Details

Autor(en) / Beteiligte

• Huff, Joel R
• Baldwin, John J
• DeSolms, S. Jane
• Guare, James P
• Hunt, Cecilia A
• Randall, William C
• Sanders, William S
• Smith, Steven J
• Vacca, Joseph P
• Zrada, Matthew M

Titel

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

Ist Teil von

• Journal of medicinal chemistry, 1988-03, Vol.31 (3), p.641-645

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1988

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.