Submission Details
Molecule(s):
O=C(O)c1n[nH]c(Cl)c1CCc1ccnc(-c2cnccc2CO)c1
O=C(O)c1c[nH]c(Cl)c1CCc1ccnc(-c2cnccc2CO)c1
OCc1ccncc1-c1cc(CCc2cn[nH]c2Cl)ccn1
MUS-SCH-c2f96c06-4
Duplicate of:
KRI-LIF-2e3dfaa5-1
OCc1ccncc1-c1cc(CCc2cn[nH]c2)ccn1
OCc1ccncc1-c1nc[nH]c1Cc1cc(Cl)ccn1
OCc1ccncc1-c1nc[nH]c1C[C@H](O)CCl
Cc1nc(CCl)c(Cc2[nH]cnc2-c2cnccc2CO)[nH]1
OCc1ccncc1-c1nc[nH]c1Cc1[nH]cnc1CCl
Nc1c(Cl)ccnc1Cc1[nH]cnc1-c1cnccc1CO
OCc1ccncc1-c1nc[nH]c1Cc1ncccc1Cl
OCc1ccncc1-c1nc[nH]c1CCc1nc[nH]c1Cl
C[C@@H](O)Cc1[nH]cnc1-c1cnccc1CO
OCc1ccncc1-c1nc[nH]c1Cc1cnc[nH]1
OCc1ccncc1-c1nc[nH]c1CCl
Design Rationale:
Looking at target site 2: x0107, x0540 and x0995 all shared a common pyridine ring co-crystallized in the same region. Using this and building from x0107, I built out from the amide group to occupy the pocket like space extending from this position. I used Cresset software's Flare tool, employing in silico docking, iteratively improving the binding score whilst also the ligand complementarity to the binding region. The methyl-OH group displaces a water molecule as well as the pyrrole/pyrazole groups. I am sorry I can't comment on the synthetic ease or routes.
Other Notes:
I have attached a pdb file with the best scoring poses of each submitted compound. They can be visualised against the target protein.