Model-based LFER parameters and QSAR of ligand-ß-adrenoceptor interactions. II. Estimation and QSAR of agonistic potency and receptor affinity in a series of ß-adrenergic phenethanolamines

Abstract

Based on an equil. model of ligand-b-adrenoceptor interactions and b-adrenergic effectuation presented in a preceding paper, LFER-related biol. parameters that characterize affinity for the receptor and agonistic potency, resp., are derived for a series of 44 phenethanolamines from measured apparent dissocn. consts. KL, and intrinsic activities aAC for adenylate cyclase activation. Hansch analyses lead to a clear sepn. of mol. features such as substituent positions and interaction types responsible for agonistic potency and affinity, resp. Thus, both parameters are proved to be of practical value, particularly as the resulting regression coeffs. in Hansch equations are directly related to energy contributions of basic interaction events.