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 sigma ligand, were synthesized. The (+)- and (-)-enantiomers bind predominantly to sigma(1) receptors and have a reduced sigma(2) affinity. Both individually restore the astroglial oxidative status modified by glutamate, counteracting also transglutaminase-2 overexpression. They exhibited in vivo anti-opioid effects on kappa opioid (KOP) receptor-mediated analgesia. Our findings demonstrate that the enantiomers display mainly sigma(1) agonist activity and that they have neuroprotective effects.
Prezzavento O, Campisi A, Parenti C, Ronsisvalle S, Aricò G, Arena E, et al. (2010). Synthesis and resolution of cis-(+/-)-methyl (1R,2S/1S2R)-2-[(4-hydroxy-4-phenylpiperidin-1-il)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [(+/-)-PPCC)]:new sigma receptor ligands with neuroprotective effect. JOURNAL OF MEDICINAL CHEMISTRY, 53, 5881-5885 [10.1021/jm100116p].
Synthesis and resolution of cis-(+/-)-methyl (1R,2S/1S2R)-2-[(4-hydroxy-4-phenylpiperidin-1-il)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [(+/-)-PPCC)]:new sigma receptor ligands with neuroprotective effect.
PISTOLOZZI, MARCO;BERTUCCI, CARLO;
2010
Abstract
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 sigma ligand, were synthesized. The (+)- and (-)-enantiomers bind predominantly to sigma(1) receptors and have a reduced sigma(2) affinity. Both individually restore the astroglial oxidative status modified by glutamate, counteracting also transglutaminase-2 overexpression. They exhibited in vivo anti-opioid effects on kappa opioid (KOP) receptor-mediated analgesia. Our findings demonstrate that the enantiomers display mainly sigma(1) agonist activity and that they have neuroprotective effects.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
