2-(4-(biphenyl-4-yl)piperazin-1-yl)ethanamine | 937664-54-5

• 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: 2-(4-(biphenyl-4-yl)piperazin-1-yl)ethanamine
• 英文别名: 2-[4-(4-Phenylphenyl)piperazin-1-yl]ethanamine
• CAS: 937664-54-5
• 化学式: C₁₈H₂₃N₃
• 分子量: 281.401
• InChiKey: PZNRNGBQIDJYMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-甲氧基-2-萘满酮 、 2-(4-(biphenyl-4-yl)piperazin-1-yl)ethanamine 在 溶剂黄146 、 sodium cyanoborohydride 、 水 、 碳酸氢钠 作用下， 以 1,2-二氯乙烷 、 甲醇 为溶剂， 反应 12.33h， 以30%的产率得到N-(2-(4-(biphenyl-4-yl)piperazin-1-yl)ethyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine
  参考文献：
  名称：

  Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol

  摘要：

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-{[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.025
• 作为产物：
  描述：

  1-(4-联苯基)-哌嗪 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-(biphenyl-4-yl)piperazin-1-yl)ethanamine
  参考文献：
  名称：

  ZM241385衍生物在人腺苷A2A受体上的结合动力学

  摘要：

  经典药物的设计和开发主要依赖于亲和力或效价驱动的结构-活性关系（SAR）。迄今为止，给定化合物的结合动力学已被很大程度上忽略，其重要性现在越来越被人们所认识。在本研究中，除了对腺苷A 2A受体（A 2A R）进行传统的SAR分析外，我们还进行了广泛的结构动力学关系（SKR）研究。由24 A 2A R化合物组成的化合物，所有三唑三嗪衍生物均类似于原型拮抗剂ZM241385（4-（2-（（7-氨基-2-（呋喃-2-基）-[1,2,4]三唑[1， 5一] [1,3,5] triazin-5-基）氨基）乙基）苯酚）在亲和力上仅显示微小差异，尽管它们与受体的解离速率差异很大。我们相信，像我们对A 2A R所做的那样，SKR和SAR分析的这种结合对于G蛋白偶联受体的超家族将具有普遍的重要性，因为它可以作为调整配体之间相互作用的新策略和受体。

  DOI：

  10.1002/cmdc.201300474

文献信息

• Binding Kinetics of ZM241385 Derivatives at the Human Adenosine A_2AReceptor
  作者：Dong Guo、Lizi Xia、Jacobus P. D. van Veldhoven、Marc Hazeu、Tamara Mocking、Johannes Brussee、Adriaan P. IJzerman、Laura H. Heitman

  DOI：10.1002/cmdc.201300474

  日期：2014.4

  compound’s binding kinetics have been largely ignored, the importance of which is now being increasingly recognized. In the present study, we performed an extensive structure–kinetics relationship (SKR) study in addition to a traditional SAR analysis at the adenosine A2A receptor (A2AR). The ensemble of 24 A2AR compounds, all triazolotriazine derivatives resembling the prototypic antagonist ZM241385 (4‐(

  经典药物的设计和开发主要依赖于亲和力或效价驱动的结构-活性关系（SAR）。迄今为止，给定化合物的结合动力学已被很大程度上忽略，其重要性现在越来越被人们所认识。在本研究中，除了对腺苷A 2A受体（A 2A R）进行传统的SAR分析外，我们还进行了广泛的结构动力学关系（SKR）研究。由24 A 2A R化合物组成的化合物，所有三唑三嗪衍生物均类似于原型拮抗剂ZM241385（4-（2-（（7-氨基-2-（呋喃-2-基）-[1,2,4]三唑[1， 5一] [1,3,5] triazin-5-基）氨基）乙基）苯酚）在亲和力上仅显示微小差异，尽管它们与受体的解离速率差异很大。我们相信，像我们对A 2A R所做的那样，SKR和SAR分析的这种结合对于G蛋白偶联受体的超家族将具有普遍的重要性，因为它可以作为调整配体之间相互作用的新策略和受体。
• Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol
  作者：Balaram Ghosh、Tamara Antonio、Bhaskar Gopishetty、Maarten Reith、Aloke Dutta

  DOI：10.1016/j.bmc.2010.06.025

  日期：2010.8

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.