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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid / analysis*
  • Benzoxazoles / chemical synthesis*
  • Benzoxazoles / pharmacokinetics
  • Benzoxazoles / pharmacology*
  • Blood-Brain Barrier
  • Chromatography, High Pressure Liquid
  • Drug Evaluation, Preclinical
  • Magnetic Resonance Spectroscopy

Substances

  • Amyloid
  • Benzoxazoles