申请人:Intermune, Inc.
公开号:EP2426134A2
公开(公告)日:2012-03-07
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.
现已发现,通过使用一种对 p38?激酶也具有抑制活性的强效 p38?激酶抑制剂化合物,可以在治疗与 p38?激酶活性增强有关的各种疾病方面取得很高的治疗效果。此外,已经发现通过修饰 p38?的抑制剂,使其对 p38?具有抑制活性,可以降低激酶 p38?和激酶 p38?的活性,而不会降低激酶 p38?的活性,以至于在对患有与激酶 p38?活性增强相关的疾病的受试者用药时观察到不期望的副作用。和p38?的活性的化合物;公开了使用所述化合物和组合物以活性化合物调节应激活化蛋白激酶(SAPK)系统的方法,其中活性化合物表现出抑制p38?MAPKs 的抑制作用。还公开了鉴定抑制 p38?和 p38?MAPKs 并能调节应激活化蛋白激酶(SAPK)系统的化合物的方法。