Studies on the Inhibition of Bovine Liver Dihydrofolate Reductase by Pyrimidine Compounds

CHIH-YUAN CHENG AND HUI-PO WANG*

School of Pharmacy, College of Medicine, National Taiwan University,Taipei, Taiwan,R.O.C.

ABSTRACT

   A series of 6-alkyl-2,4-diaminopyrimidines(compounds 1-5) and 6-methylamino-2,4-diaminopyrimidines (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 acitve showing comparable activity to that of methotrexate. The triaminopyrimidine analogues 6-12 were much less active, with IC50's ranged between 10-4~10-6M.

Key words : 6-Alkyl-2,4-diaminopyrimidines,6-Methylamino-2,4-diaminopyrimi-dines, Inhibition of dihydrofolate reductase, Folate antimetabolites