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Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold
https://repo.qst.go.jp/records/84582
https://repo.qst.go.jp/records/84582ef7d9a3c-22ae-4c01-ae9f-e2c6d596546d
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-10-01 | |||||
| タイトル | ||||||
| タイトル | Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold | |||||
| 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 |
Rong, Jian
× Rong, Jian× Wakana, Mori× Xia, Xiaotian× A. Schafroth, Michael× Zhao, Chunyu× S. Van, Richard× Tomoteru, Yamasaki× Chen, Jiahui× Xiao, Zhiwei× Haider, Ahmed× Ogasawara, Daisuke× Atsuto, Hiraishi× Shao, Tuo× Zhang, Yiding× Chen, Zhen× Pang, Fuwen× Kuan, Hu× Lin, Xie× Masayuki, Fujinaga× Katsushi, Kumata× Gou, Yuancheng× Fang, Yang× Gu, Shuyin× Wei, Huiyi× Bao, Liang× Xu, Hao× L. Collier, Thomas× Shao, Yihan× E. Carson, Richard× F. Cravatt, Benjamin× Lu, Wang× ming-rong, zhang× Liang, Huan× Wakana, Mori× Tomoteru, Yamasaki× Atsuto, Hiraishi× Zhang, Yiding× Kuan, Hu× Lin, Xie× Masayuki, Fujinaga× Katsushi, Kumata× Lu, Wang× Zhang, Ming-Rong× 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 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [18F]10 and [18F]15 ([18F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [18F]15 demonstrated a better performance. In conclusion, [18F]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans. | |||||
| 書誌情報 |
Journal of Medicinal Chemistry 巻 64, 号 19, p. 14283-14298, 発行日 2021-10 |
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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.1c00747 | |||||
| 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.1c00747 | |||||
