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：92

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.

引用

页码：552 / 558

页数：7

共 29 条

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