期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 62, 期 6, 页码 2974-2987出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.8b01759
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资金
- Flanders Innovation and Entrepreneurship
In Alzheimer's disease, the density 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 profile and no apparent off-target binding. This was confirmed in rat and monkey positron emission tomography studies using [F-18]9.
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