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    • 3. 发明申请
    • COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
    • WO2007092531A3
    • 2007-08-16
    • PCT/US2007/003319
    • 2007-02-06
    • IRM LLCDING, QiangREN, PingdaZHANG, QiongWANG, XiaSIM, TaeboALBAUGH, Pamela A.GRAY, Nathanael S.
    • DING, QiangREN, PingdaZHANG, QiongWANG, XiaSIM, TaeboALBAUGH, Pamela A.GRAY, Nathanael S.
    • C07D401/04C07D401/14C07D413/14A61K31/4427A61K31/444A61K31/4468
    • The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particulary diseases or disorders that involve abnormal activation of the Abl.Bcr-Abl, Bmx, b-RAF, c-RAFI c-SRC,KDR,CSKlFGFR3,JAK2ILck,Met,PKCalpha,SAPK2alpha)Tie2,TrkB and P70S6K kinases. These compounds have the following structure: (Formula I); in which: R 1 is selected from -NR 6 R 7 and -NR 6 C(O)R 8 ; wherein R 6 is selected from hydrogen and C 1-6 alkyl; R 7 is selected from hydrogen, C 1-6 alkyl. -NR 9 R 10 , C 6-10 aryl-C 0-4 alkyl, C 1-10 heteroaryl-C 0-4 alkyl, C 3-12 cycloalkyl-C 0-4 alkyl and C 3-8 heterocycloalkyl-C 0-4 alkyl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R 7 can be optionally substituted by 1 to 3 radicals independently selected from C 1-6 alkyl, C 1-6 alkoxy, -QNR 9 R 10 and C 3-8 heterocycloalkyl-C 0-4 alkyl; wherein Q is selected from a bond and C 1-4 alkylene; R 8 is selected from hydrogen and C 1-4 alkyl; R 9 and R 10 are independently selected from hydrogen and C 1-6 alkyl; R 2 is selected from hydrogen and C 1-6 alkyl; R 3 is selected from hydrogen and C 1-6 alkyl; R 4 is selected from hydrogen, halo, C 1-6 alkyl, C 1-6 alkoxy, halosubstituted-C 1-6 alkyl and halosubsb'tuted-C 1-6 alkoxy; R 5 is selected from -C(O)NHR 11 and -NHC(O)R 11 ; wherein R 11 is selected from C 6-10 aryl and C 1-10 heteroaryl; wherein any aryl or heteroaryl of R 11 is optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkyl, C 1-6 alkoxy, halosubstituted-C 1-6 alkyl, halosubstituted-C 1-6 alkoxy, di-C 1-4 alkyl-amino-C 1-6 alkoxy, di-C 1-4 alkyl-amino-C 1-4 alkyl(C 1-4 alkyl)amino, C 1-10 heteroaiyl-C 0-4 alkyl, C 3-8 heterocycIoalkyl-C 0-4 alkyl and C 3-8 heterocycloalkyl-oxy; wherein any heteroaryl or heterocycloalkyl substituent of R 11 is further optionally substituted by 1 to 2 radicals independently selected from C 1-6 alkyl and hydroxy-C 1-6 alkyl; X and Y are independently selected from N and CH; and the pharmaceutically acceptable salts, hydrates, solvates and isomers thereof.