NOVEL MACROCYCLIC COMPOUNDS AS METALLOPROTEASE INHIBITORS

摘要

This invention relates to macrocyclic molecules of formula (I) which inhibit metalloproteinases, including aggrecanase, and the production of tumor necrosis factor (TNF). The present invention also relates to pharmaceutical compositions comprising such compounds and to methods of using these compounds for the treatment of inflammatory diseases. A novel enzymatic assay was developed to detect potential inhibitors of aggrecanase. The assay uses active aggrecanase accumulated in media from stimulated bovine nasal cartilage (BNC) or related cartilage sources and purified cartilage aggrecan monomer or a fragment thereof as a substrate.