Document Report Card

ID: ALA1124062

Journal: J Med Chem

Title: Structure-affinity relationships of arylquinolizines at alpha-adrenoceptors.

Authors: Huff JR, Baldwin JJ, deSolms SJ, Guare JP, Hunt CA, Randall WC, Sanders WS, Smith SJ, Vacca JP, Zrada MM.

Abstract: Hexahydroaryl[a]quinolizines comprise a prominent structural element in several alpha 2-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 alpha-adrenoceptors. Affinity for alpha 1-and alpha 2-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 alpha-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.

CiteXplore: 2831365

DOI: 10.1021/jm00398a025