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. 2009 Jan 15;19(2):543-5.
doi: 10.1016/j.bmcl.2008.05.033. Epub 2008 May 15.

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

Sven H Hausner  1 , David Alagille, Andrei O Koren, Louis Amici, Julie K Staley, Kelly P Cosgrove, Ronald M Baldwin, Gilles D Tamagnan
Affiliations

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

Sven H Hausner et al. Bioorg Med Chem Lett. .

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 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.

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Figures

Scheme 1
Scheme 1
Synthesis of the target substituted benzoxazoles.
Scheme 2
Scheme 2
Synthesis of the putative [123I]-labeled SPECT imaging probe [123I]1e.
See this image and copyright information in PMC

References

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