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
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
复制标题
DOI：
10.1016/j.tetlet.2020.152060
复制
发表时间：
2020-07-02
影响因子：
1.8
通讯作者：
Liang, Steven
中科院分区：
文献类型：
--
作者：
Deng, Xiaoyun;Zhang, Yiding;Liang, Steven
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.
