Structure-activity relationship of imidazo[1,2-a]pyridines as ligands for detecting beta-amyloid plaques in the brain

J Med Chem. 2003 Jan 16;46(2):237-43. doi: 10.1021/jm020351j.


A series of novel beta-amyloid (A beta) aggregate-specific ligands, 2-(4'-dimethylaminophenyl)-6-iodoimidazo[1,2-a]pyridine, 16(IMPY), and its related derivatives were prepared. An in vitro binding study with preformed A beta aggregates showed that 16(IMPY) and its bromo derivative competed with binding of 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [125I]7(TZDM), a known ligand for A beta aggregates, with high binding affinities (K(i) = 15 and 10 nM, respectively). In vitro autoradiography of brain sections of a transgenic mouse (Tg2576) with [125I]16(IMPY) displayed high selective binding to amyloid-like structures, comparable to that observed by staining with thioflavin-S visualized under fluorescence. In vivo biodistribution after an intravenous injection of [125I]16(IMPY) in normal mice showed a high initial brain uptake and fast washout, indicating a low background activity associated with this iodinated ligand. Taken together, the data suggests that [123I]16(IMPY) may be useful for imaging A beta aggregates in patients with Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacokinetics
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Ligands
  • Male
  • Mice
  • Mice, Inbred ICR
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Structure-Activity Relationship


  • 6-iodo-2-(4'-dimethylamino-)phenyl-imidazo(1,2-a)pyridine
  • Amyloid beta-Peptides
  • Imidazoles
  • Iodine Radioisotopes
  • Ligands
  • Pyridines
  • Radiopharmaceuticals