(1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine | 282117-35-5

• 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: (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine
• 英文别名: 1-(2,4-Dimethyl-phenyl)-4-(2-phenyl-cyclopropylmethyl)-piperazine；1-(2,4-dimethylphenyl)-4-[[(1S,2S)-2-phenylcyclopropyl]methyl]piperazine
• CAS: 282117-35-5
• 化学式: C₂₂H₂₈N₂
• 分子量: 320.478
• InChiKey: PQFHVDFLICEIKC-NHCUHLMSSA-N

物化性质

• 沸点：
  469.4±45.0 °C(Predicted)
• 密度：
  1.081±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-(2,4-二甲基苯基)哌嗪 在 aluminium hydride 、 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine
  参考文献：
  名称：

  trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines:  Mixed Dopamine D₂/D₄ Receptor Antagonists as Potential Antipsychotic Agents

  摘要：

  The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D-2 and D-4 receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dichlorophenyl)piperazine (5m) and (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D-2 and D-4 receptors and had a D-2/D-4 ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.

  DOI：

  10.1021/jm990562x

文献信息

• Construction of a <i>cis</i>-Cyclopropane via Reductive Radical Decarboxylation. Enantioselective Synthesis of <i>cis-</i> and <i>trans-</i>1-Arylpiperazyl-2-phenylcyclopropanes Designed as Antidopaminergic Agents
  作者：Kazuya Yamaguchi、Yuji Kazuta、Hiroshi Abe、Akira Matsuda、Satoshi Shuto

  DOI：10.1021/jo0302206

  日期：2003.11.1

  Barton reductive radical decarboxylation as the key step. (1S,2R)-1-(tert-Butyldiphenylsilyloxy)methyl-2-carboxy-2-phenylcyclopropane (5), which was prepared from (S)-epichlorohydrin ((S)-7), was converted into its N-hydroxypyridine-2-thione ester 12, the substrate for the reductive radical decarboxylation. When 12 was treated with TMS3SiH in the presence of Et3B or AIBN, the decarboxylation and subsequent

  （1S，2S）-，（1S，2R）-和（1R，2S）-1-（2,4-二甲基苯基）哌嗪基-2-苯基环丙烷（分别为2a，3和ent-3）以Barton还原性自由基脱羧为关键步骤，从手性表氯醇合成了被设计为氟哌啶醇（1）（一种临床有效的抗精神病药）的受构象限制的类似物。由（S）-表氯醇（（S）-7）制得的（1S，2R）-1-（叔丁基二苯基甲硅烷氧基）甲基-2-羧基-2-苯基环丙烷（5）被转化为其N-羟基吡啶-2-硫酮酸酯12，为还原性自由基脱羧的底物。当在Et3B或AIBN存在下用TMS3SiH处理12时，发生了从大体积甲硅烷氧基甲基部分相反的一侧对环丙基自由基中间体进行脱羧和随后的氢化物攻击，导致选择性地形成具有顺式-环丙烷结构的相应的还原性脱羧产物4-顺式。由4-顺式容易地合成出顺式-环丙烷型目标化合物3。从（R）-表氯醇（（R）-7）开始，类似地合成了ent-3。用由Bu2Mg和i-Pr2N
• 1-phenyl-4-(1-[2-aryl]cyclopropyl) methylpiperazines: dopamine receptor ligands
  申请人：Neurogen Corporation

  公开号：US20020022630A1

  公开（公告）日：2002-02-21

  Disclosed are compounds of the formula: 1 or pharmaceutically acceptable addition salts thereof wherein: R 1 , R 2 , R 3 R 4 and R 5 , R 6 , R 7 , and R 8 represent organic and/or inorganic substituents as defined herein, which compounds are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents.

  本发明涉及以下式子的化合物或其药学上可接受的盐：1其中：R1、R2、R3、R4和R5、R6、R7和R8代表有机和/或无机取代基，如本文所定义，这些化合物对于治疗和/或预防神经心理障碍非常有用，包括但不限于精神分裂症、躁狂症、痴呆、抑郁症、焦虑症、强迫行为、物质滥用、帕金森样运动障碍和与神经阻滞剂使用有关的运动障碍。
• US6284761B1
  申请人：——

  公开号：US6284761B1

  公开（公告）日：2001-09-04
• <i>trans</i>-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines:  Mixed Dopamine D₂/D₄ Receptor Antagonists as Potential Antipsychotic Agents
  作者：Xiaoyan Zhang、Kevin Hodgetts、Stanislaw Rachwal、He Zhao、Jan W. F. Wasley、Kimberly Craven、Robbin Brodbeck、Andrzej Kieltyka、Diane Hoffman、Maria D. Bacolod、Brian Girard、Jennifer Tran、Andrew Thurkauf

  DOI：10.1021/jm990562x

  日期：2000.10.1

  The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D-2 and D-4 receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dichlorophenyl)piperazine (5m) and (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D-2 and D-4 receptors and had a D-2/D-4 ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.