Studies on 1,2,3,4-tetrahydroisoquinoline derivatives. I. Syntheses and .BETA.-adrenoceptor activities of positional isomers of trimetoquinol with respect to its 6,7-dihydroxyl groups.

Abstract

In a series of phenylethanolamine .beta.-stimulants, transformation of hydroxyl groups of the catechol type into those of the resorcinol type was reported to improve the bioavailability. Five possible positional isomers of trimetoquinol (TMQ) [(-)-(1S)-6,7,-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] with respect to its 6,7-dihydroxyl groups were synthesized and tested for bronchodilating activity in cats. Among these postional isomers, the 5,7-dihydroxyl derivative exhibited more potent bronchodilating activity and longer duration of activity than (.+-.)-TMQ and isoproterenol on intraduodenal administration.