Synthesis and α-adrenergic activities of 2- and 4-substituted imidazoline and imidazole analogues

Article abstract of DOI:10.1021/jm00082a017

Seven analogues of medetomidine and naphazoline were synthesized and evaluated for their α₁ (aorta) and α₂ (platelet) activities. The analogues were composed of 2- and 4-substituted imidazoles and imidazolines attached through a methylene bridge to either the 1- or 2-naphthalene ring system. In general the 1-naphthalene analogues were the most potent inhibitors of epinephrine-induced platelet aggregation. Of considerable interest was the fact that the 1-naphthalene analogues (2, 5-7) were partial agonists while the 2-naphthalene analogues (3, 8, 9) were antagonists in an α₁-adrenergic system (aorta). Thus, appropriately substituted naphthalene analogues of medetomidine and naphthazoline provide a spectrum of α₁- agonist, α₁-antagonist, and α₂-antagonist activity.