In work at Shanghai Curegene Pharmaceutical Co. Ltd., synthesis and optimization of a series of SARS-CoV-2 3CL protease (3CLpro, Mpro) inhibitors led to the identification of compounds [I], [II] and [III] as lead candidates suitable for further evaluation, based on their enzymatic IC50s (14, 12 and 8.6 nM, respectively), cellular EC50s (36, 26 and 52 nM, respectively) and human liver microsome (HLM) stability.