一种新型二酮膦酸，具有对HIV整合酶的特异性链转移抑制作用和抗HIV活性。
A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity.
作者信息
Chi Guochen, Nair Vasu, Semenova Elena, Pommier Yves
机构信息
The Center for Drug Discovery and the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
出版信息
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1266-9. doi: 10.1016/j.bmcl.2006.12.009. Epub 2006 Dec 15.
Abstract
We have synthesized novel phosphonic acid analogues of beta-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest.
摘要
我们合成了新型的β-二酮酸膦酸类似物。有趣的是，我们的抗HIV化合物1的膦酸电子等排体2仅为链转移步骤的抑制剂，这与化合物1形成了鲜明对比。化合物2的抗HIV活性低于1，但比L-708906的膦酸类似物活性更高且毒性更低。这些电子等排化合物代表了具有结构、合成及抗病毒研究意义的β-二酮膦酸的首个实例。
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