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Science 7 December 1990:
Vol. 250. no. 4986, pp. 1411 - 1413
DOI: 10.1126/science.1701568
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Articles
Science, Vol 250, Issue 4986, 1411-1413
Copyright © 1990 by American Association for the Advancement of Science
Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor
VJ Merluzzi,
KD Hargrave,
M Labadia,
K Grozinger,
M Skoog,
JC Wu,
CK Shih,
K Eckner,
S Hattox,
J Adams,
and
al. et
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
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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