Non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis and biological evaluation of novel quinoxalinylethylpyridylthioureas as potent antiviral agents

Antivir Chem Chemother. 2000 Mar;11(2):141-55. doi: 10.1177/095632020001100206.


New heterocyclic derivatives of ethylpyridylthiourea, quinoxalinylethylpyridylthiourea (QXPT) and analogues, inhibited human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and prevented HIV-1 cytopathogenicity in T4 lymphocytes. Several of these novel non-nucleoside RT inhibitors, with a substituted pyrroloquinoxalinone heteroaromatic skeleton, showed inhibitory activity against wild-type RT as well as against mutant RTs containing the single amino acid substitutions L1001, K103N, V106A, Y1811 and Y188L that was much greater than other non-nucleoside inhibitors such as nevirapine. Maximum potency in enzymatic assays was achieved with a fluoropyrroloquinoxaline skeleton linked to the ethylpyridylthiourea moiety (FQXPT). In cell-based assays on different cell lines and on human monocyte-macrophages, 6-FQXPT exhibited EC50 values in the nanomolar range, with a promising selectivity index. Moreover, 6-FQXPT showed synergistic antiviral activity with zidovudine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mutation
  • Nucleosides / chemistry
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Thiourea / analogs & derivatives*
  • Thiourea / chemical synthesis
  • Thiourea / pharmacology


  • N-(2-(6-fluoro-4-oxopyrrolo(1,2-a)quinoxalin-5-yl)ethyl)-N'-(2-(5-bromopyridyl))thiourea
  • Nucleosides
  • Quinoxalines
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • Thiourea