Inhibition of matrix metalloproteases by substituted biaryl oxob

Details Inhibition of matrix metalloproteases by substituted biaryl oxob Inhibition of matrix metalloproteases by substituted biaryl oxob

1997-05-15

1999-07-20

Richter, Johann

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

544183, 544237, 544298, 544285, 544287, 540504, 548531, 548210, 548221, 548183, 5483175, 5483615, 5483044, 546142, 562495, A61K 3153, C07D25310, C07C 6364

Patent

active

059256370

ABSTRACT:
Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have the generalized formulas: ##STR1## wherein r is 0-2, T is selected from ##STR2## and R.sup.40 is a mono- or bi-heterocyclic structure. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, comeal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibularjoint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from athrosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.

REFERENCES:
Sahoo, et al., Inhibition of Matrix Metalloproteinases by N-Carboxyalkyl Dipeptides: Enhanced Potency and Selectivity with Substituted P.sub.1 ' Homophenylanines, Biorganic & Medicinal Chemistry Letters, 5(20), 2441-2446 (1995).
Child, et al., Fenbufen, a New Anti-Inflammatory Analgesic: Synthesis and Structure-Activity Relationships of Analogs, Journal of Pharmaceutical Sciences, 66(4), 466-476 (1977).

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