用于正电子发射断层显像（PET）成像AMPA受体的C标记的4-环丙基-7-（3-甲氧基苯氧基）-3,4-二氢-2-苯并[1,2,4]噻二嗪1,1-二氧化物的放射性合成及初步评价
Radiosynthesis and preliminary evaluation of C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2-benzo[] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors.
作者信息
Chen Jiahui, Gan Jiefeng, Sun Jiyun, Chen Zhen, Fu Hualong, Rong Jian, Deng Xiaoyun, Shang Jingjie, Gong Jian, Shao Tuo, Collier Lee, Wang Lu, Xu Hao, Liang Steven H
机构信息
Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, 613 West Huangpu Road, Tianhe District, Guangzhou 510630, China.
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.
出版信息
Tetrahedron Lett. 2020 Mar 19;61(12). doi: 10.1016/j.tetlet.2020.151635. Epub 2020 Jan 17.
Abstract
The α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) belong to the family of ionotropic transmembrane receptors for glutamate (iGluRs) that are implicated in the pathology of neurological disorders and neurodegenerative diseases. Inspired by a recently developed positive allosteric modulator of AMPARs, 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2-benzo[ ][1,2,4]thiadiazine 1,1-dioxide (; EC = 2.0 nM), we designed a new synthetic route for -protected phenolic precursor and efficiently radiolabeled a PET ligand [C] ([C]) using a modified one-pot two-step strategy in high radiochemical yield and high molar activity. Preliminary evaluation was carried out to investigate the suitability of [C] as a potential PET probe for AMPAR imaging.
摘要
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）属于离子型谷氨酸跨膜受体（iGluRs）家族，与神经疾病和神经退行性疾病的病理过程有关。受最近开发的一种AMPARs正变构调节剂4-环丙基-7-（3-甲氧基苯氧基）-3,4-二氢-2-苯并[1,2,4]噻二嗪1,1-二氧化物（；EC = 2.0 nM）的启发，我们设计了一种新的合成路线来合成受保护的酚类前体，并使用改良的一锅两步策略以高放射化学产率和高摩尔活性高效地对PET配体[C]（[C]）进行放射性标记。进行了初步评估以研究[C]作为AMPAR成像潜在PET探针的适用性。
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