N,N-disubstituted piperazines: synthesis and affinities at alpha4beta2(*) and alpha7(*) neuronal nicotinic acetylcholine receptors.
A series of N,N-disubstituted piperazines were prepared and evaluated for binding to alpha4beta2(*) and alpha7(*) neuronal nicotinic acetylcholine receptors using rat striatum and whole brain membrane preparations, respectively. This series of compounds exhibited selectivity for alpha4beta2(*) nAChRs and did not interact with the alpha7(*) nAChRs subtype. The most potent analogues were compounds 8b and 8f (K(i)=32 microM). Thus, linking together a pyridine pi-system and a cyclic amine moiety via a piperazine ring affords compounds with low affinity, but good selectivity for alpha4beta2(*) nicotinic receptors.
Chen
Jianhong
J
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-yuan Road, China.
Norrholm
Seth
S
Dwoskin
Linda P
LP
Crooks
Peter A
PA
Bai
Donglu
D
D000818:Animals; D001923:Brain Chemistry; D008024:Ligands; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D008024:Ligands; D018722:Nicotinic Agonists; D010879:Piperazines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2