Identification of Novel Scaffolds from an Original Chemical Library as Potential Antipsychotics

Abstract The ligand‐based virtual screening of an original chemical library, using atypical antipsychotics as query compounds led to the identification of a novel scaffold with inhibitory activity at the 5‐HT2Aserotonin receptor. The hit compounds were confirmed by pharmacological evaluation at the 5‐HT2Areceptor and complemented by the selection of other representatives of the same chemical family within our chemical library. A promising scaffold of 6‐(pyperazin‐1‐yl) purine was identified, and the binding mode is illustrated with an automated docking exploration on a homology built model of the 5‐HT2Areceptor. The present results constitute an excellent starting point for the discovery of new chemical entities with antipsychotic activity.