title: BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine.
abstract: A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. The lead compound, BI-RG-587, had a 50% inhibitory concentration of 84 nM against HIV-1 reverse transcriptase activity. This compound reduced plaque formation of HIV-1 in HeLa cells expressing the CD4 receptor by 50% at 15 nM. BI-RG-587 at comparable concentrations inhibited the production of p24 antigen following the acute infection of CEM T-lymphoblastoid cells or primary human monocyte-derived macrophages with HIV-1. No inhibitory effects against HIV-2 or against three picornaviruses were detected. Zidovudine (3'-azido-3'-deoxythymidine [AZT])-susceptible and AZT-resistant isolates of HIV-1 were equally susceptible to BI-RG-587. AZT and BI-RG-587 exhibited synergistic inhibition of HIV-1BRU at all concentrations examined.
authors.affiliation: University of California, San Diego 92161.
authors.forename: D
authors.initials: D
authors.lastname: Richman
authors.forename: A S
authors.initials: AS
authors.lastname: Rosenthal
authors.forename: M
authors.initials: M
authors.lastname: Skoog
authors.forename: R J
authors.initials: RJ
authors.lastname: Eckner
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: J P
authors.initials: JP
authors.lastname: Sabo
authors.forename: V J
authors.initials: VJ
authors.lastname: Merluzzi
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D019829:Nevirapine; D010849:Picornaviridae / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D013601:T-Lymphocytes / Q000187:drug effects; D010948:Viral Plaque Assay; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine