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.