STRUCTURE-BASED DRUG DESIGN OF NONPEPTIDIC P-2 SUBSTITUENTS FOR HIV-1PROTEASE INHIBITORS

The cocrystal structures of LY289612 and LY297135 were used as a start ing point in the design of nonpeptidic HIV-1 protease inhibitors. This report details the discovery of a series of novel aromatic P-2 replac ement groups. The 3-hydroxy-2-methyl benzoic acid group, discovered in AG1254, was incorporated into the hydroxyethyl amine series to produc e the potent antiviral compound (LY309391/AG1310).