Broxaterol: pharmacological profile of a unique structural feature

A series of 1-(3-substituted-5-isoxazolyl)-2-alkylaminoethanol derivatives was synthesized in order to evaluate the effectiveness of the isoxazole ring in replacing the catechol moiety of beta-adrenergic compounds. Among the investigated compounds, 1-(3-bromo-5-isoxazolyl)-2-tert-butyl aminoethanol hydrochloride, named broxaterol hydrochloride (laboratory code Z 1170), resulted to be the most potent and selective beta 2-agonist of the series. In vitro studies confirmed the beta 2-agonist profile of broxaterol, which showed a marked bronchodilating activity in different experimental models. Interestingly, besides its direct effect in relaxing bronchial smooth muscle, broxaterol was, also, very effective in inhibiting asthmogenic mediator release both in vitro and in vivo. The preclinical studies demonstrated that the similar potency observed in vitro for both broxaterol and salbutamol resulted in a higher effectiveness of broxaterol with respect to salbutamol, when the compounds were given by oral route. These findings account for a probably greater bioavailability of broxaterol after oral administration.