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氨基磷酸酯前药方法的应用赋予了无活性药物4'-叠氮基肌苷对丙型肝炎病毒的微摩尔级效力:对双碱基/糖修饰核苷的激酶绕过作用。

The application of the phosphoramidate ProTide approach confers micromolar potency against hepatitis C virus on inactive agent 4'-azidoinosine: kinase bypass on a dual base/sugar modified nucleoside.

作者信息

McGuigan Christopher, Daverio Felice, Nájera Isabel, Martin Joseph A, Klumpp Klaus, Smith David B

机构信息

Welsh School of Pharmacy, Cardiff University, Cardiff, UK.

出版信息

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3122-4. doi: 10.1016/j.bmcl.2009.03.138. Epub 2009 Mar 29.

Abstract

Novel phosphoramidate ProTides derived from 4'-azidoinosine have been prepared and evaluated in the replicon assay against hepatitis C Virus (HCV). The parent nucleoside analogue is inactive in this assay, while the ProTides are active at low microM levels in some cases. This is a rare example of an inosine nucleoside analogue with potent antiviral activity and further supports the notion of ProTides as a drug discovery motif.

摘要

已经制备了源自4'-叠氮基肌苷的新型磷酰胺酯前药,并在针对丙型肝炎病毒(HCV)的复制子测定中进行了评估。母体核苷类似物在该测定中无活性,而在某些情况下,磷酰胺酯前药在低微摩尔水平具有活性。这是具有强效抗病毒活性的肌苷核苷类似物的罕见例子,并进一步支持了磷酰胺酯前药作为药物发现基序的概念。

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