Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4437-41. doi: 10.1016/j.bmcl.2007.06.012. Epub 2007 Jun 8.

Abstract

A series of aryl thiotetrazolylacetanilides were synthesized and found to be potent inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. The incorporation of an alkynyl fragment on the aniline provided inhibitors with excellent cellular activity and extensive SAR led to the identification of one inhibitor having good oral bioavailability in rats.

MeSH terms

  • Acetanilides / chemistry
  • Acetanilides / pharmacology*
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Biological Availability
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Models, Molecular
  • Molecular Structure
  • Mutation
  • Rats
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Acetanilides
  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase