Zhou et al. extended the SAR studies for further activity improvement. Compound 108 bearing carboxamide showed the best SARS‐CoV‐1 Mpro inhibitory activity. However, this derivative did not bind covalently to the Cys145 residue of the active site. 177 Further structural investigations at the carboxamide of 108 with a variety of substituted sulfonamides did not improve the activity. Compound 109 was the best one of that series (Figure 28). 178