QSAR STUDY OF HETEROAROMATIC MODIFICATIONS IN THE SIDE-CHAIN OF BRADYCARDIAC BENZAZEPINONES BY RESPONSE-SURFACE MODELING .1.

A literature data set on the bradycardic and hypotensive activities of benzazepinones with different monocyclic and bicyclic heteroaromatic moieties in the side chain was used to test the newly derived aromatic ity principal properties (PP) descriptors in single parameter correlat ions showing that the logarithm of the bradycardic activity is related to ''magnetic'' aromaticity (the second heteroaromatic PP), while the hypotensive effect is related to ''classical'' aromaticity (the first heteroaromatic PP). The biological properties of the ''optimum'' comp ound combining high bradycardic potency, short duration of action and high selectivity versus hypotensive effects, were modelled by PLS resp onse surfaces in terms of heteroaromatic moieties PP and C-13 NMR shif t of the attached carbon by means of the CARSO procedure. The models a llow the rationalization of the biological properties and the detectio n of optimal heteroaromatics compatible with the overall desired biolo gical behaviour.