Synthesis and .beta.-adrenergic antagonism of 2-(aryloxy)-1-(2-piperidyl)ethanols

Abstract

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.