Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT).
Ding Y, Belyanskaya S, DeLorey JL, Messer JA, Joseph Franklin G, Centrella PA, Morgan BA, Clark MA, Skinner SR, Dodson JW, Li P, Marino JP, Israel DI.
Inhibition of soluble epoxide hydrolase (sEH) has recently emerged as a new approach to treat cardiovascular disease and respiratory disease. Inhibitors based on 1,3,5-triazine chemotype were discovered through affinity selection against two triazine-based DNA-encoded libraries. The structure and activity relationship study led to the expansion of the original 1,4-cycloalkyl series to related aniline, piperidine, quinoline, aryl-ether and benzylic series. The 1,3-cycloalkyl chemotype led to the discovery of a clinical candidate (GSK2256294) for COPD.