(R)-[1-(phenylmethyl)-2-[(4-phenylmethyl)-1-piperazinyl]ethyl]amine | 339589-32-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-[1-(phenylmethyl)-2-[(4-phenylmethyl)-1-piperazinyl]ethyl]amine
• 英文别名: (2R)-1-(4-benzylpiperazin-1-yl)-3-phenylpropan-2-amine
• CAS: 339589-32-1
• 化学式: C₂₀H₂₇N₃
• 分子量: 309.454
• InChiKey: VWAWBNLGHFRWCI-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-金刚烷甲酸 、 (R)-[1-(phenylmethyl)-2-[(4-phenylmethyl)-1-piperazinyl]ethyl]amine 在 N-甲基吗啉 、 diethylcyano-phosphonate 、 盐酸 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 以44%的产率得到(R)-adamantane-1-carboxylic acid N-[1-benzyl-2-(4-benzyl-1-piperazinyl)ethyl]carboxamide dihydrochloride
  参考文献：
  名称：

  Branched adamantyl and noradamantyl aryl-and aralkylpiperazines with serotonin 5-HT 1A activity

  摘要：

  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。

  公开号：

  US20040162430A1
• 作为产物：
  描述：

  BOC-(R)-phenylalanine-N-(4-benzyl-1-piperazinyl)carboxamide 在 盐酸 、 硼烷 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 (R)-[1-(phenylmethyl)-2-[(4-phenylmethyl)-1-piperazinyl]ethyl]amine
  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：EP1276731A2

  公开（公告）日：2003-01-22
• US6828324B2
  申请人：——

  公开号：US6828324B2

  公开（公告）日：2004-12-07
• US6831084B1
  申请人：——

  公开号：US6831084B1

  公开（公告）日：2004-12-14
• [EN] BRANCHED ADAMANTYL AND NORADAMANTYL ARYL- AND ARALKYLPIPERAZINES WITH SEROTONIN 5-HT1A ACTIVITY<br/>[FR] ADAMANTYLE, NORADAMANTYLE ARYL- ET ARALKYLPIPERAZINES RAMIFIES A ACTIVITE DE TYPE SEROTONINE 5-HT1A
  申请人：AMERICAN HOME PROD

  公开号：WO2001034586A2

  公开（公告）日：2001-05-17

  This invention provides compounds and methods using them to provide neuroprotection and prevent or limit processes of neurodegeneration in mammals, including Alzeimer'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 (I), wherein X is -CH2- or a bond; Y is -(CH2)m- or -(CH2)-O-(CH2)-; m is 0 or 1; n is 0 or 1; R1 and R2 are independently selected from optionally substituted aryl or heteroaryl, the optical isomers and the pharmaceutically acceptable salts thereof.
• 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.