Yun Ding; Svetlana Belyanskaya; Jennifer L. DeLorey; Jeffrey A. Messer; G. Joseph Franklin; Paolo A. Centrella; Barry A. Morgan; Matthew A. Clark; Steven R. Skinner; Jason W. Dodson; Peng Li; Joseph P. Marino Jr.; David I. Israel
Bioorg. Med. Chem., 2021, 116216
https://doi.org/10.1016/j.bmc.2021.116216

Abstract

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.