Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality.
Based on the unique property of sulfoximine and the homodimeric C(2) structural symmetry of HIV-1 protease, a novel class of sulfoximine-based pseudosymmetric HIV-1 protease inhibitors was designed and synthesized. The sulfoximine moiety was demonstrated to be important for HIV-1 protease inhibitor potency. The most active stereoisomer (2S,2'S) displays a potency of 2.5 nM (IC(50)) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC(50)). A possible mode of action is proposed.
Lu
Ding
D
Department of Medicinal Chemistry, College of Pharmacy, 308 Harvard Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Vince
Robert
R
D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013455:Sulfur / Q000737:chemistry*