Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC

Bioorg Med Chem Lett. 2006 Feb 15;16(4):891-6. doi: 10.1016/j.bmcl.2005.11.009. Epub 2005 Nov 17.


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.

MeSH terms

  • DNA Polymerase III / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / enzymology*
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Pyrimidinones
  • DNA Polymerase III