US 2006.0035.841A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0035841A1 Eckhardt et al. (43) Pub. Date: Feb. 16, 2006

(54) D-XYLOPYRANOSYL-PHENYL-SUBSTITUTED Publication Classification CYCLES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND (51) Int. Cl. PROCESS FOR THEIR MANUFACTURE C07H 5/04 (2006.01) A61K 31/7052 (2006.01) (75) Inventors: Matthias Eckhardt, Biberach (DE); (52) U.S. Cl...... 514/23: 536/18.7 Frank Himmelsbach, Mittelbiberach (DE); Peter Eickelmann, (57) ABSTRACT Mittelbiberach (DE); Leo Thomas, Biberach (DE); Edward Leon A D-Xylopyranosyl-phenyl-Substituted cycle compound of Barsoumian, Toyonaka (JP) general formula I Correspondence Address:

MICHAEL P. MORRIS BOEHRINGER INGELHEM CORPORATION 900 RIDGEBURY ROAD P. O. BOX 368 RIDGEFIELD, CT 06877-0368 (US) (73) Assignee: Boehringer Ingelheim International GmbH, Ingelheim (DE) (21) Appl. No.: 11/199,962 (22) Filed: Aug. 9, 2005 wherein the groups R to R, Z, X, Cy and R', R7 and R' (30) Foreign Application Priority Data are defined as in claim 1, have an inhibiting effect on the Sodium-dependent glucose cotransporter SGLT. The present Aug. 11, 2004 (DE)...... DE 102004O39096 invention also relates to pharmaceutical compositions for the Sep. 23, 2004 (DE)...... DE 102004O46583 treatment of metabolic disorders. US 2006/0035.841 A1 Feb. 16, 2006

D-XYLOPYRANOSYL-PHENYL-SUBSTITUTED 0007. The invention also relates to a process for prepar CYCLES, MEDICAMENTS CONTAINING SUCH ing the compounds according to the invention. COMPOUNDS, THEIR USE AND PROCESS FOR 0008 Further aims of the present invention will imme THEIR MANUFACTURE diately become apparent to the skilled man from the remarks RELATED APPLICATIONS above and hereinafter. 0001. The present application claims the benefit of DE 102004039096 filed Aug. 11, 2004 and OBJECTS OF THE INVENTION DE102004046583 filed Sep. 23, 2004. The contents of both applications are incorporated herein. 0009. In a first aspect the invention relates to D-xylopy ranosyl-phenyl-Substituted cycles of general formula I THE INVENTION 0002 The present invention relates to D-xylopyranosyl phenyl-Substituted cycles of general formula I

wherein - denotes a Single or double bond, and wherein the groups R to R', Z, X, Cy and R', R" and R' 0010 X denotes hydrogen, C-alkyl, C-alkynyl, C are as hereinafter defined, including the tautomers, the alkenyl, Co-cycloalkyl, Co-cycloalkyl-C-3-alkyl, stereoisomers, the mixtures thereof and the Salts thereof. The Cs-o-cycloalkenyl, C-3-cycloalkenyl-C-3-alkyl, aryl, invention further relates to pharmaceutical compositions aryl-C-alkyl, heteroaryl, heteroaryl-C-alkyl, C containing a compound of formula I according to the inven alkylcarbonyl, arylcarbonyl, aminocarbonyl, aminocarbo tion as well as the use of a compound according to the nyl-C-alkyl, C-alkylaminocarbonyl, C-alkylami invention for preparing a pharmaceutical composition for nocarbonyl-C-alkyl, di-(C-alkyl)aminocarbonyl, the treatment of metabolic disorders. The invention also di-(C-alkyl)-aminocarbonyl-C-alkyl, pyrrolidin-1- relates to processes for preparing a pharmaceutical compo ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbo Sition and a compound according to the invention. nyl, hydroxycarbonyl, hydroxycarbonyl-C-alkyl, C 0.003 Compounds which have an inhibitory effect on the alkoxycarbonyl, C-alkoxycarbonyl-C-alkyl, C Sodium-dependent glucose cotransporter SGLT are proposed alkylcarbonylamino-C-alkyl, N-(C- in the literature for the treatment of diseases, particularly alkylcarbonyl)-N-(C-alkyl)-amino-C-alkyl, diabetes. arylcarbonyl-amino-C-alkyl, C-alkylsulphony lamino-C-alkyl, arylsulphonylamino-C-alkyl, Co 0004 Glucopyranosyl-substituted aromatic groups and alkoxy-C-alkyl, Co-cycloalkyloxy-C-3-alkyl, the preparation thereof and their possible activity as SGLT2 Cs-ocycloalkenyl-oxy-C-3-alkyl, aryloxy-C-3-alkyl, inhibitors are known from published International Patent