Small molecule inhibitors of HIV RT Ribonuclease H

Bioorg Med Chem Lett. 2010 Jan 1;20(1):398-402. doi: 10.1016/j.bmcl.2009.10.043. Epub 2009 Oct 15.

Abstract

Two classes of compounds, thiocarbamates 1 and triazoles 2, have been identified as HIV RT RNase H inhibitors using a novel FRET-based HTS assay. The potent analogs in each series exhibited selectivity and were active in cell-based assays. In addition, saturable, 1:1 stoichiometric binding to target was established and time of addition studies were consistent with inhibition of RT-mediated HIV replication.

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Fluorescence Resonance Energy Transfer
  • High-Throughput Screening Assays
  • Humans
  • Molecular Sequence Data
  • Ribonuclease H, Human Immunodeficiency Virus / antagonists & inhibitors*
  • Ribonuclease H, Human Immunodeficiency Virus / metabolism
  • Structure-Activity Relationship
  • Thiocarbamates / chemical synthesis
  • Thiocarbamates / chemistry*
  • Thiocarbamates / pharmacology
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Enzyme Inhibitors
  • Thiocarbamates
  • Triazoles
  • Ribonuclease H, Human Immunodeficiency Virus