Synthesis and characterization of new α7-nAChR ligands


on the July 2, 2019

Published in Eur. J. Med. Chem.

Collaborative research project led by Prof. Sylvain Routier (UMR CNRS 7311, Institut de Chimie Organique et Analytique, Université d’Orléans) and Dr. Sylvie Chalon.

Bis(het)aryl-1,2,3-triazole quinuclidines as α7 nicotinic acetylcholine receptor ligands: Synthesis, structure affinity relationships, agonism activity, [18F]-radiolabeling and PET study in rats


In this paper we describe the design and synthesis of bis(Het)Aryl-1,2,3-triazole quinuclidine α7R ligands using an efficient three-step sequence including a Suzuki-Miyaura cross coupling reaction with commercially available and home-made boron derivatives. The exploration of SAR required the preparation of uncommon boron derivatives. Forty final drugs were tested for their ability to bind the target and nine of them exhibited Ki values below nanomolar concentrations. The best scores were always obtained when the 5-phenyl-2-thiophenyl core was attached to the triazole. The selectivity of these compounds towards the nicotinic α4β2 and serotoninergic 5HT3 receptors was assessed and their brain penetration was quantified by the preparation and in vivo evaluation of two [18F] radiolabelled derivatives. It can be expected from our results that some of these compounds will be suitable for further developments and will have effects on cognitive disorders.


#Triazole #Quinuclidine #SAR #Agonism #Radiolabeling #18FPET #α7-nAChR

Contact :
Dr. Sylvie Chalon :