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Development of 2-(2-(3-(4-([18F]Fluoromethoxy- d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain.
https://repo.qst.go.jp/records/49507
https://repo.qst.go.jp/records/49507484e5abc-f303-4477-a7e6-fbbd64f8aa96
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-12-10 | |||||
| タイトル | ||||||
| タイトル | Development of 2-(2-(3-(4-([18F]Fluoromethoxy- d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain. | |||||
| 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 |
Mori, Wakana
× Mori, Wakana× Yamasaki, Tomoteru× Fujinaga, Masayuki× Ogawa, Masanao× Zhang, Yiding× Hatori, Akiko× Xie, Lin× Kumata, Katsushi× Wakizaka, Hidekatsu× Kurihara, Yusuke× Ohkubo, Takayuki× Nengaki, Nobuki× Ming-Rong, Zhang× Mori, Wakana× Yamasaki, Tomoteru× Fujinaga, Masayuki× Ogawa, Masanao× Zhang, Yiding× Hatori, Akiko× Xie, Lin× Kumata, Katsushi× Wakizaka, Hidekatsu× Kurihara, Yusuke× Ohkubo, Takayuki× Nengaki, Nobuki× Ming-Rong, Zhang |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Phosphodiesterase 10A (PDE10A) is a newly identified therapeutic target for central nervous system disorders. 2-(2-(3-(4-([18F]Fluoroethoxy)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659, [18F]5) is a useful positron emission tomography (PET) ligand for imaging of PDE10A in the human brain. However, the radiolabeled metabolite of [18F]5 can accumulate in the brain. In this study, using [18F]5 as a lead compound, we designed four new 18F-labeled ligands ([18F]6–9) to find one more suitable than [18F]5. Of these, 2-(2-(3-(4-([18F]fluoromethoxy-d2)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]9) exhibited high in vitro binding affinity (Ki = 2.9 nM) to PDE10A and suitable lipophilicity (LogD = 2.2). In PET studies, the binding potential (BPND) of [18F]9 (5.8) to PDE10A in rat brains was significantly higher than that of [18F]5 (4.6). Furthermore, metabolite analysis showed much lower levels of contamination with radiolabeled metabolites of [18F]9 in the brain than those of [18F]5. In conclusion, [18F]9 is a useful PET ligand for PDE10A imaging in brain. | |||||
| 書誌情報 |
Jounal of Medicinal Chemistry 巻 62, 号 2, p. 688-698, 発行日 2018-12 |
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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.8b01366 | |||||
| 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.8b01366 | |||||
