Submission Details
Molecule(s):
Nc1cc2c(cn1)N(Cc1cc(O)ccc1O)CCN2C(=O)CCl
O=C(CCl)N1CCN([C@@H](c2cccc(O)c2)c2ccncn2)CC1
O=C(CCl)N1CCN(Cc2cc(O)cc3c2OCO3)CC1
O=C(CCl)N1CCN(Cc2cc(O)ccc2O)C[C@@H]1O
O=C(CCl)N1CCN(Cc2cc(O)ccc2O)CC1
Design Rationale:
In addition to the covalent bond between chloroacetamide and Cys145, the benzyl group attached to the piperazine forms a conserved aromatic interaction with His41. While the -OH group in meta position is expected to make a hydrogen bond with the backbone CO of His164, the -OH group in ortho position would make a hydrogen bond with the side-chain amide of Gln189. The 2-aminopyridine fused with piperazine in the first molecule also forms a hydrogen bond between primary amine and backbone CO of Thr26.
Other Notes:
All the molecules were searched in SciFinder to identify those with easily available building blocks in Enamine and 2-3 steps of chemistry.