Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for beta-amyloid plaques

Bioorg Med Chem Lett. 2010 Mar 15;20(6):1976-80. doi: 10.1016/j.bmcl.2010.01.105. Epub 2010 Jan 25.

Abstract

The syntheses and SAR of new series of beta-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that it was possible to increase the signal-to-background ratios compared to PIB 1, as demonstrated by compounds 8 and 21.

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Benzofurans / chemical synthesis*
  • Benzofurans / pharmacokinetics*
  • Benzothiazoles / chemical synthesis*
  • Benzothiazoles / pharmacokinetics*
  • Benzoxazoles / chemical synthesis*
  • Benzoxazoles / pharmacokinetics*
  • Carbon Radioisotopes
  • Half-Life
  • Mice
  • Mice, Transgenic
  • Positron-Emission Tomography*
  • Radioligand Assay
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • Benzothiazoles
  • Benzoxazoles
  • Carbon Radioisotopes