Evaluation of furofuran as a P2 ligand for symmetry-based HIV protease inhibitors

The hexahydrofurofuranyloxy group was evaluated as a conformationally constrained P 2 ligand for symmetry-based HIV protease inhibitors. A number of compounds showed nM level activity against HIV in MT4 cells and lower protein binding than the licensed protease inhibitor ritonavir. However, replacement of 5-thiazole of ritonavir with a furofuran caused a reduction of the bioavailability in vivo.