4-<2-(Adamantanecarboxamido)ethyl>-1-(2-methoxyphenyl)piperazine | 127266-57-3

• 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: 4-<2-(Adamantanecarboxamido)ethyl>-1-(2-methoxyphenyl)piperazine
• 英文别名: N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]tricyclo[3.3.1.13,7 ]decane-1-carboxamide；N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]adamantancarboxamide；(3r,5r,7r)-N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)adamantane-1-carboxamide；N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]adamantane-1-carboxamide
• CAS: 127266-57-3
• 化学式: C₂₄H₃₅N₃O₂
• 分子量: 397.561
• InChiKey: UMZYBCYFDMPPNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-金刚烷甲酸 、 1-(2-aminoethyl)-4-(2-methoxyphenyl)piperazine 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 4-<2-(Adamantanecarboxamido)ethyl>-1-(2-methoxyphenyl)piperazine
  参考文献：
  名称：

  CNS 药物的构效关系研究，第 26 部分 4- [2-（环烷甲酰胺基）乙基] -1-（2-甲氧基苯基）-哌嗪：高亲和力 5-HT1A 激动剂

  摘要：

  环烷甲酰胺基)乙基-1-(2-甲氧基苯基)哌嗪es 8a-c、8e和8h是通过4-(2-氨基乙基)-1-(2-甲氧基苯基)哌嗪和它们的5-HT1A,5酰化得到的测定了-HT1A、5-HT2A和α受体亲和力。发现末端环烷烃部分强烈稳定 5-HT1A 和 5-HT2A 受体-配体复合物。结果表明，最活跃的 5-HT1A 配体 8e 和 8h（分别为 Ki = 2.1 和 0.21 nM）充当这些受体的有效激动剂，即这两种衍生物在下唇收缩 (LLR) 模型中都模拟了 8-OH-DPAT并且该作用易于被合理剂量的选择性 5-HT1A 受体拮抗剂 (S)-WAY-100135 阻断。

  DOI：

  10.1002/ardp.19953281108

文献信息

• 2-Methoxyphenylpiperazine derivatives
  申请人：FABRICA ESPANOLA DE PRODUCTOS QUIMICOS Y FARMACEUTICOS, S.A. (FAES)

  公开号：EP0496692A1

  公开（公告）日：1992-07-29

  New 2-methoxyphenylpiperazine derivatives are described with the following general formula: where A is a carbonyl group, an alkylaminocarbonyl or alkylaminomethylene group, and B is a substituted aryl, heteroaryl substituted or otherwise, arylalkyl, heteroarylalkyl or cycloalkyl group, and their pharmaceutically acceptable addition salts. These compounds have a pharmacologic activity at the level of serotonin 5-HT1A receptors.

  描述了具有以下一般式的新2-甲氧基苯基哌嗪衍生物：其中A是羰基，烷基氨基甲酰基或烷基氨基亚甲基基团，B是取代芳基，杂环芳基取代或其他芳基烷基，杂环芳基烷基或环烷基基团，以及它们的药物可接受的加合物盐。这些化合物在5-羟色胺5-HT1A受体水平上具有药理活性。
• 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.
• Aryl- and heteroaryl piperazinyl carboxamides having central nervous system activity
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0343961B1

  公开（公告）日：1996-01-10
• Structure-Activity Relationship Studies of CNS Agents, Part 26 4-[2-(Cycloalkanecarboxamido)ethyl]-1-(2-methoxyphenyl)-piperazines: High-Affinity 5-HT1A Agonists
  作者：Jerzy L. Mokrosz、Maria H. Paluchowska、Aleksandra Klodzińska、Sijka Charakchieva-Minol、Ewa Chojnacka-Wójcik

  DOI：10.1002/ardp.19953281108

  日期：——

  Cycloalkanecarboxamido)ethyl‐1‐(2‐methoxyphenyl)piperazin es 8a–c, 8e, and 8h were obtained by acylation of 4‐(2‐aminoethyl)‐1‐(2‐methoxyphenyl)piperazine, and their 5‐HT1A, 5‐HT1A, 5‐HT2A and α receptor affinities were determined. It was found that the terminal cycloalkane moiety strongly stabilizes both the 5‐HT1A and 5‐HT2A receptor‐ligand complexes. It was demonstrated that the most active 5‐HT1A

  环烷甲酰胺基)乙基-1-(2-甲氧基苯基)哌嗪es 8a-c、8e和8h是通过4-(2-氨基乙基)-1-(2-甲氧基苯基)哌嗪和它们的5-HT1A,5酰化得到的测定了-HT1A、5-HT2A和α受体亲和力。发现末端环烷烃部分强烈稳定 5-HT1A 和 5-HT2A 受体-配体复合物。结果表明，最活跃的 5-HT1A 配体 8e 和 8h（分别为 Ki = 2.1 和 0.21 nM）充当这些受体的有效激动剂，即这两种衍生物在下唇收缩 (LLR) 模型中都模拟了 8-OH-DPAT并且该作用易于被合理剂量的选择性 5-HT1A 受体拮抗剂 (S)-WAY-100135 阻断。