Studies on the structure activity relationship of adrenergic beta-mimetic benzylamine derivatives.

Abstract Appropriately substituted benzylamine (BZA) derivatives, fragmented derivatives of tetrahydroisoquinolines, were found to be directly acting adrenergic β-stimulants, exhibiting tracheal relaxing, positive chronotropic and free fatty acid (FFA) releasing activities. The chemical structures essential for manifestation of the β-action were i) 3,4-dihydroxybenzylamine, ii) arylmethyl group at position α, iii) 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- and catecholamine-derivatives. The tracheal relaxing, positive chronotropic and FFA-releasing actions of α-(3,4,5-trimethoxybenzyl)-N-methyl-3,4-dihydroxybenzylamine, the most active compound in the BZA-derivatives tested, were approximately one-hundred, thirty and fifty times less active than those of ISO, respectively. These results indicate that this compound is β1-selective, while trimetoquinol is β2-selective.