Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV

Bioorg Med Chem. 2007 Dec 15;15(24):7576-80. doi: 10.1016/j.bmc.2007.09.010. Epub 2007 Sep 14.


Our structure-based design strategies which specifically target the HIV-1 protease backbone, resulted in a number of exceedingly potent nonpeptidyl inhibitors. One of these inhibitors, darunavir (TMC114), contains a privileged, structure-based designed high-affinity P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF). Darunavir has recently been approved for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Crystallography, X-Ray
  • Darunavir
  • Drug Design*
  • Drug Resistance, Viral*
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • Humans
  • Ligands
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / therapeutic use


  • HIV Protease Inhibitors
  • Ligands
  • Sulfonamides
  • Darunavir