New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors

J Med Chem. 2012 Jul 26;55(14):6634-8. doi: 10.1021/jm300477h. Epub 2012 Jul 6.

Abstract

New indolylarylsulfone (IAS) derivatives bearing nitrogen containing substituents at the indole-2-carboxamide inhibited the HIV-1 WT in MT-4 cells at low nanomolar concentrations. In particular, compound 9 was uniformly effective against the mutant Y181C, Y188L, and K103N HIV-1 strains; it was highly active against the multidrug resistant mutant IRLL98 HIV-1 strain bearing the K101Q, Y181C, and G190A mutations conferring resistance to NVP, DLV, and EFV and several HIV-1 clades A in PBMC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Indoles / chemistry*
  • Mutation
  • Nitrogen / chemistry*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Sulfones / chemistry*
  • Sulfones / pharmacology*

Substances

  • Indoles
  • Reverse Transcriptase Inhibitors
  • Sulfones
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Nitrogen