Patent ID: 6747028
Filing Date: 2004-06-08
Classification: A61P,C07D,Y02P

Abstract:
A compound of formula a prodrug, addition salt, or stereochemically isomeric form thereof whereinâ€”a1&boxH;a2â€”a3&boxH;a4â€” represents a bivalent radical of formula â€”CH&boxH;CHâ€”CH&boxH;CHâ€”â€ƒâ€ƒ(a-1); wherein each hydrogen atom in the radical (a-1)may optionally be replaced by halo, C1-6alkyl, nitro, amino, hydroxy, C1-6alkyloxy, polyhaloC1-6alkyl, carboxyl, aminoC1-6alkyl, mono- or di(C1-4alkyl)aminoC1-6alkyl, C1-6alkyloxycarbonyl, hydroxyC1-6alkyl, or a radical of formula wherein Z is O, CHâ€”C(&boxH;O)â€”NR5aR5b, CH2, CHâ€”C1-6alkyl, Nâ€”OH or Nâ€”Oâ€”C1-6alkyl; Q is a radical of formula â€ƒwherein; Y1 is a bivalent radical of formula â€”NR2â€” or â€”CH(NR2R4)â€”; X1 is NR4, S, S(&boxH;O), S(&boxH;O)2, O, CH2, C(&boxH;O), C(&boxH;CH2), CH(OH), CH(CH3), CH(OCH3), CH(SCH3), CH(NR5aR5b), CH2â€”NR4 or NR4â€”CH2; X2 is a direct bond, CH2, C(&boxH;O), NR4, C1-4alkyl-NR4, NR4â€”C1-4alkyl; u is 2or 3; v is 2; and whereby each hydrogen atom in the carbocycles and the heterocycles defined in radicals (b-4), (b-5), and (b-6) may optionally be replaced by R3; with the proviso that when R3 is hydroxy or C1-6alkyloxy, then R3 can not replace a hydrogen atom in the &agr; position relative to a nitrogen atom; G is C1-10alkanediyl substituted with one or more hydroxy, C1-6alkyloxy, arylC1-6alkyloxy, C1-6akylthio, arylC1-6alkylthio, HO(â€”CH2â€”CH2â€”O)nâ€”, C1-6alkyloxy (â€”CH2â€”CH2â€”O)nâ€” or arylC1-6alkyloxy(â€”CH2â€”CH2â€”O)nâ€”; R1 is a monocyclic heterocycle or aryl; said heterocycle being selected from piperidinyl, piperazinyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, tetrahydrofuranyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl; and each heterocycle may optionally be substituted with 1 or where possible more-substituents selected from halo, hydroxy, amino, cyano, carboxy, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, C1-6alkyloxyC1-6alkyl, aryl, arylC1-6alkyl, arylC1-6alkyloxy, hydroxyC1-6alkyl, mono- or di(C1-6alkyl)amino, mono- or di(C1-6alkyl)aminoC1-6alkyl, polyhaloC1-6alkyl, C1-6alkylcarbonylamino, C1-6alkyl-SO2â€”NR5câ€”, aryl-SO2â€”NR5câ€”, C1-6alkyloxycarbonyl, â€”C(&boxH;O)â€”NR5cR5d, HO(â€”CH2â€”CH2â€”O)nâ€”, halo(â€”CH2â€”CH2â€”O)nâ€”, C1-6alkyloxy(â€”CH2â€”CH2â€”O)nâ€”, arylC1-6alkyloxy(â€”CH2â€”CH2â€”O)nâ€” and mono- or di(C1-6alkyl)amino(â€”CH2â€”CH2â€”O)nâ€”; each n independently is 1, 2, 3 or 4; R2 is hydrogen, formyl, C1-6alkylcarbonyl, Hetcarbonyl, pyrrolidinyl, piperidinyl, homopiperidinyl, C3-7cycloalkyl substituted with N(R6)2, or C1-10alkyl substituted with N(R6)2 and optionally with a second, third or fourth substituent selected from amino, hydroxy, C3-7cycloalkyl, C2-5alkanediyl, piperidinyl, mono- or di(C1-6alkyl)amino, C1-6alkyloxycarbonylamino, aryl and aryloxy; R3 is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, arylC1-6alkyl or arylC1-6alkyloxy; R4 is hydrogen, C1-6alkyl or arylC1-6alkyl; R5a, R5b, R5c and R5d each independently are hydrogen or C1-6alkyl; or R5a and R5b, or R5c and R5d taken together form a bivalent radical of formula â€”(CH2)sâ€” wherein s is 4 or 5; R6 is hydrogen, C1-4alkyl, formyl, hydroxyC1-6alkyl, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl; aryl is phenyl or phenyl substituted with 1 or more-substituents selected from halo, hydroxy, C1-6alkyl, hydroxyC1-6alkyl, polyhaloC1-6alkyl, and C1-6alkyloxy; and Het is pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl.