Submission Details
Molecule(s):
CC(C)C[C@H](NC(=O)NCc1ccccc1)C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(=O)C(=O)NCc1ccc2c(c1)OCO2
Design Rationale:
These compounds are inspired by the alpha-ketoamide bound crystal structure (6Y2F) and designed based on our experience on the lead-optimization of alpha-ketoamides for inhibiting a cysteine protease calpain2 (J Am Chem Soc. 2017,doi.org/10.1021/jacs.7b08938). To achieve the optimal binding, we kept the P1 and P2 sidechains to mimic the substrate peptide and focused on exploring larger chemical space of P1' and P3 using the fragment map-based approach described in J. Chem. Inf. Model. 2019, doi.org/10.1021/acs.jcim.8b00959. The fragment maps were obtained from http://demo.silcsbio.com/covid-19/.