Substituted 1,2,3,4-tetrahydroaminonaphthols: antihypertensive agents, calcium channel blockers, and adrenergic receptor blockers with catecholamine-depleting effects.

Substituted 1,2,3,4-tetrahydroaminonaphthols were found to be calcium channel blockers with antihypertensive properties. These compounds also possessed adrenergic beta-receptor blocking activity. From the structure-activity studies, no clear correlation emerged between the in vitro calcium channel blocking activity and the acute anti-hypertensive activity in cannulated spontaneously hypertensive rats. Extensive pharmacological testing of selected compounds indicated that aminonaphthols are antihypertensive agents with many pharmacological properties. The relative contribution of various pharmacological actions toward the observed antihypertensive activity is unclear. Since the clinically useful calcium channel blocker verapamil is structurally related to these compounds, one of the aminonaphthols, trans-3-[(3,3-diphenylpropyl)amino]-1,2,3,4-tetrahydro-6,7 -dimethoxy-2-naphthalenol (12), was compared with verapamil for calcium channel blocking activity, adrenergic blocking activity, and catecholamine-depleting activity. Both compounds were found to be equipotent in these test systems.