Synthesis and SARS-CoV-2 3CL Protease Inhibitory Effects of Oxazolidinone Derivatives

The 3-chymotrypsin-like protease (3CLpro) is an attractive target for the development of antiSARS (severe acute respiratory syndrome) drugs. In this work, a series of oxazolidinone derivatives 3a-3v were synthesized and their inhibitory activities against SARS coronavirus 2 (SARS-CoV-2) 3CLpro were evaluated by the fluorescence resonance energy transfer (FRET)-based enzymatic assay. Among synthesized compounds, 3g displayed the best inhibitory activity, with a half maximal inhibitory concentration (IC50) value of 14.47 mu M. Also, docking studies implied that compound 3g was fitted into the active pocket of 3CLpro, forming a hydrogen bond with Glu166.

Automated summary

A series of oxazolidinone derivatives were synthesized and compound 3g showed the best inhibitory activity against SARS coronavirus 2 (SARS-CoV-2) 3CLpro. Docking studies revealed that compound 3g formed a hydrogen bond with Glu166 in the active pocket of 3CLpro.