Synthesis of new (arylcarbonyloxy)aminopropanol derivatives and the determination of their physico-chemical properties

Eight hydrochlorides of 3-{2-[(2/4-fluorophenoxy)-ethylamino]}-2-hydroxypropyl-4-alkoxybenzoates and four hydrochlorides of 3- tert -butylamino-2-hydroxypropyl-4-butoxybenzoates were prepared as potential antagonists of the β 1 -adrenergic receptor (beta-blockers). A multistep synthesis of these compounds is described as well as their detailed analytical characterization. The pharmacokinetic properties of these weak base compounds are significantly influenced by their acid-base dissociation constant, p K a . The knowledge of this value is crucial for new drug development. This paper is aimed at developing a methodology that utilizes pH-dependent 1 H NMR spectroscopy for its routine analysis. The selected predicted physico-chemical parameters of the new (arylcarbonyloxy)aminopropanols ( i.e. , aryloxyaminopropanol derivatives) were compared with the model drugs esmolol and flestolol.