Lu Ding, Vince Robert
Department of Medicinal Chemistry, College of Pharmacy, 308 Harvard Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Bioorg Med Chem Lett. 2007 Oct 15;17(20):5614-9. doi: 10.1016/j.bmcl.2007.07.095. Epub 2007 Aug 23.
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.
基于磺胺肟的独特性质以及HIV-1蛋白酶的同二聚体C(2)结构对称性，设计并合成了一类新型的基于磺胺肟的假对称HIV-1蛋白酶抑制剂。已证明磺胺肟部分对HIV-1蛋白酶抑制剂的效力很重要。活性最高的立体异构体(2S,2'S)对HIV-1蛋白酶的效力为2.5 nM(IC(50))，抗HIV-1活性为408 nM(IC(50))。提出了一种可能的作用模式。
