1-(biphenyl-2-ylmethyl)-4-(3-methoxyphenyl)piperazine | 1430810-60-8

• 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-(biphenyl-2-ylmethyl)-4-(3-methoxyphenyl)piperazine
• 英文别名: 1-(Biphenyl-2-ylmethyl)-4-(3-methoxyphenyl)piperazine；1-(3-methoxyphenyl)-4-[(2-phenylphenyl)methyl]piperazine
• CAS: 1430810-60-8
• 化学式: C₂₄H₂₆N₂O
• 分子量: 358.483
• InChiKey: WZFAVDDTRQICHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  15.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 1-(biphenyl-2-ylmethyl)-4-(3-methoxyphenyl)piperazine
  参考文献：
  名称：

  Discovery of aryl-biphenyl-2-ylmethylpiperazines as novel scaffolds for 5-HT7 ligands and role of the aromatic substituents in binding to the target receptor

  摘要：

  It has been reported that 5-HT7 receptors are promising targets of depression and neuropathic pain. 5-HT7 receptor antagonists have exhibited antidepressant-like profiles, while agonists have represented potential therapeutics for pain. In the course of our ongoing efforts to discover novel 5-HT7 modulators, we designed an arylpiperazine scaffold with a substituted biphenyl-2-ylmethyl group. A series of biphenyl-2-yl-arylpiperazinylmethanes were then prepared, which showed a broad spectrum of binding affinities to the 5-HT7 receptor depending upon the substituents attached to the biphenyl and aryl functionalities. Among those synthesized compounds, the compounds 1-24 and 1-26 showed the best binding affinities to the 5-HT7 receptor with K-i values of 43.0 and 46.0 nM, respectively. Structure-activity relationship study in conjunction with molecular docking study proposed that the 5-HT7 receptor might have two distinctive hydrophobic binding sites, one specific for aromatic 2-OCH3 substituents within the arylpiperazine and the other for biphenyl methoxy group. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.038

文献信息

• BIPHENYL DERIVATIVES, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AND PREPARATION METHOD THEREOF
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20140228568A1

  公开（公告）日：2014-08-14

  Provided are biphenyl derivatives exhibiting activity towards central nervous system diseases by acting on the 5-HT 7 receptor, pharmaceutically acceptable salts thereof, a method for preparing the compounds and pharmaceutical compositions including the compounds as an active ingredient.

  提供了对中枢神经系统疾病具有作用的二苯基衍生物，通过作用于5-HT7受体，其药学上可接受的盐，制备该化合物的方法以及包括该化合物作为活性成分的制药组合物。
• Biphenyl derivatives, pharmaceutical composition comprising the same, and preparation method thereof
  申请人：Korea Institute of Science and Technology

  公开号：US08883796B2

  公开（公告）日：2014-11-11

  Provided are biphenyl derivatives exhibiting activity towards central nervous system diseases by acting on the 5-HT7 receptor, pharmaceutically acceptable salts thereof, a method for preparing the compounds and pharmaceutical compositions including the compounds as an active ingredient.

  提供了对中枢神经系统疾病具有活性的双苯衍生物，通过作用于5-HT7受体，其药学上可接受的盐，制备这些化合物的方法以及包括这些化合物作为活性成分的制药组合物。
• US8883796B2
  申请人：——

  公开号：US8883796B2

  公开（公告）日：2014-11-11
• Discovery of aryl-biphenyl-2-ylmethylpiperazines as novel scaffolds for 5-HT7 ligands and role of the aromatic substituents in binding to the target receptor
  作者：Youngjae Kim、Jeeyeon Kim、Jinsung Tae、Bryan L. Roth、Hyewhon Rhim、Gyochang Keum、Ghilsoo Nam、Hyunah Choo

  DOI：10.1016/j.bmc.2013.02.038

  日期：2013.5

  It has been reported that 5-HT7 receptors are promising targets of depression and neuropathic pain. 5-HT7 receptor antagonists have exhibited antidepressant-like profiles, while agonists have represented potential therapeutics for pain. In the course of our ongoing efforts to discover novel 5-HT7 modulators, we designed an arylpiperazine scaffold with a substituted biphenyl-2-ylmethyl group. A series of biphenyl-2-yl-arylpiperazinylmethanes were then prepared, which showed a broad spectrum of binding affinities to the 5-HT7 receptor depending upon the substituents attached to the biphenyl and aryl functionalities. Among those synthesized compounds, the compounds 1-24 and 1-26 showed the best binding affinities to the 5-HT7 receptor with K-i values of 43.0 and 46.0 nM, respectively. Structure-activity relationship study in conjunction with molecular docking study proposed that the 5-HT7 receptor might have two distinctive hydrophobic binding sites, one specific for aromatic 2-OCH3 substituents within the arylpiperazine and the other for biphenyl methoxy group. (C) 2013 Elsevier Ltd. All rights reserved.