Arai Shota, Fujiwara Koichi, Kojima Masahiro, Aoki-Saito Haruka, Yatomi Masakiyo, Saito Tsugumichi, Koga Yasuhiko, Fukuda Hayato, Watanabe Mizuki, Matsunaga Shigeki, Hisada Takeshi, Shuto Satoshi
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
J Org Chem. 2022 Aug 5;87(15):10501-10508. doi: 10.1021/acs.joc.2c01110. Epub 2022 Jul 22.
Resolvins are pro-resolving lipid mediators with highly potent anti-inflammatory effects. Because of their polyunsaturated structures, however, they are unstable to oxygen as a drug prototype. To address this issue, we designed and synthesized CP-RvE3 as oxidatively stable congeners of RvE3 by replacing the -olefin with a -cyclopropane to avoid the unstable bisallylic structure. Although the oxidative stabilities of CP-RvE3 were not improved, β-CP-RvE3 was 3.7 times more metabolically stable than RvE3. Thus, we identified β-CP-RvE3 as a metabolically stable equivalent.
消退素是具有高效抗炎作用的促消退脂质介质。然而，由于其多不饱和结构，作为药物原型，它们对氧不稳定。为了解决这个问题，我们通过用环丙烷取代烯烃以避免不稳定的双烯丙基结构，设计并合成了CP-RvE3作为RvE3的氧化稳定类似物。尽管CP-RvE3的氧化稳定性没有提高，但β-CP-RvE3的代谢稳定性比RvE3高3.7倍。因此，我们确定β-CP-RvE3为代谢稳定的等效物。
