SYNTHESIS AND BETA-ADRENERGIC PROPERTIES OF (E)-N-[3-(ALKYLAMINO)-2-HYDROXYPROPYLIDENE](METHYLOXY) AMINES SUBSTITUTED WITH AN AROMATIC GROUP ON THEIR [(METHYLOXY)IMINO] METHYL MOIETY (MOIMM) - AN INVESTIGATION INTO THE BIOPHARMACOLOGICAL EFFECTS OF AN ARYL SUBSTITUTION IN THE CLASS OF MOIM BETA-BLOCKING DRUGS

N-Isopropyl-(5a-g) and N-t-butyl-substituted(6a-g) (E)-N-[3-(amino)-2-hydroxypropylidene](arylmethyloxy)amines, which present an aromatic ring (Ar) linked to the CH2 carbon of the [(methyloxy)imino]methyl moiety (MOIMM), were synthesized with the aim of comparing their beta-adrenergic properties with those of the previously studied completely aliphatic analogs 1,2 and 3,4. Compounds 5 and 6 were tested for their affinity towards beta(1)- and beta(2)-adrenoceptors by radioligand binding experiments; the compounds with the highest affinity were also assayed for their beta(1) and beta(2)-adrenergic activity by functional tests on isolated preparations. The biopharmacological results show that, for the MOIM derivatives studied (1-6), the presence of an Ar substituent linked to the MOIM, as in 5 and 6, does not have any appreciable effect on the beta(1)-adrenergic properties in terms of affinity and activity; this type of substituent, on the contrary, appears to be capable of improving the beta(2)-adrenergic properties, as far as the receptor affinity is concerned. These results are discussed on the basis of a comparison of the conformational and electronic characteristics.