5-substituted 2h-pyrazole-3-carboxylic acid derivatives as...

C - Chemistry – Metallurgy – 07 – D

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C07D 231/16 (2006.01) A61K 31/415 (2006.01) C07D 231/14 (2006.01)

Patent

CA 2501134

The present invention relates to certain pyrazole carboxylic acid derivatives of Formula (Ia), and pharmaceutically acceptable salts thereof, as antilipolytic agents and against for the receptor RUP25, wherein: R2 is H, halogen, C1-12 alkyl or C1-12 haloalkyl; and R3 is C3-6 cycloalkyl, C1-12 alkyl, C1-12 haloalkyl, C3-6 cycloalkyl-C1-4-alkylene, aryl-C1-4-alkylene or heteroaryl-C1-4-alkylene, wherein said aryl-C1-4-alkylene and heteroaryl-C1-4- alkylene can be optionally substituted 1 to 5 substituents selected from the substituents listed in the claims. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for pharmaceutical compositions in combination with other active agents, for example, those agents belonging to the class of .alpha.-glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers, thiazolidinedione and the like.

L'invention concerne certains dérivés d'acide pyrazole carboxylique de formule (Ia), et des sels de ceux-ci, acceptables au plan pharmaceutique, à utiliser en tant qu'agents antilipolytiques et contre le récepteur RUP25. Dans ladite formule (Ia) R¿2? représente H, halogène, alkyle C¿1?-¿12? ou haloalkyle C¿1?-¿12? ; et R¿3? représente cycloalkyle C¿3?-¿6?, alkyle C¿1?-¿12?, halolakyleC¿1?-¿12?, cycloalkyleC¿3?-¿6?-alkylène-C¿1?-¿4?, aryle-alkylèneC¿1?-¿4?, ou hétéroaryle-alkylèneC¿1?-¿4?, lesdits aryle-alkylèneC¿1?-¿4 ?et hétéroaryle-alkylèneC¿1?-¿4? pouvant être éventuellement substitués par 1 à 5 substituants choisis parmi les substituants répertoriés dans les revendications. L'invention porte également sur des compositions pharmaceutiques contenant des composés de l'invention, et sur des procédés d'utilisation des composés et des compositions de l'invention dans le traitement de troubles métaboliques, dont la dyslipédimie, l'athérosclérose, la coronaropathie, la résistance à l'insuline, le diabète de type 2, le syndrome X et similaire. L'invention se rapporte également à des compositions pharmaceutiques combinées à d'autres agents actifs, tels que des agents appartenant à la classe des inhibiteurs de l'alpha glucosidase, des inhibiteurs de l'aldose réductase, des biguanides, des inhibiteurs de la HMG-CoA réductase, des inhibiteurs de synthèse du squalène, des fibrates, des activateurs du catabolisme des LDL, des inhibiteurs de l'enzyme de conversion de l'angiotensine, des activateurs de sécrétion d'insuline, de thiazolidinedione et similaire.

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