Trifluoromethyl-Containing 3-Alkoxymethyl- and 3-Aryloxymethyl-2-pyridinones Are Potent Inhibitors of HIV-1 Non-Nucleoside Reverse Transcriptase.

Abstract 3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1. It was found that several compounds were potent inhibitors of HIV-1 with the most potent compound 24 exhibiting an IC90=32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC90s against several clinically meaningful mutant virus strains.