Design of alpha 7 nicotinic acetylcholine receptor ligands in quinuclidine, tropane and quinazoline series. Chemistry, molecular modeling, radiochemistry, in vitro and in rats evaluations of a [F-18] quinuclidine derivative

摘要

In this report, we describe the synthesis of a novel library of alpha 7 nAChR ligands based on the modulation of the quinuclidine, quinazoline and tropane moieties. Spirane derivatives were newly synthesized under stereo specific 1,3 dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor with Ki measured between 14 and 133 nM. The best fluorinated candidate was selected and radiolabeled. The potent [F-18]4 PET tracer was evaluated in rats and its brain accumulation quantified. (C) 2014 Elsevier Masson SAS. All rights reserved.