N-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide

• 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-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide
• 英文别名: N-[2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl]tricyclo[3.3.1.03,7]nonane-3-carboxamide
• 化学式: C₂₂H₃₀ClN₃O
• 分子量: 387.953
• InChiKey: ATJGTJMAQUFMFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-甲基碳酸胺 、 2-[4-(3-氯苯基)哌嗪-1-基]乙胺 在 N,N'-羰基二咪唑 作用下， 以 氯仿 为溶剂， 反应 50.0h， 生成 N-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide
  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

• Extended release compositions
  申请人：Kramer J. Stephen

  公开号：US20050095286A1

  公开（公告）日：2005-05-05

  A pharmaceutical composition is provided, which includes: at least one active ingredient selected from the group including adatanserin, a compound having formula I, a compound having formula II, abaperidone, pharmaceutically acceptable salt thereof, prodrug thereof, and a mixture thereof; at least one high or medium viscosity hydroxypropylmethylcellulose (HPMC); at least one high or medium viscosity hydroxyethylcellulose (HEC); wherein the HPMC and HEC are present in a HPMC/HEC weight ratio ranging from 1/0.5 to 1/1.5; wherein adatanserin, abaperidone, and the compounds having formulas (I) and (II) are defined herein.

  本发明提供了一种药物组合物，其中包括：至少一种选自包括阿达坦色林、具有式 I 的化合物、具有式 II 的化合物、阿巴匹酮、其药学上可接受的盐、其原药及其混合物的活性成分；至少一种高粘度或中等粘度羟丙基甲基纤维素（HPMC）；至少一种高粘度或中等粘度羟乙基纤维素（HEC）；其中，HPMC 和 HEC 的 HPMC/HEC 重量比为 1/0.5至1/1.5；其中阿达坦色林、阿巴匹利酮和具有式(I)和(II)的化合物在本文中定义。
• 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
• US5010078A
  申请人：——

  公开号：US5010078A

  公开（公告）日：1991-04-23
• US5106849A
  申请人：——

  公开号：US5106849A

  公开（公告）日：1992-04-21
• US5254552A
  申请人：——

  公开号：US5254552A

  公开（公告）日：1993-10-19