Matrix metalloproteinase inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 209/48 (2006.01) A61K 31/4035 (2006.01) A61P 29/00 (2006.01) C07D 401/06 (2006.01)

Patent

CA 2661299

The present invention relates to .beta.-hydroxy and amino substituted carboxylic acids, which act as matrix metalloprotease inhibitors, particularly diastereomerically pure .beta.-hydroxy carboxylic acids, corresponding processes for the synthesis of and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over- activation of a matrix metalloproteinase using the compounds.

La présente invention concerne des acides carboxyliques à substitution .beta.-hydroxy et amino qui agissent en tant qu'inhibiteurs de la métalloprotéase matricielle, en particulier des acides .beta.-hydroxy carboxyliques purs sur le plan diastéréomérique. L'invention concerne également les procédés correspondants de synthèse des composés de la présente invention et des compositions pharmaceutiques contenant lesdits composés. Les composés de la présente invention sont utilisables pour le traitement de diverses maladies inflammatoires, auto-immunes et allergiques, telles que l'asthme, la polyarthrite rhumatoïde, la bronchopneumopathie chronique obstructive (Chronic Obstructive Pulmonary Disease : COPD), la rhinite, l'arthrose, le psoriasis arthropathique, le psoriasis, la fibrose pulmonaire, les retards de cicatrisation, l'inflammation pulmonaire, le syndrome de détresse respiratoire aiguë, la parodontite, la sclérose en plaques, la gingivite, l'athérosclérose, la prolifération néointimale qui conduit à la resténose et à l'insuffisance cardiaque ischémique, les attaques, les maladies rénales, la métastase tumorale et d'autres affections inflammatoires caractérisées par la sur-expression et la sur-activation d'une métalloprotéase matricielle, à l'aide des composés.

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