3-FURANYL ANALOGS OF TOXOFLAVINE AS KINASE INHIBITORS

摘要

The present invention concerns the compounds of formula (I) the N-oxide form s, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents an integer being 0 or 1; n represents an integer being 0, 1 or 2; R1 represents C1-4alkyl, C1-4alkyl substituted with pyridinyl, phenyl, piperidinyl or piperidinyl substituted with C1-4-alkyloxycarbonyl; R2 represents hydrogen or C1-4 alkyl; R3 represents hydrogen or C1-4alkyl; or R2 and R3 taken together with the carbo n atom to which they are attached form cyclopentyl or piperidinyl wherein said cyclopentyl or piperidinyl each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from C1-4alkyloxycarbonyl, phenylcarbonyl or -C(=NH)-NH2; R4 represents halo or C1-4alkyloxy; R5 represents Het2, C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy, halo, Het3 or NR6R7, or C1-4alkyloxy substituted with one or where possible more substituents being selected from Het4 or -C(=O)-Het4; R6 and R7 are eac h independently selected from hydrogen, C1-4alkyl, Het5 or C1-4alkyl substitut ed with one or where possible more substituents being selected from hydroxy or Het5; Het2 represents piperazinyl; Het3 represents a heterocycle selected fr om morpholinyl, pyrrolidinyl, piperidinyl, or piperazinyl wherein said monocycl ic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from C1 - 4alkyl preferably methyl, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl , hydroxyC1 -4alkyloxyC1-4alkyl, C1-4alkyloxyC1-4alkyl or C1-4alkyloxy; Het4 represents a heterocycle selected from morpholinyl or piperazinyl wherein sa id monocyclic heterocycles each independently may optionally be substituted wit h one, or where possible two or three C1-4alkyl substituents, preferably methy l; Het5 represents a heterocycle selected from pyridinyl, 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 aminosulfonyl, C1- 4alkyloxycarbonyl or mono- or di(C1-4alkyl)aminosulfonyl.