An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives

On the basis of results previously obtained from structural and theoretical studies on @-adrenergicd rugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at P-adrenoceptors; the P2/PI selectivity ratio indicated that they are more active on the tracheal than on the cardiac @-receptor. The chemical reactivity of the AOEDs was studied through the calculation of the electrostatic molecular potential (EMP) on a model compound in its preferred conformation. The results showed that the EMP trend agrees with that previously calculated for other @-blockingd rugs.