D-xylopyranosyl-phenyl-substituted cycles, medicaments containing such compounds, their use and process for their manufacture

A D-Glucopyranosyl-phenyl-substituted compound of formula I

• wherein
• denotes a single or double bond, and
• Cy denotes a 5- or 6-membered saturated or monounsaturated carbocycle, which may comprise one, two or three heteroatoms selected independently of one another from N, O and S, and
• which is substituted by R4, R5 and R6 through a single bond and by R3 through a single or double bond,
• and
• wherein one or two methylene groups may be replaced by CO or a sulphanyl group may be replaced by SO or SO2, and
• wherein one or more H atoms bound to carbon may be replaced by fluorine,
• Z denotes —O—, —CH2—, —CH═, —NRN—, —CO—, —S—, —SO— or —SO2—, while H atoms of the methylene or methanylylidene bridge may be substituted independently of one another by CH3 or F;
• R1 denotes hydrogen, fluorine, chlorine, bromine, iodine, C1-6-alkyl, C2-6-alkynyl, C2-6-alkenyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C5-7-cycloalkenyl, C5-7-cycloalkenyl-C1-3-alkyl, C1-4-alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C 1-4-alkylaminocarbonyl, di-(C1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C1-4-alkyl)piperazin-1-ylcarbonyl, C1-4-alkoxycarbonyl, amino, C1-4-alkylamino, di-(C1-3-alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-(C1-4-alkyl)piperazin-1-yl, C1-4-alkylcarbonylamino, C1-6-alkyloxy, C3-7-cycloalkyloxy, C5-7-cycloalkenyloxy, aryloxy, C14-alkylsulphanyl, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, C3-7-cycloalkylsulphanyl, C3-7-cycloalkylsulphinyl, C3-7-cycloalkylsulphonyl, C5-7cyclo -alkenylsulphanyl, C5-7-cycloalkenylsulphinyl, C5-7-cycloalkenylsulphonyl, arylsulphanyl, arylsulphinyl, arylsulphonyl, hydroxy, cyano or nitro,
• while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups may be partly or completely fluorinated or may be mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl, and
• in cycloalkyl and cycloalkenyl groups one or two methylene groups may be replaced independently of one another by O, S, CO, SO or SO2,and
• in N-heterocycloalkyl groups a methylene group may be replaced by CO or SO2, and
• R2 denotes hydrogen, fluorine, chlorine, bromine, hydroxy, C1-4-alkyl, C1-4-alkoxy, cyano or nitro, while alkyl groups may be mono- or polysubstituted by fluorine, or
• in the event that R1 and R2 are bound to two adjacent C atoms of the phenyl ring, R1 and R2 may be joined together such that R1 and R2 together form a C3-5-alkylene, C3-5-alkenylene or butadienylene bridge, which may be partly or completely fluorinated or may be mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl, and wherein one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO2 or NRN, and wherein in the case of a butadienylene bridge one or two methyne groups may be replaced by an N atom,
• R3 denotes hydrogen, fluorine, chlorine, bromine, C1-6-alkyl, C2-6-alkynyl, C2-6-alkenyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl, C5-7-cycloalkenyl, C5-7-cycloalkenyl-C1-3-alkyl, aryl, heteroaryl, aryl-C1-3-alkyl, heteroaryl-C1-3-alkyl, C1-4-alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C1-4-alkylaminocarbonyl, di-(C1-3-alkyl)amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C1-4-alkyl)piperazin-1-ylcarbonyl, hydroxycarbonyl, C 1-4-alkoxycarbonyl, C1-4-alkylamino, di-(C1-3-alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-(C1-4-alkyl)piperazin-1-yl, C1-4-alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, C1-4-alkylsulphonylamino, arylsulphonylamino, C1-6-alkoxy, C3-7-cycloalkyloxy, C5-7-cycloalkenyloxy, aryloxy, heteroaryloxy, C1-4-alkylsulphanyl, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, C3-7-cycloalkylsulphanyl, C3-7-cycloalkylsulphinyl, C3-7-cycloalkylsulphonyl, C5-7-cycloalkenylsulphanyl, C5-7-cycloalkenylsulphinyl, C5-7-cycloalkenylsulphonyl, arylsulphanyl, arylsulphinyl, arylsulphonyl, amino, hydroxy, cyano or nitro,
• while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups may be partly or completely fluorinated or may be mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl, and
• in cycloalkyl and cycloalkenyl groups one or two methylene groups may be replaced independently of one another by O, S, CO, SO or SO2, and
• in N-heterocycloalkyl groups a methylene group may be replaced by CO or SO2, or
• R3 denotes a group Y attached to Cy by a double bond,
• R4 denotes hydrogen, fluorine, chlorine, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)amino, C1-3-alkylcarbonylamino, C1-3-alkyl, C1-3-alkoxy, hydroxycarbonyl, C1-3-alkoxycarbonyl or methyl or methoxy substituted by 1 to 3 fluorine atoms, or
• in the event that R3 and R4 are bound to the same C atom of the Cy ring, R3 and R4 may be joined together such that R3 and R4 together form a C2-6-alkylene or C4-6-alkenylene bridge, which may be partly or completely fluorinated or may be mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl and wherein one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO2 or NRN, or
• in the event that R3 and R4 are bound to two adjacent atoms of the Cy ring, R3 and R4 may be joined together such that R3 and R4 together with the two adjacent atoms of the Cy ring form an anellated saturated or mono- or polyunsaturated 5- or 6-membered carbocycle, wherein one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO2 or NRN and/or one or two methyne groups may be replaced by N, and which may be mono- or polyfluorinated or mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl or in the case of an aromatic anellated ring may be mono- or disubstituted by identical or different substituents L,
