Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N- or C-linked imidazoles

A compound of formula (I)

• a pharmaceutically acceptable acid addition salt or a stereochemically isomeric form thereof, wherein
• the dotted line represents an optional bond;
• X is oxygen or sulfur;
• —A— is a bivalent radical of formula
• —CH═CH— (a-1), —CH2—S— (a-6), —CH2—CH2— (a-2), —CH2—CH2—S— (a-7), —CH2—CH2—CH2— (a-3), —CH═N— (a-8), —CH2—O— (a-4), —N═N— (a-9), or —CH2—CH2—O— (a-5), —CO—NH— (a-10);
• wherein optionally one hydrogen atom may be replaced by C1-4alkyl or Ar1;
• R1 and R2 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxy C1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar2, Ar2—C1-6alkyl, Ar2-oxy, Ar2—C1-6alkyloxy;
• or
• when on adjacent positions R1 and R2 taken together may form a bivalent radical of formula
• —O—CH2—O— (b-1), —O—CH2—CH2—O— (b-2), —O—CH═CH— (b-3), —O—CH2—CH2— (b-4), —O—CH2—CH2—CH2— (b-5), or —CH═CH—CH═CH— (b-6);
• R3 and R4 each independently are hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxy, Ar3-oxy, C1-6alkylthio, di(C1-6alkyl)amino, trihalomethyl, trihalomethoxy, or when on adjacent positions R3 and R4 taken together may form a bivalent radical of formula
• —O—CH2—O— (c-1), —O—CH2—CH2—O— (c-2), or —CH═CH—CH═CH— (c-3);
• R5 is a radical of formula
• wherein R13 is hydrogen, halo, Ar4, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-6alkyl or C1-6alkylS(O)2C1-6alkyl;
• R14 is hydrogen, C1-6alkyl or di(C1-4alkyl)aminosulfonyl;
• R6 is hydrogen, hydroxy, halo, C1-6alkyl, cyano, haloC1-6alkyl, hydroxyC-1-6alkyl, cyanoC1-6alkyl, aminoC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkylthioC1-6alkyl, aminocarbonyl-C1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, C1-6alkylcarbonylC1-6alkyl, C1-6alkyloxycarbonyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, Ar5, Ar5—C1-6alkyloxyC1-6alkyl;
• or a radical of formula
• —O—R7 (e-1), —S—R7 (e-2), or —N—R8R9 (e-3);
• wherein
• R7 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, Ar6, Ar6—C1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, or a radical of formula —Alk—OR10 or —Alk—NR11R12;
• R8 is hydrogen, C1-6alkyl, Ar7 or Ar7—C1-6alkyl;
• R9 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylaminocarbonyl, Ar8, Ar8-C1-6alkyl, C1-6alkylcarbonyl-C1-6alkyl, Ar8-carbonyl, Ar8—C1-6alkylcarbonyl, aminocarbonylcarbonyl, C1-6alkyloxyC1-6alkylcarbonyl, hydroxy, C1-6alkyloxy, aminocarbonyl, di(C1-6alkyl)aminoC1-6alkylcarbonyl, amino, C1-6alkylamino, C1-6alkylcarbonylamino, or a radical or formula —Alk—OR10 or —Alk—NR11R12;
• wherein Alk is C1-6alkanediyl;
• R10 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, hydroxyC1-6alkyl, Ar9 or Ar9—C1-6alkyl;
• R11 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, Ar10 or Ar10—C1-6alkyl;
• R12 is hydrogen, C1-6alkyl, Ar11 or Ar11-C1-6alkyl;
• and
• Ar1 to Ar11 are each independently selected from phenyl;
• or phenyl substituted with halo, C1-6alkyl, C1-6alkyloxy or trifluoromethyl.