2. Academic Validation
  3. 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

  • J Med Chem. 2019 Mar 28;62(6):2974-2987. doi: 10.1021/acs.jmedchem.8b01759.
Frederik J R Rombouts 1,  Lieven Declercq,  José-Ignacio Andrés 2,  Astrid Bottelbergs 1,  Lu Chen 3,  Laura Iturrino 2,  Joseph E Leenaerts 1,  Jonas Mariën 1,  Fengbin Song 3,  Cindy Wintmolders 1,  Stijn Wuyts 1,  Chunfang A Xia 4,  Paula Te Riele 1,  Guy Bormans,  Rik Vandenberghe,  Hartmuth Kolb 4,  Diederik Moechars 1
Affiliations

Affiliations

  • 1 Janssen Research & Development, Janssen Pharmaceutica N. V. , Turnhoutseweg 30 , B-2340 Beerse , Belgium.
  • 2 Janssen Research & Development, Janssen-Cilag S. A. , C/Jarama 75A , 45007 Toledo , Spain.
  • 3 Janssen Research & Development , Welsh & McKean Roads , Spring House , Pennsylvania 19477 , United States.
  • 4 Janssen Research & Development , 3210 Merryfield Row , San Diego , California 92121 , United States.
PMID: 30810314 DOI: 10.1021/acs.jmedchem.8b01759
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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