Cardioselectivity as a function of molecular structure in β-adrenoceptor blocking agents of the 1-(para-substituted aryloxy)-3-(isopropylamino) propan-2-ol type

Article abstract of DOI:10.1021/jm00207a025

The relationship between molecular structure and cardioselectivity is described in the 1-(para-substituted aryloxy)-3-(isopropylamino)propan-2-ol type of β-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 β₂-adrenoceptor subtype which does not occur in the β₁ 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 (β₁/β₂=25), whereas the cis isomer is β₂ selective (β₁/β₂=0.1).