(S)-[1-methyl-2-(4-benzyl-1-piperazinyl)ethyl]amine

• 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: (S)-[1-methyl-2-(4-benzyl-1-piperazinyl)ethyl]amine
• 英文别名: (2S)-1-(4-benzylpiperazin-1-yl)propan-2-amine
• 化学式: C₁₄H₂₃N₃
• 分子量: 233.357
• InChiKey: HERRMNLUNPHMHU-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 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：

  (S)-[1-methyl-2-(4-benzyl-1-piperazinyl)ethyl]amine 在 palladium on activated charcoal N-甲基吗啉 、 氰基磷酸二乙酯 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 (S)-adamantane-1-carboxylic acid N-[1-methyl-2-(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
• 作为产物：
  描述：

  BOC-(S)-alanine-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 (S)-[1-methyl-2-(4-benzyl-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

• Synthesis, Biological Evaluation, and Molecular Modeling Studies of Chiral Chloroquine Analogues as Antimalarial Agents
  作者：Srinivasarao Kondaparla、Utsab Debnath、Awakash Soni、Vasantha Rao Dola、Manish Sinha、Kumkum Srivastava、Sunil K. Puri、Seturam B. Katti

  DOI：10.1128/aac.02347-17

  日期：2018.12

  quantitative structure-activity relationship (3D-QSAR) studies of all in-house data sets (168 molecules) of chiral CQ analogues to explain the structure-activity relationships (SAR). Our new findings specify the significance of the H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against the 3D7 strain indicated the favorable and unfavorable sites

  在重点研究中，我们设计，合成和生物评估了手性共轭新氯喹（CQ）类似物，并用取代的哌嗪作为抗疟剂。体外和体内研究表明，化合物7c表现出有效的活性（体外50％抑制浓度，菌株3D7的抑制浓度为56.98 nM，菌株K1的抑制浓度为97.76 nM；在体内的选择性指数[最高剂量为12.5 mg / kg [体重]，3,510）作为新型抗疟药物。其他化合物（化合物6b，6d，7d，7h，8c，8d，9a和9c）也显示出对CQ敏感菌株（3D7）的中等活性，并且对恶性疟原虫的CQ抗性菌株（K1）的活性更高。 ，我们对手性CQ类似物的所有内部数据集（168个分子）进行了对接和三维定量构效关系（3D-QSAR）研究，以解释构效关系（SAR）。我们的新发现指定了与血红素侧链的H键相互作用对生物活性的重要性。此外，针对3D7菌株的3D-QSAR研究表明，CQ类似物的有利位置和不利位置会引入空间，疏水和正电基团，以提高抗疟活性。
• Triterpene amine derivatives
  申请人：DFH THERAPEUTICS

  公开号：US11236122B2

  公开（公告）日：2022-02-01

  The present invention concerns novel pharmaceutically active triterpene amine derivatives, pharmaceutical compositions containing the same, their use as medicaments, and the use of the compounds for the manufacture of specific medicaments. The present invention also concerns a method of treatment involving administration of the triterpene amine compounds. Specifically, the compounds are derivatives of betulinic acid having substitutions at one or more of the C-3, C-28 and C-19 positions as further described herein. The novel compounds are useful as antiretroviral agents. In particular, the novel compounds are useful for the treatment of Human Immunodeficiency Virus-1 (HIV-1).

  本发明涉及新型具有药用活性的三萜胺衍生物、含有三萜胺衍生物的药物组合物、其作为药物的用途，以及使用这些化合物制造特定药物。本发明还涉及一种涉及三萜胺化合物给药的治疗方法。具体来说，这些化合物是白桦脂酸的衍生物，在 C-3、C-28 和 C-19 位上有一个或多个取代位，如本文进一步描述的那样。这些新型化合物可用作抗逆转录病毒药物。特别是，这些新型化合物可用于治疗人类免疫缺陷病毒-1（HIV-1）。
• TRITERPENE AMINE DERIVATIVES
  申请人：DFH THERAPEUTICS

  公开号：US20210253627A1

  公开（公告）日：2021-08-19

  The present invention concerns novel pharmaceutically active triterpene amine derivatives, pharmaceutical compositions containing the same, their use as medicaments, and the use of the compounds for the manufacture of specific medicaments. The present invention also concerns a method of treatment involving administration of the triterpene amine compounds. Specifically, the compounds are derivatives of betulinic acid having substitutions at one or more of the C-3, C-28 and C-19 positions as further described herein. The novel compounds are useful as antiretroviral agents. In particular, the novel compounds are useful for the treatment of Human Immunodeficiency Virus-1 (HIV-1).
• 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.