title: Synthesis and In Vitro Evaluation of Imidazo[1,2-b]pyridazines as Ligands for β-Amyloid Plaques.
abstract: A series of imidazo[1,2-b]pyridazine derivatives were synthesized and evaluated for binding to amyloid plaques in vitro using synthetic aggregates of Aβ1-40. Binding affinities of these compounds were found to range from 11.0 to >1000 nM, depending on the various substitution patterns in the 6-position and 2-position. 2-(4'-Dimethylaminophenyl)-6-(methylthio)imidazo[1,2-b]pyridazine (4) showed high binding affinity (K i = 11.0 nM) and might be useful for the development of novel positron emission tomography radiotracers for imaging Aβ plaques.
authors.affiliation: Department of Radiology.
authors.forename: Fanxing
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Institute for Degenerative Disorders, New Haven, Connecticut 06510.
authors.forename: David
authors.initials: D
authors.lastname: Alagille
authors.affiliation: Institute for Degenerative Disorders, New Haven, Connecticut 06510.
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
authors.affiliation: Center for Neurodegenerative Disease and Department of Neurology.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ciliax
authors.affiliation: Center for Neurodegenerative Disease and Department of Neurology.
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
authors.affiliation: Department of Radiology.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
keywords: Imidazo[1,2-b]pyridazine; positron emission tomography; structure−activity relationship; β-amyloid plaque