Discovery and SAR of a series of 4,6-diamino-1,3,5-triazin-2-ol as novel non-nucleoside reverse transcriptase inhibitors of HIV-1

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6592-6. doi: 10.1016/j.bmcl.2010.09.034. Epub 2010 Sep 21.

Abstract

The discovery and SAR study of a series of 4,6-diamino-1,3,5-triazin-2-ol compounds as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are reported. The lead compounds in this series showed excellent activity against wild-type and drug-resistant RT enzymes and viral strains. In addition, compounds from this series demonstrated favorable pharmacokinetic profile in rat. A preliminary modeling study was conducted to understand the binding mode of this series of compounds.

MeSH terms

  • Animals
  • Drug Discovery*
  • Models, Molecular
  • Rats
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Triazines / chemical synthesis*
  • Triazines / pharmacology*

Substances

  • Reverse Transcriptase Inhibitors
  • Triazines