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

  • Science. 1990 Dec 7;250(4986):1411-3. doi: 10.1126/science.1701568.
V J Merluzzi  1 ,  K D Hargrave ,  M Labadia ,  K Grozinger ,  M Skoog ,  J C Wu ,  C K Shih ,  K Eckner ,  S Hattox ,  J Adams, et al.
Affiliations
  • 1. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
PMID: 1701568 DOI: 10.1126/science.1701568
Abstract

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.

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