Discovery of <i>N</i>-(4-[<sup>18</sup>F]Fluoro-5-methylpyridin-2-yl)isoquinolin-6-amine (JNJ-64326067), a New Promising Tau Positron Emission Tomography Imaging Tracer
作者:Frederik J. R. Rombouts、Lieven Declercq、José-Ignacio Andrés、Astrid Bottelbergs、Lu Chen、Laura Iturrino、Joseph E. Leenaerts、Jonas Mariën、Fengbin Song、Cindy Wintmolders、Stijn Wuyts、Chunfang A. Xia、Paula te Riele、Guy Bormans、Rik Vandenberghe、Hartmuth Kolb、Diederik Moechars
DOI:10.1021/acs.jmedchem.8b01759
日期:2019.3.28
and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure-activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic
在阿尔茨海默氏病中,聚集的tau蛋白的密度和扩散与神经退行性变和认知能力下降密切相关,从而使聚集的tau成像成为令人信服的生物标记。围绕异喹啉命中进行结构-活性关系探索,然后探索耐受的氟化位置,使我们能够鉴定出9(JNJ-64326067),这是一种有效且选择性的聚集tau蛋白,具有良好的药代动力学特征且无明显脱靶捆绑。这在使用[18F] 9的大鼠和猴子正电子发射断层扫描研究中得到了证实。