Development of [F-18]Thiazolylacylaminopyridine-Based Glycogen synthase Kinase-3 beta ligands for positron emission tomography imaging

作者全名："Jia, Jianhua; Yi, Lan; Xia, Zhu; Yang, Meixian; Qiu, Dachuan; Zhao, Zhenghuan; Peng, Zhiping"

作者地址："[Jia, Jianhua; Yi, Lan; Yang, Meixian; Qiu, Dachuan; Zhao, Zhenghuan; Peng, Zhiping] Chongqing Med Univ, Coll Basic Med Sci, Dept Radiol Med, Chongqing 400016, Peoples R China; [Xia, Zhu] Chongqing Med Univ, Affiliated Hosp 1, Dept Nucl Med, Chongqing 400016, Peoples R China"

通信作者："Jia, JH; Peng, ZP (通讯作者)，Chongqing Med Univ, Coll Basic Med Sci, Dept Radiol Med, Chongqing 400016, Peoples R China."

来源：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

ESI学科分类：CHEMISTRY

WOS号：WOS:001017831200001

JCR分区：Q2

影响因子：2.5

年份：2023

卷号：88

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Glycogen synthase kinase-3 beta; [F-18]Thiazolylacylaminopyridines; PET imaging agents; Alzheimer's disease

摘要："Glycogen synthase kinase-3 beta (GSK-3 beta) regulates numerous of CNS-specific signaling pathways, and is particularly implicated in various pathogenetic mechanisms of Alzheimer's disease (AD). A noninvasive method for detecting GSK-3 beta in AD brains via positron emission tomography (PET) imaging could enhance the understanding of AD pathogenesis and aid in the development of AD therapeutic drugs. In this study, an array of fluorinated thiazolyl acylaminopyridines (FTAAP) targeting GSK-3 beta were designed and synthesized. These compounds showed moderate to high affinities (IC50 = 6.0 - 426 nM) for GSK-3 beta in vitro. A potential GSK-3 beta tracer, [F-18]8, was successfully radiolabeled. [F-18]8 had unsatisfactory initial brain uptake despite its suitable lipophilicity, molecular size and good stability. Further structural refinement of the lead compound is needed to develop promising [F-18]-labeled radiotracers for the detection of GSK-3 beta in AD brains."

基金机构："Natural Science and Technology Research Project of Chongqing Education Commission [KJQN202100416, CXQT71017]"

基金资助正文：This work was supported by the Natural Science and Technology Research Project of Chongqing Education Commission (KJQN202100416 and CXQT71017) .