1-(2-methoxyphenyl)-4-(4-(1-phenyl-1H-1,2,3-triazol-4-yl)butyl)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-(2-methoxyphenyl)-4-(4-(1-phenyl-1H-1,2,3-triazol-4-yl)butyl)piperazine
• 英文别名: BAK 04-27；1-(2-Methoxyphenyl)-4-[4-(1-phenyltriazol-4-yl)butyl]piperazine；1-(2-methoxyphenyl)-4-[4-(1-phenyltriazol-4-yl)butyl]piperazine
• 化学式: C₂₃H₂₉N₅O
• 分子量: 391.516
• InChiKey: ADUUVPPWHWVJFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  46.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-methoxyphenyl)-4-(4-(1-phenyl-1H-1,2,3-triazol-4-yl)butyl)piperazine 、 草酸 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 1-(2-methoxyphenyl)-4-(4-(1-phenyl-1H-1,2,3-triazol-4-yl)butyl)piperazine oxalate
  参考文献：
  名称：

  Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands

  摘要：

  A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D-2 and D-3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D-3 receptors and moderate selectivity for the dopamine D-3 versus D-2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D-2 and D-3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D-4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D-2 and D-3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D-3 receptors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.023
• 作为产物：
  描述：

  5-hexynyl p-toluenesulfonate 在 copper(l) iodide 、 potassium carbonate 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 24.0h， 生成 1-(2-methoxyphenyl)-4-(4-(1-phenyl-1H-1,2,3-triazol-4-yl)butyl)piperazine
  参考文献：
  名称：

  使用点击化学方法研究新的1,2,3-三唑连接的多巴胺D3受体配体

  摘要：

  多巴胺D3受体（D3R）是各种神经系统疾病（包括精神分裂症，帕金森氏病，不安腿综合征和药物成瘾）的药物治疗目标。用于开发D3R选择性拮抗剂和部分激动剂的常用分子模板在两个药效基团，苯基哌嗪部分和扩展的芳基环系统之间结合了丁基酰胺连接基。本文所述的一系列化合物并入了该化学模板的变化，用1,2,3-三唑基取代了连接链中的酰胺官能团。尽管D3R配体的4-苯基哌嗪类中的酰胺连接基以前被认为对高D3R亲和力和选择性至关重要，但是1,2，3-三唑部分用作合适的生物等排取代物，并保持化合物的所需D3R结合功能。此外，使用小鼠肝微粒体评估CYP450介导的I期代谢，我们确定与包含酰胺的类似物相比，新型包含1,2,3-三唑的化合物可适度改善代谢稳定性。1,2,3-三唑部分允许使用铜催化的叠氮化物-炔烃环加成点击化学对化学亚基库进行模块化连接，从而增加了可针对D3R选择性治疗剂进行设计，合成和开发的化学实体的

  DOI：

  10.1016/j.bmc.2015.01.017

文献信息

• Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands
  作者：Xin Peng、Qi Wang、Yogesh Mishra、Jinbin Xu、David E. Reichert、Maninder Malik、Michelle Taylor、Robert R. Luedtke、Robert H. Mach

  DOI：10.1016/j.bmcl.2014.12.023

  日期：2015.2

  A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D-2 and D-3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D-3 receptors and moderate selectivity for the dopamine D-3 versus D-2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D-2 and D-3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D-4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D-2 and D-3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D-3 receptors. (C) 2014 Elsevier Ltd. All rights reserved.
• Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3 receptor ligands
  作者：Thomas M. Keck、Ashwini K. Banala、Rachel D. Slack、Caitlin Burzynski、Alessandro Bonifazi、Oluyomi M. Okunola-Bakare、Martin Moore、Jeffrey R. Deschamps、Rana Rais、Barbara S. Slusher、Amy Hauck Newman

  DOI：10.1016/j.bmc.2015.01.017

  日期：2015.7

  addiction. A common molecular template used in the development of D3R-selective antagonists and partial agonists incorporates a butylamide linker between two pharmacophores, a phenylpiperazine moiety and an extended aryl ring system. The series of compounds described herein incorporates a change to that chemical template, replacing the amide functional group in the linker chain with a 1,2,3-triazole

  多巴胺D3受体（D3R）是各种神经系统疾病（包括精神分裂症，帕金森氏病，不安腿综合征和药物成瘾）的药物治疗目标。用于开发D3R选择性拮抗剂和部分激动剂的常用分子模板在两个药效基团，苯基哌嗪部分和扩展的芳基环系统之间结合了丁基酰胺连接基。本文所述的一系列化合物并入了该化学模板的变化，用1,2,3-三唑基取代了连接链中的酰胺官能团。尽管D3R配体的4-苯基哌嗪类中的酰胺连接基以前被认为对高D3R亲和力和选择性至关重要，但是1,2，3-三唑部分用作合适的生物等排取代物，并保持化合物的所需D3R结合功能。此外，使用小鼠肝微粒体评估CYP450介导的I期代谢，我们确定与包含酰胺的类似物相比，新型包含1,2,3-三唑的化合物可适度改善代谢稳定性。1,2,3-三唑部分允许使用铜催化的叠氮化物-炔烃环加成点击化学对化学亚基库进行模块化连接，从而增加了可针对D3R选择性治疗剂进行设计，合成和开发的化学实体的