• R5 denotes hydrogen, fluorine, chlorine, cyano, C1-3-alkyl, C1-3-alkoxy or methyl or methoxy substituted by 1 to 3 fluorine atoms, or
• R4 and R5 are attached to one another such that R4 and R5 together form a C1-4-alkylene or C2-4-alkenylene bridge, which together with 2, 3 or 4 atoms of the Cy ring forms an anellated or bridged cycle and which may be partly or completely fluorinated or mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl, and wherein one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO2 or NRN, and
• R6 denotes hydrogen, C1-3-alkyl or fluorine, or R4, R5 and R6 are attached to one another such that R4, R5 and R6 together form a C3-6-alkanetriyl bridge, which together with the Cy ring forms a bridged bicyclic or tricyclic system, while the alkanetriyl bridge may be mono- or polyfluorinated or mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-3-alkoxy and C1-3-alkyl, and wherein one or two methylene groups may be replaced independently of one another by O, CO, SO2 or NRN, and
• Y denotes oxygen, or methylidene, fluoromethylidene, chloromethylidene, C1-6-alkyl-methylidene, C2-6-alkenyl-methylidene, C2-6-alkynyl-methylidene, C3-7-cycloalkyl-methylidene, C5-7-cycloalkenyl-methylidene, C3-7-cycloalkylidene, C5-7-cycloalkenylidene, C3-7-cycloalkyl-C1-3-alkyl-methylidene, C5-7-cycloalkenyl-C1-3-alkyl-methylidene, arylmethylidene, heteroarylmethylidene, aryl-C1--alkyl-methylidene or heteroaryl-C1-3-alkyl-methylidene,
• while alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylidene and cycloalkenylidene groups may be partly or completely fluorinated or mono- or disubstituted by identical or different substituents selected from chlorine, cyano, hydroxy, C1-3-alkoxy, C1-4-alkylsulphanyl and C1-4-alkyl, and
• the above-mentioned unsubstituted methylidene group or the above-mentioned monosubstituted methylidene groups may additionally be monosubstituted by fluorine, chlorine, C1-3-alkyl, trifluoromethyl, C1-4-alkoxy, cyano or nitro, and
• in cycloalkyl, cycloalkenyl, cycloalkylidene and cycloalkenylidene groups one or two methylene groups may be replaced independentiy of one another by O, S, CO, SO, SO2 or NRN,or
• Y denotes a group according to partial formula
• wherein
• D denotes carbonyl or sulphonyl,
• RY denotes hydrogen, fluorine, chlorine, cyano, trifluoromethyl or C1-4-alkyl,
• B denotes a single bond, —O— or —NRN—, RB denotes hydrogen, C1-6-alkyl, C3-6-alkenyl, C3-6-alkynyl, C3-7-cycloalkyl, C5-7-cycloalkenyl, C3-7-cycloalkyl-C1-3-alkyl, C5-7-cycloalkenyl-C1-3-alkyl, aryl, heteroaryl, aryl-C1-3-alkyl or heteroaryl-C1-3-alkyl,
• while alkyl, cycloalkyl and cycloalkenyl groups may be partly or completely fluorinated or may be mono- or disubstituted by identical or different substituents selected from chlorine, cyano, hydroxy, C1-3-alkoxy and C1-3-alkyl, or
• RB and B are joined together to form a heterocyclic ring selected from pyrrolidine, morpholine, piperidine, piperazine and 4-(C1-4-alkyl)-piperazine, while the heterocyclic ring is bound to the group D via the imino group,
• RN independently of one another denote H or C1-4-alkyl,
• L selected independently of one another from among fluorine, chlorine, bromine, iodine, C1-3-alkyl, difluoromethyl, trifluoromethyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy and cyano,
• R7a, R7b,
• R7c, R7d independently of one another have a meaning selected from among hydrogen, (C1-18-alkyl)carbonyl, (C1-18-alkyl)oxycarbonyl, arylcarbonyl and aryl-(C1-3-alkyl)-carbonyl,
• while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may be mono- or disubstituted independently of one another by identical or different groups L;
• and
• by the heteroaryl groups mentioned in the definition of the above-mentioned groups is meant a pyrrolyl, furanyl, thienyl, imidazolyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group,
• or a pyrrolyl, furanyl, thienyl, imidazolyl or pyridyl group, wherein one or two methyne groups are replaced by nitrogen atoms,
• or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, wherein one to three methyne groups are replaced by nitrogen atoms,
• while the above-mentioned heteroaryl groups may be mono- or disubstituted independently of one another by identical or different groups L;
• while by the N-heterocycloalkyl group mentioned in the definition of the above-mentioned groups is meant a saturated carbocyclic ring which comprises an imino group in the ring, which may comprise another optionally substituted imino group or an O or S atom in the ring, and
• unless otherwise stated, the above-mentioned alkyl groups may be straight-chain or branched,
• the tautomers, their stereoisomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof,
• but excluding the following compounds:
• 3-[(3-β-D-glucopyranosyl-4,5-dimethoxyphenyl)methyl]-4-[(3,4-dimethoxyphenyl)methyl]-dihydro-2(3H)-furanone;
• 3-[(3-β-D-glucopyranosyl-4-hydroxy-5-methoxyphenyl)methyl]-4-[(3,4-dimethoxyphenyl)methyl]-dihydro-3-methyl-(3H)-furanone;
• and
• 3-[(3-β-D-glucopyranosyl-4-hydroxy-5-methoxyphenyl)methyl]-4-[(3-methoxy-4-hydroxyphenyl)methyl]-dihydro-2(3H)-furanone.