Compounds and compositions as protein kinase inhibitors

Details Compounds and compositions as protein kinase inhibitors Compounds and compositions as protein kinase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 401/04 (2006.01) A61K 31/4427 (2006.01) A61K 31/444 (2006.01) A61K 31/4468 (2006.01) C07D 401/14 (2006.01) C07D 413/14 (2006.01)

Patent

CA 2637225

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: R1 is selected from -NR6R7 and -NR6C(O)R8; wherein R6 is selected from hydrogen and C1-6alkyl; R7 is selected from hydrogen, C1-6alkyl. -NR9R10, C6- 10aryl-C0-4alkyl, C1-10heteroaryl-C0-4alkyl, C3-12cycloalkyl-C0-4alkyl and C3- 8heterocycloalkyl-C0-4alkyl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R7 can be optionally substituted by 1 to 3 radicals independently selected from C1-6alkyl, C1-6alkoxy, -QNR9R10 and C3- 8heterocycloalkyl-C0-4alkyl; wherein Q is selected from a bond and C1- 4alkylene; R8 is selected from hydrogen and C1-4alkyl; R9 and R10 are independently selected from hydrogen and C1-6alkyl; R2 is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen and C1-6alkyl; R4 is selected from hydrogen, halo, C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkyl and halosubsb'tuted-C1-6alkoxy; R5 is selected from -C(O)NHR11 and -NHC(O)R11; wherein R11 is selected from C6-10aryl and C1-10heteroaryl; wherein any aryl or heteroaryl of R11 is optionally substituted with 1 to 3 radicals independently selected from halo, C1-6alkyl, C1-6alkoxy, halosubstituted-C1- 6alkyl, halosubstituted-C1-6alkoxy, di-C1-4alkyl-amino-C1-6alkoxy, di-C1- 4alkyl-amino-C1-4alkyl(C1-4alkyl)amino, C1-10heteroaiyl-C0-4alkyl, C3- 8heterocycIoalkyl-C0-4alkyl and C3-8heterocycloalkyl-oxy; wherein any heteroaryl or heterocycloalkyl substituent of R11 is further optionally substituted by 1 to 2 radicals independently selected from C1-6alkyl and hydroxy-C1-6alkyl; X and Y are independently selected from N and CH; and the pharmaceutically acceptable salts, hydrates, solvates and isomers thereof.

La présente invention concerne une classe atypique de composés, compositions pharmaceutiques comprenant de tels composés et procédés d'utilisation de tels composés pour traiter ou empêcher les troubles et les désordres associés à une activité anormale ou déréglée de kinase, particulièrement les maladies ou troubles qui impliquent une activation anormale des kinases Abl, Bcr-Abl, Bmx, b-RAF, c-RAF, c-SRC, KDR, CSK, FGFR3, JAK2, Lck, Met, PKC, SAPK2, Tie2, TrkB et P70S6K.

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