L-696,229 specifically inhibits human immunodeficiency virus type 1 reverse transcriptase and possesses antiviral activity in vitro

M. E. Goldman, J. A. O'Brien, T. L. Ruffing, J. H. Nunberg, W. A. Schleif, J. C. Quintero, P. K.S. Siegl, J. M. Hoffman, A. M. Smith, E. A. Emini

Research output: Contribution to journalArticlepeer-review

Abstract

L-696,229 {3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-pyridin-2(1H)- one} is a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity that possesses antiviral activity in cell culture (W. S. Saari, J. M. Hoffman, J. S. Wai, T. E. Fisher, C. S. Rooney, A. M. Smith, C. M. Thomas, M. E. Goldman, J. A. O'Brien, J. H. Nunberg, J. C. Quintero, W. A. Schleif, E. A. Emini, and P. S. Anderson, J. Med. Chem. 34:2922-2925, 1991). In the present study, the RT-inhibitory activity and antiviral properties were characterized in detail. The inhibition of RT activity was template-primer dependent with 50% inhibitory concentrations of 0.018 to 0.50 μM and was noncompetitive with respect to deoxynucleoside triphosphates. L-696,229 inhibited RT activity in a mutually exclusive manner with respect to either phosphonoformate or azidothymidine triphosphate and was a weak partial inhibitor of the RNase H activity associated with HIV-1 RT. The compound did not significantly inhibit other retroviral or cellular polymerases at 300 μM. L-696,229 inhibited the spread of HIV-1 infection in cell cultures with all cell types and viral isolates tested, including human peripheral blood mononuclear cells and a virus isolate resistant to azidothymidine.

Original languageEnglish
Pages (from-to)1019-1023
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume36
Issue number5
DOIs
StatePublished - 1992

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