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Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor.
https://repo.qst.go.jp/records/47207
https://repo.qst.go.jp/records/47207eac0d9b9-2d0e-494e-8b23-48d0a2147153
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-08-06 | |||||
| タイトル | ||||||
| タイトル | Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 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 |
Oi, Norihito
× Oi, Norihito× Suzuki, Michiyuki× Terauchi, Taro× Tokunaga, Masaki× Nakatani, Yosuke× Yamamoto, Noboru× Fukumura, Toshimitsu× Zhang, Ming-Rong× Suhara, Tetsuya× Higuchi, Makoto× 大井 紀人× 鈴木 成教× 徳永 正希× 中谷 陽介× 張 明栄× 須原 哲也× 樋口 真人 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4-methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling, and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [(11)C]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX2Rs). In vivo PET study of [(11)C]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers. | |||||
| 書誌情報 |
Journal of medicinal chemistry 巻 56, 号 16, p. 6371-6385, 発行日 2013-08 |
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| 出版者 | ||||||
| 出版者 | American Chemical Society | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0022-2623 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 23879299 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/jm400772t | |||||
