methyl (1RS,2SR)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl (1RS,2SR)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate
• 英文别名: (+)-Methyl(1R,2S)-2-[(4-Hydroxy-4-phenylpiperidin-1-yl)-methyl]-1-(4-nitrophenyl)cyclopropanecarboxylate；methyl (1R,2S)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropane-1-carboxylate
• 化学式: C₂₄H₂₉NO₃
• 分子量: 379.499
• InChiKey: BDSYECBSUUOPCT-QPPBQGQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-methylphenyl)-3-oxabicyclo[3.1.0]hexan-2-one 在 氯化亚砜 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 methyl (1RS,2SR)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate
  参考文献：
  名称：

  Novel Sigma Receptor Ligands:  Synthesis and Biological Profile

  摘要：

  The aim of the present study was to investigate the biological profile of new substituted 1-phenyl-2-cyclopropylmethylamines. High affinity for both sigma subtypes was achieved when 4-phenylpiperidin-4-ol (4a-e) and 4-benzylpiperidine moieties were present (5a-e). (1R,2S/1S,2R)-2-[4-Hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate (4b) showed high affinity for the sigma(1) sites (K-i = 1.5 nM) and the most favorable sigma(1)/sigma(2) selectivity (K-i(sigma(2))/K-i(sigma(1)) = 33.9). Binding affinity studies showed that 4b binding on N-methyl-d-aspartate (NMDA), dopaminergic (D-1, D-2, D-3), muscarinic, histaminergic H-1, adrenergic (alpha(1), alpha(2)), serotoninergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT6), DA (DAT), and 5-HT (SERT) transporters was not significant. Interestingly, sigma ligands differently induced the expression of tissue transglutaminase (TG-2) in primary astroglial cell cultures. We suggest that 4b may act as a sigma(1)/sigma(2) agonist and that the sigma ligands may modulate TG-2 differently.

  DOI：

  10.1021/jm0611197

文献信息

• Synthesis and Resolution of <i>cis</i>-(±)-Methyl (1<i>R</i>,2<i>S</i>/1<i>S</i>,2<i>R</i>)-2-[(4-Hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [(±)-PPCC)]: New σ Receptor Ligands with Neuroprotective Effect
  作者：Orazio Prezzavento、Agata Campisi、Carmela Parenti、Simone Ronsisvalle、Giuseppina Aricò、Emanuela Arena、Marco Pistolozzi、Giovanna M. Scoto、Carlo Bertucci、Angelo Vanella、Giuseppe Ronsisvalle

  DOI：10.1021/jm100116p

  日期：2010.8.12

  The enantiomers of cis-(±)-methyl (1R,2S/1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [1, (±)-PPCC], a selective σ ligand, were synthesized. The (+)- and (−)-enantiomers bind predominantly to σ1 receptors and have a reduced σ2 affinity. Both individually restore the astroglial oxidative status modified by glutamate, counteracting also transglutaminase-2

  的对映体顺式- （±） -甲基（1 - [R，2小号/ 1小号，2 - [R）-2 - [（4-羟基-4-苯基哌啶-1-基）甲基] -1-（4-甲基苯基）合成了选择性的σ配体环丙烷羧酸酯[ 1，（±）-PPCC]。的（+） -和（ - ） -对映异构体结合主要对σ 1个受体和具有降低的σ 2的亲和力。两者都可以单独恢复由谷氨酸修饰的星形胶质细胞的氧化状态，也可以抵消转谷氨酰胺酶2的过表达。他们对κ阿片样物质（KOP）受体介导的镇痛表现出体内抗阿片样物质作用。我们的研究结果表明，对映异构体显示主要σ 1 激动剂活性，并且它们具有神经保护作用。
• Novel Sigma Receptor Ligands:  Synthesis and Biological Profile
  作者：Orazio Prezzavento、Agata Campisi、Simone Ronsisvalle、Giovanni Li Volti、Agostino Marrazzo、Vincenzo Bramanti、Giuseppe Cannavò、Luca Vanella、Alfredo Cagnotto、Tiziana Mennini、Riccardo Ientile、Giuseppe Ronsisvalle

  DOI：10.1021/jm0611197

  日期：2007.3.1

  The aim of the present study was to investigate the biological profile of new substituted 1-phenyl-2-cyclopropylmethylamines. High affinity for both sigma subtypes was achieved when 4-phenylpiperidin-4-ol (4a-e) and 4-benzylpiperidine moieties were present (5a-e). (1R,2S/1S,2R)-2-[4-Hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate (4b) showed high affinity for the sigma(1) sites (K-i = 1.5 nM) and the most favorable sigma(1)/sigma(2) selectivity (K-i(sigma(2))/K-i(sigma(1)) = 33.9). Binding affinity studies showed that 4b binding on N-methyl-d-aspartate (NMDA), dopaminergic (D-1, D-2, D-3), muscarinic, histaminergic H-1, adrenergic (alpha(1), alpha(2)), serotoninergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT6), DA (DAT), and 5-HT (SERT) transporters was not significant. Interestingly, sigma ligands differently induced the expression of tissue transglutaminase (TG-2) in primary astroglial cell cultures. We suggest that 4b may act as a sigma(1)/sigma(2) agonist and that the sigma ligands may modulate TG-2 differently.