Naphthalene carboxamides as inhibitors of human cytomegalovirus DNA polymerase

Bioorg Med Chem Lett. 2000 Sep 18;10(18):2079-81. doi: 10.1016/s0960-894x(00)00402-9.

Abstract

ortho-Hydroxynaphthalene carboxamides have been identified as inhibitors of HCMV DNA polymerase. SAR investigations have demonstrated that both the amide and hydroxy functionalities are required for activity. Substitution on the naphthalene ring has led to inhibitors with submicromolar IC50s against HCMV polymerase. These compounds have been found to be >100-fold selective for inhibition of HCMV polymerase versus human alpha polymerase and display antiviral activity in a cell-based plaque reduction assay.

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Cytomegalovirus / enzymology*
  • DNA Polymerase I / antagonists & inhibitors
  • DNA-Directed DNA Polymerase
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Naphthols / chemistry
  • Naphthols / pharmacology*
  • Nucleic Acid Synthesis Inhibitors* / chemistry
  • Nucleic Acid Synthesis Inhibitors* / pharmacology
  • Structure-Activity Relationship
  • Viral Proteins*

Substances

  • Amides
  • Enzyme Inhibitors
  • Naphthols
  • Nucleic Acid Synthesis Inhibitors
  • UL54 protein, Human herpesvirus 5
  • Viral Proteins
  • DNA Polymerase I
  • DNA-Directed DNA Polymerase