Merck + Co., Inc.

Scott A Polo

William K Hagmann

Philippe L Durette

Soumya P Sahoo

Sander G Mills

Malcolm MacCoss

Shrenik K Shah

Paul E Finke

Conrad P Dorn

James B Doherty

Charles G Caldwell

Kevin Tyler Chapman

Ihor E Kopka

Craig K Esser

New substituted azetidinones of the general Formula (I) which have been found to be potent elastase inhibitors and thereby useful anti-inflammatory and antidegenerative agents are described, wherein n is

Substituted azetidinones as anti-inflammatory and antidegenerative agents

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##

Substituted N-carboxyalkylpeptidyl derivatives as antidegenerative

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Yardley, PA, United States of America

Scott A Polo