@article{oai:repo.qst.go.jp:00082744,
 author = {Chen, Zhen and Mori, Wakana and Rong, Jian and A. Schafroth, Michael and Shao, Tuo and S. Van, Richard and Ogasawara, Daisuke and Yamasaki, Tomoteru and Hiraishi, Atsuto and Hatori, Akiko and Chen, Jiahui and Zhang, Yiding and Kuan, Hu and Fujinaga, Masayuki and Sun, Jiyun and Yu, Qingzhen and L. Collier, Thomas and Shao, Yihan and F. Cravatt, Benjamin and Josephson, Lee and Ming-Rong, Zhang and Liang, Huan and Wakana, Mori and Tomoteru, Yamasaki and Atsuto, Hiraishi and Akiko, Hatori and Zhang, Yiding and Kuan, Hu and Masayuki, Fujinaga and Zhang, Ming-Rong and Liang, Huan},
 issue = {6},
 journal = {Acta Pharmaceutica Sinica B},
 month = {Dec},
 note = {Abstract Monoacylglycerol lipase (MAGL) is a serine hydrolase, which metabolizes 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) in the central nervous system (CNS). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile SNAr reaction to form 2-[18F]fluoropyridinyl scaffold. Excellent blood−brain barrier penetration and high in vivo binding specificity was validated for radioligand [18F]14 (also named as [18F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent 18F-labeled MAGL PET tracers. 
KEY WORDS Monoacylglycerol lipase (MAGL); Central nervous system (CNS); 2-Arachidonylglycerol (2-AG); Arachidonic acid (AA); Positron emission tomography (PET); Fluorine-18},
 pages = {1686--1695},
 title = {Development of a highly-specific 18F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping},
 volume = {11},
 year = {2020}
}