Document Detail

C-5-disubstituted barbiturates as potential molecular probes for noninvasive matrix metalloproteinase imaging.
MedLine Citation:
PMID:  15857146     Owner:  NLM     Status:  MEDLINE    
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.
Hans-Jörg Breyholz; Michael Schäfers; Stefan Wagner; Carsten Höltke; Andreas Faust; Helmut Rabeneck; Bodo Levkau; Otmar Schober; Klaus Kopka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  48     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-28     Completed Date:  2005-06-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3400-9     Citation Subset:  IM    
Department of Nuclear Medicine, University Hospital of the Westfälische Wilhelms-Universität, Münster, Germany.
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MeSH Terms
Barbiturates / chemical synthesis*,  chemistry
Binding Sites
Iodine Radioisotopes
Isotope Labeling
Matrix Metalloproteinase 2 / chemistry
Matrix Metalloproteinase 9 / chemistry
Matrix Metalloproteinases / chemistry*
Piperazines / chemical synthesis*,  chemistry
Positron-Emission Tomography
Protease Inhibitors / chemical synthesis*,  chemistry
Protein Binding
Pyrimidines / chemical synthesis*,  chemistry
Radioligand Assay
Radiopharmaceuticals / chemical synthesis*,  chemistry
Structure-Activity Relationship
Tomography, Emission-Computed, Single-Photon
Reg. No./Substance:
0/5-(4-(2-hydroxyethyl)piperazin-1-yl)-5-(4-(4-iodophenoxy)phenyl)pyrimidine-2,4,6-trione; 0/Barbiturates; 0/Iodine Radioisotopes; 0/Piperazines; 0/Protease Inhibitors; 0/Pyrimidines; 0/Radiopharmaceuticals; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 2; EC Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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