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Synthesis and In Vitro Pharmacological Evaluation of 5‐(Alkoxymethyl)‐2‐(3‐alkylamino‐2‐hydroxypropoxy)phenylethanones Related to Acebutolol and Celiprolol
Author(s) -
Bruchatá Katarína,
Némethy Andrej,
Čižmáriková Ružena,
Račanská Eva,
Habala Ladislav
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600136
Subject(s) - celiprolol , acebutolol , chemistry , isopropyl , chronotropic , stereochemistry , carbon 13 nmr , moiety , alkoxy group , molecule , alkyl , medicinal chemistry , organic chemistry , propranolol , medicine , heart rate , blood pressure , radiology
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 (β 1 ) and trachea (β 2 ) and expressed as p A 2 values against isoprenaline tachycardia. The assumed cardioselectivity was expressed as β 1 /β 2 ratio and the values of compounds with an alkoxy group (CH 3 O, iC 3 H 5 O, C 5 H 11 O, CH 2 CHCH 2 O, CH 3 OCH 2 CH 2 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.