Synthesis of Potent C 2-Symmetric, Diol-Based HIV-1 Protease Inhibitors. Investigation of Thioalkyl and Thioaryl P1/P1‘ Substituents

The synthesis of novel, potent diol-based HIV-1 protease inhibitors, having either -SAr, -SCH2Ar, or -SCH2R groups as P1/P1‘ substituents is described. They can be prepared using a straightforward synthesis involving a thiol nucleophilic ring opening of a diepoxide. Inhibitor 13 was found to be a potent inhibitor of HIV-1 PR, showing good antiviral activity in a cell-based assay.