A novel series of ketoglutamide tripeptides bearing a phthalhydrazido warhead group were identified as reversible SARS‐CoV‐1 Mpro inhibitors (81–84; Figure 24). 166  Among them, compound 83 showed the best inhibition (IC50, 0.6 µM). SAR studies revealed the presence of β and β'‐amino functionality adjacent to the keto and the intramolecular hydrogen bond to the carbonyl group made the keto center more electrophilic and inclined to build a hemithioacetal with Cys‐SH at the active site. Additionally, the hydrophobic P3‐benzyloxy moiety, the P1‐lactam, and the nitro group significantly contributed to the activity increment.