C-5-disubstituted barbiturates as potential molecular probes for noninvasive matrix metalloproteinase imaging

J Med Chem. 2005 May 5;48(9):3400-9. doi: 10.1021/jm049145x.


Studies have demonstrated a positive correlation between inflammation, metastasis, or atherosclerosis and the unbalanced or culminated expression of matrix metalloproteinases (MMPs). The molecular imaging of locally upregulated MMP activity in vivo is a clinical challenge. Actually, radioligands based on nonpeptidyl MMP inhibitors (MMPIs) are currently in development as putative radiopharmaceutical agents for the noninvasive in vivo assessment of activated MMPs. Nonpeptidyl MMPIs bind to the zinc active site of the activated enzyme via mono- (e.g. carboxylate) or bidentate (e.g. hydroxamate) complexation thereby exhibiting a broad-spectrum MMP binding potency. Thus, these mentioned endopeptidase inhibitors should be useable lead compounds for the redevelopment as diagnostic MMPI radiotracers. Recently, the non-hydroxamate C-5-disubstituted pyrimidine-2,4,6-triones were disclosed as subgroup-selective MMP inhibitors. We here describe a set of fine-tuned barbiturates as a new class of MMPI radiotracers for the noninvasive in vivo visualization of activated MMPs using scintigraphic techniques such as SPECT or PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Barbiturates / chemical synthesis*
  • Barbiturates / chemistry
  • Binding Sites
  • Humans
  • Iodine Radioisotopes
  • Isotope Labeling
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinases / chemistry*
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Positron-Emission Tomography
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protein Binding
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Radioligand Assay
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Structure-Activity Relationship
  • Tomography, Emission-Computed, Single-Photon


  • 5-(4-(2-hydroxyethyl)piperazin-1-yl)-5-(4-(4-iodophenoxy)phenyl)pyrimidine-2,4,6-trione
  • Barbiturates
  • Iodine Radioisotopes
  • Piperazines
  • Protease Inhibitors
  • Pyrimidines
  • Radiopharmaceuticals
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9