Further SARs of 159 and 165 were investigated to improve the activity. However, no significant improvement in the activity was observed for the prepared compounds either in the enzymatic or cell‐based bioassay. Compounds 167–169 (Figure 36) displayed the best inhibitory activities. Especially, the m‐fluoro‐substituted benzamide derivative 168 (IC50, 0.15 µM; EC50, 5.4 µM) showed the best inhibition activity against PLpro. It also inhibited SARS‐CoV‐1 in the cell‐based bioassay. Both compounds 168 and 169 were metabolically more stable when compared to 167.