Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues

Jacob M. Hoffman, Anthony M. Smith, Clarence S. Rooney, Thorsten E. Fisher, John S. Wai, Craig M. Thomas, Dona L. Bamberger, James L. Barnes, Theresa M. Williams, James H. Jones, Brandon D. Olson, Julie A. O'Brien, Mark E. Goldman, Jack H. Nunberg, Julio C. Quintero, William A. Schleif, Emilio A. Emini, Paul S. Anderson

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Abstract

A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalimido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H-one (9, L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by >95% in MT4 human T-lymphoid cell culture (CIC95 = 50–100 nM), was selected for clinical evaluation as an antiviral agent.

Original languageEnglish
Pages (from-to)953-966
Number of pages14
JournalJournal of Medicinal Chemistry
Volume36
Issue number8
DOIs
StatePublished - 1993

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