heteroaryloxy-C-alkyl, C-alkylsulphanyl-C-alkyl, Applications WO 98/31697, WO 01/27128, WO 02/083066, C-alkylsulphinyl, C-alkylsulphonyl, C-alkylsul WO 03/099836, WO 2004/063209, WO 2004/080990, WO phinyl-C-alkyl, C-alkylsulphonyl-C-alkyl, aryl 2004/013118, WO 2004/052902, WO 2004/052903, WO Sulphanyl-C-alkyl, arylsulphonyl-C-alkyl, aryl-C- 05/12326 and US application US 2003/0114390. alkyl-Sulphonyl-C-alkyl, C-alkylsulphonyloxy-C- AIM OF THE INVENTION alkyl, arylsulphonyloxy-C-alkyl, aryl-C-alkyl 0005 The aim of the present invention is to indicate new Sulphonyloxy-C-alkyl, Co-cyclo-alkylsulphanyl-C- pyranosyl-Substituted phenyls, particularly those which 3-alkyl, Co-cycloalkylsulphinyl, Cs-10 have an effect on Sodium-dependent glucose cotransporter cycloalkylsulphinyl-C-alkyl, C3-1o SGLT, particularly SGLT2. A further aim of the present cycloalkylsulphonyl, Co-cycloalkylsulphonyl-C- invention is to indicate pyranosyl-Substituted phenyls which, alkyl, Cso-cycloalkenylsulphanyl-C-alkyl, by comparison with known Structurally similar compounds, cycloalkenylsulphinyl, Cso-cycloalkenyl-Sulphinyl-C- have a greater inhibitory effect on the Sodium-dependent 3-alkyl, Co-cycloalkenylsulphonyl, glucose cotransporter SGLT2 in vitro and/or in vivo and/or cycloalkenylsulphinyl-C-alkyl, bromomethyl, have improved pharmacological or pharmacokinetic prop iodomethyl or cyano, erties. while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl 0006 Moreover the present invention also sets out to groups may be partly or totally fluorinated or mono- or prepare new pharmaceutical compositions which are Suit disubstituted by identical or different substituents selected able for the prevention and/or treatment of metabolic dis from chlorine, cyano, hydroxy, mercapto, C-alkoxy and orders, particularly diabetes. C-alkyl, and US 2006/0035.841 A1 Feb. 16, 2006 in cycloalkyl and cycloalkenyl groups one or two methylene rine, hydroxy, C-alkoxy and C-alkyl and wherein groups may be replaced independently of one another by one or two methylene groups may be replaced indepen O, S, CO, SO or SO, and dently of one another by O, S, CO, SO, SO or NRS, and in N-heterocycloalkyl groups a methylene group may be wherein in the case of a butadienylene bridge one or two replaced by CO or SO, and methyne groups may be replaced by an N atom, and 0.015 R denotes hydrogen, fluorine, chlorine, bromine, X representing hydroxymethyl is preferably excluded, C6-alkyl, C2-alkynyl, C2-alkenyl, Co-cycloalkyl, 0.011) Cy denotes a 5- or 6-membered Saturated or Co-cycloalkyl-C-alkyl, Cso-cycloalkenyl, Cso monounsaturated carbocyclic ring, which may comprise cycloalkenyl-C-alkyl, aryl, heteroaryl, aryl-C-alkyl, one, two or three heteratoms Selected independently of heteroaryl-C-alkyl, C-alkylcarbonyl, arylcarbonyl, one another from N, O and S, and heteroarylcarbonyl, aminocarbonyl, C-alkylaminocar bonyl, di-(C-alkyl)aminocarbonyl, pyrrolidin-1-ylcar is substituted by R", RandR through a single bond and by bonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, R through a single or double bond, and piperazin-1-ylcarbonyl, 4-(C-alkyl)piperazin-1-ylcar wherein one or two methylene groups may be replaced by bonyl, hydroxycarbonyl, C-alkoxycarbonyl, aryl-C- CO or a Sulphanyl group by SO or SO, and alkoxycarbonyl, C-alkylamino, di-(C-alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piper wherein additionally one or more H atoms bound to carbon azin-1-yl, 4-(C-alkyl)piperazin-1-yl, C-alkylcarbo may be replaced by fluorine, nylamino, arylcarbonylamino, heteroarylcarbonylamino, 0012 Z denotes -O-, -CH-, -CH=, -NRN-, C-alkylsulphonylamino, arylsulphonylamino, C.