Raza Abbas, Sham Yuk Yin, Vince Robert
Center for Drug Design, Academic Health Center, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455, USA.
Bioorg Med Chem Lett. 2008 Oct 15;18(20):5406-10. doi: 10.1016/j.bmcl.2008.09.044. Epub 2008 Sep 13.
A new class of potent sulfoximine inhibitors for HIV-1 protease has been designed and synthesized. Substitution of the sulfoximine moiety into different parent compounds yields different inhibition effects. While our previously studied sulfoximine-based inhibitors display potency of 2.5 nM (IC(50)) against HIV-1 protease, introduction of the sulfoximine moiety into the asymmetric Indinavir yielded only micromolar inhibition. Docking studies showed structural variations in their modes of binding which explains this unexpected observation. The implication of these observations in the development of other sulfoximine inhibitors is discussed.
已设计并合成了一类新型的用于HIV-1蛋白酶的高效亚砜亚胺抑制剂。将亚砜亚胺部分取代不同的母体化合物会产生不同的抑制效果。虽然我们之前研究的基于亚砜亚胺的抑制剂对HIV-1蛋白酶显示出2.5 nM（IC(50)）的效力，但将亚砜亚胺部分引入不对称的茚地那韦仅产生微摩尔级的抑制作用。对接研究表明它们的结合模式存在结构差异，这解释了这一意外观察结果。讨论了这些观察结果对其他亚砜亚胺抑制剂开发的意义。
