Following previous studies focused on the search for new molecules targeting GluN2B-containing NMDA, a small series of 1-(1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl)ethanone derivatives has been synthesized by using Microwave Assisted Organic Synthesis (MAOS). Given that GluN2B ligands frequently exert off-target effects we also tested their affinity towards sigma receptors. Binding assay revealed that only the 1-(5-hydroxy-1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl)ethanone (7a) retained GluN2B affinity. Interestingly, the 5-methoxyindoles 5a and 6a were efficient and selective ligands toward σ₂ receptor (Ki values of 10nM and 20 nM, respectively). Thus, in this case the discovery of new σ₂ receptor selective ligands was an unexpected result emerging from the screening of cross-activity against other CNS receptors.
|Titolo:||From NMDA receptor antagonists to discovery of selective σ₂ receptor ligands|
|Data di pubblicazione:||2014|
|Citazione:||From NMDA receptor antagonists to discovery of selective σ₂ receptor ligands / Gitto R; De Luca L; Ferro S; Scala A; Ronsisvalle S; Parenti C; Prezzavento O; Buemi MR; Chimirri A.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 22:1(2014), pp. 393-397.|
|Appare nelle tipologie:||1.1 Articolo in rivista|