1,2-annelated quinoline derivatives

A compound of formula (I)

• 194
• or a pharmaceutically acceptable acid addition salt or a stereochemically isomeric form thereof, wherein
• ═X1—X2—X3— is a trivalent radical of formula
• 3 ═N—CR6═CR7— (x-1), ═CR6—CR7═CR8— (x-6), ═N—N═CR6— (x-2), ═CR6—N═CR7— (x-7), ═N—NH—C(═O)— (x-3), ═CR6—NH—C(═O)— (x-8), or ═N—N═N— (x-4), ═CR6—N═N— (x-9);
• ═N—CR6═N— (x-5),
• wherein each R6, R7 and R8 are independently hydrogen, C1-4alkyl, hydroxy, C1-4alkyloxy, aryloxy, C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, cyano, amino, thio, C1-4alkylthio, arylthio or aryl;
• >Y1—Y2— is a trivalent radical of formula
• >CH—CHR9— (y-1), >C═N— (y-2), >CH—NR9— (y-3),or >C═CR9— (y-4);
• wherein each R9 independently is hydrogen, halo, halocarbonyl, aminocarbonyl, hydroxyC1-4alkyl, cyano, carboxyl, C1-4alkyl, C1-4alkyloxy, C1-4alkyloxyC1-4alkyl, C1-4alkyloxycarbonyl, mono- or di(C1-4alkyl)amino, mono- or di(C1-4alkyl)aminoC1-4alkyl, aryl;
• r and s are each independently 0, 1, 2, 3, 4 or 5;
• t is 0, 1, 2or 3;
• each R1 and R2 are independently hydroxy, halo, cyano, C1-6alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkylthio, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)amino, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, aryl, arylC1-6alkyl, aryloxy or arylC1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, aminocarbonyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminocarbonyl, mono- or di(C1-6alkyl)aminoC1-6alkyl;
• or
• two R1 or R2 substituents adjacent to one another on the phenyl ring may independently form together a bivalent radical of formula
• —O—CH2—O— (a-1), —O—CH2—CH2—O— (a-2), —O═CH═CH— (a-3), —O—CH2—CH2— (a-4), —O—CH2—CH2—CH2— (a-5), or —CH═CH—CH═CH— (a-6);
• R3 is hydrogen, halo, C1-6alkyl, cyano, haloC1-6alkyl, hydroxyC1-6alkyl, cyanoC1-6alkyl, aminoC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkylthioC1-6alkyl, aminocarbonylC1-6alkyl, hydroxycarbonyl, hydroxycarbonylC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, C1-6alkylcarbonylC1-6alkyl, C1-6alkyloxycarbonyl, aryl, arylC1-6alkyloxyC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl;
• or a radical of formula
• —O—R10 (b-1), —S—R10 (b-2), —NR11R12 (b-3),
• wherein
• R10 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, aryl, arylC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, or a radical of formula -Alk-OR13 or -Alk-NR14R15;
• R11 is hydrogen, C1-6alkyl, aryl or arylC1-6alkyl;
• R12 is hydrogen, C1-6alkyl, aryl, hydroxy, amino, C1-6alkyloxy, C1-6alkylcarbonylC1-6alkyl, arylC1-6alkyl, C1-6alkylcarbonylamino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonyl, aminocarbonyl, arylcarbonyl, haloC1-6alkylcarbonyl, arylC1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkyloxyC1-6alkylcarbonyl, mono- or di(C1-6alkyl)aminocarbonyl wherein the alkyl moiety may optionally be substituted by one or more substituents independently selected from aryl or C1-3alkyloxycarbonyl, aminocarbonylcarbonyl, mono- or di(C1-6alkyl)aminoC1-6alkylcarbonyl, or a radical or formula -Alk-OR13 or -Alk-NR14R15;
• wherein
• Alk is C1-6alkanediyl;
• R13 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, hydroxyC1-6alkyl, aryl or arylC1-6alkyl;
• R14 is hydrogen, C1-6alkyl, aryl or arylC1-6alkyl;
• R15 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, aryl or arylC1-6alkyl;
• R4 is a radical of formula
• 195
• wherein R16 is hydrogen, halo, aryl, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, mono- or di(C1-4alkyl)amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylthioC1-6alkyl, C1-6alkylS(O)C1-6alkyl or C1-6alkylS(O)2C1-6alkyl;
• R16 may also be bound to one of the nitrogen atoms in the imidazole ring of formula (c-1) or (c-2), in which case the meaning of R16 when bound to the nitrogen is limited to hydrogen, aryl, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-6alkyl or C1-6alkylS(O)2C1-6alkyl;
• R17 is hydrogen, C1-6alkyl, C1-6alkyloxyC1-6alkyl, arylC1-6alkyl, trifluoromethyl or di(C1-4alkyl)aminosulfonyl;
• R5 is C1-6alkyl, C1-6alkyloxy or halo;
• aryl is phenyl, naphthalenyl or phenyl substituted with 1 or more substituents each independently selected from halo, C1-6alkyl, C1-6alkyloxy or trifluoromethyl.