A series of 2-amino-5-bromo-4(3H)-pyrimidinone derivatives bearing different substituents at the C-6 position were synthesized using a highly regioselective lithiation-substitution protocol, and the effect of structural variation at the C-6 position on their antiviral activity in cell culture was evaluated. Although some of the derivatives were found to be active against various virus strains, they were effective only close to their toxicity threshold.