112114-08-6Relevant academic research and scientific papers
Structure-affinity relationships of arylquinolizines at α-adrenoceptors
Huff,Baldwin,DeSolms,Guare Jr.,Hunt,Randall,Sanders,Smith,Vacca,Zrada
, p. 641 - 645 (1988)
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.
