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.
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 / Prezzavento O; Campisi A; Parenti C; Ronsisvalle S; Aricò G; Arena E; Pistolozzi M; Scoto GM; Bertucci C; Vanella A; Ronsisvalle G.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 53:(2010), pp. 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.