Submission Details
Molecule(s):
CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2CCNS(=O)(=O)c2ccccc2)[nH]c1=O
O=c1cccc(-c2ccccc2CCNS(=O)(=O)c2ccccc2)[nH]1
O=C(Nc1cccnc1)Nc1ccccc1-c1cccc(=O)[nH]1
CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2NC(=O)Nc2cccnc2)[nH]c1=O
CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2CCC(=O)N[C@@H](C[C@@H]2CCNC2=O)C(=O)C(=O)NC2CC2)[nH]c1=O
CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2CC(=O)N[C@@H](C[C@@H]2CCNC2=O)C(=O)C(=O)NC2CC2)[nH]c1=O
CC(C)(C)OC(=O)Nc1ccc(-c2cccc(CCC(=O)N[C@@H](C[C@@H]3CCNC3=O)C(=O)C(=O)NC3CC3)c2)[nH]c1=O
CC(C)(C)OC(=O)Nc1ccc(-c2cccc(CC(=O)N[C@@H](C[C@@H]3CCNC3=O)C(=O)C(=O)NC3CC3)c2)[nH]c1=O
CC(C)(C)OC(=O)Nc1ccc(-c2cccc(CCC(=O)N[C@@H](C[C@@H]3CCNC3=O)C(=O)C(=O)N3CCN(S(=O)(=O)c4ccccc4)CC3)c2)[nH]c1=O
O=C(CCc1cccc(-c2cccc(=O)[nH]2)c1)N[C@@H](C[C@@H]1CCNC1=O)C(=O)C(=O)N1CCN(S(=O)(=O)c2ccccc2)CC1
CC(C)(C)OC(=O)Nc1ccc(-c2cccc(CC(=O)N[C@@H](C[C@@H]3CCNC3=O)C(=O)C(=O)N3CCN(S(=O)(=O)c4ccccc4)CC3)c2)[nH]c1=O
O=C(Cc1cccc(-c2cccc(=O)[nH]2)c1)N[C@@H](C[C@@H]1CCNC1=O)C(=O)C(=O)N1CCN(S(=O)(=O)c2ccccc2)CC1
O=c1cccc(-c2c(F)cccc2CCNS(=O)(=O)c2ccccc2)[nH]1
O=C(Nc1cccnc1)Nc1cccc(F)c1-c1cccc(=O)[nH]1
CC(C)(C)OC(=O)Nc1ccc(-c2c(F)cccc2CCNS(=O)(=O)c2ccccc2)[nH]c1=O
CC(C)(C)OC(=O)Nc1ccc(-c2c(F)cccc2NC(=O)Nc2cccnc2)[nH]c1=O
Design Rationale:
Using the crystollagraphic data published by Hilgenfeld et al. (Science 2020), we derived these structures. Thereby, we focused on derivatives with a good synthetic accessibility. Maintaining the pyridinone-moiety, we tried to mimic the binding modes of fragments 0072, 0434, 0678, 0692 and 0770 as well as inhibitor 13b (pdb: 6y2g). The central aromatic ring might be well positioned in the hydrophobic S2 pocket-connecting the residues that address p1 and p3. The structures putativley combine the key interactions of the above mentioned fragments in a single molecule.