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Design, Synthesis, and Evaluation of (4 R)-1-{3-[2-(F)Fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one ([F]T-401) as a Novel Positron-Emission Tomography Imaging Agent for Monoacylglycerol Lipase.
https://repo.qst.go.jp/records/75870
https://repo.qst.go.jp/records/758704795ca65-6d5f-42e9-b4ea-3df6218a7bde
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-05-21 | |||||
| タイトル | ||||||
| タイトル | Design, Synthesis, and Evaluation of (4 R)-1-{3-[2-(F)Fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one ([F]T-401) as a Novel Positron-Emission Tomography Imaging Agent for Monoacylglycerol Lipase. | |||||
| 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 |
Hattori, Yasushi
× Hattori, Yasushi× Aoyama, Kazunobu× Maeda, Jun× Arimura, Naoto× Takahashi, Yasuko× Sasaki, Masako× Fujinaga, Masayuki× Seki, Chie× Nagai, Yuji× Kawamura, Kazunori× Yamasaki, Tomoteru× Ming-Rong, Zhang× Higuchi, Makoto× Koike, Tatsuki× Hattori, Yasushi× Maeda, Jun× Fujinaga, Masayuki× Seki, Chie× Nagai, Yuji× Kawamura, Kazunori× Yamasaki, Tomoteru× Ming-Rong, Zhang× Higuchi, Makoto |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase involved in endocannabinoid and inflammatory signaling. Positron-emission tomography (PET) imaging of MAGL serves to validate target engagement of therapeutic MAGL inhibitors as well as to investigate MAGL levels under normal and disease conditions. However, PET radioligands with reversible binding kinetics for MAGL, which allow quantitative assessment of MAGL, are hitherto unavailable. In this study, we designed and synthesized fluoro-containing PET probes starting from a recently identified piperazinyl pyrrolidine-2-one derivative with reversible binding to MAGL. By tailoring the lipophilicity of the molecule to optimize nonspecific binding and blood-brain barrier permeability, we successfully identified two compounds that show high uptake to regions enriched with MAGL. PET imaging of wild-type and MAGL-deficient mice as well as a macaque monkey indicated that [F]5 ((4 R)-1-{3-[2-(F)fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one, [F]T-401) specifically binds to MAGL with adequate reversibility, yielding a high contrast for MAGL within an appropriate imaging time. | |||||
| 書誌情報 |
Journal of medicinal chemistry 巻 62, 号 5, p. 2362-2375, 発行日 2019-02 |
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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 | 30753069 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acs.jmedchem.8b01576 | |||||
| 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.8b01576 | |||||
