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Identification and Development of a New Positron Emission Tomography Ligand 4-(2-Fluoro-4-[11C]methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide for Imaging Metabotropic Glutamate Receptor Subtype 2 (mGlu2)
https://repo.qst.go.jp/records/80793
https://repo.qst.go.jp/records/80793671795c0-8329-4557-bd2a-810e21a6e498
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-10-09 | |||||
| タイトル | ||||||
| タイトル | Identification and Development of a New Positron Emission Tomography Ligand 4-(2-Fluoro-4-[11C]methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide for Imaging Metabotropic Glutamate Receptor Subtype 2 (mGlu2) | |||||
| 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 |
Yamasaki, Tomoteru
× Yamasaki, Tomoteru× Zhang, Xiaofei× Kumata, Katsushi× Zhang, Yiding× Deng, Xiaoyun× Fujinaga, Masayuki× Chen, Zhen× Mori, Wakana× Kuan, Hu× Wakizaka, Hidekatsu× Hatori, Akiko× Xie, Lin× Ogawa, Masanao× Nengaki, Nobuki× Van, Richard× Shao, Yihan× J. Sheffler, Douglas× D. P. Cosford, Nicholas× Liang, Huan× Ming-Rong, Zhang× Tomoteru, Yamasaki× Katsushi, Kumata× Zhang, Yiding× Masayuki, Fujinaga× Wakana, Mori× Kuan, Hu× Hidekatsu, Wakizaka× Akiko, Hatori× Lin, Xie× Masanao, Ogawa× Nobuki, Nengaki× Liang, Huan× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Metabotropic glutamate receptor 2 (mGlu2) is a known target for treating several central nervous system (CNS) disorders. To develop a viable positron emission tomography (PET) ligand for mGlu2, we identified new candidates 5a–i that are potent negative allosteric modulators (NAMs) of mGlu2. Among these candidates, 4-(2-fluoro-4-methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide (5i, also named as [11C]MG2-1812) exhibited high potency, high subtype selectivity, and favorable lipophilicity. Compound 5i was labeled with positron-emitting carbon-11 (11C) to obtain [11C]5i in high radiochemical yield and high molar activity by O-[11C]methylation of the phenol precursor 12 with [11C]CH3I. In vitro autoradiography with [11C]5i showed heterogeneous radioactive accumulation in the brain tissue sections, ranked in the order: cortex > striatum > hippocampus > cerebellum ≫ thalamus > pons. PET study of [11C]5i indicated in vivo specific binding of mGlu2 in the rat brain. Based on the [11C]5i scaffold, further optimization for new candidates is underway to identify a more suitable ligand for imaging mGlu2. | |||||
| 書誌情報 |
Journal of Medicinal Chemistry 巻 2020, 号 63, p. 11469-11483, 発行日 2020-09 |
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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.9b01991 | |||||
| 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.9b01991 | |||||
