α-hydroxyamide derived aminodiols as potent inhibitors of hiv protease

Abstract A novel series of HIV protease inhibitors has been prepared. Replacement of the P 2 carbamate of compound 1 [IC 50 = 125 nM] with an α-hydroxy amide moiety results in a significant increase in anti-HIV protease activity [e. g., compound 25a ; IC 50 = 15 nM]. Furthermore, isomers with (R) absolute configuration at the P 2 site show greater inhibitory activity than the corresponding (S)-isomers. A proposed binding mode based on molecular modeling is used to rationalize the structure-activity relationships.