Synthesis of 5- and 6-substituted 2-(4-dimethylaminophenyl)-1,3-benzoxazoles and their in vitro and in vivo evaluation as imaging agents for amyloid plaque.
A series of novel 5- and 6-substituted 2-(4-dimethylaminophenyl)-1,3-benzoxazoles was synthesized and their potential as imaging probes for Alzheimer's Disease (AD)-related amyloid plaque was evaluated in vitro and in vivo. In vitro binding affinities for Abeta1-40 peptide of several of these compounds were in the low-nanomolar range . The lowest K(i) of 9.3nM was found for N-(2-(4-(dimethylamino)phenyl)-1,3-benzoxazol-5-yl)-4-iodobenzamide (1e). Its (123)I-radiolabeled form ([(123)I]1e) was subsequently prepared by iododestannylation of the corresponding tributylstannyl precursor and evaluated in vivo in a baboon model using SPECT imaging. Contrary to our expectations, 1e did not cross the blood-brain barrier (BBB) to any significant extent.
Hausner
Sven H
SH
School of Medicine, Department of Psychiatry and Diagnostic Radiology, Yale University, VACHS, West Haven, CT 06516, USA.
Alagille
David
D
Koren
Andrei O
AO
Amici
Louis
L
Staley
Julie K
JK
Cosgrove
Kelly P
KP
Baldwin
Ronald M
RM
Tamagnan
Gilles D
GD
D000682:Amyloid / Q000032:analysis*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy
D000682:Amyloid; D001583:Benzoxazoles