Synthesis of a Novel Series of Phosphonate-Functionalized 1,2,3-Triazoles as Potential Candidates for Allosteric Modulation of α7 Nicotinic Acetylcholine Receptors

Abstract

Nicotinic acetylcholine receptors (nAChR) are ligand-gated ion channels formed by the assembly of five subunits. Receptor activity could be subjected to both positive and negative modulation at allosteric sites by endogenous neurotransmitters as well as synthetic ligands such as steroids, bivalent cations, alcohols, and a range of drugs. The subtype of α7 nAChR has been considered a potential therapeutic target for Alzheimer’s disease, schizophrenia and other neurological and psychiatric disorders. In this work we present the synthesis of a novel series of phosphonate-functionalized 1,4-disubstituted 1,2,3-triazoles with potential activity over α7 AChR. These compounds were synthetized through the copper-catalyzed Huisgen 1,3-dipolar cycloaddition of organic azides and alkynes. Copper nanoparticles (CuNPs) immobilized on different supports were prepared using the CuCl2-Li-DTBB reducing system previously reported by our group.