1-(2-methoxyphenyl)-4-(3-(1-phenyl-1H-1,2,3-triazol-4-yl)propyl)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-(3-(1-phenyl-1H-1,2,3-triazol-4-yl)propyl)piperazine
• 英文别名: 1-(2-Methoxyphenyl)-4-[3-(1-phenyltriazol-4-yl)propyl]piperazine；1-(2-methoxyphenyl)-4-[3-(1-phenyltriazol-4-yl)propyl]piperazine
• 化学式: C₂₂H₂₇N₅O
• 分子量: 377.489
• InChiKey: XQESGARESDXCGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 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-(3-(1-phenyl-1H-1,2,3-triazol-4-yl)propyl)piperazine 、 草酸 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成
  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：

  戊-4-炔基对甲苯磺酸酯 在 sodium carbonate 、 copper(II) sulfate 作用下， 以 水 、 乙腈 、 叔丁醇 为溶剂， 反应 23.25h， 生成 1-(2-methoxyphenyl)-4-(3-(1-phenyl-1H-1,2,3-triazol-4-yl)propyl)piperazine
  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

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.