Correlation between affinity toward adrenergic receptors and approximate electrostatic potentials of phenylethylamine derivatives. 1. Effects of the side chain

The molecular electrostatic potential (VN) in the region of the nitrogen lone pair of a series of substituted propylamines is used in a correlation with the dissociation constants of parent phenylethylamine-type ligands obtained on beta-adrenoceptors by Bilezikian et al. It is shown that VN is a more effective index for quantitative structure-activity relationship studies than an optimal set of substituent constants used in additive, linear models. No significant correlation between the total electronic charge on the nitrogen and the binding potencies was obtained in the examined series. Protonation energies of the propylamines have been computed, but no meaningful correlation with the dissociation constants was obtained.