Synthesis and β-Adrenergic Properties of (Z)-N-[3-(Alkylamino)-2-hydroxypropylidene](aryl-methyloxy)amines: Effects of the Configuration Around the Methyloxyiminomethyl (MOIM) Double Bond on the Biopharmacological Properties of MOIM-type β-Blocking Agents

The N-isopropyl- (3a–g) and N-tert-butyl-substituted (4a–g) (Z)-N-(3-(amino)-2-hydroxypropylidene)(arylmethyloxy)amines were synthesized in order to compare their β1- and β2-adrenergic properties with those of their previously studied corresponding analogues with the E configuration (1a–g and 2a–g). Compounds 3 and 4 were tested for their affinity for β1- and β2-adrenoceptors by radioligand binding experiments, and the compounds with the highest affinity were also assayed for their activity towards the same types of β-adrenoceptors by functional tests on isolated preparations. The Z-methyloxyiminomethyl (Z-MOIM) compounds 3 and 4 proved to possess, on the whole, affinity (Ki) and activity (pIC50) indices similar to those of the E isomers 1 and 2, thus indicating that for the MOIM-type β-adrenergic antagonists 1–4, the type of configuration around the MOIM double bond does not have any appreciable effect either on the affinity or on the activity towards β-adrenoceptors. These results are rationalized on the basis of the steric and electronic analogies existing between the MOIM groups of 1–4 in the two types of configurations (E and Z).