| abstract |
Matrix metalloproteinases (MMPs) are a group of enzymes involved in the pathological degradation of connective tissue and underlying membranes. These zinc-containing endopeptidases are composed of several subtypes of enzymes, which include collagenases, stromellisins and gelatinases. TNF-α (TACE) conversion enzymes, a pro-inflammatory cytokine, catalyze the formation of TNF-α from a membrane-bound pro-TNF-α protein. Small molecules, such as MMP and TACE inhibitors, are expected to have the potential to treat a range of disease states. The present invention provides non-peptide inhibitors of matrix metalloproteinases (MMP) and enzymes for the conversion of TNF-α (TACE), low molar mass, for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal diseases, bone disease, diabetes (resistance according to insulin) and HIV infection. The compounds of this invention are represented by formula (I) wherein R1, R2, R3 and R4 are described herein. |