N, N –Disubstituted piperazines and homopiperazines: Synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors

Abstract

A series of N, N– disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural α4β2* and α7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogs were compounds 8-19 (K_i = 10.4 μM), 8–13 (K_i = 12.0 μM), and 8–24 (K_i = 12.8 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for α4β2* nAChRs.

Keywords::

• Piperazines
• homopiperazines
• neuronal nicotinic acetylcholine receptors
• α_it;4β_it;2* receptors

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China and the National Institute on Drug Abuse (DA017548).