Examples of "NASA" warheads. See: Enhanced Suppression of a Protein−Protein Interaction in Cells Using Small-Molecule Covalent Inhibitors Based on an N‑Acyl‑N‑alkyl Sulfonamide Warhead Tsuyoshi Ueda, Tomonori Tamura, Masaharu Kawano, Keiya Shiono, Fruzsina Hobor, Andrew J. Wilson, and Itaru Hamachi J. Am. Chem. Soc. 2021, 143, 4766−4774
I can't, for some reason, access/visualise the frag XChem library so I'm doing these by eye, so some insight would be helpful. These warheads are useful for Tyr and non-Cys residues but the fact that they can potentially be spaced out from the N(CO) may enable one to avoid the issues of stability/synthesis of previous N(CO)-COCH=CH2 Michael acceptors. I added some simpler esters for comparison.