methyl (1RS,2SR)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-phenylcyclopropanecarboxylate | 932736-88-4

• 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-phenylcyclopropanecarboxylate
• 英文别名: (-)-Methyl(1S,2R)-2-[(4-Hydroxy-4-phenylpiperidin-1-yl)-methyl]-1-phenylcyclopropanecarboxylate；methyl (1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-phenylcyclopropane-1-carboxylate
• CAS: 932736-88-4
• 化学式: C₂₃H₂₇NO₃
• 分子量: 365.472
• InChiKey: UNOGZCNQPVUIQG-NZQKXSOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  草酸 、 methyl (1RS,2SR)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-phenylcyclopropanecarboxylate 以 乙醚 为溶剂， 生成 (-)-methyl (1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-phenylcyclopropanecarboxylate oxalate
  参考文献：
  名称：

  Novel Potent and Selective σ Ligands: Evaluation of Their Agonist and Antagonist Properties

  摘要：

  Novel enantiomers and diastereoisomers structurally related to sigma ligand (+)-MR200 were synthesized to improve sigma(1)/sigma(2) subtype selectivity. The selective sigma(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of kappa opioid analgesia. The sigma(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.

  DOI：

  10.1021/jm200144j
• 作为产物：
  描述：

  (1R,5S)-1-phenyl-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， 反应 29.0h， 生成 methyl (1RS,2SR)-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-phenylcyclopropanecarboxylate
  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

• 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.
• Novel Potent and Selective σ Ligands: Evaluation of Their Agonist and Antagonist Properties
  作者：Agostino Marrazzo、Enrique J. Cobos、Carmela Parenti、Giuseppina Aricò、Giuseppina Marrazzo、Simone Ronsisvalle、Lorella Pasquinucci、Orazio Prezzavento、Nicola A. Colabufo、Marialessandra Contino、Luis G. González、Giovanna M. Scoto、Giuseppe Ronsisvalle

  DOI：10.1021/jm200144j

  日期：2011.5.26

  Novel enantiomers and diastereoisomers structurally related to sigma ligand (+)-MR200 were synthesized to improve sigma(1)/sigma(2) subtype selectivity. The selective sigma(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of kappa opioid analgesia. The sigma(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.