Synthesis and Pharmacokinetics of 2-ethanols - Structural Isomers of [beta]2 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 [beta]2 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 [mu]g/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.