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 alpha-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 microM with a therapeutic index of 46.
Sun
Chun-Lai
CL
National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, People's Republic of China.
Pang
Rui-Fang
RF
Zhang
Hang
H
Yang
Ming
M
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011753:Pyrones / Q000138:chemical synthesis*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D013329:Structure-Activity Relationship
D017320:HIV Protease Inhibitors; D011753:Pyrones