Lysine derivatives as potent HIV protease inhibitors. Discovery, synthesis and structure-activity relationship studies

A screening assay program carried out on commercially available N-protected amino acids showed that Nα-sulfonamide-Nε-Fmoc-l-lysine 9 displayed an 8.5 μM inhibition constant. Addition of an isobutyl group at the Nα-position allowed the discovery of the lead candidate 11 exhibiting a 5.0 nM Ki. The discovery, synthesis and SAR studies are described.