STUDIES ON THE STRUCTURE ACTIVITY RELATIONSHIP OF ADRENERGIC β-MIMETIC BENZYL AMI NE DERIVATIVES

Abstract

Appropriately substituted benzylamine (BZA) derivatives, fragmented derivatives of tetrahydroisoquinolines, were directly acting adrenergic .beta.-stimulants, exhibiting tracheal relaxing, positive chronotropic and free fatty acid (FFA) releasing activities [in guinea pigs and rats]. The chemical structures essential for manifestation of the .beta.-action were 3,4-dihydroxybenzylamine arylmethyl group at position .alpha., lower alkyl group on the N atom. The structure activity relationships of BZA-derivatives were almost similar to, but partly different from those of tetrahydroisoquinoline[ISO]- and catecholamine-derivatives. The tracheal relaxing, positive chronotropic and FFA-releasing actions of .alpha.-(3,4,5-trimethoxybenzyl)-N-methyl-3,4-dihydroxybenzylamine, the most active compound in the BZA-derivatives tested, were approximately 100, 30 and 50 times less active than those of ISO, respectively. This compound is .beta.1-selective, while trimetoquinol is .beta.2-selective.