title: 2-Substituted-4,5-dihydroxypyrimidine-6-carboxamide antiviral targeted libraries.
abstract: 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.
authors.affiliation: Department of Chemical Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Boyd
authors.forename: John
authors.initials: J
authors.lastname: Mason
authors.forename: Parimala
authors.initials: P
authors.lastname: Hanumesh
authors.forename: Jeanine
authors.initials: J
authors.lastname: Price
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Russell
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Webb
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D011743:Pyrimidines; D054852:Small Molecule Libraries