2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-8-[4-(trifluoromethyl)benzoyl]-1,4-dioxa-8-azaspiro[4.5]decane

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-8-[4-(trifluoromethyl)benzoyl]-1,4-dioxa-8-azaspiro[4.5]decane
• 英文别名: [3-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-1,4-dioxa-8-azaspiro[4.5]decan-8-yl]-[4-(trifluoromethyl)phenyl]methanone；[3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-1,4-dioxa-8-azaspiro[4.5]decan-8-yl]-[4-(trifluoromethyl)phenyl]methanone
• 化学式: C₂₇H₃₂F₃N₃O₄
• 分子量: 519.564
• InChiKey: AEOKAVWIADBGHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-苄基哌啶酮 在 5%-palladium/activated carbon 、 氢气 、 对甲苯磺酸 、 potassium iodide 作用下， 以 乙醇 、 氯仿 、 乙二醇甲醚 、 甲苯 为溶剂， 反应 62.0h， 生成 2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-8-[4-(trifluoromethyl)benzoyl]-1,4-dioxa-8-azaspiro[4.5]decane
  参考文献：
  名称：

  Structure–affinity/activity relationships of 1,4-dioxa-spiro[4.5]decane based ligands at α<alpha>1 and 5-HT1A receptors

  摘要：

  Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a highly selective and potent 5-HT1AR ligand. In the present work we adopted an in-parallel synthetic strategy to rapidly explore a new set of arylpiperazine (7-32) that is structurally related to 1. The compounds were tested for binding affinity and functional activity at 5-HT1AR and alpha < alpha > 1-adrenoceptor subtypes and SAR studies were drawn. In particular, compounds 9, 27 and 30 emerged as promising alpha < alpha > 1 receptor antagonists, while compound 10 behaves as the most potent and efficacious agonist. All the compounds were docked into the 5-HT1AR theoretical model and the results were in agreement with the biological experimental data. These findings may represent a new starting point for developing more selective alpha < alpha > 1 or 5-HT1AR ligands. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.070

文献信息

• Structure–affinity/activity relationships of 1,4-dioxa-spiro[4.5]decane based ligands at α&lt;alpha&gt;1 and 5-HT1A receptors
  作者：Silvia Franchini、Umberto M. Battisti、Annamaria Baraldi、Adolfo Prandi、Paola Fossa、Elena Cichero、Annalisa Tait、Claudia Sorbi、Gabriella Marucci、Antonio Cilia、Lorenza Pirona、Livio Brasili

  DOI：10.1016/j.ejmech.2014.09.070

  日期：2014.11

  Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a highly selective and potent 5-HT1AR ligand. In the present work we adopted an in-parallel synthetic strategy to rapidly explore a new set of arylpiperazine (7-32) that is structurally related to 1. The compounds were tested for binding affinity and functional activity at 5-HT1AR and alpha < alpha > 1-adrenoceptor subtypes and SAR studies were drawn. In particular, compounds 9, 27 and 30 emerged as promising alpha < alpha > 1 receptor antagonists, while compound 10 behaves as the most potent and efficacious agonist. All the compounds were docked into the 5-HT1AR theoretical model and the results were in agreement with the biological experimental data. These findings may represent a new starting point for developing more selective alpha < alpha > 1 or 5-HT1AR ligands. (C) 2014 Elsevier Masson SAS. All rights reserved.