Novel Substituted Tetracyclic Tetrahydrofuran, Pyrrolidine and Tetrahydrothiophene Derivatives and Their Use as a Medicament

A compound according to Formula (I)

• an N-oxide form, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein:
• the dotted line represents an optional bond;
• i and j are integers, independently from each other, equal to zero, 1, 2, 3 or 4
• 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;
• alkyloxy;
• alkylcarbonyl and alkyloxycarbonyl;
• X represents CR6R7, O, S, S(═O), S(═O)2 or NR8;
• wherein:
• R6 and R7 each independently 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)2O—, —O(CH2)3—;
• 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;
• C is a group of formula (c-1), (c-2), (c-3), (c-4) or (c-5);
• wherein
• Y1 and Y2 each independently are S;
• O;
• S(═O);
• S(═O)2 or NR10;
• wherein R10 is selected from the group of hydrogen, cyano, alkyl, alkyloxyalkyl, formyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkylcarbonyl, arylcarbonyl, arylalkyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl and arylalkylsulfonyl;
• R10 and R11 may form together a bivalent radical (e-1) to (e-5);
• —CH2—NH—CH2— (e-1)
• —CH2—NH—CH2—CH2— (e-2)
• —CH2CH2—NH—CH2— (e-3)
• —CH=N—CH2— (e-4)
• —CH2—N═CH2— (e-5)
• wherein optionally in each radical (e-1) to (e-5) one or more
• hydrogens are replaced by one or more substituents selected from alkyl, —O-alkyl, —S-alkyl ═O, ═S, ═S(═O) and ═S(═O)2;
• R12 is hydrogen or alkyl
• R13, R14 each independently are hydrogen, hydroxy or oxo;
• R11 is a group of formula (d-1);
• wherein:
• n is zero, 1, 2, 3, 4, 5 or 6;
• R1 and R2 each independently are hydrogen;
• alkyl;
• alkylcarbonyl;
• alkyloxyalkyl;
• alkylcarbonyloxyalkyl;
• alkyloxycarbonylalkyl;
• arylalkyl;
• arylcarbonyl;
• alkyloxycarbonyl;
• aryloxycarbonyl;
• arylalkylcarbonyl;
• alkyloxycarbonylalkylcarbonyl;
• 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;
• or
• R1 and R2 taken together with the nitrogen atom to which they are attached may form a radical of formula (a-1), (a-2), (a-3), (a-4), (a-5) or (a-6);
• wherein:
• p is zero, 1, 2, 3 or 4;
• q is 1 or 2;
• m is zero, 1, 2, or 3;
• each R3 independently is selected from the group of hydrogen;
• halo;
• hydroxy;
• cyano;
• alkyl;
• alkyloxyalkyl;
• aryloxyalkyl;
• mono- or di(alkyl)aminoalkyl;
• hydroxycarbonylalkyl;
• alkyloxycarbonylalkyl;
• mono- or di(alkyl)aminocarbonylalkyl;
• mono- or di(aryl)aminocarbonylalkyl;
• mono- or di(alkyl)aminocarbonyloxyalkyl;
• alkyloxycarbonyloxyalkyl;
• arylaminocarbonyloxyalkyl;
• arylalkylaminocarbonyloxyalkyl;
• aryl;
• alkyloxy;
• aryloxy;
• alkylcarbonyloxy;
• arylcarbonyloxy;
• arylalkylcarbonyloxy;
• alkylcarbonyl;
• arylcarbonyl;
• aryloxycarbonyl;
• hydroxycarbonyl;
• alkyloxycarbonyl;
• alkylcarbonylamino;
• arylalkylcarbonylamino;
• arylcarbonylamino;
• alkyloxycarbonylamino;
• aminocarbonylamino;
• mono- or di(arylalkyl)aminocarbonylamino;
• alkyl-sulphonylalkylaminocarbonylamino;
• or two R3-radicals may form together a bivalent radical
• —CR5R5—CR5R5—O— (b-1)
• —O—CR5R5—CR5R5— (b-2)
• —O—CR5R5—CR5R5— (b-3)
• —O—CR5R5—CR5R5—CR5R5— (b-4)
• —CR5R5—CR5R5—CR5R5— (b-5)
• —O—CR5R5—CR5R5 CR5R5—O— (b-6)
• —O—CR5R5—CR5R5—CR5R5—CR5R5— (b-7)
• —CR5R5—CR5R5—CR5R5—CR5R5—O— (b-8)
• —O—CR5R5—CR5R5CR5R5R—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;
• arylalkyl;
• alkyloxyalkyl;
• alkylcarbonyloxyalkyl;
• alkyloxycarbonylalkyl;
• arylcarbonylalkyl;
• alkylsulphonyloxyalkyl;
• aryloxyaryl;
• alkyloxycarbonylaryl;
• alkylcarbonyl;
• arylalkylcarbonyl;
• alkyloxycarbonylalkylcarbonyl;
• arylcarbonyl;
• alkyloxycarbonyl;
• aryloxycarbonyl;
• arylalkyloxycarbonyl;
• mono- or di(alkyl)aminocarbonyl;
• mono- or di(aryl)aminocarbonyl;
• mono-or di(arylalkyl)aminocarbonyl;
• mono- or di(alkyloxycarbonylalkyl)aminocarbonyl;
• alkyloxyalkylaminocarbonyl;
• mono-, di- or tri(alkyl)amidino;
• mono-, di- or tri(aryl)amidino;
• mono-, di- or tri(arylalkyl)amidino;
• alkylsulphonyl;
• arylalkylsulphonyl or arylsulphonyl;
• aryl is phenyl or naphthyl;
• each radical optionally substituted with 1, 2 or 3 substituents selected from the group of halo, nitro, cyano, hydroxy, alkyloxy or alkyl;
• alkyl represents a straight or branched saturated hydrocarbon radical having from 1 to 10 carbon atoms, a cyclic saturated hydrocarbon radical having from 3 to 8 carbon atoms or a saturated hydrocarbon radical containing a straight or branched moiety having from 1 to 10 carbon atoms and a cyclic moiety having from 3 to 8 carbon atoms, optionally substituted with one or more halo, cyano, oxo, hydroxy, formyl, carboxyl or amino radicals;
• and
• halo represents fluoro, chloro, bromo and iodo.