Nonnucleoside HIV-1 reverse-transcriptase inhibitors, part 5.1) synthesis and anti-HIV-1 activity of novel 6-naphthylthio HEPT analogues

Abstract

As part of a series of studies to discover new HIV reverse-transcriptase inhibitors, various novel 6 α- and 6 β-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 6α-naphthylthio HEPT derivatives (7a - w) showed good activity [for 7e, IC50 value of 0.048 μM and selectivity index (SI) value of 735; for 7h, IC50 value of 0.057 μM and SI value of 579; for 7k, IC50 value of 0.063 μM and SI value of 565], 6 β-naphthylthio HEPT derivatives (8a - f) showed low activity, but the introduction of α nitro group to the C-1 position of the 6 β-naphthyl ring in the 6 β-naphthylthio series (11a - c) resulted in a dramatic increase in anti-HIV-1 activity. © 2005 Pharmaceutical Society of Japan.