Structure-activity relationships in further series of amino-halogen substituted phenyl-aminoethanols.

Series of 1-(4-amino-phenyl)-2-aminoethanol derivatives having different substituents in the phenyl nucleus were compared with 1-(4-amino-3,5-dichloro-phenyl)-2-tert.-butylamino-ethanol (clenbuterol) with regard to their action on the adrenergic beta-receptors of guinea pigs, cats and rats. The exchange of the two chlorine atoms of clenbuterol led to substances with a potent beta 2-mimetic activity, surpassing that of clenbuterol, in the bronchial muscles and/or to a beta 1-blocking action in the heart with a relatively low beta 1-intrinsic activity. The strongest action was found with the chloro-cyano, fluoro-cyano and mono-cyano substituted compounds. The chloro-fluoro, bromo-fluoro, mono-fluoro and chloro-trifluoromethyl substituted compounds showed a good oral absorption, comparable to that of clenbuterol. Because of a particularly low beta 1-intrinsic activity in the heart with a long-lasting beta 2-mimetic action on the bronchial muscles also after oral administration, the 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) must come of all the structures investigated particularly into consideration as broncholytic agent for therapeutic use.