title: Disubstituted Bis-THF Moieties as New P2 Ligands in Nonpeptidal HIV-1 Protease Inhibitors.
abstract: A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. 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. A number of PIs have been synthesized that show equivalent and greater activity for HIV-1 mutant strains as compared to wild-type HIV-1. The activity on the purified enzyme was confirmed for a selection of analogues.
authors.affiliation: School of Chemistry, University of Southampton , Highfield, Southampton SO17 1BJ, United Kingdom.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hohlfeld
authors.affiliation: School of Chemistry, University of Southampton , Highfield, Southampton SO17 1BJ, United Kingdom.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Tomassi
authors.affiliation: Tibotec , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Jörg Kurt
authors.initials: JK
authors.lastname: Wegner
authors.affiliation: Tibotec , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Kesteleyn
authors.affiliation: School of Chemistry, University of Southampton , Highfield, Southampton SO17 1BJ, United Kingdom.
authors.forename: Bruno
authors.initials: B
authors.lastname: Linclau
keywords: HIV protease; bis-THF bis-diol; darunavir; inhibitors