Submission Details
Molecule(s):
O=C(CC[C@@H]1CCNC1=O)C(=O)NCc1cccc(C(=O)N2CCSCC2)c1
N[C@@H](C[C@@H]1CCNC1=O)C(=O)C(=O)NCc1cccc(C(=O)N2CCSCC2)c1
Design Rationale:
Overlay of PDB id 6y2g (protease with alpha-keto-amide inhibitor 13g) and fragment 0786 to generate a novel covalent inhibitor. Trimmed down the inhibitor 13g to increase chance that the new scaffold will fit and to make it chemically more feasible. It will improve on 13g that it is a less peptide-like inhibitor. If this workd it can later be combined with other fragments. Zhang et al Science 2020 α-ketoamide inhibitors, 10.1126/science.abb3405.