Synthesis and Biological Evaluation of 9‐Oxo‐9H‐indeno[1,2‐b]pyrazine‐2,3‐dicarbonitrile Analogues as Potential Inhibitors of Deubiquitinating Enzymes |
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| Authors: | Matteo Colombo Dr Stefania Vallese Dr Ilaria Peretto Dr Xavier Jacq Dr Jean‐Christophe Rain Dr Frédéric Colland Dr Philippe Guedat Dr |
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| Affiliation: | 1. NiKem Research, via Zambeletti 25, 20021 Baranzate, Milan (Italy), Fax: (+39)?2356947606;2. Hybrigenics, 3–5 Impasse Reille, 75014 Paris (France), Fax: (+33)?158103849 |
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| Abstract: | High‐throughput screening highlighted 9‐oxo‐9H‐indeno1,2‐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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| Keywords: | drug discovery heterocycles inhibitors proteases ubiquitin |
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