2024-03-28T09:18:39Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/839262023-07-27T07:23:34Zhdl_2115_20044hdl_2115_124Synthesis of Resolvin E1 and Its Conformationally Restricted Cyclopropane Congeners with Potent Anti-Inflammatory EffectIshimura, KoheiFukuda, Hayato1000040837853Fujiwara, Koichi1000030455597Muromoto, RyutaHirashima, KokiMurakami, Yuto1000020507173Watanabe, MizukiIshihara, Jun1000020212219Matsuda, Tadashi1000070241346Shuto, Satoshiopen accessThis document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS medicinal chemistry letters, copyright c American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00639.https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00639Resolvin E1anti-inflammatorycyclopropane congenerproresolving lipid mediator499RvE1 (1) is an endogenous lipid mediator with very potent anti-inflammatory activity, which is due to the inhibition of neutrophil chemotaxis and inflammatory cytokine production and the promotion of macrophage phagocytosis. On the basis of the conformational analysis of RvE1, we designed its four cyclopropane congeners (2a-d), in which the conformationally flexible terminal C1-C4 moiety of RvE1 was rigidified by introducing stereoisomeric cyclopropanes. The four congeners and also RvE1 were efficiently synthesized via a common synthetic route. The evaluation of the anti-inflammatory effects of the compounds in mice resulted in the identification of trans-beta-CP-RvE1 (2d), which was significantly more active than RvE1, as a potential lead for antiinflammatory drugs of a novel mechanism of action.American Chemical Society2021-01-21engjournal articleAMhttp://hdl.handle.net/2115/83926https://doi.org/10.1021/acsmedchemlett.0c006391948-5875ACS medicinal chemistry letters122256261https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/83926/1/RvE1-ACSMCL-0119_final_unmarked.pdfapplication/pdf581.22 KB2021-01-21