Difluorobutyric acid metalloprotease inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 213/55 (2006.01) A61K 31/192 (2006.01) A61K 31/4164 (2006.01) A61K 31/426 (2006.01) A61K 31/428 (2006.01) A61K 31/4402 (2006.01) A61K 31/4406 (2006.01) A61K 31/4409 (2006.01) A61P 9/00 (2006.01) A61P 17/00 (2006.01) A61P 19/00 (2006.01) A61P 27/00 (2006.01) A61P 29/00 (2006.01) C07C 45/44 (2006.01) C07C 47/23 (2006.01) C07C 47/24 (2006.01) C07C 47/277 (2006.01) C07C 57/30 (2006.01) C07C 59/64 (2006.01) C07C 69/734 (2006.01) C07C 323/56 (2006.01) C07C 323/62 (2006.01) C07D 207/34 (2006.01) C07D 209/12 (

Patent

CA 2401728

Compounds which are inhibitors of metalloproteases and which are effective in treating conditions characterized by excess metalloprotease activity. In particular, the compounds have a structure according to the following Formula (I): where A, G, R1, R2, R3, X, Y and Z have the meanings described in the specification. This invention also includes optical isomers, diastereomers and enantiomers of Formula I, pharmaceutically-acceptable salts, biohydrolyzable, esters thereof and conjugates thereof. Also described are pharmaceutical compositions comprising these compounds, and methods of treating metalloprotease-related maladies using the compounds or the pharmaceutical compositions. This invention also includes intermediates useful for the synthesis of the compounds of Formula (I).

L'invention concerne des composés inhibiteurs de métalloprotéases, efficaces dans des conditions de traitement, caractérisés par un excès d'activité de leurs enzymes. Ces composés présentent, en particulier, une structure représentée par la formule (I), dans laquelle A, G, R?1¿, R?2¿, R?3¿, X, Y et Z sont tels que décrits dans les spécifications. L'invention concerne également des isomères, des diastéréomères et des énantiomères optiques représentés par la formule (I), ainsi que des sels pharmaceutiquement acceptables, des esters biohydrolysables de ceux-ci, et des conjugués de ceux-ci. L'invention concerne, en outre, des compositions pharmaceutiques comprenant lesdits composés, et des méthodes permettant de traiter des maladies induites par une métalloprotéase à l'aide desdits composés ou desdites compositions pharmaceutiques. L'invention concerne enfin des intermédiaires utilisés pour effectuer la synthèse des composés représentés par la formule (I).

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