Submission Details
Molecule(s):
O=C(CN(Cc1cccnc1)C(=O)NC1CCN(S(=O)(=O)c2ccccc2)CC1)N1CCOCC1
Design Rationale:
Attempts to bridge sites revealed by fragments. Urea O for Asn142 backbone H-bond (from x0397). Piperidine spacer replaces piperazine of x0771, x0689, aryl sulfonamide occupies the pocket revealed by same. Pyridine fits semi-hydrophobic pocket revealed by multiple non-covalent fragments eg x0678. Morpholine amide O satisfies HB to Glu166 revealed by eg x0678. Morpholine ring occupies remainder of space taken up by eg x0678. Compound is a simplified scaffold designed as a rapid test of the bridging strategy. It is designed with modular synthesis in mind, with simple widely available building blocks and chemistry. If it has activity it is intended to be followed up with array synthesis to identify more optimal subsitutents to occupy each pocket