Fluorescent Agonists of the α7 Nicotinic Acetylcholine Receptor Derived from 3‐Amino‐Quinuclidine

Abstract

bHiQScreen S arl, 6 route de Compois, CH-1222 V esenaz Geneva Here, we investigated whether fluorescence labeled small molecule agonists of the a7 nicotinic acetylcholine receptor (nAChR) might be identified to enhance receptor studies. Enantiomerically pure 3-amino-quinuclidines appended with fluorophores at the 3-amino group were synthesized and tested by electrophysiology on human a7 nAChR in Xenopus oocytes, uncovering (R)-4 and (R)-9 as the first examples of fluorescent a7 nAChR agonists. These molecules elegantly incorporate the fluorescent reporter group as part of the pharmacophore itself and provide a new class of tool compounds for the study of these ligand-gated ion channels.