Discovery of small-molecule inhibitors of the ATPase activity of human papillomavirus E1 helicase

J Med Chem. 2004 Jan 1;47(1):18-21. doi: 10.1021/jm034206x.

Abstract

The Boehringer Ingelheim compound collection was screened for inhibitors of the ATPase activity of human papillomavirus E1 helicase to develop antiviral agents that inhibit human papillomavirus (HPV) DNA replication. This screen led to the discovery of (biphenyl-4-sulfonyl)acetic acid 1, which inhibits the ATPase activity of HPV type 6 E1 helicase with a low micromolar IC(50) value. A hit-to-lead exercise rapidly converted 1 into a low nanomolar lead series.

MeSH terms

  • Acetates / chemical synthesis*
  • Acetates / chemistry
  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Adenosine Triphosphatases / chemistry
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry
  • Humans
  • Oncogene Proteins, Viral / antagonists & inhibitors*
  • Oncogene Proteins, Viral / chemistry
  • Papillomaviridae / enzymology*
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry

Substances

  • Acetates
  • Antiviral Agents
  • Biphenyl Compounds
  • E1 protein, Human papillomavirus type 6
  • Oncogene Proteins, Viral
  • Sulfones
  • Adenosine Triphosphatases