HIV integrase inhibitors with nucleobase scaffolds: Discovery of a highly potent anti-HIV agent

Abstract

HIV integrase is essential for HIV replication. However, there are currently no integrase inhibitors in clinical use for AIDS. We have discovered a conceptually new β-diketo acid that is a powerful inhibitor of both the 3′-processing and strand transfer steps of HIV-1 integrase. The in vitro anti-HIV data of this inhibitor were remarkable as exemplified by its highly potent antiviral therapeutic efficacy against HIVTEKI and HIV-1 NL4-3 replication in PBMC (TI >4,000 and >10,000, respectively). © 2006 American Chemical Society.