Synthesis and Biological Evaluation of 9‐Oxo‐9H‐indeno1,2‐bpyrazine‐2,3‐dicarbonitrile Analogues as Potential Inhibitors of Deubiquitinating Enzymes

High-throughput screening highlighted 9-oxo-9H-indeno1,2-bpyrazine-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.