Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity

J Med Chem. 2007 Oct 4;50(20):5034-8. doi: 10.1021/jm070488f. Epub 2007 Sep 6.

Abstract

Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. These compounds were highly effective against the 112 and the AB1 strains in lymphocytes and inhibited at nanomolar concentration the multiplication of the IIIBBa-L strain in macrophages. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Drug Resistance, Viral
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Lymphocytes / drug effects
  • Lymphocytes / virology
  • Macrophages / drug effects
  • Macrophages / virology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacology

Substances

  • Indoles
  • Reverse Transcriptase Inhibitors
  • Sulfones
  • HIV Reverse Transcriptase