Encoded Library Technologies/NCE Molecular Discovery, GSK, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Encoded Library Technologies/NCE Molecular Discovery, GSK, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Bioorg Med Chem. 2021 Jul 1;41:116216. doi: 10.1016/j.bmc.2021.116216. Epub 2021 May 13.
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.
抑制可溶性环氧化物水解酶 (sEH) 最近已成为治疗心血管疾病和呼吸道疾病的新方法。基于 1,3,5-三嗪化学型的抑制剂是通过针对两个三嗪基 DNA 编码库进行亲和筛选而发现的。结构和活性关系研究导致将原始的 1,4-环烷基系列扩展到相关的苯胺、哌啶、喹啉、芳基醚和苄基系列。1,3-环烷基化学型导致发现了一种用于 COPD 的临床候选药物（GSK2256294）。
