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, 1H NMR and 13C 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 (CH3O, iC3H5O, C5H11O, CH2CHCH2O, CH3OCH2CH2O) 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/dm3 showed also negative chronotropic effects. Thirteen aryloxyaminopropanol‐type 2‐hydroxyphenylethanone‐derived analogs were synthesized and their activities as potential β‐blockers were investigated. Compounds with an alkoxy group (CH3O, iC3H5O, C5H11O, CH2CHCH2O, CH3OCH2CH2O) in the lipophilic part and with tert‐butyl in the hydrophilic part of the molecul...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research