Hydroxamic and carbocyclic acids as metalloprotease inhibitors

Details Hydroxamic and carbocyclic acids as metalloprotease inhibitors Hydroxamic and carbocyclic acids as metalloprotease inhibitors

1996-04-16

1997-11-25

Conrad, Joseph

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Radical -xh acid, or anhydride, acid halide or salt thereof...

514563, 514575, 546348, 548100, 5483381, 562405, 562430, 562440, 562444, 562452, 562455, 562512, 562801, A61K 31195, A61K 3119, C07D21172

Patent

active

056913818

ABSTRACT:
The present invention provides novel hydroxamic acids and carbocyclic acids and derivatives thereof and to pharmaceutical compositions and methods of use of these novel compounds for the inhibition of matrix metalloproteinases, such as stromelysin, and inhibit the production of tumor necrosis factor alpha, and for the treatment of arthritis and other related inflammatory diseases. These novel compounds are represented by Formula I below: ##STR1##

REFERENCES:
Mankin, Henry J. et al., Biochemical and Metabolic Abnormalities in Articular Cartilage from Osteo-Arthritic Human Hips, Apr. 1970, pp. 424-434.
Ehrlich, Michael G. et al., Correlation Between Articular Cartilage Collagenase Activity and Osteoarthritis, Sep./Oct. 1978, p. 761.
Pelletier, Jean-Pierre et al., Collagenase and Collagenolytic Activity in Human Osteoarthritic Carilage, Jan. 1983, p. 63.
Martel-Pelletier, Johanne et al, Neutral Protease Capable of Proteoglycan Digesting Activity in Osteoarthritic and Noraml Human Articular Cartilage, Mar. 1984, p. 305.
Okada, Yasunori, Localization of Matrix Metalloproteinase 3 (Stromelysin) in Osteoarthritic Cartilage and Synovium, 1992, p. 680.
Wahl, Robert C. & Richard P. Dunlap, Biochemistry and Inhibition of Collagenase and Stromelysin, 1990, p. 177.
Ogita, Takeshi et al., Matlystatins, New Inhibiotrs of Typeiv Collagenases from Actinomadura Atramentaria, Nov. 1992, p. 1723.
Stetler-Stevenson, William G., Type IV Collagenases in Tumor Invasion and Metastasis, 1990, p. 289.

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