- CO-, -S-, -SO- or SO-, while H atoms of the alkoxy, Co-cycloalkyloxy, Cs-o-cycloalkenyloxy, ary methylene or methanylylidene bridge may be Substituted loxy, heteroaryloxy, C-alkylsulphanyl, C-alkylsul independently of one another by CH or F; phinyl, C-alkylsulphonyl, Co-cycloalkylsulphanyl, 0013) R' denotes hydrogen, fluorine, chlorine, bromine, Co-cycloalkylsulphinyl, Co-cycloalkylsulphonyl, iodine, C6-alkyl, C6-alkynyl, C2-alkenyl, Co-cy Cso-cycloalkenylsulphanyl, Cso-cycloalkenylsulphi cloalkyl, Co-cycloalkyl-C-3-alkyl, Cs-o-cycloalkenyl, nyl, Cso-cycloalkenylsulphonyl, arylsulphanyl, arylsul Co-cycloalkenyl-C-alkyl, C-alkylcarbonyl, aryl phinyl, arylsulphonyl, amino, hydroxy, cyano or nitro, carbonyl, heteroarylcarbonyl, aminocarbonyl, C-alky while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl laminocarbonyl, di-(C-alkyl)aminocarbonyl, pyrroli groups may be partly or totally fluorinated or mono- or din-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4- disubstituted by identical or different substituents selected ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C- from chlorine, hydroxy, C-alkoxy and C-alkyl, and alkyl)piperazin-1-ylcarbonyl, C-alkoxycarbonyl, amino, C-alkylamino, di-(C-alkyl)amino, pyrroli in cycloalkyl and cycloalkenyl groups one or two methylene din-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, groups may be replaced independently of one another by 4-(C-alkyl)piperazin-1-yl, C-alkylcarbonylamino, O, S, CO, SO or SO, and C6-alkyloxy, Co-cycloalkyloxy, Cso-cycloalkeny in N-heterocycloalkyl groups a methylene group may be loxy, aryloxy, C-alkylsulphanyl, C-alkylsulphinyl, replaced by CO or SO, or C-alkylsulphonyl, Co-cycloalkylsulphanyl, Co cycloalkylsulphinyl, Co-cycloalkylsulphonyl, Co R denotes a group Y connected to Cy through a double cycloalkenylsulphanyl, Co-cycloalkenylsulphinyl, bond, Co-cycloalkenylsulphonyl, arylsulphanyl, arylsulphi 0016) R' denotes hydrogen, fluorine, chlorine, cyano, nyl, arylsulphonyl, hydroxy, cyano or nitro, nitro, amino, C-alkyl-amino, di-(C-alkyl)amino, while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl C-3-alkylcarbonylamino, C-3-alkyl, C-3-alkoxy, groups may be partly or totally fluorinated or mono- or hydroxycarbonyl, C-alkoxycarbonyl or methyl or disubstituted by identical or different substituents selected methoxy substituted by 1 to 3 fluorine atoms, or from chlorine, hydroxy, C-alkoxy and C-alkyl, and in the event that R and R" are bound to the same C atom of in cycloalkyl and cycloalkenyl groups one or two methylene the Cy ring, R and R' may be joined together such that groups may be replaced independently of one another by R and R together form a C6-alkylene or C6-alk O, S, CO, SO or SO, and enylene bridge which may be partly or wholly fluorinated or mono- or disubstituted by identical or different Sub in N-heterocycloalkyl groups a methylene group may be Stituents selected from chlorine, hydroxy, C-alkoxy and replaced by CO or SO, and C-alkyl and wherein one or two methylene groups may 0014) R' denotes hydrogen, fluorine, chlorine, bromine, be replaced independently of one another by O, S, CO, hydroxy, C-alkyl, C-alkoxy, cyano or nitro, while SO, SO, or NRN.or alkyl groups may be mono- or poly Substituted by fluorine, in the event that Rand R" are bound to two adjacent atoms O of the Cy ring, RandR' may be joined together such that in the event that R' and R are bound to two adjacent C Rand R' together with the two adjacent atoms of the Cy atoms of the phenyl ring, R' and R may be joined ring form an anellated Saturated or mono- or polyunsatu together Such that R' and R together form a Cas-alky rated 5- or 6-membered carbocyclic group wherein one or lene, C-s-alkenylene or butadienylene bridge, which may two methylene groups may be replaced independently of be partly or wholly fluorinated or mono- or disubstituted one another by O, S, CO, SO, SO or NRN and/or one or by identical or different Substituents selected from chlo two methyne groups may be replaced by N, and may be US 2006/0035.841 A1 Feb. 16, 2006

