Chen_2006_J.Enzyme.Inhib.Med.Chem_21_667

A series of N, N- disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural alpha4beta2* and alpha7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for alpha4beta2* nAChRs and did not interact with the alpha7* nAChRs subtype. The most potent analogs were compounds 8-19 (K(i) = 10.4 microM), 8-13 (K(i) = 12.0 microM), and 8-24 (K(i) = 12.8 microM). Thus, linking together a pyridine pi-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for alpha4beta2* nAChRs.