Inhibitors of copper-containing amine oxidases

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 273/04 (2006.01) A61K 31/14 (2006.01) A61K 31/15 (2006.01) A61K 31/40 (2006.01) A61K 31/445 (2006.01) A61K 31/472 (2006.01) A61K 31/5395 (2006.01) A61P 1/04 (2006.01) A61P 17/00 (2006.01) A61P 29/00 (2006.01) A61P 43/00 (2006.01) C07D 498/04 (2006.01) C07D 498/10 (2006.01)

Patent

CA 2414799

The present invention is directed to 1,3,4-oxadiazine compounds that function as inhibitors of copper-containg amine oxidases commonly known as semicarbazide-sensitive amine oxidases (SSAO), including the human SSAO known as Vascular Adhesion Protein-1 (VAP-1). These SSAO inhibitors have therapeutic utility as drugs to treat conditions and diseases including, but not limited to, a number of inflammatory conditions and diseases (in particular chronic inflammatory conditions such as chronic arthritis, inflammatory bowel diseases, and chronic skin dermatoses), diseases related to carbohydrate metabolism and to abberations in adipocyte differentiation or function and smooth muscle cell function, and vascular diseases. The compounds have the general formula (I): or a tautomer, isomer, hydrazino alcohol degradation product, or a pharmaceutically acceptable solvate, hydrate, or salt thereof, wherein R1, R2, R3, R4, R5,R6, R7, and R8 are as defined her ein.

L'invention concerne des composés du type 1,3,4-oxydiazine jouant le rôle d'inhibiteurs d'amine oxydases contenant du cuivre, généralement connues sous le nom d'amine oxydases sensibles au semicarbazide (SSAO), y compris la SSAO humaine connue en tant que protéine-1 d'adhésion vasculaire (VAP-1). Ces inhibiteurs de SSAO peuvent être utilisés, sur le plan thérapeutique, comme médicaments pour traiter des états et des maladies comprenant, de façon non exclusive, un certain nombre d'états et de maladies inflammatoires (en particulier d'états inflammatoires chroniques, telles que l'arthrite chronique, les maladies intestinales inflammatoires et les dermatoses chroniques), les maladies associées au métabolisme des hydrates de carbone et aux aberrations de la différenciation ou de la fonction adipocytaires et de la fonction cellulaire des muscles lisses, et les maladies vasculaires. Lesdits composés correspondent à la formule générale (I), dans laquelle R?1¿, R?2¿, R?3¿, R?4¿, R?5¿, R?6¿, R?7¿ et R?8¿ correspondent à la définition donnée dans la description. L'invention concerne également un tautomère, un isomère, un produit de dégradation alcoolique hydrazino, ou un solvate, hydrate ou sel pharmaceutiquement acceptable de ces composés.

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