Synthesis and Pharmacokinetics of 2-(4-amino-3,5-dichlorophenyl)-2-(alkylamino)ethanols - Structural Isomers of β2 Agonists Clenproperol and Clenpenterol

Methods for the synthesis of 2-(4-amino-3,5-dichlorophenyl)-2-(isopropylamino)ethanol and 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol, which are structural isomer of the β2 agonists clenproperol and clenpenterol, were developed. The pharmacokinetics of these compounds were studied on p.o. administration to rats at doses of 270 and 540 μg/kg. Chromatomass spectrometry studies showed that increases in dose led to proportionate increases in the maximum blood substance concentration. Times to maximum concentration were 0.25 – 1.5 h. The times during which substances were detectable in blood with a sensitivity of 0.1 ng/ml were determined: values were 72 h for 2-(4-amino-3,5-dichlorophenyl)-2-(isopropylamino)ethanol and more than 96 h for 2-(4-amino-3,5-dichlorophenyl)-2-(tert-amylamino)ethanol. Halogen atoms present in the molecules of the study compounds prevented their rapid metabolic inactivation. The main pharmacokinetic parameters were computed: area under pharmacokinetic curve; half-elimination time; mean retention time; plasma clearance.