4-Hydroxy-5,6-dihydro-2H-pyran-2-ones. 3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S1' and S1' of the HIV-1 protease enzyme

Article abstract of DOI:10.1016/S0960-894X(99)00332-7

56-Dihydro-2H-pyran-2-ones are potent inhibitors of HIV-1 protease which bind to the S₁ S₂ S₁' S₂' pockets have a unique binding mode with the catalytic aspartyl groups the flap region of the enzyme. Efforts to explore 3-position heterocyclic scaffolds that bind to the S₁' S₂' pockets have provided a number of selected analogs that display high HIV-1 protease inhibitory activity.