Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted-benzyl)-2,4-diaminopyrimidines

Abstract

In a previous publication, correlation equations were presented for the inhibition of bovine liver and E. coli dihydrofolate reductase (DHFR) by 5-(substituted benzyl)-2,4-diaminopyrimidines. These equations showed differences in the way the 2 enzymes interact with substituents, which explain the high selectivity of drugs like trimethoprim. The equations were tested and further developed. The previously published correlation equation for E. coli DHFR accurately predicted the potency of a commercial competitor of trimethoprim (tetroxoprim) now in clinical use. New and effective competitors for trimethoprim can be designed using the 2 correlation equations.