Discovery of N-(4-[18 F]Fluoro-5-methylpyridin-2-yl)isoquinolin-6-amine (JNJ-64326067), a New Promising Tau Positron Emission Tomography Imaging Tracer

Journal of Medicinal Chemistry
Frederik RomboutsDiederik Moechars

Abstract

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 [18F]9.

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Citations

Nov 11, 2019·International Journal of Molecular Sciences·Jan Torben SchilleHugo Murua Escobar
Jun 15, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Mark E SchmidtHartmuth Kolb
Aug 14, 2020·ACS Chemical Neuroscience·Raeann M DaltonJacob M Hooker
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Mar 21, 2021·Brain : a Journal of Neurology·Steven Y YapKerstin Sander

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