(R)-adamantane-1-carboxylic acid N-[1-benzyl-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl]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: (R)-adamantane-1-carboxylic acid N-[1-benzyl-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl]carboxamide
• 英文别名: (R)-N-[1-(phenylmethyl)-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl]tricyclo[3.3.1.1^3,7]-decane-1-carboxamide；N-[(2R)-1-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)propan-2-yl]adamantane-1-carboxamide
• 化学式: C₂₈H₃₇N₅O
• 分子量: 459.635
• InChiKey: DSJKVFVLCHZWFJ-JJXGVTDJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-adamantane-1-carboxylic acid N-[1-benzyl-2-(4-benzyl-1-piperazinyl)ethyl]carboxamide dihydrochloride 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、248.21 kPa 条件下， 生成 (R)-adamantane-1-carboxylic acid N-[1-benzyl-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl]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

• Branched adamantyl and noradamantyl aryl-and aralkylpiperazines with serotonin 5-HT 1A activity
  申请人：Wyeth

  公开号：US20040162430A1

  公开（公告）日：2004-08-19

  This invention provides compounds and methods using them to provide neuroprotection and prevent or limit processes of neurodegeneration in mammals, including Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, AIDS dementia, retinal disease, diabetic peripheral neuropathy, multiple sclerosis, stroke, acute thromboembolic stroke, focal ischemia, global ischemia, transient ischemic attack, ischemia resulting from surgery, head trauma, spinal trauma, hypoxia, fetal hypoxia, and neuroprotection., the compounds having the structure: 1 wherein X is —CH 2 — or a bond; Y is —(CH 2 )m— or —(CH 2 )—O—(CH 2 )—; m 0 or 1; n is 0 or 1; R 1 and R 2 are independently selected from optionally substituted aryl or heteroaryl; the optical isomers and the pharmaceutically acceptable salts thereof.

  这项发明提供了化合物及其使用方法，用于在哺乳动物中提供神经保护，并预防或限制神经退行性过程，包括阿尔茨海默病、亨廷顿病、帕金森病、艾滋病痴呆、视网膜疾病、糖尿病周围神经病变、多发性硬化、中风、急性血栓栓塞性中风、局灶性缺血、全脑缺血、短暂性缺血性发作、手术后缺血、头部创伤、脊柱创伤、缺氧、胎儿缺氧和神经保护。这些化合物具有以下结构： 1 其中X为—CH 2 —或键；Y为—(CH 2 )m—或—(CH 2 )—O—(CH 2 )—；m为0或1；n为0或1；R 1 和R 2 分别选自可选择取代的芳基或杂环基；其光学异构体和药用盐。