Nonnucleoside HIV-1 reverse-transcriptase inhibitors, part 5. Synthesis and anti-HIV-1 activity of novel 6-naphthylthio HEPT analogues

Chem Pharm Bull (Tokyo). 2005 Aug;53(8):886-92. doi: 10.1248/cpb.53.886.


As part of a series of studies to discover new HIV reverse-transcriptase inhibitors, various novel 6alpha- and 6beta-naphthylthio 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio) thymine (HEPT) derivatives were synthesized, and in vitro anti-HIV-1 activity was evaluated. The results revealed that most of 6alpha-naphthylthio HEPT derivatives (7a-w) showed good activity [for 7e, IC50 value of 0.048 microM and selectivity index (SI) value of 735; for 7h, IC50 value of 0.057 microM and SI value of 579; for 7k, IC50 value of 0.063 microM and SI value of 565], 6beta-naphthylthio HEPT derivatives (8a-f) showed low activity, but the introduction of alpha nitro group to the C-1 position of the 6beta-naphthyl ring in the 6beta-naphthylthio series (11a-c) resulted in a dramatic increase in anti-HIV-1 activity.

MeSH terms

  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Spectrophotometry, Infrared
  • Thymine / analogs & derivatives*
  • Thymine / chemical synthesis
  • Thymine / pharmacology


  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • Thymine