2. Academic Validation
  3. Disubstituted Bis-THF Moieties as New P2 Ligands in Nonpeptidal HIV-1 Protease Inhibitors

Disubstituted Bis-THF Moieties as New P2 Ligands in Nonpeptidal HIV-1 Protease Inhibitors

  • ACS Med Chem Lett. 2011 Mar 31;2(6):461-5. doi: 10.1021/ml2000356.
Konrad Hohlfeld 1,  Cyrille Tomassi 1,  Jörg Kurt Wegner 2,  Bart Kesteleyn 2,  Bruno Linclau 1
Affiliations

Affiliations

  • 1 School of Chemistry, University of Southampton , Highfield, Southampton SO17 1BJ, United Kingdom.
  • 2 Tibotec , Turnhoutseweg 30, 2340 Beerse, Belgium.
PMID: 24900331 DOI: 10.1021/ml2000356
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.

Keywords

HIV protease; bis-THF bis-diol; darunavir; inhibitors.

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