mono- or polyfluorinated or mono- or disubstituted by 0021 L is selected independently of one another from the identical or different Substituents selected from chlorine, group consisting of fluorine, chlorine, bromine, iodine, hydroxy, C-alkoxy and C-alkyl or in the case of an C-alkyl, difluoromethyl, trifluoromethyl, C-alkoxy, aromatic anellated cyclic group may be mono- or disub difluoromethoxy, trifluoromethoxy and cyano, stituted by identical or different Substituents L, 0022 R7, R7, 0017 R denotes hydrogen, fluorine, chlorine, cyano, C-alkyl, C-alkoxy or methyl or methoxy Substituted 0023) R' independently of one another have a meaning Selected from among hydrogen, (C-s-alkyl)carbonyl, (C by 1 to 3 fluorine atoms, or s-alkyl)oxycarbonyl, arylcarbonyl and aryl-(C- R" and Rare joined together so that RandR together form alkyl)-carbonyl, a C-alkylene or C-alkenylene bridge which forms an anellated or bridged cyclic group with 2, 3 or 4 atoms of while by the aryl groups mentioned above in the definitions the Cy ring and may be partly or wholly fluorinated or of the above groups are meant phenyl or naphthyl groups, mono- or disubstituted by identical or different substitu which may be mono- or disubstituted independently of ents Selected from chlorine, hydroxy, C-alkoxy and one another by identical or different groups L., and C-alkyl, and wherein one or two methylene groups may by the heteroaryl groups mentioned in the definitions of the be replaced independently of one another by O, S, CO, above-mentioned groups is meant a pyrrolyl, furanyl, SO, SO, or NRN, and thienyl, imidazolyl, pyridyl, indolyl, benzofuranyl, ben 0018) R' denotes hydrogen, C-alkyl or fluorine, or R', Zothio-phenyl, quinolinyl or isoquinolinyl group, R and R are joined together such that R, R and R' together form a C-alkanetriyl bridge, which together or a pyrrolyl, furanyl, thienyl, imidazolyl or pyridyl group, with the Cy ring forms a bridged bicyclic or a tricyclic wherein one or two methyne groups are replaced by System, while the alkanetriyl bridge may be mono- or nitrogen atoms, polyfluorinated or mono- or disubstituted by identical or or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or different substituents selected from chlorine, hydroxy, isoquinolinyl group, wherein one to three methyne groups C-alkoxy and C-alkyl, and wherein one or two methylene groups may be replaced independently of one are replaced by nitrogen atoms, another by O, CO, SO or NRN, and while the above-mentioned heteroaryl groups may be mono or disubstituted independently of one another by identical 0019 Y denotes oxygen, or or different groups L.; methylidene, fluoromethylidene, chloromethylidene, C alkyl-methylidene, C-alkenyl-methylidene, C-alky and by the N-heterocycloalkyl group mentioned in the nyl-methylidene, C-7-cycloalkyl-methylidene, C5-7-cy definition of the above-mentioned groups is meant a cloalkenyl-methylidene, C7-cycloalkylidene, C-7- Saturated carbocyclic ring which comprises an imino cycloalkenylidene, C-7-cycloalkyl-C-alkyl group in the ring, and which may comprise another methylidene, C.s 7-cycloalkenyl-C-alkyl-methylidene, optionally Substituted imino group or an O or S atom in cyclo-Cae-alkyleneimino-C-alkyl-methylidene, aryl the ring, and methylidene, heteroarylmethylidene, aryl-C-alkyl-me unless otherwise Stated the above-mentioned alkyl groups thylidene or heteroaryl-C-alkyl-methylidene, may be Straight-chain or branched, while alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, the tautomers, the Stereoisomers, the mixtures thereof and cyclo-Cae-alkyleneimino, cycloalkylidene and cycloalk the Salts thereof, particularly the physiologically accept enylidene groups may be partly or totally fluorinated or able salts thereof. mono- or disubstituted by identical or different substitu ents Selected from chlorine, cyano, hydroxy, C-alkoxy, 0024. The compounds of general formula I according to C-alkylsulphanyl and C-alkyl, and the invention and the physiologically acceptable Salts thereof have valuable pharmacological properties, particu the above-mentioned