Although the above‐described inhibitors with 1,4‐Michael acceptors (e.g., α,β‐vinyl ethyl ester, –CH═CH–C(O)–OEt) showed enzymatic or cell‐based in‐vitro activities, they can be cleaved to their carboxylic acids by plasma esterases; for instance, AG7088 (29) was inactive in the plasma of rodents and rabbits. 144 ,  145  Therefore, scientists explored different reactive groups that are stable in vivo.