SYNTHESIS AND EVALUATION OF 2-PYRIDINONE DERIVATIVES AS HIV-1-SPECIFIC REVERSE-TRANSCRIPTASE INHIBITORS .2. ANALOGS OF 3-AMINOPYRIDIN-2(1H)-ONE

A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC.dG as template.primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methylpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.