Synthesis and evaluation of 6-(dibromomethyl)-5-nitropyrimidines as potential antitumor agents.

A series of 2,4,6-trisubstituted-5-nitropyrimidines have been prepared and evaluated for inhibition of proliferation of L1210 and H.Ep.2 cells in vitro. The most potent compound was 6-(dibromomethyl)-2-methoxy-4-morpholino-5-nitropyrimidine (11) (L1210, IC50 = 0.32 microM; H.Ep.2, IC50 = 1.6 microM). Of the 6-substituents incorporated, only CHBr2, CH2Br, and CHO were compatible with antiproliferative activity, while a wider variety of 4-substituents were tolerated. At concentrations near the IC50 for antiproliferative activity, a delayed resumption of cell proliferation in L1210 cultures indicated that the activity of the compounds was short-lived and suggested they might act by an alkylation mechanism.