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 was described in the 1-(p-substituted aryl-oxy)-3-(isopropylamino)propan-2-ol type of .beta.-adrenoceptor blocking agents. Cardioselectivity requires that the aromatic substitution in the position p to the amino alcohol side chain will have a minimal linear length of 5.0 .ANG.. Highest cardioselectivity was obtained when the p substituent was a rigid group coplanar with the aromatic ring. This may result from steric hindrance for binding at the .beta.2-adrenoceptor subtype which does not occur in the .beta.1 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 was cardioselective (.beta.1/.beta.2 = 25); the cis isomer was .beta.2 selective (.beta.1/.beta.2 = 0.1).

This publication has 2 references indexed in Scilit: