Substituted N-carboxyalkylpeptidyl derivatives as antidegenerati

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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514 18, 530331, 562445, 562575, A61K 3805

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059325518

ABSTRACT:
Novel N-carboxyalkylpeptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. The matrix metalloendoproteinases are a family of zinc-containing proteinases including but not limited to stromelysin, collagenase, and gelatinase, that are capable of degrading the major components of articular cartilage and basement membranes. The inhibitors claimed herein may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to a permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation. ##STR1##

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K.T. Chapman, et al., Journ. Med. Chem., 36: 4293-4301 (1993) Inhibition of Matrix Metalloproteinases by N-Carboxyalkyl Peptides.
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Biochemical Pharmacology, vol. 36, No. 7, 1987 pp. 995-1002, Pergamon Journals Ltd; C.B. Caputo, et al.: "Proteoglycan degradtion by a chondrocyte Metalloptrotease".
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