摘要 |
The present invention relates to the discovery of novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (e.g. gelatinases, stromelysins and collagenases) and TNF- alpha converting enzyme (TACE, tumor necrosis factor- alpha converting enzyme) which are useful for the treatment of diseases in which theses 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, graft rejection, cachexia, anorexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease, 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. The TACE and MMP inhibiting ortho-sulfonamido aryl hydroxamic acids of the present invention are represented by formula (I) where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons of the heteroaryl ring of group A where: A is a 5-6 membered heteroaryl having from 1 to 3 heteroatoms independently selected from N, O and S fused to a phenyl ring, or another 5-6 membered heteroaryl having from 1 to 3 heteroatoms independently selected from N, O and S, and either; and Z, R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7>, R<8> and R<9> are described in the specification, and the pharmaceutically acceptable salts thereof and the optical isomers and diastereomers thereof.
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申请人 |
AMERICAN CYANAMID COMPANY |
发明人 |
LEVIN, JEREMY, IAN;ZASK, ARIE;GU, YANSONG;ALBRIGHT, JAY, DONALD;DUI, XUMEI |