Synthesis and β-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 β-blocking drugs

Article abstract of DOI:10.1016/0223-5234(96)88293-6

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 β-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 β₁- and β₂-adrenoceptors by radioligand binding experiments; the compounds with the highest affinity were also assayed for their β₁- and β₂-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 β₁-adrenergic properties in terms of affinity and activity; this type of substituent, on the contrary, appears to be capable of improving the β₂-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.