Synthesis and Evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as β-Amyloid PET Ligands and Identification of MK-3328

  • ACS Med Chem Lett. 2011 Apr 18;2(7):498-502. doi: 10.1021/ml200018n.
Scott T Harrison  1 ,  James Mulhearn  1 ,  Scott E Wolkenberg  1 ,  Patricia J Miller  1 ,  Stacey S O'Malley  1 ,  Zhizhen Zeng  1 ,  David L Williams Jr  1 ,  Eric D Hostetler  1 ,  Sandra Sanabria-Bohórquez  1 ,  Linda Gammage  1 ,  Hong Fan  1 ,  Cyrille Sur  1 ,  J Christopher Culberson  1 ,  Richard J Hargreaves  1 ,  Jacquelynn J Cook  1 ,  George D Hartman  1 ,  James C Barrow  1
Affiliations
  • 1. Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
PMID: 24900338 DOI: 10.1021/ml200018n
Abstract

5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as potential (18)F containing β-amyloid PET ligands. In competition binding assays using human AD brain homogenates, compounds 14b, 16b, and 17b were identified as having favorable potency versus human β-amyloid plaque and were radiolabeled for further evaluation in in vitro binding and in vivo PET imaging experiments. These studies led to the identification of 17b (MK-3328) as a candidate PET ligand for the clinical assessment of β-amyloid plaque load.

Keywords
Alzheimer’s disease; PET; fluorine-18; oxazolo[5,4-b]pyridine; positron emission tomography; β-amyloid plaque.
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