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Background:   In continuation of our search for new anti-HIV and anti-HCV agents, the suggestion, synthesis and structure elucidation of a new series of 2,6-diamino-4-alkylthio- or (2-benzylhydrazinyl)-5- p-chlorophenylazopyrimidines), 2,6-diamino-4-(2-benzylhydrazinyl)-5-(aryl-[1,1′-biphenyl]-4-yl)pyrimidines, 2,6-diamino-4-(aryl)-5-(aryl[1,1′-biphenyl]-4-yl) pyrimidines), 6-(aryl)-1,3-dimethyl-5-nitro pyrimidine-2,4-dione and 6-amino-4-methoxy- N,N-dimethyl-6-arylpyrimidines were described.Methods:   The anti-HIV-1 (strain III B ) and HIV-2 (strain ROD) activity of the newly synthesized pyrimidine analogues was evaluated in vitro in human MT-4 cells using the MT-4/MTT assay. Similarly, the same compounds were evaluated in vitro for their selective antiviral activity against HCV in the Huh 5–2 replicon system (type 1b, Con1 strain).Results:   None of the tested compounds exhibited inhibition of HIV-1 and HIV-2 replication in cell culture. Even though many compounds yielded a 50% effective concentration in the HCV replicon system with selectivity indexes up to 6.9, none of the compounds matched the selection criteria of a selective inhibitor of virus replication in this assay (that is, &gt;70% inhibition at concentrations that do not elicit an anti-metabolic effect on the host cells).Conclusions:   Structural modification of these compounds might optimize their anti-HCV activity by introducing diverse and potent functional groups at the pyrimidine backbone, like nitrile residue. Because of the nature of the molecules, these new derivatives will also be evaluated for their potential anti-HIV activity.

Exploration of the in vitro Antiviral Activity of a Series of New Pyrimidine Analogues on the Replication of HIV and HCV