Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV.
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.
Ghosh
Arun K
AK
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Dawson
Zachary L
ZL
Mitsuya
Hiroaki
H
D002986:Clinical Trials as Topic; D018360:Crystallography, X-Ray; D000069454:Darunavir; D015195:Drug Design; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000627:therapeutic use
D017320:HIV Protease Inhibitors; D008024:Ligands; D013449:Sulfonamides; D000069454:Darunavir