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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

Authors
Journal
Bioorganic & Medicinal Chemistry Letters
0960-894X
Publisher
Elsevier
Publication Date
Volume
19
Issue
2
Identifiers
DOI: 10.1016/j.bmcl.2008.05.033
Keywords
  • Amyloid Plaques
  • Imaging
  • Spect
  • Benzoxazole
  • Labeling

Abstract

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 K i 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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