Discovery of a novel series of inhibitors of human cytomegalovirus primase

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4879-83. doi: 10.1016/j.bmcl.2006.06.066. Epub 2006 Jun 30.

Abstract

Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Bone Marrow / drug effects
  • Cell Line
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / enzymology*
  • DNA Primase / antagonists & inhibitors*
  • DNA Primase / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Pyrimidines / chemistry
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Pyrimidines
  • DNA Primase
  • pyrimidine