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

Article Details

Citation

Copy to clipboard

Mauleon D, Pujol MD, Rosell G

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

J Med Chem. 1988 Nov;31(11):2122-6.

PubMed ID

2903245 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Propranolol	Beta-1 adrenergic receptor	Kd (nM)	2.51	N/A	N/A	Details