1-(4'-piperidin-1-ylmethyl-biphenyl-4-ylmethyl)piperidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4'-piperidin-1-ylmethyl-biphenyl-4-ylmethyl)piperidin-2-one
• 英文别名: 1-[[4-[4-(Piperidin-1-ylmethyl)phenyl]phenyl]methyl]piperidin-2-one
• 化学式: C₂₄H₃₀N₂O
• 分子量: 362.515
• InChiKey: DQOHQFYLWISJMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  联苯二氯苄 以 甲苯 为溶剂， 生成 1-(4'-piperidin-1-ylmethyl-biphenyl-4-ylmethyl)piperidin-2-one
  参考文献：
  名称：

  Dibasic non-imidazole histamine H3 receptor antagonists with a rigid biphenyl scaffold

  摘要：

  A class of rigid, dibasic, non-imidazole H-3 antagonists was developed, starting from a series of previously described flexible compounds. The original polymethylene chain between two tertiary amine groups was replaced by a rigid scaffold, composed by a phenyl ring or a biphenyl fragment. Modulation of the distance between the two amine groups, and of their alkyl substituents, was driven by superposition of molecular models and docking into a receptor model, resulting in the identification of 1,1'-[biphenyl-4,4'diylbis(methylene)]bis-piperidine (5) as a subtype-selective H-3 antagonist with high binding affinity (pK(i) = 9.47) at human H-3 histamine receptor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.092

文献信息

• Synthesis and structure–activity relationships for biphenyl H3 receptor antagonists with moderate anti-cholinesterase activity
  作者：Giovanni Morini、Mara Comini、Mirko Rivara、Silvia Rivara、Fabrizio Bordi、Pier Vincenzo Plazzi、Lisa Flammini、Francesca Saccani、Simona Bertoni、Vigilio Ballabeni、Elisabetta Barocelli、Marco Mor

  DOI：10.1016/j.bmc.2008.10.029

  日期：2008.12

  different. Many potent compounds showed good selectivity profiles over the other histamine receptors. Interestingly, some derivatives displayed a moderate ability to inhibit rat brain cholinesterase, for example compound 12 (1-[2-(4'-piperidinomethyl-biphenyl-4-yl)ethyl]piperidine) has a pIC(50)=5.96 for cholinesterase inhibition and high H(3) receptor binding affinity and antagonist potency (pK(i)=8

  组胺H（3）受体拮抗作用和乙酰胆碱酯酶抑制作用的组合最近已被提议作为一种为认知疾病设计公认的新治疗剂的方法。4，4'-联苯片段已被我们报告为一种刚性的支架，导致有效和选择性的非咪唑H（3）拮抗剂。从这些前提出发，当前的工作提出了一系列扩展的组胺H（3）受体拮抗剂，其特征在于一个中心的4,4'-联苯支架，其中一价和二价化合物的结构活性特征是进一步探索并确定了它们抑制大鼠脑胆碱酯酶活性的能力。在带有相同取代基的对称化合物和在不对称化合物中调节端基的空间性质和碱性。在一个末端具有哌啶环而在另一末端具有不同的基团。连接联苯支架与末端基团的接头的长度也被调节。对大鼠和人H（3）受体的结合研究证明，对二元化合物的结合亲和力最高，按nM浓度的顺序排列，并且两个末端基团的空间要求不同。与其他组胺受体相比，许多有效的化合物表现出良好的选择性。有趣的是，某些衍生物显示出适中的抑制大鼠脑胆碱酯酶的能力，例如化合物12（1-
• Dibasic non-imidazole histamine H3 receptor antagonists with a rigid biphenyl scaffold
  作者：Giovanni Morini、Mara Comini、Mirko Rivara、Silvia Rivara、Simone Lorenzi、Fabrizio Bordi、Marco Mor、Lisa Flammini、Simona Bertoni、Vigilio Ballabeni、Elisabetta Barocelli、Pier Vincenzo Plazzi

  DOI：10.1016/j.bmcl.2006.04.092

  日期：2006.8

  A class of rigid, dibasic, non-imidazole H-3 antagonists was developed, starting from a series of previously described flexible compounds. The original polymethylene chain between two tertiary amine groups was replaced by a rigid scaffold, composed by a phenyl ring or a biphenyl fragment. Modulation of the distance between the two amine groups, and of their alkyl substituents, was driven by superposition of molecular models and docking into a receptor model, resulting in the identification of 1,1'-[biphenyl-4,4'diylbis(methylene)]bis-piperidine (5) as a subtype-selective H-3 antagonist with high binding affinity (pK(i) = 9.47) at human H-3 histamine receptor. (c) 2006 Elsevier Ltd. All rights reserved.