| 摘要 |
PURPOSE: Provided are novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (e.g. gelatinases, stromelysins and collagenases) and TNF-.agr. converting enzyme(TACE, tumor necrosis factor-.agr. converting enzyme). CONSTITUTION: A TACE and MMP inhibiting ortho-sulfonamido aryl hydroxamic acids are represented by formula (1) where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons on group A where: A is a 5 to 7 membered, monocyclic, non-aromatic heterocyclic ring having from 1 to 2 heteroatoms independently selected from N, O, and S, optionally substituted by R1, R2, R3 and R4; a -C3-C7-cycloalkyl containing 0-2 double bonds and optionally substituted with R1, R2, R3 and R4; or -CHR5=CHR6-; and Z, R1, R2, R3, R4, R5, R6, R7, R8 and R9 are described in the specification. These inhibitors are useful for the treatment of diseases in which these enzymes 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, HIV infection.
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