unsubstituted methylidene group or larly an inhibitory effect on the Sodium-dependent glucose the above-mentioned monosubstituted methylidene cotransporter SGLT, particularly SGLT2. Moreover com groups may additionally be monoSubstituted by fluorine, pounds according to the invention may have an inhibitory chlorine, C-alkyl, trifluoromethyl, C-alkoxy, cyano effect on the Sodium-dependent glucose cotransporter or nitro, and SGLT1. Compared with a possible inhibitory effect on a methylene bridge bound directly to the methylidene group SGLT1 the compounds according to the invention preferably may be replaced by -CO-, -SO-, -COO-, inhibit SGLT2 selectively. -CO-NR or -SO-NRN-, and 0025 The present invention also relates to the physi in cycloalkyl, cycloalkenyl, cycloalkylidene and cycloalk ologically acceptable Salts of the compounds according to enylidene groups one or two methylene groups may be the invention with inorganic or organic acids. replaced independently of one another by O, S, CO, SO, 0026. Therefore, the invention also relates to the use of SO or NRS, and the compounds according to the invention, including the in cyclo-Cae-alkyleneimino groups a methylene group may physiologically acceptable Salts, as pharmaceutical compo be replaced by CO or SO; and Sitions. 0020 RN independently of one another denote H or 0027. This invention also relates to pharmaceutical com C-alkyl, positions, containing at least one compound according to the US 2006/0035.841 A1 Feb. 16, 2006 invention or a physiologically acceptable Salt according to above-mentioned ethylene bridge together with two oxy the invention, optionally together with one or more inert gen atoms and the two associated carbon atoms of the carriers and/or diluents. pyranose form a Substituted dioxane ring, particularly a 0028. A further subject of this invention is the use of at 2,3-dimethyl-2,3-di(C-alkoxy)-1,4-dioxane ring, and least one compound according to the invention or a physi alkyl, aryl and/or benzyl groups may be mono- or ologically acceptable Salt of Such a compound for preparing poly Substituted by halogen or C-alkoxy and benzyl a pharmaceutical composition which is Suitable for the groups may also be substituted by a di-(C-alkyl)amino treatment or prevention of diseases or conditions which can group; and be influenced by inhibiting the Sodium-dependent glucose 0037) R, R, R independently of one another represent cotransporter SGLT, particularly SGLT2. C-alkyl, aryl or aryl-C-alkyl, wherein the aryl or 0029. This invention also relates to the use of at least one alkyl groups may be mono- or poly Substituted by halogen; compound according to the invention or one of the physi while by the aryl groups mentioned in the definition of the ologically acceptable Salts thereof, for preparing a pharma above groups are meant phenyl or naphthyl groups, pref ceutical composition which is Suitable for the treatment of erably phenyl groups; metabolic disorders. and wherein the groups X, R' to Rand the bridge Z and the 0030 This invention also relates to the use of at least one Cy ring are defined as hereinbefore and hereinafter; compound according to the invention or one of the physi ologically acceptable Salts thereof for preparing a pharma is reacted with a reducing agent in the presence of an acid, ceutical composition for inhibiting the Sodium-dependent and any protective groups present are cleaved Simulta glucose cotransporter SGLT, particularly SGLT2. neously or afterwards, or 0031. The invention further relates to a process for pre b) in order to prepare compounds of general formula I paring a pharmaceutical composition according to the inven wherein R', R" and R' represent hydrogen, tion, characterised in that a compound according to the invention or one of the physiologically acceptable Salts in a compound of general formula III thereof is incorporated in one or more inert carriers and/or diluents by a non-chemical method.

