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.
Boyd
Vincent A
VA
Department of Chemical Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Mason
John
J
Hanumesh
Parimala
P
Price
Jeanine
J
Russell
Charles J
CJ
Webb
Thomas R
TR
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D029082:Sendai virus / Q000187:drug effects*; D054852:Small Molecule Libraries; D013237:Stereoisomerism
D000998:Antiviral Agents; D011743:Pyrimidines; D054852:Small Molecule Libraries