Metabolically stabilized benzothiazoles for imaging of amyloid plaques.
Six new N-11C-labeled aminophenylbenzothiazoles substituted with fluorine in different positions have been synthesized and evaluated as amyloid-beta binding ligands. Our structure-property relationship studies show that the substitution pattern of the phenyl ring and the benzothiazole moiety has an influence on the metabolic stability, which in turn has an effect on the brain uptake kinetics. Two lead compounds have been identified with improved physicochemical characteristics for Abeta-plaque imaging in vivo.
Henriksen
Gjermund
G
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany. G.Henriksen@lrz.tum.de
Hauser
Andrea I
AI
Westwell
Andrew D
AD
Yousefi
Behrooz H
BH
Schwaiger
Markus
M
Drzezga
Alexander
A
Wester
Hans-Jürgen
HJ
D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D058225:Plaque, Amyloid / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals