4-Hydroxy-5,6-dihydro-2H-pyran-2-ones. 3. Bicyclic and heteroaromatic ringsystems as 3-position scaffolds to bind to S-1 ' and S-2 ' of the HIV-1 protease enzyme.

5,6-Dihydro-2H-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. Effo rts 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 H IV-1 protease inhibitory activity, (C) 1999 Elsevier Science Ltd. All right s reserved.