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 ANALOGS

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 III(B). 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 III(B) infection by >95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent.