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Synthesis and Preliminary Studies of 11C-labeled Tetrahydro-1,7-Naphthyridine-2-Carboxamides for PET Imaging of Metabotropic Glutamate Receptor 2
https://repo.qst.go.jp/records/80546
https://repo.qst.go.jp/records/80546e5bc54e5-2756-49bb-976f-9157a3eb1118
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-08-27 | |||||
| タイトル | ||||||
| タイトル | Synthesis and Preliminary Studies of 11C-labeled Tetrahydro-1,7-Naphthyridine-2-Carboxamides for PET Imaging of Metabotropic Glutamate Receptor 2 | |||||
| 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 |
Zhang, Xiaofei
× Zhang, Xiaofei× Zhang, Yiding× Chen, Zhen× Shao, Tuo× Van, Richard× Kumata, Katsushi× Deng, Xiaoyun× Fu, Hualong× Yamasaki, Tomoteru× Rong, Jian× Kuan, Hu× Hatori, Akiko× Xie, Lin× Yu, Qingzhen× Ye, Weijian× Xu, Hao× J. Sheffler, Douglas× D. P. Cosford, Nicholas× Shao, Yihan× Tang, Pingping× Lu, Wang× Ming-Rong, Zhang× Liang, Huan× Zhang, Yiding× Katsushi, Kumata× Tomoteru, Yamasaki× Kuan, Hu× Akiko, Hatori× Lin, Xie× 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 | Selective modulation of metabotropic glutamate receptor 2 (mGlu2) represents a novel therapeutic approach for treating brain disorders, including schizophrenia, depression, Parkinson’s disease (PD), Alzheimer’s disease (AD), drug abuse and addiction. Imaging mGlu2 using positron emission tomography (PET) would allow in vivo quantification under physiological and pathological conditions and facilitate drug discovery by enabling target engagement studies. However, to date, few successful efforts have been disclosed to visualize mGlu2 in vivo, indicating an unmet and urgent clinical need. Herein we report the synthesis and preclinical evaluation of a focused library of mGlu2 modulators amenable for radiolabeling. The promising candidate 4-(2,4-difluorophenyl)-7-((2-methoxypyridin -4-yl)methyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-2-carboxamide (21b), exhibited high potency and excellent subtype selectivity, which was then evaluated by in vitro autoradiography and in vivo PET imaging studies after labeling with carbon-11. Ligand [11C]21b (also known as [11C]MG2-1904) demonstrated high brain uptake and excellent in vitro/in vivo specific binding towards mGlu2 with high metabolic stability in the brain. As proof-of-concept, our preliminary work demonstrated a successful example of visualizing mGlu2 in vivo derived from negative allosteric modulators (NAMs), which represents a promising chemotype for further development and optimization aimed for clinical translation. | |||||
| 書誌情報 |
Theranostics 巻 10, 号 24, p. 11178-11196, 発行日 2020-09 |
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| 出版者 | ||||||
| 出版者 | IVYSPRING | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1838-7640 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.7150/thno.42587 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.thno.org/v10p11178.htm | |||||
