Preparation and use of ortho-sulfonamido heteroaryl hydroxamic a

Details Preparation and use of ortho-sulfonamido heteroaryl hydroxamic a Preparation and use of ortho-sulfonamido heteroaryl hydroxamic a

1999-06-11

2000-12-19

Shah, Mukund J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514447, 5462811, 5462814, 549 68, C07D40912, C07D33338, A61K 31381

Patent

active

06162814&

ABSTRACT:
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 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, 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
eovascularization. The TACE and MMP inhibiting ortho-sulfonamide aryl hydroxamic acids of the present invention are represented by the formula ##STR1## where the hydroxamic acid moiety and the sulfanamido moiety are bonded to adjacent carbons on group A where A is defined as:

REFERENCES:
patent: 5455258 (1995-10-01), Macpherson et al.
patent: 5506242 (1996-04-01), Macpherson et al.
patent: 5552419 (1996-09-01), Macpherson et. al.
J. Med. Chem., 40, 2525, MacPherson er al. (1997).

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