2,5-Diarylisothiazolone: novel inhibitors of cytokine-induced cartilage destruction
| Autor: | Stephen W. Wright, Bruce Freimark, Jean M. Williams, M. A. Pratta, Ronald L. Magolda, E. C. Arner, Susan R. Sherk, Joseph J. Petraitis, John V. Giannaras |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Magnetic Resonance Spectroscopy
Spectrophotometry Infrared medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Matrix metalloproteinase Organ culture Biochemistry Structure-Activity Relationship Organ Culture Techniques Reductive metabolism Osteoarthritis Drug Discovery medicine Nasal septum Animals Cartilage destruction Enzyme Inhibitors Molecular Biology Chemistry Hydrolysis Cartilage Organic Chemistry Thiazoles medicine.anatomical_structure Cytokine Microsome Molecular Medicine Cattle Interleukin-1 |
| Zdroj: | Bioorganic & Medicinal Chemistry. 4:851-858 |
| ISSN: | 0968-0896 |
| Popis: | A series of 2,5-diarylisothiazolones is reported that inhibit the IL-1β-induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, nonpeptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases. |
| Databáze: | OpenAIRE |
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