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Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide:a deuterium-substituted radioligand for peripheral benzodiazepine receptor
https://repo.qst.go.jp/records/44203
https://repo.qst.go.jp/records/4420371b4a4e1-f502-4288-b865-ea310501d4e5
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-06-08 | |||||
| タイトル | ||||||
| タイトル | Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide:a deuterium-substituted radioligand for peripheral benzodiazepine receptor | |||||
| 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, Ming-Rong
× Zhang, Ming-Rong× Maeda, Jun× Ito, Takehito× Okauchi, Takashi× Ogawa, Masanao× Noguchi, Junko× Suhara, Tetsuya× Halldin, Christer× Suzuki, Kazutoshi× 張 明栄× 前田 純× 岡内 隆× 小川 政直× 須原 哲也× ハルディン クリスタ× 鈴木 和年 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide ([18F]2)is a potent ligand (IC50,1.71 nM) for peripheral benzodiazepine receptor (PBR).However,in vivo evaluation on rodents and primates showed that this ligand was unstable and rapidly metabolized to [18F]F- by defluorination of the [18F]fluoromethyl moiety. In this study, we designed a deuterium-substituted analogue, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide ([18F]5) as a radioligand for PBR to reduce the in vivo metabolic rate of the non-deuterated [18F]2. The design principle was based on the hypothesis that the deuterium substitution may reduce the rate of defluorination initiated by cleavage of the C-H bond without altering the binding affinity for PBR. The non-radioactive 5 was prepared by reacting diiodomethane-d2 (CD2I2, 6) with a phenol precursor 7, followed by treatment with tetrabutylammonium fluoride. The ligand [18F]5 was synthesized by the alkylation of 7 with [18F]fluoromethyl iodide-d2 ([18F]FCD2I, [18F]9). Compound 5 displayed a similar in vitro affinity to PBR (IC50,1.90 nM) with 2. In vivo evaluation demonstrated that [18F]5 was metabolized by defluorination to [18F]F-as a main radioactive component, but its metabolic rate was slower than that of [18F]2 in the brain of mice. The deuterium substitution decreased the radioactivity level of [18F]5 in the bone of mouse, augmented by the percentage of specific binding to PBR in the rat brain determined by ex vivo autoradiography. However,the PET image of[18F]5 for monkey brain showed high radioactivity in the brain and skull, suggesting a possible species difference between rodents and primates. | |||||
| 書誌情報 |
Bioorganic & Medicinal Chemistry 巻 13, p. 1811-1818, 発行日 2005-12 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0968-0896 | |||||
