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

Abstract 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 EC 50 value at 1.7 μM with a therapeutic index of 46.