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 |
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Authors: | Sven H Hausner David Alagille Andrei O Koren Louis Amici Julie K Staley Kelly P Cosgrove Ronald M Baldwin Gilles D Tamagnan |
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Institution: | 1. School of Medicine, Department of Psychiatry and Diagnostic Radiology, Yale University, VACHS, West Haven, CT 06516, USA;2. Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA |
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Abstract: | 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 Aβ1–40 peptide of several of these compounds were in the low-nanomolar range . The lowest Ki of 9.3 nM was found for N-(2-(4-(dimethylamino)phenyl)-1,3-benzoxazol-5-yl)-4-iodobenzamide (1e). Its 123I-radiolabeled form (123I]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. |
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