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

Abstract

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.

• Authors: Arun K Ghosh, Zachary L Dawson, Hiroaki Mitsuya
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 24 Pg. 7576-80 (Dec 15 2007) ISSN: 1464-3391 [Electronic] England
• PMID: 17900913 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• HIV Protease Inhibitors
• Ligands
• Sulfonamides
• Darunavir

Topics

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