Synthesis and preliminary evaluation of 18F-labeled 1-(6,7-dimethyl-4-(methylamino)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-2-(trans-2-(6-fluoropyridin-3-yl)cyclopropyl)ethan-1-one for imaging muscarinic acetylcholine receptor subtype 4

被引：1

作者：

Deng, Xiaoyun ^{[1
,2
]}

Zhang, Yiding ^{[3
]}

Rong, Jian ^{[1
,2
]}

Kumata, Katsushi ^{[3
]}

Shao, Tuo ^{[1
,2
]}

Wang, Gangqiang ^{[4
]}

Hatori, Akiko ^{[3
]}

Mori, Wakana ^{[3
]}

Yu, Qingzhen ^{[1
,2
]}

Hu, Kuan ^{[3
]}

Fujinaga, Masayuki ^{[3
]}

Shao, Yihan ^{[5
]}

Josephson, Lee ^{[1
,2
]}

Sun, Shaofa ^{[4
]}

Zhang, Ming-Rong ^{[3
]}

Liang, Steven ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA

[2] Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA

[3] Natl Inst Quantum & Radiol Sci & Technol, Natl Inst Radiol Sci, Dept Radiopharmaceut Dev, Chiba 2638555, Japan

[4] Hubei Univ Sci & Technol, Coll Nucl Technol & Chem & Biol, Hubei Collaborat Innovat Ctr Nonpower Nucl Techno, Xianning, Peoples R China

[5] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA

来源：

TETRAHEDRON LETTERS | 2020年 / 61卷 / 27期

基金：

美国国家卫生研究院;

关键词：

Muscarinic acetylcholine receptor subtype 4 (M-4); Fluorine; 18; Positron emission tomography (PET); Autoradiography; Alzheimer's disease; IDENTIFICATION; LOCALIZATION; XANOMELINE; DISCOVERY; AGONIST; DISEASE; BRAIN;

D O I：

10.1016/j.tetlet.2020.152060

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Positive allosteric modulators of muscarinic acetylcholine receptor subtype 4 have been identified as promising activators for the treatment of neurological disorders and neurodegenerative diseases, including schizophrenia, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Herein we report the synthesis and preliminary evaluation of a F-18-labeled positron emission tomography ligand based on a M-4 activator (7). F-18-Isotopologue of 7 was prepared in a reasonable radiochemical yield with high radiochemical purity (>99%) and high molar activity (>37 GBq/mu mol). In vitro autoradiography studies indicated that the ligand possessed moderate in vitro specific binding. Dynamic PET studies in vivo demonstrated that [F-18]7 (also named as [1(8)F]M4R-1911) failed to cross the blood-brain barrier. Therefore, further chemical scaffold optimization in chemotype of 7 is necessary to overcome limited brain permeability and improve specific binding. (C) 2020 Elsevier Ltd. All rights reserved.

引用

页数：6

共 36 条

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