Hydroxamic acid compounds as metalloprotease and TNF inhibitors

Details Hydroxamic acid compounds as metalloprotease and TNF inhibitors Hydroxamic acid compounds as metalloprotease and TNF inhibitors

1996-04-16

1997-12-30

Dentz, Bernard

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514394, 514399, 546334, 546118, 5483097, 548180, 548204, 548217, 548235, 548247, 548253, 5483381, 5483751, 562623, A61K 31435, A61K 31415, C07D47104, C07D23516

Patent

active

057030928

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 matrixmetalloproteinases, such as stromelysin and other matrix metalloproteinases, and also inhibit the production of tumor necrosis factor (TNF), and are therefore useful for the treatment of arthritis and other related inflammatory diseases. These novel compounds are represented by Formula I below: ##STR1##

REFERENCES:
patent: 5304604 (1994-04-01), Davidson et al.
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.
J. Med. Chem., "Matrix Metalloproteinase Inhibitors Containing a (Carboxyalkyl)amino Zinc Ligand: Modification of the P1 and P2' Residues", vol. 37, 1994, pp. 674-688.

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