Synthesis and In Vitro Pharmacological Evaluation of 5-(Alkoxymethyl)-2-(3-alkylamino-2-hydroxypropoxy)phenylethanones Related to Acebutolol and Celiprolol.
The structure-activity relationships of 13 analogs of aryloxyaminopropanol type derived from 2-hydroxyphenylethanone as potential β-blockers are described. The synthesized compounds possess an isopropyl or a tert-butyl group in the hydrophilic part of the molecule and an alkoxymethyl substitution in the lipophilic moiety. The target compounds were prepared by an established four-step method and their structures were confirmed by interpretation of their UV, IR, (1) H NMR and (13) C NMR spectra, and by elemental analysis. The β-adrenolytic efficacy of the prepared racemic compounds was determined on isolated guinea pig atria (β1 ) and trachea (β2 ) and expressed as pA2 values against isoprenaline tachycardia. The assumed cardioselectivity was expressed as β1 /β2 ratio and the values of compounds with an alkoxy group (CH3 O, iC3 H5 O, C5 H11 O, CH2 CHCH2 O, CH3 OCH2 CH2 O) in the lipophilic part and with tert-butyl in the hydrophilic part of the molecule were found to be comparable or higher than those of the standards acebutolol and celiprolol. All evaluated substances at a concentration of 10(-7)  mol/dm(3) showed also negative chronotropic effects.
['Bruchatá|Katarína|K|', 'Némethy|Andrej|A|', 'Čižmáriková|Ružena|R|', 'Račanská|Eva|E|', 'Habala|Ladislav|L|']
D000070:Acebutolol D000319:Adrenergic beta-Antagonists D000818:Animals D017272:Celiprolol D006168:Guinea Pigs D006325:Heart Atria D006339:Heart Rate D006632:Histamine D007545:Isoproterenol D011412:Propanolamines D013329:Structure-Activity Relationship D014132:Trachea
2-Hydroxyphenylethanone Cardioselectivity Isolated atria Isolated trachea