Derivatives of 4,6-diamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one: potential antagonist ligands for imaging the A2A adenosine receptor by positron emission tomography (PET)

Eur J Med Chem. 2005 May;40(5):421-37. doi: 10.1016/j.ejmech.2004.12.005. Epub 2005 Feb 25.

Abstract

The importance of the brain A2A adenosine receptor (A(2A)AR) in movement disorders urges the development of radiolabeled ligands for imaging those receptors by positron emission tomography (PET). This study evaluated one class of A(2A)AR antagonists, derivatives of 4-amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one, 10a, as agents for imaging brain A(2A)ARs by PET.. Modifications of a literature synthesis of 10a efficiently generated analogs 10b-s for pharmacological evaluation. Radioligand binding experiments showed affinities for the rat brain A(2A)AR in the low nanomolar range but similar affinities for the A1AR and substantial unspecific binding. Autoradiography employing [3H]10a, showing that high unspecific binding obscured specific binding to both the A1AR and A(2A)AR. Thus, compounds 10b-s are unsuitable as ligands for imaging brain A(2A)ARs by PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists*
  • Animals
  • Autoradiography
  • Binding, Competitive / physiology
  • Brain / diagnostic imaging
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Positron-Emission Tomography / methods
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology
  • Radioligand Assay
  • Rats
  • Spectrometry, Mass, Electrospray Ionization
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology
  • Tritium

Substances

  • Adenosine A2 Receptor Antagonists
  • Ligands
  • Quinoxalines
  • Triazoles
  • Tritium