3-PHENYL ANALOGS OF TOXOFLAVINE AS KINASE INHIBITORS

摘要

The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein n represents an integer being 0, 1 or 2; m represents an integer being 0 or 1; R<1> represents C1-4alkyl; R<2 >represents C1-4alkyl; R<3 >represents C1-4alkyl; or R<2 >and R<3 >taken together with the carbon atom to which they are attached form a C3-8cycloalkyl or Het<1> wherein said C3-8cycloalkyl or Het<1> each independently may optionally be substituted with C1-4alkyloxycarbonyl; R<4 >represents halo or C1-4alkyloxy; R<5> represents C1-4alkyloxycarbonyl, -O-(mono- or di(C1-4alkyl)aminosulfonyl), C1-4alkyl substituted with one or where possible more substituent being selected from Het<3> or NR<6>R<7>, C1-4alkyloxy substituted with one or where possible more substituents being selected from amino, Het<4 >or NR<8>R<9>; R<6> and R<7 >are each independently selected from hydrogen, C1-4alkyl, C1-4alkyloxyC1-4alkyl, -Het<5> or C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy, or Het<5>; R<8> and R<9> are each independently selected from hydrogen, C1-4alkyl, -Het<7> or mono- or di(C1-4alkyl)aminosulphonyl; Het<3 >represents a heterocycle selected from piperidinyl, or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from hydroxy, aminosulfonyl, amino, mono-or di(C1-4 alkyl)aminosulfonyl, hydroxyC1-4alkyloxyC1-4alkyl or C1-4alkyloxy; Het<4 >represents a heterocycle selected from morpholinyl, piperidinyl or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from C1-4alkyl, C1-4alkyloxycarbonyl or mono- or di(C1-4alkyl)aminosulfonyl; Het<5> represents a heterocycle selected from pyridinyl or piperidinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from aminosulfonyl, or mono- or di(Cl­4alkyl)aminosulfonyl; Het<7> represents piperidinyl.