Abstract: The synthesis of a series of 2,4-diamino-5-substituted amino pyrimidines and 2,4-diamino-5-substituted amino pyrimidines were carried out by condensation of 2,4,5-triaminopyrimidines or 2,4,5-triamino-6-methyl pyrimidines with substituted benzaldehydes to form the corresponding Schiff' bases, followed by hydrogenation, nitrosation or formylation.Using plasmodium yoelii-Anopheles stephensi system, these compounds were primarily screened for their causal prophylactic activities against the parasites. Out of these compounds 12 were found to possess antimalarial effect of varying degrees. Two of them,2,4-diamino-5-(3′,4-dichloro-benzlidene amino)pyrimidine (compound Ⅴ₃) and 2,4-diamino-5-(4′-bromo-benzyl)-N-nitroso-amino pyrimidine (compound Ⅶ₄) administered orally at a dose of 10 mg/kg in 3 consecutive days (D₀～D₂) were more effective than the remaining ten, as shown by the protection of the tested mice from being infected.