III 0032. The present invention further relates to a process for preparing the compounds of general formula I according to the invention, characterised in that a) in order to prepare compounds of general formula I as defined hereinbefore and hereinafter, 0033) a compound of general formula II

II wherein Z, X, Cy, R, RR and R to R are defined as hereinbefore and hereinafter, while at least one of the groups R, R and R does not represent hydrogen, the groups R, RandR which do not represent hydrogen are removed, particularly hydrolysed; and if necessary any protective group used in processa) or b) in the reactions described above is cleaved again and/or if desired a compound of general formula I thus obtained is wherein Selectively derivatised at a hydroxy group or is Substituted 0034) R' denotes H, C-alkyl, (C-s-alkyl)carbonyl, and/or (Cs-alkyl)oxycarbonyl, arylcarbonyl or aryl-(C- if desired a compound of general formula I thus obtained is alkyl)-carbonyl, wherein the alkyl or aryl groups may be resolved into its Stereoisomers and/or mono- or poly Substituted by halogen; if desired a compound of general formula I thus obtained is 0035) R, R, converted into the Salts thereof, particularly for pharma 0036), R independently of one another have one of the ceutical use is converted into the physiologically accept meanings given hereinbefore and hereinafter for the able salts thereof. groups R', R", R", or denote a benzyl group or an R"RRSigroup or a ketal or acetal group, particularly an DETAILED DESCRIPTION OF THE alkylidene or arylalkylidene ketal or acetal group, while INVENTION in each case two adjacent groups R, R, R, R may 0038. Unless otherwise stated the groups, residues and form a cyclic ketal or acetal group or a 1,2-di(C- substituents, particularly R' to R', X, Y, Z, Cy, L, RS, R, alkoxy)-1,2-di(C-alkyl)-ethylene bridge, while the R", R', are defined as above and hereinafter. US 2006/0035.841 A1 Feb. 16, 2006

0039. If residues, substituents or groups occur several bonyl, C-alkoxycarbonyl, C-alkylcarbonylamino-C- times in a compound, they may have the same or different alkyl, N-(C-alkylcarbonyl)-N-(C-alkyl)-amino-Ca meanings. alkyl, arylcarbonylamino-C-alkyl, C1-4- alkylsulphonylamino-C-alkyl, C-alkoxy-C-alkyl, 0040. The term aryl used above and hereinafter, for C-7-cycloalkyloxy-C2-alkyl, Cs 7-cycloalkenyloxy-C2-a- example in the groups X, Y, R and R, preferably denotes alkyl, aryloxy-C-alkyl, heteroaryloxy-C-alkyl, C phenyl. According to the general definition and unless alkylsulphanyl-C-alkyl, C-alkylsulphinyl-C-alkyl or otherwise Stated, the aryl group, particularly the phenyl C-alkylsulphonyl-C-alkyl, group, may be mono- or disubstituted by identical or dif ferent groups L. 0046 while alkoxy, alkenyl, alkynyl, cycloalkyl and 0041. The term heteroaryl used above and hereinafter, for cycloalkenyl groups may be partly or totally fluorinated or example in the groups X, Y, R and R, preferably denotes mono- or disubstituted by identical or different substituents pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, imi Selected from chlorine, cyano, hydroxy, C-alkoxy and dazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiaz C-alkyl, and methyl groups may be partly or totally fluorinated or monoSubstituted by chlorine or cyano, and