Synthesis and activity of 3-pyridylamine ligands at central nicotinic receptors

A series of thirty 2-(3-pyridylaminomethyl)azetidine, pyrrolidine and piper idine analogues as nicotinic acetylcholine receptor (nAChR) ligands was exp lored. In general, pyrrolidinyl and many azetidinyl compounds were found to bind with enhanced affinity relative to the piperidines. In the three seri es, the parallel structural changes (stereochemistry, N-methylation and/or chloro substitution) do not consistently lead to parallel shifts in affinit y. The more active compounds (K-i affinity values ranging from 8.9 to 90 nM ) were about as analgesic as nicotine in a tail-flick assay in mice after s ubcutaneous injections. (C) 2000 Editions scientifiques et medicales Elsevi er SAS.