Studies on the inhibition of bovine liver dihydrofolate reductase by pyrimidine compounds

Abstract

A series of 6-alkyl-2,4-diaminopyrimidines (compounds 1-5) and 6-methylamino-2,4-diaminopyimidines (compounds 6-12), prepared as nonclassical folate antimetabolites, were subjected to inhibition study on bovine liver dihydrofolate reductase. The 2,4-diaminopyrimidine compounds showed IC50's at 10-7-10-9M, with compound 5 as the most active showing comparable activity to that of methotrexate. The triaminopyrimidine analogues 6-12 were much less active, with IC50's ranged between 10-4-10-6 M.