Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT)

[Display omitted] 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. Th...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2021-07, Vol.41, p.116216-116216, Article 116216
Hauptverfasser: 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.
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container_end_page 116216
container_issue
container_start_page 116216
container_title Bioorganic & medicinal chemistry
container_volume 41
creator 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.
description [Display omitted] 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.
doi_str_mv 10.1016/j.bmc.2021.116216
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subjects DNA-encoded library technology
Soluble epoxide hydrolase
title Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT)
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