Merck + Co., Inc.

Craig K Esser

William K Hagmann

Philippe L Durette

Ihor E Kopka

Charles G Caldwell

Soumya P Sahoo

Kevin Tyler Chapman

Richard L Tolman

William F Hoffman

Shrenik K Shah

Bruce E Witzel

Donald W Graham

Gary H Rasmusson

Malcolm Maccoss

Ravindra N Guthikonda

Nathan G Steinberg

Kenny Kin Wong

Scott A Polo

Renee Chabin

Novel N-carboxyalkylpeptidyl compounds represented by the formula ##STR1## which are found to be useful inhibitors of matrix metalloendoproteinases which degrade major components of articular cartilage and basement membranes causing degenerative diseases such as arthritis, periodontal disease, corneal ulceration and the like, and certain cancers, are described.

Substituted N-carboxyalkylpeptidyl derivatives as antidegenerative agents

Substituted 2-aminopyridines as inhibitors of nitric oxide synthase

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

Described are new 16-substituted and 7,16-disubstituted 4-aza-5.alpha.-androstan-3-ones and related compounds as 5.alpha.-reductase inhibitors.

Substituted 4-aza-5.alpha.-androstan-ones as 5.alpha.-reductase

Carboxy-peptidyl derivatives as antidegenerative active agents

Compounds of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.1 is selected from the group consisting of hydrogen and C.sub.1-10 alkyl;

15-substituted 4-azasteroids

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Belford, NJ, United States of America

Craig K Esser