INHIBITION DES MATRICES METALLOPROTEASES PAR LA SUBSTITUTION D'ACIDE BIARYL OXOBUTYRIQUE

LA MATRICE METALLOPROTEASE INHIBITANT LES COMPOSES, LES COMPOSITIONS PHARMACEUTIQUES ET LA METHODE DE TRAITEMENT DE LA MALADIE EN UTILISANT CES COMPOSES SONT PRESENTES. LES COMPOSES DE CETTE INVENTION ONT LES FORMULES GENERALISEES : R40 is A MONO-OU BI-HETEROCYCLIC STRUCTURE. CES COMPOSES SONT UTILES POUR INHIBITANT LES MATRICES METALLOPROTEASES ET COMBATTANT LES CONDITIONS OU MMP'S : (a) ALLEGER LES EFFETS D'OSTEOARTHRITIS. RHEUMATOID ULCERATION DE LA CORNEE, PROTEINURIA. MALADIE ANEURYSMAL AORTIQUE. EPIDERMLYSIS DISTROPHOBIQUE. BULLOSA DES CONDITIONS MENANT A DES REACTIONS INFLAMMATOIRES OSTEOPENIAS EN MEDIATION PAR L'ACTIVITE MMP. MALADIE TEMPERO MANDIBULAIRE DES JOINTS DES MALADIES DEMYELANTE DU SYSTEME NERVEUX : (b) RETARDER LA TUMEUR METASTASIS ET LA PERTE DEGENERATIVE DU CARTILAGE SUIVANT UNE BLESSURE TRAUMATIQUE DES JOINTS : (C) REDUIT LA THROMBOSIS CORONAIRE DE LA RUPTURE DE LA PLAQUE ATHROSCLEROTIQUE ; OU (e) EFFET DU CONTROLE DE LA NAISSANCE. CETTE PRESENTE INVENTION DONNE AUSSI DES COMPOSITIONS ET METHODES PHARMACEUTIQUES POUR TRAITER CES CONDITIONS . Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have generalized formula (1) wherein r is 0-2, T is selected from (a) and (b) and R 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, 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 of 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.