Synthesis and Biochemical Evaluation of 8 H -Indeno[1,2- d ]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors.

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CL pro ) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8 H -indeno[1,2- d ]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CL pro . Among them, the representative compound 7a displayed inhibitory activity with an IC 50 of 1.28 ± 0.17 μM against SARS-CoV-2 3CL pro . Molecular docking of 7a against 3CL pro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CL pro .