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 cel ls in vitro. The most potent compound was momethyl)-2-methoxy-4-morpho lino-5-nitropyrimidine (11) (L1210, IC50 0.32 mu M; H.Ep.2, IC50 = 1.6 mu M). Of the 6-substituents incorporated, only CHBr2, CH2Br, and CHO were compatible with antiproliferative activity, while a wider variet y of 4-substituents were tolerated. At concentrations near the IC50 fo r antiproliferative activity, a delayed resumption of cell proliferati on in L1210 cultures indicated that the activity of the compounds was short-lived and suggested they might act by an alkylation mechanism.