Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations

J Med Chem. 2004 Jul 15;47(15):3892-6. doi: 10.1021/jm031147e.

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) active against NNRTI-resistant mutants were obtained by introducing two methyl groups at positions 3 and 5 of the benzenesulfonyl moiety of L-737,126 (1) and coupling one to three glycinamide/alaninamide units to its carboxyamide function. In cell-based assays, the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant mutants [Y181C, K103N-Y181C, and triple mutant (K103R, V179D, P225H) highly resistant to efavirenz] superior to that of the parent indole derivative 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Drug Resistance, Viral
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Indoles / toxicity
  • Mutation
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Reverse Transcriptase Inhibitors / toxicity
  • Sulfones / chemical synthesis
  • Sulfones / pharmacology*
  • Sulfones / toxicity

Substances

  • 3-benzenesulfonyl-5-chloroindole-2-carboxamide
  • Anti-HIV Agents
  • Indoles
  • Reverse Transcriptase Inhibitors
  • Sulfones