Novel beta(2)-agonists with a 5-hydroxy-4H-benzo[1,4]oxazin-3-one moiety as head group are described. Systematic chemical variations at the phenethylamine residue of these compounds lead to the discovery of compound 6m as potent, full agonist of the beta(2)-adrenoceptor with a high beta(1)/beta(2)-selectivity. Molecular modeling revealed an interaction between the carboxylic acid group of 6m and a lysine residue (K305) of the beta(2)-receptor as putative explanation for the high observed selectivity. Further, compound 6m displayed in a guinea pig in vivo model a complete reversal of acetylcholine induced bronchoconstriction which lasted over the complete study time of 5h.