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  1. 原著論文

Synthesis and Preliminary Evaluation of C-11-Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4

https://repo.qst.go.jp/records/73404
https://repo.qst.go.jp/records/73404
f17f2033-2325-4b3b-9d46-621fe9bd87de
Item type 学術雑誌論文 / Journal Article(1)
公開日 2019-02-06
タイトル
タイトル Synthesis and Preliminary Evaluation of C-11-Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4
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 Deng, Xiaoyun

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Deng, Xiaoyun

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Hatori, Akiko

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WEKO 780297

Hatori, Akiko

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Chen, Zhen

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Chen, Zhen

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Kumata, Katsushi

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Kumata, Katsushi

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Shao, Tuo

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Shao, Tuo

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Zhang, Xiaofei

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Zhang, Xiaofei

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Yamasaki, Tomoteru

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Yamasaki, Tomoteru

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Kuan, Hu

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Kuan, Hu

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Yu, Qingzhen

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Yu, Qingzhen

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Ma, Longle

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Ma, Longle

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Wang, Gangqiang

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Wang, Gangqiang

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Lu, Wang

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Lu, Wang

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Shao, Yihan

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Shao, Yihan

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Josephson, Lee

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Josephson, Lee

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Sun, Shaofa

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Sun, Shaofa

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Ming-Rong, Zhang

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Ming-Rong, Zhang

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Liang, Huan

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Liang, Huan

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Hatori, Akiko

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Kumata, Katsushi

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WEKO 780314

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Yamasaki, Tomoteru

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WEKO 780315

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Kuan, Hu

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Lu, Wang

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Ming-Rong, Zhang

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Liang, Huan

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抄録
内容記述タイプ Abstract
内容記述 Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M1–M5) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M1/M4‐preferring agonist, in patients of schizophrenia and Alzheimer's disease, M1‐ or M4‐selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of 11C‐labeled positron emission tomography (PET) ligands based on a validated M4R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [11C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay‐corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq μmol−1). In vitro autoradiography studies indicated that these three ligands possess moderate‐to‐high in vitro specific binding to M4R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability.
書誌情報 ChemMedChem

巻 14, 号 3, p. 303-309, 発行日 2018-12
出版者
出版者 Wiley
ISSN
収録物識別子タイプ ISSN
収録物識別子 1860-7179
DOI
識別子タイプ DOI
関連識別子 10.1002/cmdc.201800710
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