CoMFA analysis of the human β1-adrenoceptor binding affinity of a series of phenoxypropanolamines

Abstract

A series of 36 phenoxypropanolamines was examined to determine the structure-activity relationships of β-adrenoceptor (β-AR) antagonists for the human β1-AR. The binding affinities of all the compounds were determined for human β1-ARs expressed in Chinese hamster ovary cells and the antagonist potency for rat atrial β1-ARs was determined for 32 of these compounds for comparative purposes. The compounds, based upon a phenoxypropanolamine core structure with various meta-, ortho-, para- and amine-substituents, displayed binding affinities (pKi) for the human β1-AR ranging from 5.49 to 9.35. Antagonist potencies (pA2) in the rat ranged from 5.52 to 9.56 and correlated with the human binding aff..