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C-5-disubstituted barbiturates as potential molecular probes for noninvasive matrix metalloproteinase imaging.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2005 May 05; Vol. 48 (9), pp. 3400-9. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Barbiturates chemistry
Binding Sites
Humans
Iodine Radioisotopes
Isotope Labeling
Matrix Metalloproteinase 2 chemistry
Matrix Metalloproteinase 9 chemistry
Piperazines chemistry
Positron-Emission Tomography
Protease Inhibitors chemistry
Protein Binding
Pyrimidines chemistry
Radioligand Assay
Radiopharmaceuticals chemistry
Structure-Activity Relationship
Tomography, Emission-Computed, Single-Photon
Barbiturates chemical synthesis
Matrix Metalloproteinases chemistry
Piperazines chemical synthesis
Protease Inhibitors chemical synthesis
Pyrimidines chemical synthesis
Radiopharmaceuticals chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 48
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15857146
- Full Text :
- https://doi.org/10.1021/jm049145x