Method of modulating stress-activated protein kinase system

Details Method of modulating stress-activated protein kinase system Method of modulating stress-activated protein kinase system

C - Chemistry, Metallurgy

07

D

C07D 495/04 (2006.01) A61K 31/4365 (2006.01) A61P 29/00 (2006.01)

Patent

CA 2630752

It has now been discovered that a high therapeutic effect in treating various disorders associated with enhanced activity of kinase p38 may be achieved by using a potent p38 kinase inhibitor compound which also has inhibitory activity against p38. Furthermore, reducing the activities of both kinase p38 and kinase p38 without reducing the activity of a kinase p38 to such an extent that undesired side effects are observed upon administration to a subject having a disorder associated with enhanced activity of kinase p38 has been discovered to be achievable by modifying inhibitors of p38 such that the modification engenders inhibitory activity against p38. Described are compounds with activity against p38 and p38. Disclosed are methods of using described compounds and compositions to modulate a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits inhibition of the p38 and p38 MAPKs. Also disclosed are methods for identifying compounds which inhibit p38 and p38 MAPKs and which can modulate a stress activated protein kinase (SAPK) system.

Selon la présente invention, on a découvert qu'on peut obtenir un effet thérapeutique élevé dans le traitement de divers troubles liés à une activité améliorée de la kinase p38 en utilisant un puissant composé inhibiteur de la kinase p38.gamma. qui possède également une activité inhibitrice vis-à-vis de p38.alpha.. De plus, on peut parvenir à une diminution des activités des kinases p38.gamma. et p38.alpha. sans réduire l'activité d'une kinase p38.alpha. à un point tel que des effets secondaires non souhaités sont observés suite à l'administration à un sujet souffrant d'un trouble lié à une activité améliorée de la kinase p38 et, ce, en modifiant des inhibiteurs de p38.alpha. de manière que la modification produit une activité inhibitrice vis-à-vis de p38.gamma.. Cette invention a aussi pour objet des méthodes d'utilisation des composés et des compositions susmentionnés afin de moduler un système de protéine kinase activée par le stress (SAPK) avec un composé actif, ce dernier présentant une inhibition des protéines kinases activées par les mitogènes (MAPK) p38.gamma. et p38.alpha.. Ladite invention a, enfin, trait à des méthodes d'identification de composés qui inhibent MAPK p38.gamma. et p38.alpha. et qui modulent un système SAPK.

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