Inhibition of matrix metalloproteases by substituted...

C - Chemistry – Metallurgy – 07 – C

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C07C 59/88 (2006.01) A61K 31/19 (2006.01) A61K 31/215 (2006.01) A61K 31/445 (2006.01) A61K 31/535 (2006.01) C07C 17/16 (2006.01) C07C 45/46 (2006.01) C07C 59/90 (2006.01) C07C 69/738 (2006.01) C07C 235/84 (2006.01) C07D 295/15 (2006.01) C07D 295/192 (2006.01)

Patent

CA 2253870

Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and the use of such compounds in the disease treatment is presented. The compounds of the invention have generalized formula (I), wherein T is a substituent, M is CO2H or an amide or ester derivative thereof, and R24 is a substituted amide moiety. These compounds are useful for inhibiting matrix metalloproteases and, therefore combatting conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, peptic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint 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 their use in the treatment of such conditions. Image

L'invention concerne des composés inhibiteurs de métalloprotéases matricielles, leurs compositions pharmaceutiques et une méthode de traitement de maladies à l'aide de ces composés. Les composés de l'invention ont la formule (I) dans laquelle R<25> représente une fraction phényléthyle substituée. Ces composés sont utiles pour inhiber des métalloprotéases matricielles et, par conséquent, combattre des états auxquels les métalloendo-protéinases matricielles (MMP) contribuent, tels que l'ostéo-arthrose, la polyarthrite rumatoïde, l'arthrite septique, les maladies périodontiques, l'ulcération de la cornée, la protéinurie, les maladies aortiques anévrismales, l'épidermolyse dystrophobique, les lésions bulleuses, des états conduisant à des réactions inflammatoires, des ostéopénies induites par l'activité des MMP, des maladies des articulations temporomendibulaires, des maladies démyélinisantes du système nerveux, la métastase de tumeurs ou la perte de cartilage dégénérative suite à des lésions articulaires traumatiques, et la thrombose coronaire résultant de la rupture des plaques athéroscléreuses. La présente invention concerne également des compositions pharmaceutiques et des méthodes de traitement de ces états.

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