Structure-affinity relationships of arylquinolizines at α-adrenoceptors

Article abstract of DOI:10.1021/jm00398a025

Hexahydroaryl[a]quinolizines comprise a prominent structural element in several α₂-adrenoceptor antagonists. Eight hexahydroheteroarylquinolizines were prepared as minimal ligands to investigate the relationship between the nature of the aromatic ring and affinity of these molecules for α-adrenoceptors. Affinity for α₁- and α₂-adrenoceptors was assessed by displacement of [³H]prasozin and [³H]clonidine, respectively. Lipophilicity of the aryl portion of the molecules, reflected by their partition coefficient between octanol and pH 7.4 buffer, correlated well with affinity at both receptor subtypes. Although some compounds showed nanomolar affinity for α-adrenoceptors, no subtype selectivity was observed. These results suggest that the aromatic ring enhances binding at both receptors chiefly through hydrophobic interactions and contributes little to subtype selectivity.