Submission Details
Molecule(s):
O=C1NC[C@@H](c2cccc(Cl)c2)C(=O)N1c1cncc2ccccc12
Design Rationale:
This is a variation of a proposed amide annulation (VLA-UCB-50c39ae8-3) which has the potential to accept a hydrogen bond from G143. This design replaces a methylene adjacent to the carbonyl with nitrogen and I would expect this structural modification to increase the hydrogen bond basicity of both carbonyl oxygens. The NH provides a vector for structural elaboration although I would recommend synthesizing the submitted compound (structural prototype) before attempting to do this.
Other Notes:
There are four structures in the PDB format file that accompanies this submission. (1) ADA-UCB-6c2cb422-1 protein structure (2) ADA-UCB-6c2cb422-1 ligand structure (3) Binding mode predicted for submitted structure (4) Pose generated for 5-membered ring analog (hydantoin) showing poor overlay with crystallographic ligand in comparison with submitted structure (6-membered ring). I will provide more detail by discussing this submission.