title: Cardioselectivity as a function of molecular structure in beta-adrenoceptor blocking agents of the 1-(para-substituted aryloxy)-3-(isopropylamino)propan-2-ol type.
abstract: The relationship between molecular structure and cardioselectivity is described in the 1-(para-substituted aryl-oxy)-3-(isoprophylamino)propan-2-ol type of beta-adrenoceptor blocking agents. Cardioselectivity in the aforementioned series requires that the aromatic substitution in the position para to the amino alcohol side chain will have a minimal linear length of 5.0 A. Highest cardioselectivity is obtained when this para substituent is a rigid group coplanar with the aromatic ring. This may result from steric hindrance for binding at the beta2-adrenoceptor subtype which does not occur in the beta1 subtype. Evidence in favor of this suggestion was obtained by the finding that the trans isomer of 1-[4-(1-propenyl)-2-methoxyphenoxy]-3-(isopropylamino)propan-2-ol is cardioselective (beta1/beta2 = 25), whereas the cis isomer is beta2 selective (beta1/beta2 = 0.1).
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008968:Molecular Conformation; D009928:Organ Specificity; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines