7-(propyl(2-(4-(pyridin-3-yl)piperazin-1-yl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-2-ol | 1245728-22-6

• 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: 7-(propyl(2-(4-(pyridin-3-yl)piperazin-1-yl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-2-ol
• 英文别名: D-243；7-[propyl-[2-(4-pyridin-3-ylpiperazin-1-yl)ethyl]amino]-5,6,7,8-tetrahydronaphthalen-2-ol
• CAS: 1245728-22-6
• 化学式: C₂₄H₃₄N₄O
• 分子量: 394.56
• InChiKey: LFLWSALOEDMVRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  42.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-methoxy-N-propyl-N-(2-(4-(pyridin-3-yl)piperazin-1-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-amine 在 三溴化硼 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 以49.2%的产率得到7-(propyl(2-(4-(pyridin-3-yl)piperazin-1-yl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-2-ol
  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

文献信息

• 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.