Design and synthesis of a hybrid series of potent and selective agonists of α7 nicotinic acetylcholine receptor

alpha 7 nicotinic acetylcholine receptor agonists are promising therapeutic candidates for the treatment of cognitive impairment. As a follow up of our internal medicinal chemistry program we investigated a novel series of alpha 7 nAChR agonists. Starting from molecular docking studies on two series of molecules recently developed in our laboratories, an alternative scaffold was designed attempting to combine the optimal features of these previously identified urea and pyrazole compounds. Based on our previous SAR knowledge and on predicted drug-like properties, a small library was synthesized in parallel manner, affording compounds with excellent alpha 7 nAChR activity, selectivity and preliminary ADME profile. (C) 2014 Elsevier Masson SAS. All rights reserved.