N-1-adamantyl-N'-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylurea

• 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: N-1-adamantyl-N'-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylurea
• 英文别名: N-[2-[4-(2-pyrimidyl)-1-piperazinyl]ethyl]-N'-tricyclo[3.3.1.1(3,7)]dec-1-ylurea；N-1-adamantyl-N'-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]urea；1-(1-adamantyl)-3-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]urea
• 化学式: C₂₁H₃₂N₆O
• 分子量: 384.525
• InChiKey: FFAYIKMJZHQVBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  盐酸金刚烷胺 、 2-(4-(嘧啶-2-基)哌嗪-1-基)乙胺 、 氯甲酸三氯甲酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以71%的产率得到N-1-adamantyl-N'-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylurea
  参考文献：
  名称：

  Synthesis and SAR of Adatanserin:  Novel Adamantyl Aryl- and Heteroarylpiperazines with Dual Serotonin 5-HT_1A and 5-HT₂ Activity as Potential Anxiolytic and Antidepressant Agents

  摘要：

  Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT1A receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl] ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT1A receptors (K-i = 8 nM) and acceptable selectivity versus D-2 receptors (K-i = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl] ethylamide, demonstrated high affinity for 5-HT1A binding sites (K-i = 1 nM for both) and moderate affinity for 5-HT2 receptors (K-i = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT1A agonist activity in vivo in rat serotonin syndrome and 5-HT2 antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT1A partial agonist and 5-HT2 antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.

  DOI：

  10.1021/jm9806704

文献信息

• US4882432A
  申请人：——

  公开号：US4882432A

  公开（公告）日：1989-11-21
• Synthesis and SAR of Adatanserin:  Novel Adamantyl Aryl- and Heteroarylpiperazines with Dual Serotonin 5-HT_1A and 5-HT₂ Activity as Potential Anxiolytic and Antidepressant Agents
  作者：Magid A. Abou-Gharbia、Wayne E. Childers、Horace Fletcher、Georgia McGaughey、Usha Patel、Michael B. Webb、John Yardley、Terrance Andree、Carl Boast、Robert J. Kucharik、Karen Marquis、Herman Morris、Rosemary Scerni、John A. Moyer

  DOI：10.1021/jm9806704

  日期：1999.12.1

  Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT1A receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl] ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT1A receptors (K-i = 8 nM) and acceptable selectivity versus D-2 receptors (K-i = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl] ethylamide, demonstrated high affinity for 5-HT1A binding sites (K-i = 1 nM for both) and moderate affinity for 5-HT2 receptors (K-i = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT1A agonist activity in vivo in rat serotonin syndrome and 5-HT2 antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT1A partial agonist and 5-HT2 antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.