N,N-Disubstituted piperazines: synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors

A series of N,N-disubstituted piperazines were prepared and evaluated for binding to α4β2* and α7* neuronal nicotinic acetylcholine receptors using rat striatum and whole brain membrane preparations, respectively. This series of compounds exhibited selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogues were compounds 8b and 8f (Ki=32 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a piperazine ring affords compounds with low affinity, but good selectivity for α4β2* nicotinic receptors.