Synthesis and evaluation of 5-fluoro-2-aryloxazolo[5,4- b ]pyridines as β-amyloid PET ligands and identification of MK-3328

Scott T. Harrison, James Mulhearn, Scott E. Wolkenberg, Patricia J. Miller, Stacey S. O'Malley, Zhizhen Zeng, David L. Williams, Eric D. Hostetler, Sandra Sanabria-Bohórquez, Linda Gammage, Hong Fan, Cyrille Sur, J. Christopher Culberson, Richard J. Hargreaves, Jacquelynn J. Cook, George D. Hartman, James C. Barrow

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as potential 18F 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.

Original languageEnglish (US)
Pages (from-to)498-502
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume2
Issue number7
DOIs
StatePublished - Jul 14 2011
Externally publishedYes

Keywords

  • Alzheimer's disease
  • PET
  • fluorine-18
  • oxazolo[5,4-b]pyridine
  • positron emission tomography
  • β-amyloid plaque

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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