BOC-(S)-alanine-N-(4-benzyl-1-piperazinyl)carboxamide | 671212-36-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: BOC-(S)-alanine-N-(4-benzyl-1-piperazinyl)carboxamide
• 英文别名: tert-butyl N-[(2S)-1-(4-benzylpiperazin-1-yl)-1-oxopropan-2-yl]carbamate
• CAS: 671212-36-5
• 化学式: C₁₉H₂₉N₃O₃
• 分子量: 347.458
• InChiKey: YQKUSDJSWHQNFM-HNNXBMFYSA-N

物化性质

• 沸点：
  496.5±45.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  BOC-(S)-alanine-N-(4-benzyl-1-piperazinyl)carboxamide 在 palladium on activated charcoal 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以46%的产率得到(S)-tert-butyl 1-oxo-1-(piperazin-1-yl)propan-2-ylcarbamate
  参考文献：
  名称：

  Structure–activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs

  摘要：

  Structure-activity relationships on two novel potent cognition enhancing drugs, unifiram (DM232, 1) and sunifiram (DM235, 2), are reported. Although none of the compounds synthesised reached the potency of the parent drugs, some fairly active compounds have been identified that may represent new leads to develop other cognition enhancing drugs. An interesting result of this research is the identification of two compounds (13 and 14) that are endowed with amnesing activity (the opposite of the activity of the original molecules) and are nearly equipotent to scopolamine. Moreover, two compounds of the series (5 and 6) were found endowed with analgesic activity on a rat model of neuropathic pain at the dose of 1 mg/kg. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.025
• 作为产物：
  描述：

  1-苄基哌嗪 、 N-叔丁氧羰基-L-丙氨酸 在 氰基磷酸二乙酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 BOC-(S)-alanine-N-(4-benzyl-1-piperazinyl)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

• 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.
• Structure–activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs
  作者：Serena Scapecchi、Elisabetta Martini、Dina Manetti、Carla Ghelardini、Cecilia Martelli、Silvia Dei、Nicoletta Galeotti、Luca Guandalini、Maria Novella Romanelli、Elisabetta Teodori

  DOI：10.1016/j.bmc.2003.10.025

  日期：2004.1

  Structure-activity relationships on two novel potent cognition enhancing drugs, unifiram (DM232, 1) and sunifiram (DM235, 2), are reported. Although none of the compounds synthesised reached the potency of the parent drugs, some fairly active compounds have been identified that may represent new leads to develop other cognition enhancing drugs. An interesting result of this research is the identification of two compounds (13 and 14) that are endowed with amnesing activity (the opposite of the activity of the original molecules) and are nearly equipotent to scopolamine. Moreover, two compounds of the series (5 and 6) were found endowed with analgesic activity on a rat model of neuropathic pain at the dose of 1 mg/kg. (C) 2003 Elsevier Ltd. All rights reserved.