Imidazol derivatives as Raf kinase inhibitors

Abstract

Compounds of formula (I): wherein X is O, CH 2 , S or NH, or the moiety X—R 1 is hydrogen; V is CH or N; R 1 is hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, aryl, arylC 1-6 alkyl, heterocyclyl, heterocyclylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl any of which except for hydrogen may be optionally substituted; R 2 and R 3 independently represent optionally substituted C 1-6 alkyl, or R 2 and R 3 together with the carbon atom to which they are attached form an optionally substituted C 3-7 cycloalkyl or C 3-7 cycloalkenyl ring; or R 2 and R 3 together with the carbon atom to which they are attached form an optionally substituted 5 to 7-membered heterocyclyl ring containing up to 3 heteroatoms selected from N, O, S.R 4 and R 5 independently represent hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, aryl, arylC 1-6 alkyl, heteroaryl, heteroarylC 1-6 alkyl, heterocyclyl, or heterocyclylC 1-6 alkyl, any of which except for hydrogen may be optionally substituted or R 4 and R 5 together with the nitrogen atom to which they are attached form 4- to 8-membered ring; Ar is an aryl or heteroaryl ring either of which may be optionally substituted; one of X 1 and X 2 is N and the other is NR 6 , wherein R 6 is hydrogen, C 1-6 alkyl, or arylC 1-6 alkyl or pharmaceutically acceptable salts thereof, their use as inhibitors of Raf kinases, and pharmaceutical compositions containing them.

1 . A method for the therapeutic treatment of disorders in mammals associated with neuronal degeneration resulting from: 
 ischemic events, including cerebral ischemia after cardiac arrest, stroke or multi-infarct dementia, and cerebral ischemic events, including head injury, surgery or childbirth, which comprises administering to said mammal, an effective amount of a compound according to formula (I):                          wherein    X is O, CH 2 , S or NH, or the moiety X—R 1  is hydrogen;    V is CH or N;    R 1  is hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, aryl, arylC 1-6 alkyl, heterocyclyl, heterocyclylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl any of which except for hydrogen may be optionally substituted;    R 2  and R 3  independently represent optionally substituted C 1-6 alkyl, or R 2  and R 3  together with the carbon atom to which they are attached form an optionally substituted C 3-7 cycloalkyl or C 3-7 cycloalkenyl ring, or R 2  and R 3  together with the carbon atom to which they are attached from an optionally substituted 5 to 7-membered heterocyclyl ring containing up to 3 heteroatoms selected from N, O, and S; R 4  and R 5  independently represent hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, aryl, arylC 1-6 alkyl, heteroaryl, heteroarylC 1-6 alkyl, heterocyclyl, or heterocyclylC 1-6 alkyl, any of which, except for hydrogen, may be optionally substituted, or R 4  and R 5  together with the nitrogen atom to which they are attached form 4- to 8-membered ring;    Ar is an aryl or heteroaryl ring either of which may be optionally substituted; one of X 1  and X 2  is N and the other is NR 6 , wherein R 6  is hydrogen, C 1-6 alkyl, or arylC 1-6 alkyl; or a pharmaceutically acceptable salt thereof.