title: Synthesis and beta-adrenergic antagonist activity of heterocyclic propanolamines.
abstract: The synthesis and beta-adrenergic antagonist activities of a group of 1-(heteroaryloxy)- and 1-(heteroaryl)-3-alkylamino-2-propanols is described. beta 1-Adrenolytic (atria) structure-activity correlations indicated that replacement of the 1-naphthyl moiety of propranolol by a 4-quinolyl- (10), 2-quinolyl- (24), or 2-pyrimidyl- (26) heterocyclic moiety resulted in a 10-16 fold reduction in activity. The 1-(4-quinolyloxy)- (10) and 1-(2-quinolyloxy)- (24-25) heteroaryl moieties provided more potent activity than the structurally related 1-[2-(2H-isoquinolin-1-one)]- (31-32) or 1-[3-(3H-quinazolin-4-one)]- (35-36) moieties. All compounds tested exhibited weak beta 2-adrenolytic activity on trachea. Although the most potent beta 1-antagonist, 1-(2-pyrimidyloxy)-3-isopropylamino-2-propanol (26), was 13-fold less potent than metoprolol, it exhibited a beta 1/beta 2 selectivity ratio superior to the cardioselective metoprolol.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Vo
authors.forename: M W
authors.initials: MW
authors.lastname: Wolowyk
authors.forename: E E
authors.initials: EE
authors.lastname: Knaus
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000319:Adrenergic beta-Antagonists; D006571:Heterocyclic Compounds; D011412:Propanolamines; D008790:Metoprolol