N, N -disubstituted piperazines and homopiperazines: synthesis and affinities at alpha4beta2* and alpha7* neuronal nicotinic acetylcholine receptors.
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.
Chen
Jianhong
J
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536-0082, USA.
Deaciuc
Agripina G
AG
Dwoskin
Linda P
LP
Crooks
Peter A
PA
Bai
Donglu
D
D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D010879:Piperazines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2