Synthesis and Biological Evaluation of 9-Oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile Analogues as Potential Inhibitors of Deubiquitinating Enzymes

被引：95

作者：

Colombo, Matteo ^{[1
]}

Vallese, Stefania ^{[1
]}

Peretto, Ilaria ^{[1
]}

Jacq, Xavier ^{[2
]}

Rain, Jean-Christophe ^{[2
]}

Colland, Frederic ^{[2
]}

Guedat, Philippe ^{[2
]}

机构：

[1] NiKem Res, I-20021 Milan, Italy

[2] Hybrigenics, F-75014 Paris, France

来源：

CHEMMEDCHEM | 2010年 / 5卷 / 04期

关键词：

drug discovery; heterocycles; inhibitors; proteases; ubiquitin; ANTINEOPLASTIC AGENTS; UBIQUITIN; PROTEASE; HAUSP; P53;

D O I：

10.1002/cmdc.200900409

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating enzyme USP8.

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页码：552 / 558

页数：7

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