Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase

3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-I. It was found that several compounds were potent inhibitors of HIV-I with the most potent compound 24 exhibiting an IC90 = 32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC(90)s against several clinically meaningful mutant virus strains. (C) 2001 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.