Synthesis, beta-adrenergic activity, and platelet antiaggregatory activity of a positional isomer of trimetoquinol: 1-(2',4',5'-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline.
A positional isomer of trimetoquinol (1), 1-(2',4',5'-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (3), was synthesized and found to possess less beta-adrenergic activity than 1 in isolated guinea pig atrial and tracheal preparations. The analogue 3 was an effective antiaggregatory agent in human and rabbit platelet-rich plasma preparations, while 1 was effective only as an inhibitor of arachidonic acid induced aggregation in human platelets. These findings indicate that both qualitative and quantitative differences in biological activity have occurred as a result of changing the position of the methoxy groups on the 1-benzyl substituent of 1.
D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000138:chemical synthesis*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects; D014213:Tretoquinol / Q000138:chemical synthesis* / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D007546:Isoquinolines; C024531:1-(2',4',5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; D014213:Tretoquinol