Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P-3 ligands

The 2-isopropyl thiazolyl group is a highly optimized P-3 ligand for C-2 sy mmetry-based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we report that incorporation of this P-3 ligand into a piperazine hyd roxyethylamine series also yielded novel, highly potent inhibitors. In tiss ue culture assays, the presence of human serum was less deleterious to the activity of these inhibitors than to that of ritonavir. Furthermore, potent activity against ritonavir resistant HIV was observed. (C) 1998 Elsevier S cience Ltd. All rights reserved.