Combinations of signal transduction inhibitors

A - Human Necessities – 61 – K

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Details

A61K 31/519 (2006.01) A61K 31/166 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2561516

The present invention relates to methods for treating cancer comprising utilizing a combination of signal transduction inhibitors. More specifically, the present invention relates to combinations of so called cell cycle inhibitors with mitogen stimulated kinase signal transduction inhibitors, more specifically combinations of CDK inhibitors with mitogen stimulated kinase signal transduction inhibitors, more preferably MEK inhibitors. Other embodiments of the invention relate to additional combinations of the aforesaid combinations with standard anti-cancer agents such as cytotoxic agents, palliatives and antiangiogenics.Most specifically this invention relates to combinations of 6-acetyl-8-cyclopentyl-5-methyl-2~(5-piperazin-1-yl- pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one including salt forms, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor, in combination with one or more MEK inhibitors, most preferably N-[(R)-2,3-dihydroxy-propoxy]-3,4- difluoro-2-(2-fluoro-4~iodo-phenylamino)-benzamide. The aforementioned combinations are useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.

La présente invention concerne des méthodes de traitement du cancer consistant à utiliser une combinaison d'inhibiteurs de transduction de signaux. La présente invention concerne, plus spécifiquement, des combinaisons d'inhibiteurs de cycle cellulaire et d'inhibiteurs de transduction de signaux de kinases stimulées par effet mitogène, plus particulièrement des combinaisons d'inhibiteurs CDK et d'inhibiteurs de transduction de signaux de kinases stimulées par effet mitogène, et plus préférablement des inhibiteurs MEK. Dans d'autre modes de réalisation, l'invention concerne des combinaisons supplémentaires desdites combinaisons et d'agents anticancéreux classiques, par exemple des agents cytotoxiques, des agents palliatifs et des agents antiangiogéniques. L'invention concerne plus spécifiquement des combinaisons de 6-acétyl-8-cyclopentyl-5-méthyl-2-(5-pipérazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, y compris sous forme de sel, constituant un inhibiteur sélectif de la kinase 4 dépendant de la cycline (CDK4), avec un ou plusieurs inhibiteurs MEK, de préférence N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phénylamino)-benzamide. Lesdites combinaisons sont utilisées dans le traitement de l'inflammation et des maladies à prolifération cellulaire telles que le cancer et la resténose.

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