Submission Details
Molecule(s):
O=C1NC[C@@H](c2cccc(Cl)c2)C(=O)N1c1cccnc1
O=C1CCN(c2cccc(Cl)c2)C(=O)N1c1cccnc1
O=c1[nH]cc(-c2cccc(Cl)c2)c(=O)n1-c1cccnc1
O=c1ccn(-c2cccc(Cl)c2)c(=O)n1-c1cncc2ccccc12
O=c1ccn(-c2cccc(Cl)c2)c(=O)n1-c1cccnc1
O=C1N[C@@H](c2cccc(Cl)c2)C(=O)N1c1cncc2ccccc12
O=C1N[C@@H](c2cccc(Cl)c2)C(=O)N1c1cccnc1
O=C1N[C@@H](c2ccc(Cl)cc2)C(=O)N1c1cncc2ccccc12
O=C1N[C@@H](c2ccc(Cl)cc2)C(=O)N1c1cccnc1
Design Rationale:
The designs in this submission are intended to present amidic carbonyl oxygens to both backbone NHs of E166 (like 3-aminoquinoline-like inhibitors) and G143 (like quinolones). The two carbonyl groups that flank the heteroaromatic ring will tend to force it out of coplanarity with respect to the amides and it is possible that the advantage of isoquinoline over pyridine will be smaller for these structural types than in the 3-aminoquinoline-like series.
Other Notes:
The x10789 structure was used for modelling and the pdb file associated with this submission includes this protein structure, a number of ligands from other relevant crystal structures and the suggested binding poses (generated using molecular mechanics energy minimization) for designs. I will provided detailed notes for the submission in the discussion.