open access

https://hdl.handle.net/2115/83926

Synthesis of Resolvin E1 and Its Conformationally Restricted Cyclopropane Congeners with Potent Anti-Inflammatory Effect

英語

proresolving lipid mediator

2021-01-21

American Chemical Society

ACS medicinal chemistry letters

12(2)

256-261

RvE1 (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.

学術雑誌論文

Accepted Manuscript

https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00639

This 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.

1948-5875