SYNTHESIS AND ALPHA-ADRENERGIC ACTIVITIES OF 2-SUBSTITUTED AND 4-SUBSTITUTED IMIDAZOLINE AND IMIDAZOLE ANALOGS

Seven analogues of medetomidine and naphazoline were synthesized and evaluated for their alpha(1) (aorta) and alpha(2) (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 alpha(1) adrenergic system (aorta). Thus, appropriately substituted naphthalene analogues of medetomidine and naphthazoline provide a spectrum of alpha(1)-agonist, alpha(1)-antagonist, and alpha(2)-antagonist activity.