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ID: ALA1154546

Journal: Bioorg Med Chem Lett

Title: 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: Hausner SH, Alagille D, Koren AO, Amici L, Staley JK, Cosgrove KP, Baldwin RM, Tamagnan GD.

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.

CiteXplore: 19081717

DOI: 10.1016/j.bmcl.2008.05.033