Radiosynthesis and preliminary evaluation of 11C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors
Radiosynthesis and preliminary evaluation of 11C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors
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DOI：
10.1016/j.tetlet.2020.151635
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发表时间：
2020-03-19
影响因子：
1.8
通讯作者：
Liang, Steven H.
中科院分区：
文献类型：
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作者：
Chen, Jiahui;Gan, Jiefeng;Liang, Steven H.
Alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic酸受体(AMPAR)属于谷氨酸离子亲和性跨膜受体(IGluRs)家族，参与神经系统疾病和神经退行性疾病的病理过程。受最近开发的AMPAR正变构调节剂4-cyclopropy1-7-(3-methoxyphenoxy)-3，4-dihydro-2H-benzo[e][1，2，4]thiadiazine 1，1-二氧化物(16；EC50=2.0 nM)的启发，我们设计了一条新的N-保护酚类前体13的合成路线，并采用改进的一锅两步法高效地标记了配体[C-11]AMPA-1905([C-11]16)，获得了高的放化产率和高摩尔活度。初步的体内评价是为了研究[C-11]16作为潜在的用于AMPAR成像的PET探针的适宜性。(C)2020爱思唯尔有限公司。保留所有权利。
The alpha-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-cyclopropy1-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (16; EC50 = 2.0 nM), we designed a new synthetic route for N-protected phenolic precursor 13 and efficiently radiolabeled a PET ligand [C-11]AMPA-1905 ([C-11]16) using a modified one-pot two-step strategy in high radiochemical yield and high molar activity. Preliminary in vivo evaluation was carried out to investigate the suitability of [C-11]16 as a potential PET probe for AMPAR imaging. (C) 2020 Elsevier Ltd. All rights reserved.