Chiral 2-(3′-(5′-p-chlorophenyl)isoxazolidinyl)ethanolamines as conformationally restrained analogs of methyloxyiminomethyl (MOIM) β-adrenergic antagonists: Synthesis, configuration and β-adrenergic properties

Article abstract of DOI:10.1016/0223-5234(96)80366-7

The chiral N-isopropyl- and N-t-butyl-substituted 2-(3′-(5′-p-chlorophenyl)isoxazolidinyl)ethanolamines 2, 3, which can be viewed as conformationally restrained analogs of the corresponding methyloxyiminomethyl (MOIM) β-adrenergic antagonists 1, were synthesized from optically active precursors with a known absolute configuration. The structure and configuration of the intermediate and final products 2, 3 were assigned on the basis of a comparison of the ¹H-NMR spectral data of all compounds, crystallographic analysis of one of the intermediates [(2R,5′S)-7] and knowledge of the configuration of the chiral starting compounds 4. The new isoxazoline derivatives 2, 3 were tested for their affinity towards β₁- and β₂-adrenoceptors by radioligand binding experiments; compounds showing affinity indices lower than 10 μM on β₁-adrenoceptors were also assayed for their β-adrenergic activity by functional tests on isolated preparations. The results showed that the cyclic derivatives 2, 3 possess a capacity to interact with β-receptors which is clearly lower than that of the corresponding MOIM analogs 1.