三环羟基-1H-吡咯并吡嗪-1,4-二酮类 HIV-1 整合酶抑制剂的研制。
Development of tricyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors.
机构信息
Chemical Biology Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702, USA.
出版信息
Bioorg Med Chem Lett. 2011 May 15;21(10):2986-90. doi: 10.1016/j.bmcl.2011.03.047. Epub 2011 Mar 21.
Abstract
New tricyclic HIV-1 integrase (IN) inhibitors were prepared that combined structural features of bicyclic pyrimidinones with recently disclosed 4,5-dihydroxy-1H-isoindole-1,3(2H)-diones. This combination resulted in the introduction of a nitrogen into the aryl ring and the addition of a fused third ring to our previously described inhibitors. The resulting analogues showed low micromolar inhibitory potency in in vitro HIV-1 integrase assays, with good selectivity for strand transfer relative to 3'-processing.
摘要
新型三环 HIV-1 整合酶（IN）抑制剂的合成，将双环嘧啶酮结构特征与最近公布的 4,5-二羟基-1H-异吲哚-1,3(2H)-二酮相结合。这种组合将氮原子引入芳环，并在我们之前描述的抑制剂中加入了一个融合的三环。所得类似物在体外 HIV-1 整合酶试验中显示出低微摩尔抑制活性，与 3'-加工相比，对链转移具有良好的选择性。
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