Synthesis and beta-adrenergic antagonist activity of novel (3-oxazolinyl-1,4-dihydropyridyl) propanolamines.
A novel class of 1-(1-[4-phenyl(n-butyl or methyl)-3-(4,4-dimethyloxazolin-2-yl)-1,4- dihydropyridyl])-3-tert-butyl(or isopropyl)amino-2-propanols (7-12) were synthesized for evaluation as beta-adrenergic antagonists. Replacement of the naphthyloxy moiety of propranolol by a 1-[1-(4-n-butyl)-3-(4,4-dimethyloxazolin-2-yl)-1,4-dihydropyrid yl] group resulted in a significant decrease in cardiac beta 1-adrenergic antagonist activity which indicates that this group is not a suitable isostere for an aryloxy moiety. 1-(1-[4-n-Butyl-3-(4,4-dimethyloxazolin-2-yl)-1,4-dihydropyridy l])-3- isopropylamino-2-propanol (10) showed a modest beta 2-adrenergic antagonist selectivity for trachea (beta 2/beta 1 = 3:1).
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
D
D
Vo
M W
MW
Wolowyk
E E
EE
Knaus
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D004095:Dihydropyridines; D011412:Propanolamines