Submission Details
Molecule(s):
O=C(CCl)N1CCO[C@H](c2ccc(F)cc2)[C@@H]1Nc1cccnc1
O=C(CCl)N1CCO[C@H](c2ccc(F)cc2)[C@@H]1Nc1cnccn1
Design Rationale:
I combined fragments 0759 and part of fragment 0107. It is a covalent inhibitor, provides ample hydrophobic interactions to drive binding, and provides some specificity via a key hydrogen bond(s) of the pyridine/pyrazine ring with residues H163 and N142, resp., as well as the trifurcated nature of the compound. Moieties with the pyridine ring dock well in that pockeSt (using GLIDE/Schrodinger).
Other Notes:
I am a protein crystallographer with also a background in structure-based and fragment-based ligand design.