Abstract: The methylene group between the phenyl ring and the diaminopyrimidine ring of trimethoprim (TMP) was bioisosteristically displaced by thio or imino groups in order to study the rolein the inhibitory activity of the bridge moiety in the molecule of benzyl pyrimidines. The Hansch approach was used in the study of quantitative structure-activity relationships (QSAR). On the basis of QSAR studies the role of the bridge moiety in inhibiting Escherichia coli dihydrofolate reductase was discussed.

Key words: 5-Substituted-2, 4-diaminopyrimidine, Dihydrofolate reductase inhibitor, Quantita-tive structure-activity relationships (QSAR)