Novel tetracyclic tetrahydrofuran derivatives

A compound of Formula (I)

• the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein:
• n is an integer, equal to zero, 1, 2, 3, 4, 5 or 6
• i, j are integers, independently from each other, equal to zero, 1, 2, 3 or 4;
• r is an integer, equal to zero, 1, 2 or 3
• R1 and R2 are, each independently from each other, selected from the group of hydrogen;
• alkyl;
• alkenyl;
• aryl;
• arylalkyl;
• arylalkenyl;
• alkyloxyalkyl;
• arylcarbonylalkyl;
• alkylcarbonyloxyalkyl;
• alkyloxycarbonylalkyl;
• alkylcarbonyl;
• arylcarbonyl;
• arylalkylcarbonyl;
• alkyloxycarbonyl;
• aryloxycarbonyl;
• alkyloxycarbonylalkylcarbonyl;
• mono- or di(alkyl)aminocarbonyl;
• mono- or di(aryl)aminocarbonyl;
• mono- or di(arylalkyl)aminocarbonyl;
• aminocarbonylalkyl;
• mono- or di(alkyloxycarbonylalkyl)aminocarbonyl;
• mono- or di(alkyl)aminocarbonylalkyl;
• mono- or di(aryl)aminocarbonylalkyl;
• mono- or di(alkyl)aminocarbonylalkenyl;
• mono- or di(alkylsulphonyl)aminocarbonylalkyl;
• mono- or di(arylsulphonyl)aminocarbonylalkyl;
• alkylsulphonyl;
• arylsulphonyl;
• arylalkylsulphonyl;
• mono- or di(alkyl)aminothiocarbonyl;
• mono-or di(aryl)aminothiocarbonyl;
• mono-or di(arylalkyl)aminothiocarbonyl;
• mono-, di- or tri(alkyl)amidino;
• mono-, di- or tri(alkyl)amidinoalkyl;
• mono-, di- or tri(aryl)amidino and mono-, di- or tri(arylalkyl)amidino;
• pyrrolidinyl, optionally substituted with one or more oxo moieties;
• tetrazolylalkyl;
• or
• R1 and R2 taken together with the nitrogen atom to which they are attached may form a radical of Formula (a-1) to (a-7):
• wherein:
• p is an integer, equal to zero, 1, 2, 3 or 4
• q is an integer, equal to 1 or 2;
• m is an integer, equal to zero, 1, 2 or 3
• each R3 is, independently from each other, selected from the group of halo;
• hydroxy;
• alkyloxy;
• aryloxy;
• alkyl;
• aryl;
• alkylcarbonyl;
• alkyloxycarbonyl;
• arylcarbonyl;
• aryloxycarbonyl and mono-or di(alkyl)amino;
• or
• two R3-radicals may form together a bivalent radical of Formula
• —CR5R5—CR5R5—O— (b-1);
• —O—CR5R5—CR5R5— (b-2);
• —O—CR5R5—CR5R5—O— (b-3);
• —O—CR5R5—CR5R5—CR5R5— (b-4);
• —CR5R5—CR5R5—CR5R5—O— (b-5);
• —O—CR5R5—CR5R5CR5R5—O— (b-6);
• —O—CR5R5—CR5R5—CR5R5—CR5R5—O— (b-7);
• —CR5R5—CR5R5—CR5R5—CR5R5—O— (b-8);
• and
• —O—CR5R5—CR5R5—CR5R5—O— (b-9);
• wherein R5 is selected from the group of hydrogen;
• halo;
• hydroxy;
• alkyloxy and alkyl;
• R4 is selected from the group of hydrogen;
• alkyl;
• alkylcarbonyl;
• arylcarbonyl;
• alkyloxycarbonyl;
• aryloxycarbonyl;
• arylalkylcarbonyl;
• alkyloxycarbonylalkylcarbonyl;
• arylalkyl;
• alkyloxyalkyl;
• alkylcarbonyloxyalkyl;
• alkyloxycarbonylalkyl;
• mono- or di(alkyl)aminocarbonyl;
• mono- or di(aryl)aminocarbonyl;
• mono- or di(arylalkyl)aminocarbonyl;
• mono- or di(alkyloxycarbonylalkyl)aminocarbonyl;
• alkylsulphonyl;
• arylsulphonyl;
• arylalkylsulphonyl;
• mono- or di(alkyl)aminothiocarbonyl;
• mono- or di(aryl)aminothiocarbonyl;
• mono- or di(arylalkyl)aminothiocarbonyl;
• mono-, di- or tri(alkyl)amidino;
• mono-, di- or tri(aryl)amidino and mono-, di- or tri(arylalkyl)amidino;
• A and B are, each independently from each other, aryl or an heteroaryl radical selected from the group of furyl;
• thienyl;
• pyrrolyl;
• oxazolyl;
• thiazolyl;
• imidazolyl;
• isoxazolyl;
• isothiazolyl;
• oxadiazolyl;
• triazolyl;
• pyridinyl;
• pyridazinyl;
• pyrimidinyl;
• pyrazinyl;
• indolyl;
• indolizinyl;
• isoindolyl;
• benzofuryl;
• isobenzofuryl;
• benzothienyl;
• indazolyl;
• benzimidazolyl;
• benzthiazolyl;
• quinolizinyl;
• quinolinyl;
• isoquinolinyl;
• phthalazinyl;
• quinazolinyl;
• quinoxalinyl;
• chromenyl;
• naphthyridinyl and naphthalenyl;
• each R9 is, independently from each other, selected from the group of hydrogen;
• halo cyano;
• hydroxy;
• carboxyl;
• nitro;
• amino;
• mono- or di(alkyl)amino;
• alkylcarbonylamino;
• aminosulfonyl;
• mono- or di(alkyl)aminosulfonyl;
• alkyl;
• alkenyl;
• alkyloxy;
• alkylcarbonyl and alkyloxycarbonyl;
• R10 is selected from the group of hydrogen;
• alkyl;
• halo and cyano;
• Y is O;
• S;
• S(═O);
• S(═O)2 or NR8;
• X is CR6R7;
• O;
• S;
• S(═O);
• S(═O)2 or NR8;
• wherein
• R6 and R7 each independently from each other, are selected from the group of hydrogen;
• hydroxy;
• alkyl and alkyloxy;
• or
• R6 and R7 taken together may form a radical selected from the group of methylene (═CH2);
• mono- or di(cyano)methylene;
• a bivalent radical of Formula —(CH2)2—, —(CH2)3—, —(CH2)4—, —(CH2)5—, —O—(CH2)2—O—, —O—(CH2)3O—;
• or, together with the carbon atom to which they are attached, a carbonyl;
• R8 is selected from the group of hydrogen;
• alkyl;
• alkylcarbonyl;
• arylcarbonyl;
• arylalkyl;
• arylalkylcarbonyl;
• alkylsulfonyl;
• arylsulfonyl and arylalkylsulfonyl;
• aryl is phenyl, optionally substituted with 1, 2 or 3 substitutents independently from each other, selected from the group of halo, hydroxy, alkyloxy and alkyl;
• alkyl 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;
• each radical optionally substituted with one or more radicals selected from the group of halo, cyano, oxo, hydroxy, formyl, carboxyl and amino;
• alkenyl is a straight or branched unsaturated hydrocarbon radical having from 1 to 6 carbon atoms;
• or a cyclic unsaturated hydrocarbon radical having from 3 to 6 carbon atoms;
• each radical optionally substituted with one or more radicals selected from the group of halo, cyano, oxo, hydroxy, formyl, carboxyl or amino radicals;
• and
• halo is fluoro, chloro, bromo or iodo.