National Center for
5AHA: Disubstituted bis-THF moieties as new P2 ligands in non-peptidal HIV- 1 Protease Inhibitors (II)
J. Med. Chem. (2015) 58 p.4029-4038
A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. Very high affinity protease inhibitors (PIs) with an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1 mutants containing clinically observed, primary mutations were identified using a cell-based assay. Crystal structure analysis was conducted on a number of PI analogues in complex with HIV-1 protease.