3-Phenyl analogs of toxoflavine as kinase inhibitors

A compound having the formula

• 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;
• R1 represents hydrogen, Ar1, C1-4alkyl or C1-4alkyl substituted with morpholinyl or pyridinyl;
• R2 represents hydrogen, phenyl, C1-4alkyl, C1-4alkyloxycarbonyl or C1-4alkyl substituted with hydroxy, phenyl or -oxy-halophenyl;
• R3 represents hydrogen, phenyl, C1-4alkyl, C1-4alkyloxycarbonyl or C1-4alkyl substituted with hydroxy, phenyl or -oxy-halophenyl;
• or
• R2 and R3 taken together with the carbon atom to which they are attached form a C3-8cycloalkyl or Het1 wherein said C3-8cycloalkyl or Het1 each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from C1-4alkyloxycarbonyl, —C1-4alkyl-Ar3 C1-4alkylsulfonyl, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl or —C(═NH)—NH2;
• R4 represents halo, nitro, hydroxy or C1-4alkyloxy;
• R5 represents formyl, hydroxy, cyano, phenyl, —O—Ar2, NR6R7, C1-4alkyl, C1-4alkyloxy, C1-4alkylsulfonyl, C1-4alkylcarbonyl, C1-4alkyloxycarbonyl, —O-(mono- or di(C1-4alkyl)aminosulfonyl), Het2, —SO2-Het6, C2-6alkenyl optionally substituted with phenyl,
• C1-4alkyl substituted with one or where possible more substituent being selected from hydroxy, halo, Het3, NR6R7 or formyl,
• C1-4alkyloxy substituted with one or where possible more substituents being selected from halo, amino, mono- or di(C1-4alkyl)aminosulfonyl, aminosulfonyl, Het4, NR8R9 or —C(═O)-Het4;
• R6 and R7 are each independently selected from hydrogen, C1-4alkyl,
• C1-4alkyloxyC1-4alkyl, Het5 or C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy, Het5, C1-4alkyloxycarbonyl, or
• C1-4alkylsulfonyl;
• R8 and R9 are each independently selected from hydrogen, C1-4alkyl, C1-4alkyloxycarbonyl, Het7, mono- or di(C1-4alkyl)aminosulphonyl or aminosulphonyl;
• Het1 represents piperidinyl or dihydroindenyl;
• Het2 represents a heterocycle selected from piperidinyl, morpholinyl, 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 C1-4alkyloxycarbonyl;
• Het3 represents a heterocycle selected from morpholinyl, pyrrolidinyl, pyrrolyl, 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, C1-4alkyl, C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, aminosulfonyl, NR10R11, imidazolyl, tetrahydropyrimidinyl, amino, mono- or di(C1-4alkyl)aminosulfonyl, hydroxyC1-4alkyloxyC1-4alkyl, C1-4alkyloxyC4alkyl or C1-4alkyloxy;
• R10 and R11 are each independently selected from hydrogen, C1-4alkyl,
• C1-4alkyloxycarbonyl, aminosulfonyl, or mono- or di(C1-4alkyl)aminosulfonyl;
• Het4 represents a heterocycle selected from morpholinyl, piperidinyl, imidazolyl 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, C1-4alkyl, C1-4alkyloxycarbonyl, aminosulfonyl or mono- or di(C1-4alkyl)aminosulfonyl or Het4 represents a monovalent radical represented by formula (i);
• Het5 represents a heterocycle selected from pyridinyl, pyrimidinyl, pyrrolidinyl, 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 C1-4alkyl, C1-4alkyloxycarbonyl, aminosulfonyl, C1-4alkylaminosulfonyl or mono- or di(C1-4alkyl)aminosulfonyl;
• Het6 represents morpholinyl;
• Het7 represents pyridinyl, piperidinyl, piperazinyl or pyrimidinyl optionally substituted with C1-4alkylphenyl, C1-4alkyloxycarbonyl aminosulfonyl, or mono- or di(C1-4alkyl)aminosulfonyl;
• Ar1 represents an aryl substituent selected from phenyl or naphthalenyl wherein said aryl substituents each independently may optionally be substituted with one, or where possibly two or three substituents each independently selected from nitro or C1-4alkyloxycarbonyl;
• Ar2 represents phenyl optionally substituted with one or where possible two or three substituents each independently selected from the group consisting of halo and nitro;
• Ar3 represents an aryl substituent selected from the group consisting of phenyl,