Synthesis of [beta]2-Agonist Metabolites of 2-Ethanols and their Excretion with Urine in Comparison to the Initial Compounds

Metabolites of [beta]2-agonists 2-(4-amino-3,5-dichlorophenyl)-2-(alkylamino)ethanols, derivatives of hippuric and mandelic acids, were synthesized. The excretion profiles of the target compounds and metabolites with urine were studied in experiments on laboratory animals. 2-(4-Amino-3,5-dichlorophenyl)-2-(isopropylamino) ethanol (9.7% of the administered dose) and 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol (0.7%) were isolated unchanged after a single peroral administration of the compounds at doses of 270 and 540 [mu]g/kg. The times for determination of the target components and metabolites in urine of laboratory animals at a method sensitivity of 0.1 ng/mL were established as 120 h after administration for 2-(4-amino-3,5-dichlorophenyl)-2-(isopropylamino)ethanol and 96 h for 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol. The metabolite of 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol, a hippuric acid derivative, was detected in urine longer (120 h) than the initial compound.