1. Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC.
- Author
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Rose Y, Ciblat S, Reddy R, Belley AC, Dietrich E, Lehoux D, McKay GA, Poirier H, Far AR, and Delorme D
- Subjects
- Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Microbial Sensitivity Tests, Molecular Structure, Pyrimidinones chemical synthesis, Pyrimidinones chemistry, Staphylococcus aureus drug effects, Structure-Activity Relationship, DNA Polymerase III antagonists & inhibitors, Enzyme Inhibitors pharmacology, Pyrimidinones pharmacology, Staphylococcus aureus enzymology
- Abstract
The preparation and biological evaluation of 5-substituted-6-hydroxy-2-(anilino)pyrimidinones as a new class of DNA polymerase IIIC inhibitors, required for the replication of chromosomal DNA in Gram-positive bacteria, are described. These new dGTP competitive inhibitors displayed good levels of in vitro inhibition and antibacterial activity against Staphylococcus aureus. A new class of dATP competitive inhibitors, 6-substituted-2-amino-5-alkyl-pyrimidin-4-ones, whose antibacterial activity was unaffected by serum, were identified.
- Published
- 2006
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