Novel substituted tetracyclic imidazole derivatives, processes for their preparation, pharamaceutical compositions comprising them and their use as a medicine

A compound according to the general Formula (I),

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• the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof, wherein:
• m is 1 or 2;
• n is 0, 1 or 2;
• a, b, c independently are a single or a double bond;
• X is a covalent bond or a bivalent C1-6alkanediyl radical wherein one or more —CH2— groups may be optionally replaced with —O—, —S—, —
• NR7—;
• wherein:
• R7 is hydrogen, alkyl, Ar, Ar-alkyl, Het, Het-alkyl, hydroxyalkyl, alkyloxy, alkyoxyalkyl, alkyloxyalkyloxyalkyl, aminoalkyl, mono- or dialkylaminoalkyl, formyl, alkylcarbonylaminoalkyl, alkylcarbonyloxyalkyl, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, hydroxyalkyloxyalkyl, aminocarbonyl, aminocarbonylalkyl, alkyloxycarbonyl, alkylcarbonyl or alkylcarbonyloxyalkyloxyalkyl;
• Y is a bivalent C1-4alkanediyl or C2-4 alkenediyl radical;
• Z is N, in which case a is a double bond and b is a single bond;
• or is N—R7 in which case a is a single bond and R7 is defied as above;
• R1, R2 independently are hydrogen, hydroxy, alkyl, alkyloxy, Ar, Ar-alkyl, di(Ar-)alkyl, Het or Het-alkyl,
• -A-B— independently is a bivalent radical of formula
• -E-CR8═CR8— (a-1);
• —CR8═CR8-E- (a-2);
• or —CR8═CR8—CR8═CR8— (a-3);
• wherein:
• R8 each independently is hydrogen, halo, hydroxy, alkyl or alkyloxy;
• E is a bivalent radical of formula —O—, —S— or —NR7— wherein.
• R7 is defined as above;
• —C-D- independently is a bivalent radical of formula
• —CR8═CR8—CR8═CR8— (b-1);
• —N═CR8—CR8═CR8— (b-2);
• —CR8═N—CR8═CR8— (b3);
• —CR8═CR8—N═CR8 (b-4) or —CR8═CR8—CR8═N— (b-5);
• wherein R8 is defined as above;
• R3 is hydrogen, halo, hydroxy, alkyl, oxo, alkyloxy, Ar, Ar-alkyl, di(Ar-)alkyl, Het or Het-alkyl;
• R4 is hydrogen, alkyl, amino, alkylamino, Ar-amino, Het-amino, Het-alkylamino, alkylcarbonylamino, Ar-carbonylamino, Het-carbonylamino, alkylaminocarbonylamino, Ar-aminocarbonylamino, Het-aminocarbonylamino, alkyloxyalkylamino, Ar-oxyalkylamino or Het-oxyalkylamino;
• R5 is hydrogen or alkyl;
• or R4 and R5 together may form a radical of Formula
• -M-CR9═CR10— (c-1);
• —CR10—CR9-M- (c-2);
• -M-CR8R8—CR8R8— (c-3);
• —CR8R8—CR8R8-M- (c-4);
• —CR8═N—NR7— (c-5);
• —NR7—N═CR8— (c-6);
• —CR9═CR10—CR9═CR10— (c-7);
• —CR8R8—CR8R8—CR8R8-M— (c-8);
• -M—CR8R8—CR8R8—CR8R8— (c-9);
• —CR8R8—CR8═N—NR7— (c-10);
• —NR7—N═CR8═CR8R8— (c-11);
• ═N—CR9═CR10— (c-12);
• or —CR9═CR10—N═ (c-13);
• wherein:
• R7 and R8 are defined as above;
• R9, R10 independently are hydrogen, alkyl, halo or haloalkyl;
• or R9 and R10 together may form a bivalent radical of formula —CR8═CR8—CR8═CR8— wherein R8 is defined as above;
• and
• M is a bivalent radical of formula —CH2—, —O—, —S— or —NR7— wherein R7 is defined as above;
• Ar is a homocycle selected from the group of naphthyl and phenyl, each optionally substituted with 1, 2 or 3 substituents, each substituent independently selected from the group of hydroxy, halo, cyano, nitro, amino, mono- or dialkylamino, alkyl, haloalkyl, alkyloxy, haloalkyloxy, carboxyl, alkyloxycarbonyl, aminocarbonyl and mono- or dialkylaminocarbonyl;
• Het is a monocyclic heterocycle selected from the group of pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl;
• or a bicyclic heterocycle selected from the group of quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuryl, isoindolyl and benzothienyl;
• each monocyclic and bicyclic heterocycle may optionally be substituted on a carbon atom with one or more halo, oxo, hydroxy, alkyl or alkyloxy radicals;
• alkyl is a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms;
• or is a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms;
• or is a a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms attached to a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms;
• wherein each carbon atom can be optionally substituted with one or more halo, hydroxy, alkyloxy or oxo radicals;
• halo is a substituent selected from the group of fluoro, chloro, bromo and iodo;
• and
• haloalkyl is a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms or a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms, wherein one or more carbonatoms are substituted with one or more halo-atoms.