Submission Details
Molecule(s):
Cc1ncc(NC(=O)C2CCOc3ccc(Cl)cc32)c2ccccc12
O=C(Nc1cnc(F)c2ccccc12)C1CCOc2ccc(Cl)cc21
O=C(Nc1cnc(C(F)F)c2ccccc12)C1CCOc2ccc(Cl)cc21
O=C(Nc1cnc(C(F)(F)F)c2ccccc12)C1CCOc2ccc(Cl)cc21
O=C(Nc1cnc(F)c2ccc(F)cc12)C1CCOc2ccc(Cl)cc21
O=C(Nc1c(F)nc(F)c2ccccc12)C1CCOc2ccc(Cl)cc21
O=C(Nc1c(F)nc(F)c2ccc(F)cc12)C1CCOc2ccc(Cl)cc21
Design Rationale:
Aldehyde oxidase is a hard-to-predict metabolic fate of many pyridine, quinoline-type systems (C=N usually oxidised). Many compound withdrawn after marketing due to adverse events, hard to show in cross-species models. Baran litmus test, by adding CHF2 (simple LC-MS test) predicts A.O. liability. https://pubs.acs.org/doi/10.1021/jm4017976
Other Notes:
We do this in our lab. Send us some model substrates and we can check and, to boot, we also then make the CHF2 compound, which can be sent back for assay, if you like!