Synthesis and beta-adrenergic antagonist activity of novel (3-cyanodihydropyridyl)propanolamines.
The synthesis and beta-adrenergic antagonist activities of 1-(1-dihydropyridyl)-3-alkylamino-2-propanols (9-16) in which the aryloxy group of aryloxypropanolamines (1) is replaced by a 1-[2-t-(n-)butyl-3-cyano-1,2-dihydropyridyl] (9-12) or 1-[6-t-(n-)butyl-3-cyano-1,6-dihydropyridyl] (13-16) moiety is described. These replacements resulted in a substantial reduction in beta 1 (atria) and beta 2 (trachea) adrenergic antagonist activities relative to the reference drug metoprolol. Structure-activity correlations indicate the relative potency order is 1,2-dihydropyridyl greater than 1,6-dihydropyridyl, n-Bu greater than t-Bu for dihydropyridyl substituents, and that this class of compounds are non-selective beta-antagonists with a beta 1/beta 2 selectivity ratio close to unity.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
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D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines