Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor

Science. 1990 Dec 7;250(4986):1411-3. doi: 10.1126/science.1701568.


A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to deoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerases. BI-RG-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (greater than 8000) in culture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / physiology
  • Humans
  • Kinetics
  • Molecular Structure
  • Nevirapine
  • Nucleic Acid Synthesis Inhibitors
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology*
  • Reverse Transcriptase Inhibitors*
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Nucleic Acid Synthesis Inhibitors
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • Nevirapine