title: Synthesis and In Vitro Pharmacological Evaluation of 5-(Alkoxymethyl)-2-(3-alkylamino-2-hydroxypropoxy)phenylethanones Related to Acebutolol and Celiprolol.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Department of Chemical Theory of Drugs, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Bruchatá
authors.affiliation: Faculty of Pharmacy, Department of Chemical Theory of Drugs, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Némethy
authors.affiliation: Faculty of Pharmacy, Department of Chemical Theory of Drugs, Comenius University in Bratislava, Bratislava, Slovakia. cizmarikova@fpharm.uniba.sk.
authors.forename: Ružena
authors.initials: R
authors.lastname: Čižmáriková
authors.affiliation: Faculty of Pharmacy, Department of Pharmacology and Toxicology, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Eva
authors.initials: E
authors.lastname: Račanská
authors.affiliation: Faculty of Pharmacy, Department of Chemical Theory of Drugs, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Habala
mesh_terms: D000070:Acebutolol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D017272:Celiprolol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D000070:Acebutolol; D006632:Histamine; D017272:Celiprolol; D007545:Isoproterenol
keywords: 2-Hydroxyphenylethanone; Cardioselectivity; Isolated atria; Isolated trachea