Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the &-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as PZ ligands for HIV-1 protease inhibitors. Subsequently, we have found that the urethane of 3 (S)-hydroxysulfolane further increased the in uitro potency of these inhibitors. Furthermore, introduction of a small 2- ...
