PREPARATION AND USE OF ORTHO-SULFONAMIDO HETEROARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS

摘要

PURPOSE: Novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases(MMP, e.g. gelatinases, stromelysins and collagenases) and TNF-.agr. converting enzyme(TACE, tumor necrosis factor-.agr. converting enzyme) are provided. CONSTITUTION: Ortho-sulfonamido heteroaryl hydroxamic acids of formula(A) are useful for the treatment of diseases in which the enzymes MMP and TACE are implicated, such as arthritis, tumor growth and metastasis, angiogenesis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint injury, demyelinating diseases of the nervous system, graft rejection,cachexia, anorexia, inflammation, fever, insulin resistance, septic shock,congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel diseases, HIV infection, age related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis/neovascularization.