Synthesis, NMR studies and conformational analysis of oxazolidine derivatives of the β-adrenoreceptor antagonists metoprolol, atenolol and timolol

Abstract

Formaldehyde-derived oxazolidine derivatives 4-7 of the β-adrenoreceptor antagonists metoprolol 1, atenolol 2 and timolol 3 have been synthesised. Conformational analysis of 1-3 and the oxazolidine derivatives 4-7 has been performed using 1H NMR spectroscopy and computational methods. The 1H NMR studies show that for the aryloxypropanolamine β-adrenoreceptor antagonists there is a predominance of the conformer in which the amine group is approximately antiperiplanar or trans to the aryloxymethylene group. Both 1H NMR data and theoretical studies indicate that the oxazolidine derivatives 4-7 and the aryloxypropanolamine β-adrenoreceptor antagonists 1-3 adopt similar conformations around the β..