Synthesis and beta-adrenergic antagonism of 2-(aryloxy)-1-(2-piperidyl)ethanols.
A series of erythro- and threo-2-(aryloxy)-1-(2-piperidyl)ethanol derivatives (3) was synthesized from 2-(2-oxiranyl)pyridine for evaluation as beta-antagonists. Most compounds displayed high competitive beta-blocking potency, but they lacked significant beta 1/beta 2 selectivity. The 1-naphthoxy derivative erythro-3b was 17 (beta 1) and 33 (beta 2) times more potent than its open-chain analogue, propranolol. Within the whole series, erythro-3 diastereomers were more potent beta-blockers than the threo-3 isomers, and the potency of the latter seems to be rather insensitive to structural modification. The effect of N-methylation and of interposition of an alkyl chain between the aromatic ring and the side chain, while being detrimental to beta-blocking activity, was less marked than in the classic (aryloxy)propanolamine blockers.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000478:Alkylation; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007536:Isomerism; D008745:Methylation; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D010880:Piperidines