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Synthesis and preliminary evaluation of novel 11C-labeled GluN2B-selective NMDA receptor negative allosteric modulators
https://repo.qst.go.jp/records/80190
https://repo.qst.go.jp/records/801903bb82b63-4943-467b-bba5-ad0b6a2f7173
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-07-16 | |||||
| タイトル | ||||||
| タイトル | Synthesis and preliminary evaluation of novel 11C-labeled GluN2B-selective NMDA receptor negative allosteric modulators | |||||
| 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 |
Ji-yun, Sun
× Ji-yun, Sun× Kumata, Katsushi× Chen, Zhen× Zhang, Yiding× Jia-hui, Chen× Hatori, Akiko× Hua-long, Fu× Rong, Jiang× Xiao-yun, Deng× Yamasaki, Tomoteru× Xie, Lin× Kuan, Hu× Fujinaga, Masayuki× Qing-zhen, Yu× Shao, Tuo× Lee Collier, Thomas× Josephson, Lee× Yi-han, Shao× Yun-fei, Du× Lu, Wang× Xu, Hao× Ming-Rong, Zhang× Liang, Huan× Katsushi, Kumata× Zhang, Yiding× Akiko, Hatori× Tomoteru, Yamasaki× Lin, Xie× Kuan, Hu× Masayuki, Fujinaga× 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 | N-methyl-D-aspartate receptors (NMDARs) play critical roles in the physiological function of the mammalian central nervous system (CNS), including learning, memory, and synaptic plasticity, through modulating excitatory neurotransmission. Attributed to etiopathology of various CNS disorders and neurodegenerative diseases, GluN2B is one of the most well-studied subtypes in preclinical and clinical studies on NMDARs. Herein, we report the synthesis and preclinical evaluation of two 11C-labeled GluN2B-selective negative allosteric modulators (NAMs) containing N,N-dimethyl-2-(1H-pyrrolo[3,2-b]pyridin-1-yl)acetamides for positron emission tomography (PET) imaging. Two PET ligands, namely [11C]31 and [11C]37 (also called N2B-1810 and N2B-1903, respectively) were labeled with [11C]CH3I in good radiochemical yields (decay-corrected 28% and 32% relative to starting [11C]CO2, respectively), high radiochemical purity (>99%) and high molar activity (>74 GBq/μmol). In particular, PET ligand [11C]31 demonstrated moderate specific binding to GluN2B subtype by in vitro autoradiography studies. However, because in vivo PET imaging studies showed limited brain uptake of [11C]31 (up to 0.5 SUV), further medicinal chemistry and ADME optimization are necessary for this chemotype attributed to low binding specificity and rapid metabolism in vivo. | |||||
| 書誌情報 |
Acta Pharmacologica Sinica 巻 42, p. 491-498, 発行日 2020-07 |
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| 出版者 | ||||||
| 出版者 | Nature | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1671-4083 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41401-020-0456-9 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.nature.com/articles/s41401-020-0456-9 | |||||
