Furanone derivatives as inhibitors of cathepsin s

Details Furanone derivatives as inhibitors of cathepsin s Furanone derivatives as inhibitors of cathepsin s

C - Chemistry, Metallurgy

07

D

C07D 409/12 (2006.01) A61K 31/365 (2006.01) A61K 31/381 (2006.01) A61K 31/40 (2006.01) A61K 31/4015 (2006.01) A61P 37/02 (2006.01) C07D 307/22 (2006.01) C07D 307/32 (2006.01) C07D 307/68 (2006.01) C07D 307/85 (2006.01) C07D 309/14 (2006.01) C07D 309/30 (2006.01) C07D 405/12 (2006.01) C07D 405/14 (2006.01) C07D 409/14 (2006.01)

Patent

CA 2374297

Cathepsin S is a highly active cysteine protease belonging to the papain superfamily. It is found mainly in lymph nodes, spleen, and macrophages and this limited occurrence suggests the potential involvement of this enzyme in the pathogenesis of degenerative disease. The invention relates to novel protease inhibitors, particularly inhibitors of the cysteine proteases of the papain superfamily and more particularly to Cathepsin S. The inhibitors are Furanone derivatives of Formula (II) which have a characteristic non-hydrogen substituent R5. They are selective over other members of the family and in particular show selectivity over other members of the Cathepsin family such as L and K.

La cathepsine S est une protéase à cystéine très active appartenant à la super-famille de la papaïne. On la trouve principalement dans les ganglions lymphatiques, la rate, et dans les macrophages et cette présence limitée suggère une implication potentielle de cette enzyme dans la pathogénèse de maladie dégénérative. La présente invention concerne des inhibiteurs de protéase, en particulier des inhibiteurs de protéases à cystéine de la super-famille de la papaïne et plus particulièrement de la cathepsine S. Ces inhibiteurs sont des dérivés furanones de formule (II) qui possèdent un substituant non hydrogène caractéristique R5. Ils présentent une sélectivité par rapport aux autres membres de la famille et, en particulier, présentent une sélectivité sur d'autres membres de la famille des cathepsines telles que les cathepsines L et K.

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