Design, synthesis, and biological evaluation of novel 4-hydroxypyrone derivatives as HIV-1 protease inhibitors

Twenty-four 4-hydroxypyrone derivatives were synthesized with a facile synthetic method to develop novel HIV protease inhibitors. Most of them were shown to display good antiviral activities in SIV-infected CEM cells. The introduction of α-naphthylmethyl group to C-6 of 5,6-dihydropyran-2-ones led to an effective antiviral compound that showed an EC50 value at 1.7 μM with a therapeutic index of 46.

Graphical abstractSynthesis and biological evaluation of 24 4-hydroxypyrone derivatives are described. Compound 4C was the most potent inhibitor in this study, with an EC50 value at 1.7 μM and a therapeutic index of 46.Figure optionsDownload full-size imageDownload as PowerPoint slide