Novel open-ring analogues of N5,N10-methylenetetrahydrofolic acid with selective activity against brain tumor

A series of 5-(4-substituted-1-piperazinyl)pyrimidines were synthesized as open-ring analogues of N5,N10-methylene-tetrahydrofolic acid. Compounds 6, 7, 8, 9 and 11 showed selective cytotoxicity on SNB75 human CNS cancer cell line with growth inhibition (GI50) ranged from 1.39 × 10−7 M to less than 10−8 M.