Inhibition of chlorphentermine binding in rat lung: Application of connectivity theory

Abstract

Using the recently developed theory of molecular connectivity, the structural requirements of compounds inhibiting the binding of chlorphentermine in rat lung were examined. Only two indices, 4χ p ν and 7χ p ν , were necessary to adequately describe the activity of the set of compounds considered. Further analysis of the factors determining the values of the indices revealed that the magnitude of each index was directly related to the number of pathways and inversely related to the atomic valencies constituting the indices. The relative number of pathways was found to be a function of the degree of cyclisation and substitution on or near the cyclic substructures. The effect of atomic valencies on index values was conveniently examined by introducing an ‘average valence’ term i δ p ν . It was concluded firstly that inhibition of chlorphentermine binding in rat lung was greatest for multicyclic compounds with low valence atoms substituted on or near the ring substructures, and secondly that the ability of the connectivity theory to define the activity of a relatively non-homogeneous data set indicates its potential in quantitative structure-activity studies.