2-Substituted-4,5-dihydroxypyrimidine-6-carboxamide antiviral targeted libraries

To identify novel potentially broad spectrum antiviral compounds against RNA viruses, we have developed the parallel synthesis of a structurally interesting class of 2-substituted-4,5-dihydroxypyrimidine-6-carboxamides. Variously 2-substituted-4,5-dihydroxypyrimidine-6-carboxylate methyl esters were initially prepared and were then diversified via a facile amidation reaction. This strategy affords libraries of thousands of diverse drug-like compounds for screening. Biological evaluation of a set of these compounds, via a small initial screen, identified antiviral compounds against a representative RNA virus (Sendai virus, a paramyxovirus). We provide details on the synthetic protocols and the in vitro antiviral activity studies, as part of our initial investigation of the resulting targeted libraries.