Submission Details
Molecule(s):
O=C1CC[C@@H](c2cccc(Cl)c2)C(=O)N1c1cncc2ccccc12
O=C1CO[C@@H](c2cccc(Cl)c2)C(=O)N1c1cncc2ccccc12
O=C1CN[C@@H](c2cccc(Cl)c2)C(=O)N1c1cncc2ccccc12
CN1CC(=O)N(c2cncc3ccccc23)C(=O)[C@@H]1c1cccc(Cl)c1
Design Rationale:
Like dihydrouracils (e.g. PET-UNK-abc197b8-1) these cyclic imide designs are intended to hybridize the 3-aminopyridine-like and quinolone series. While the carbonyl oxygens are likely to be weaker hydrogen bond acceptors than the corresponding oxygens in dihydrouracils, the potential for reaction with the catalytic cysteine is greater for the cyclic imides.
Other Notes:
The first two designs are single enantiomers of racemic designs (VLA-UCB-1dbca3b4-10 VLA-UNK-db5e3064-1) that had been previously submitted. The pdb file associated with the submission contains the X10789 structure (protein/ligand) and energy-minimized protein/ligand structures for the 4 designs. Of the 4 designs, I would anticipate design #2 (racemate: VLA-UNK-db5e3064-1) to be the one with the greatest potential to react with the catalytic cysteine.