4-Hydroxy-5,6-Dihydro-2 H-pyran-2-ones. 3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S 1′ and S 2′ of the HIV-1 protease enzyme

Abstract

5,6-Dihydro-2 H-pyran-2-ones are potent inhibitors of HIV-1 protease, which bind to the S 1, S 2, S 1′, and S 2′ pockets and have a unique binding mode with the catalytic aspartyl groups and the flap region of the enzyme. Efforts to explore 3-position heterocyclic scaffolds that bind to the S 1′ and S 2′ pockets have provided a number of selected analogs that display high HIV-1 protease inhibitory activity.