Novel IL-5 inhibiting 6-azauracil derivatives for marking and identifying receptors and imaging organs

A compound of formula

• 45
• a N-oxide, a pharmaceutically acceptable addition salt or a stereochemically-isomeric form thereof, wherein:
• p represents an integer being 0, 1, 2, 3 or 4;
• q represents an integer being 0, 1, 2, 3, 4 or 5;
• X represents O, S, NR3 or a direct bond;
• R1 represents hydrogen, hydroxy, halo, amino, mono- or di(C1-4alkyl)amino, C1-6alkyl, C1-6alkyloxy, C3-7cycloalkyl, aryl, arylC1-6alkyl, aminoC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl or mono- or di(C1-4alkyl)aminoC1-4alkylamino;
• R2 represents aryl, Het1, C3-7cycloalkyl, C1-6alkyl or C1-6alkyl substituted with one or two substituents selected from hydroxy, cyano, amino, mono- or di(C1-4alkyl)amino, C1-6alkyloxy, C1-6alkylsulfonyloxy, C1-6alkyloxycarbonyl, C3-7cycloalkyl, aryl, aryloxy, arylthio, Het1, Het1oxy and Het1thio;
• and if X is O, S or NR3, then R2 may also represent aminocarbonyl, aminothiocarbonyl, C1-4alkylcarbonyl, C1-4alkylthiocarbonyl, arylcarbonyl or arylthiocarbonyl;
• R3 represents hydrogen or C1-4alkyl;
• each R4 independently represents C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with Het3, R6 or NR7R8;
• each R6 independently represents C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with Het3, R6 or NR7R8;
• each R6 independently represents C1-6alkylsulfonyl, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl, mono- or di(benzyl)aminosulfonyl, polyhaloC1-6alkylsulfonyl, C1-6alkylsulfinyl, phenylC1-4alkylsulfonyl, piperazinylsulfonyl, aminopiperidinylsulfonyl, piperidinylaminosulfonyl, N—C14alkyl-N-piperidinylaminosulfonyl;
• each R7 and each R8 are independently selected from hydrogen, C1-4alkyl, hydroxyC1-4alkyl, dihydroxyC1-4alkyl, aryl, arylC1-4alkyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, arylcarbonyl, C1-4alkylcarbonyloxyC1-4alkylcarbonyl, hydroxyC1-4alkylcarbonyl, C1-4alkyloxycarbonylcarbonyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, arylaminocarbonyl, arylaminothiocarbonyl, Het3aminocarbonyl, Het3aminothiocarbonyl, C3-7cycloalkyl, pyridinylC1-4alkyl, Het3 and R6;
• R9 and R10 are each independently selected from hydrogen, C1-4alkyl, hydroxyC1-4alkyl, dihydroxyC1-4alkyl, phenyl, phenylC1-4alkyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, phenylcarbonyl, C1-4akylcarbonyloxyC1-4alkylcarbonyl, hydroxyC1-4alkylcarbonyl, C1-4alkyloxycarbonylcarbonyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, phenylaminocarbonyl, phenylaminothiocarbonyl, Het3aminocarbonyl, Het3aminothiocarbonyl, C3-7cycloalkyl, pyridinylC1-4alkyl, Het3 and R6;
• each R11 independently being selected from hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C1-4alkyloxy, carboxyl, C1-4alkyloxycarbonyl, trihaloC1-4akylsulfonyloxy, R6, NR7R8, C(═O)NR7R8, aryl, aryloxy, arylcarbonyl, C3-7cycloalkyl, C3-7cycloalkyloxy, phthalimide-2-yl, Het3 and C(═O)Het3;
• R12 and R13 are each independently selected from hydrogen, C1-4-alkyl, hydroxyC1-4alkyl, dihydroxyC1-4alkyl, phenyl, phenylC1-4alkyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, phenylcarbonyl, C1-4alkylcarbonyloxyC4alkylcarbonyl, hydroxyC1-4alkylcarbonyl, C1-4alkyloxycarbonylcarbonyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, phenylaminocarbonyl, phenylaminothiocarbonyl, C3-7cycloalkyl, pyridinylC1-4alkyl and
• aryl represents phenyl optionally substituted with one, two or three substituents each independently selected from nitro, azido, halo, hydroxy, C1-4alkyl, C1-4alkyloxy, polyhaloC1-4alkyl, NR9R10, R6, phenyl, Het3 and C1-4alkyl substituted with NR9R10;
• Het1 represents a heterocycle selected from pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, furanyl, tetrahydrofuranyl, thienyl, thiolanyl, dioxolanyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyranyl, pyridazinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, dithianyl, trithianyl, triazinyl, benzothienyl, isobenzothienyl, benzofuranyl, isobenzofuranyl, benzothiazolyl, benzoxazolyl, indolyl, isoindolyl, indolinyl, purinyl, 1H-pyrazolo[3,4-d]pyrimidinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phtalazinyl, quinazolinyl, quinoxalinyl, thiazolopyridinyl, oxazolopyridinyl, imidazo[2,1-b]thiazolyl;
• wherein said heterocycles each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from Het2, R11 and C1-4alkyl optionally substituted with Het2 or R11;
• Het2 represents a monocyclic heterocycle selected from pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, furanyl, tetrahydrofuranyl, thienyl, thiolanyl, dioxolanyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyranyl, pyridazinyl, dioxanyl, dithianyl, trithianyl and triazinyl;
• wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from R11 and C1-4alkyl optionally substituted with R11;
• Het3 represents a monocyclic heterocycle selected from pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl;
• wherein said monocyclic heterocycles each independently may optionally be substituted with, where possible, one, two or three substituents each independently selected from C1-4alkyl, C1-4alkyloxy, carboxyl, C1-4alkyloxycarbonyl;
• C1-4alkylcarbonyl, phenylC1-4alkyl, piperidinyl, NR12R13, R6 and C1-4alkyl substituted with R6 or NR12R13.