A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl) ethane-1,2-dione derivatives that have been screened in [H-3]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50 = 5.5 nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50 nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents. (C) 2013 Elsevier Ltd. All rights reserved.
|Titolo:||Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors.|
|Data di pubblicazione:||2014|
|Citazione:||Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors. / Gitto, R; De Luca, L; Ferro, S; Russo, E; De Sarro, G; Chisari, Mariangela; Ciranna, Lucia; Alvarez Builla, J; Alajarin, R; Buemi, Mr; Chimirri, A.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 22:3(2014), pp. 1040-1048.|
|Appare nelle tipologie:||1.1 Articolo in rivista|