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

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

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:JOURNAL OF MEDICINAL CHEMISTRY 2019-03, Vol.62 (6), p.2974-2987
Hauptverfasser: Rombouts, Frederik J.R, Declercq, Lieven, Andres, Jose-Ignacio, Bottelbergs, Astrid, Chen, Lu, Iturrino, Laura, Leenaerts, Joseph E, Marien, Jonas, Song, Fengbin, Wintmolders, Cindy, Wuyts, Stijn, Xia, Chunfang A, te Riele, Paula, Bormans, Guy, Vandenberghe, Rik, Kolb, Hartmuth, Moechars, Diederik
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:0022-2623