A theorem on de novo group contributions.
A theorem has been proved stating that the correlation coefficient calculated between two types of pharmacological potencies of series of compounds may be approximated by calculating the weighted correlation coefficient between the corresponding sets of Free-Wilsonian (de novo) group contributions. Comparison of activities of series with no common derivatives is also possible. De novo substituent constants also depend on other groups, if these emerge at the same substitution site. A simple method has been developed in order to take into account this interdependence. De novo substituent constants extracted from pharmacological potencies of phenylethylamine derivatives have been collected. Moderate but significant correlations have been demonstrated between sets of de novo substituent constants related to inhibition of uptake1, uptake2, phenyl-N-methyltransferase (PNMT), and of the pressor activity of epinephrine as well as for those extracted from potencies of substrates of PNMT. The method was compared with Zahradnik's approach. It was concluded that the existing moderate correlations between de novo group contributions are due to similar nonspecific drug-receptor interactions or transport processes.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008962:Models, Theoretical; D010627:Phenethylamines / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010627:Phenethylamines