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Synthesis and Biological Evaluation of 9‐Oxo‐9H‐indeno[1,2‐b]pyrazine‐2,3‐dicarbonitrile Analogues as Potential Inhibitors of Deubiquitinating Enzymes
ChemMedChem ( IF 3.6 ) Pub Date : 2010-02-23 , DOI: 10.1002/cmdc.200900409
Matteo Colombo , Stefania Vallese , Ilaria Peretto , Xavier Jacq , Jean-Christophe Rain , Frédéric Colland , Philippe Guedat

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.

中文翻译:

9-氧-9H-茚并[1,2-b]吡嗪-2,3-二甲腈类似物作为去泛素化酶的潜在抑制剂的合成及生物学评价

高通量筛选突出-9-氧代9 ħ -茚并[1,2 b ]吡嗪-2,3-二腈(1)作为泛素特异性蛋白酶的活性抑制剂(USPS),一个家庭参与水解酶的从蛋白质底物中去除泛素。检查了化合物1的化学行为。此外,新化合物(1的类似物)的合成和体外评估还导致了去泛素化酶USP8的有效和选择性抑制剂的鉴定。
更新日期:2010-02-23
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