Synthesis and Resolution of cis-(±)-Methyl (1R,2S/1S,2R)-2-[(4-Hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [(±)-PPCC)]

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• 作者：Orazio Prezzavento ; Agata Campisi ; Carmela Parenti ; Simone Ronsisvalle ; Giuseppina Aric ; Emanuela Arena ; Marco Pistolozzi ; Giovanna M. Scoto ; Carlo Bertucci ; Angelo Vanella ; Giuseppe Ronsisvalle
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：August 12, 2010
• 年：2010
• 卷：53
• 期：15
• 页码：5881-5885
• 全文大小：770K
• 年卷期：v.53,no.15(August 12, 2010)
• ISSN：1520-4804

文摘

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 overexpression. They exhibited in vivo anti-opioid effects on κ opioid (KOP) receptor-mediated analgesia. Our findings demonstrate that the enantiomers display mainly σ₁ agonist activity and that they have neuroprotective effects.