Synthesis of 1-substituted analogues of trimetoquinol possessing differential and selective beta-adrenergic properties.

The synthesis of the 1,1-disubstituted tetrahydroisoquinoline analogues, 1-methyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (2) and 1-benzyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3), is described. The profile of beta-adrenergic activity for these analogues was determined and compared to that of trimetoquinol (1) in isolated guinea pig atrial, tracheal, and rat adipocyte preparations. Unexpected selective beta1-blocking activity in guinea pig trachea was noted with analogue 3. With the exception of 2 in guinea pig atria, 2 and 3 did not possess any beta-stimulant activity. Substitution at the 1 position of trimetoquinol (1) has revealed qualitative differences in beta-adrenergic activity.