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Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton
https://repo.qst.go.jp/records/75641
https://repo.qst.go.jp/records/7564125b4719e-ca97-4d3d-b3f3-585c77014f5c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-04-18 | |||||
| タイトル | ||||||
| タイトル | Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Chen, Zhen
× Chen, Zhen× Mori, Wakana× Deng, Xiaoyun× Cheng, Ran× Ogasawara, Daisuke× Zhang, Genwei× A. Schafroth, Michael× Dahl, Kenneth× Fu, Hualong× Hatori, Akiko× Shao, Tuo× Zhang, Yiding× Yamasaki, Tomoteru× Zhang, Xiaofei× Rong, Jian× Yu, Qingzhen× Kuan, Hu× Fujinaga, Masayuki× Xie, Lin× Kumata, Katsushi× Gou, Yuancheng× Chen, Jingjin× Gu, Shuyin× Bao, Liang× Lu, Wang× Lee Collier, Thomas× Vasdev, Neil× Shao, Yihan× Jun-An, Ma× F. Cravatt, Benjamin× Fowler, Christopher× Josephson, Lee× Ming-Rong, Zhang× Liang, Huan× Mori, Wakana× Hatori, Akiko× Zhang, Yiding× Yamasaki, Tomoteru× Kuan, Hu× Fujinaga, Masayuki× Xie, Lin× Kumata, Katsushi× Lu, Wang× Ming-Rong, Zhang× Liang, Huan |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of “tail switching” on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with 11C or18F. [11C]8 ([11C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [11C]17 ([11C]PAD) and [18F]37 ([18F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms. | |||||
| 書誌情報 |
Journal of Medicinal Chemistry 巻 62, 号 7, p. 3336-3353, 発行日 2019-03 |
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| 出版者 | ||||||
| 出版者 | ACS Publications | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0022-2623 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acs.jmedchem.8b01778 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01719 | |||||
