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

作者：Marrazzo Agostino^*; Cobos Enrique J; Parenti Carmela; Arico Giuseppina; Marrazzo Giuseppina; Ronsisvalle Simone; Pasquinucci Lorella; Prezzavento Orazio; Coabufo Nicola A; Contino Marialessandra; Gonzalez Luis G; Scoto Giovanna M; Ronsisvalle Giuseppe

来源：Journal of Medicinal Chemistry, 2011, 54(10): 3669-3673.

DOI：10.1021/jm200144j

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.

• 出版日期2011-5-26