@article{oai:repo.qst.go.jp:00047553,
 author = {Wang, Lu and Mori, Wakana and Cheng, Ran and Yui, Joji and Hatori, Akiko and Ma, Longle and Zhang, Yiding and H., Rotstein Benjamin and Fujinaga, Masayuki and Shimoda, Yoko and Yamasaki, Tomoteru and Xie, Lin and Nagai, Yuji and Minamimoto, Takafumi and Higuchi, Makoto and Vasdev, Neil and Zhang, Ming-Rong and H., Liang Steven and 森 若菜 and 由井 譲二 and 羽鳥 晶子 and 張 一鼎 and 藤永 雅之 and 下田 陽子 and 山崎 友照 and 謝 琳 and 永井 裕司 and 南本 敬史 and 樋口 真人 and 張 明栄},
 issue = {8},
 journal = {Theranostics},
 month = {May},
 note = {Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [11C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [11C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL.},
 pages = {1145--1159},
 title = {Synthesis and Preclinical Evaluation of Sulfonamido-based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase},
 volume = {6},
 year = {2016}
}