Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1

J Med Chem. 2004 Feb 26;47(5):1175-82. doi: 10.1021/jm030255y.

Abstract

GW4511, GW4751, and GW3011 showed IC50 values < or =2 nM against wild type HIV-1 and <10 nM against 16 mutants. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. The antiviral data together with the favorable pharmacokinetic data of GW4511 suggested that these benzophenones possess attributes of a new NNRTI drug candidate.

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Benzophenones / chemical synthesis*
  • Benzophenones / chemistry
  • Benzophenones / pharmacology
  • Cell Line
  • Crystallography, X-Ray
  • Drug Resistance, Viral
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Inhibitory Concentration 50
  • Mutation
  • Protein Binding
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Benzophenones
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase