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. eCollection 2011 Jul 14.

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.