2-Arylimidazo[2,1- b]benzothiazoles: A new family of amyloid binding agents with potential for PET and SPECT imaging of Alzheimer’s brain

• Published in: Bioorganic & medicinal chemistry letters 2011-05, Vol.21 (10), p.2966-2968
• Main Authors: Alagille, David, DaCosta, Herve, Baldwin, Ronald M., Tamagnan, Gilles D.
• Format: Article
• Language: English
• Subjects: 2-Aryl-imidazo[2,1- b]benzothiazole; Alzheimer Disease - diagnosis; Alzheimer’s disease; amyloid; Amyloid - chemistry; Amyloid - metabolism; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; binding agents; binding capacity; Binding, Competitive; Biological and medical sciences; Biological Assay; brain; chemistry; Humans; image analysis; Imidazoles - chemical synthesis; Imidazoles - chemistry; Medical sciences; Neuropharmacology; new family; PET imaging; Pharmacology. Drug treatments; Positron-Emission Tomography; Protein Binding; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; SPECT imaging; Tomography, Emission-Computed, Single-Photon; β-Amyloid
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.03.052

We designed and synthesized a small series of 2-aryl-imidazo[2,1- b]benzothiazole, representing a combination of motifs from the two most potent amyloid imaging agents, PIB and IMPY. The binding affinity of the new compounds ranged from 6 to 133 nM. Among the best compounds, 3b ( K i = 6 nM) can be labeled with 11CH 3 for PET imaging whereas 3j ( K i = 10.9 nM) can be labeled with 123I for SPECT imaging.