Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4174-7. doi: 10.1016/j.bmcl.2006.05.096. Epub 2006 Jun 14.

Abstract

A novel sulfanyltriazole was discovered as an HIV-1 non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay. Chemical modifications and molecular modeling studies were carried out to establish its SAR and understand its interactions with the enzyme. These modifications led to the identification of sulfanyltriazoles with low nanomolar potency for inhibiting HIV-1 replication and promising activities against selected NNRTI resistant mutants. These novel and potent sulfanyltriazoles could serve as advanced leads for further optimization.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Drug Resistance, Viral
  • Enzyme Inhibitors / pharmacology
  • HIV-1 / metabolism*
  • Inhibitory Concentration 50
  • Models, Chemical
  • Models, Molecular
  • Mutation
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Sulfur Compounds / chemistry
  • Temperature
  • Triazoles / chemistry*
  • Virus Replication

Substances

  • Anti-HIV Agents
  • Enzyme Inhibitors
  • Reverse Transcriptase Inhibitors
  • Sulfur Compounds
  • Triazoles