Cardioselectivity of beta-adrenoceptor blocking agents 1. 1-[(4-Hydroxyphenethyl)amino]-3-(aryloxy)propan-2-ols.
A series of 1-[(4-hydroxyphenethyl)amino]-3-(aryloxy)propan-2-ols was synthesized together with several 1-[(3,4-dimethoxyphenethyl)amino]-3-(aryloxy)propan-2-ols. Their affinity to beta 1- and beta-2-adrenoceptors was determined and compared with the affinity of known beta-blockers. We were able to confirm the substantial cardioselectivity of 1-(3,4-dimethoxyphenethyl)-3-[(4-substituted aryl)oxy]propan-2-ols when compared to those with a 1-(4-hydroxyphenethyl) group. An increase in the size of the 4 substitutent of the 3-(aryloxy) moiety to caproamido leads to a substantially higher affinity for the beta 1--adrenoceptor of rat ventricular muscle in the presence of the 3,4-dimethoxyphenethyl than in the presence of the 4-hydroxyphenethyl or isopropyl group; this combination also gave the highest cardioselectivity.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D011412:Propanolamines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000526:Alprenolol