Jia, LimengMiao, CaihongDong, FuguiLi, WeiWang, MinZheng, Qi-HuangXu, Zhidong2020-03-022020-03-022019-07Jia, L., Miao, C., Dong, F., Li, W., Wang, M., Zheng, Q.-H., & Xu, Z. (2019). Facile synthesis of carbon-11-labeled sEH/PDE4 dual inhibitors as new potential PET agents for imaging of sEH/PDE4 enzymes in neuroinflammation. Bioorganic & Medicinal Chemistry Letters, 29(13), 1654–1659. https://doi.org/10.1016/j.bmcl.2019.04.036https://hdl.handle.net/1805/22206To develop PET tracers for imaging of neuroinflammation, new carbon-11-labeled sEH/PDE4 dual inhibitors have been synthesized. The reference standard N-(4-methoxy-2-(trifluoromethyl)benzyl)benzamide (1) and its corresponding desmethylated precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)benzamide (2) were synthesized from (4-methoxy-2-(trifluoromethyl)phenyl)methanamine and benzoic acid in one and two steps with 84% and 49% overall chemical yield, respectively. The standard N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA, 4) and its precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (5) were synthesized from methyl 4-piperidinecarboxylate, propionyl chloride and (4-methoxy-2-(trifluoromethyl)phenyl)methanamine in two and three steps with 62% and 34% overall chemical yield, respectively. The target tracers N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)benzamide ([11C]1) and N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide ([11C]MPPA, [11C]4) were prepared from their corresponding precursors 2 and 5 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 25–35% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (AM) at EOB was 370–740 GBq/μmol with a total synthesis time of 35–40-minutes from EOB.enPublisher Policysoluble epoxide hydrolasephosphodiesterase 4carbon-11-labeled sEH/PDE4 dual inhibitorsArticle