具有亚砜亚胺功能的强效HIV-1蛋白酶抑制剂的发现。
Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality.
作者信息
Lu Ding, Vince Robert
机构信息
Department of Medicinal Chemistry, College of Pharmacy, 308 Harvard Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
出版信息
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。
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