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.
D000273:Adipose Tissue / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis*; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000138:chemical synthesis*; D050356:Lipid Metabolism; D008297:Male; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D014213:Tretoquinol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D014213:Tretoquinol