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ID: ALA3286186

Journal: Eur J Med Chem

Title: Design of α7 nicotinic acetylcholine receptor ligands in quinuclidine, tropane and quinazoline series. Chemistry, molecular modeling, radiochemistry, in vitro and in rats evaluations of a [(18)F] quinuclidine derivative.

Authors: Pin F, Vercouillie J, Ouach A, Mavel S, Gulhan Z, Chicheri G, Jarry C, Massip S, Deloye JB, Guilloteau D, Suzenet F, Chalon S, Routier S.

Abstract: In this report, we describe the synthesis of a novel library of α7 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 [(18)F]4 PET tracer was evaluated in rats and its brain accumulation quantified.

CiteXplore: 24904968

DOI: 10.1016/j.ejmech.2014.04.057