]-4-(2-methoxyphenyl)piperazine
  参考文献：
  名称：

  Click chemistry based synthesis of dopamine D4 selective receptor ligands for the selection of potential PET tracers

  摘要：

  Taking advantage of click chemistry, a library of N-arylpiperazinylmethyl triazoles bearing fluoro substituted appendages was synthesized and the target compounds were investigated for dopamine and serotonin receptor binding. With the aim to bias their hydrophilicity and to optimize their D4 receptor affinity and selectivity, a concise series of triazoles containing fluoroalkyl, fluoroalkoxy, fluoroalkoxyphenyl, and deoxyfluoroglucosyl substituents was studied. The D4 receptor affinity and selectivity could be tuned by altering the chemical moiety attached to the triazole unit. Among the test compounds, the fluoroethoxyphenyl derivative 15b showed weak partial agonism at D4 and a K-i value of 14 nM, while its fluoropropoxyphenyl homologue 16a turned out to act as a neutral D4 antagonist (K-i = 5.1 nM). Both, 15b and 16a revealed an excellent balance between D4 receptor affinity and subtype selectivity, providing lead candidates for the development of F-18-labeled radioligands for D4 receptor imaging studies by positron emission tomography (PET). (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.026

文献信息

• Click chemistry based synthesis of dopamine D4 selective receptor ligands for the selection of potential PET tracers
  作者：Ashutosh Banerjee、Simone Maschauer、Harald Hübner、Peter Gmeiner、Olaf Prante

  DOI：10.1016/j.bmcl.2013.09.026

  日期：2013.11

  Taking advantage of click chemistry, a library of N-arylpiperazinylmethyl triazoles bearing fluoro substituted appendages was synthesized and the target compounds were investigated for dopamine and serotonin receptor binding. With the aim to bias their hydrophilicity and to optimize their D4 receptor affinity and selectivity, a concise series of triazoles containing fluoroalkyl, fluoroalkoxy, fluoroalkoxyphenyl, and deoxyfluoroglucosyl substituents was studied. The D4 receptor affinity and selectivity could be tuned by altering the chemical moiety attached to the triazole unit. Among the test compounds, the fluoroethoxyphenyl derivative 15b showed weak partial agonism at D4 and a K-i value of 14 nM, while its fluoropropoxyphenyl homologue 16a turned out to act as a neutral D4 antagonist (K-i = 5.1 nM). Both, 15b and 16a revealed an excellent balance between D4 receptor affinity and subtype selectivity, providing lead candidates for the development of F-18-labeled radioligands for D4 receptor imaging studies by positron emission tomography (PET). (c) 2013 Elsevier Ltd. All rights reserved.