Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT). (1st July 2021)

• Record Type: Journal Article
• Authors: Ding, Yun; Belyanskaya, Svetlana; DeLorey, Jennifer L.; Messer, Jeffrey A.; Joseph Franklin, G.; Centrella, Paolo A.; Morgan, Barry A.; Clark, Matthew A.; Skinner, Steven R.; Dodson, Jason W.; Li, Peng; Marino, Joseph P.; Israel, David I.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 41(2021)
• Publication Date: 2021-07-01
• Subjects: DNA-encoded library technology -- Soluble epoxide hydrolase; ELT encoded library technology -- DEL DNA-encoded library -- sEH soluble epoxide hydrolase -- HP DNA headpiece -- SAR structure activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116216
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.