olyl, thiazolyl or thiadiazolyl. According to the general alkyl groups with 2 or more C atoms may be partly or wholly definition and unless otherwise Stated, the heteroaryl group fluorinated or mono- or disubstituted by identical or different may be mono- or disubstituted by identical or different Substituents Selected from chlorine, cyano, hydroxy, mer groupS L. capto and C-alkoxy, 0042. The group X preferably denotes hydrogen, cyano, C6-alkyl, C2-alkynyl, C2-alkenyl, Co-cycloalkyl-C- while in the above-mentioned cycloalkyl and cycloalkenyl 3-alkyl, Cs-o-cycloalkenyl-C-3-alkyl, aryl, aryl-C-3-alkyl, groups one or two methylene groups may be replaced heteroaryl, heteroaryl-C-alkyl, aminocarbonyl, C-alky independently of one another by O, S, CO, SO or SO, and laminocarbonyl, C-alkylaminocarbonyl-C-alkyl, in N-heterocycloalkyl groups a methylene group may be di-(C-alkyl)aminocarbonyl, C-alkyrSulphonylamino C-alkyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, replaced by CO or SO, and morpholin-4-ylcarbonyl, C-alkylcarbonyl, C-alkoxy while the aryl and heteroaryl are as hereinbefore defined and carbonyl, C-alkylcarbonylamino-C-alkyl, N-(C- aryl and heteroaryl groups may be mono- or disubstituted alkylcarbonyl)-N-(C-alkyl)-amino-C-alkyl, arylcarbo independently of one another by identical or different groups nylamino-C-alkyl, Calkoxy-CI--alkyl, Cs-1o L. cycloalkyloxy-C-alkyl, Cso-cycloalkenyloxy-C- alkyl, aryloxy-C-alkyl, heteroaryloxy-C-alkyl, C 0047. If the group X denotes a cycloalkyl or cycloalkenyl alkylsulphanyl-C-alkyl, C-alkylsulphinyl-C-alkyl or group wherein one or two methylene groups are replaced C-alkylsulphonyl-C-alkyl, independently of one another by O, S, CO, SO or SO, preferred definitions of the group X are Selected from among 0.043 while alkyl, alkenyl, alkynyl, cycloalkyl and tetrahydrofuranyl, tetrahydrofuranonyl, tetrahydrothienyl, cycloalkenyl groups may be partly or totally fluorinated or tetrahydropyranyl, tetrahydropyranonyl, dioxanyl and tri mono- or disubstituted by identical or different Substituents OXanyl. Selected from chlorine, cyano, hydroxy, mercapto, C.- alkoxy and C-alkyl, and 0048 If the group X denotes an N-heterocycloalkyl group wherein a methylene group is replaced by CO or SO2, in the above-mentioned cycloalkyl and cycloalkenyl groups preferred meanings of the group X are Selected from among one or two methylene groups may be replaced independently pyrrolidinone, piperidinone, piperazinone and morpholi of one another by O, S, CO, SO or SO, and Oc. in N-heterocycloalkyl groups a methylene group may be 0049 Particularly preferred radicals of the group X are replaced by CO or SO, and hydrogen, cyano, C6-alkyl, C2-alkynyl, C2-alkenyl, the terms aryland heteroaryl are as hereinbefore defined and C-alkylcarbonyl, C-alkoxycarbonyl, aminocarbonyl, aryl and heteroaryl groups may be mono- or disubstituted C-alkylaminocarbonyl, di-(C-alkyl)aminocarbonyl, independently of one another by identical or different groups C-alkylsulphonylamino-C-alkyl, C-alkylsulphonyl L., and C-3-alkyl, X representing hydroxymethyl is preferably excluded. while alkyl groups may be mono- or polyfluorinated or monoSubstituted by chlorine or cyano and X representing 0044 According to the definitions of the group X the alkyl with 2 or more C atoms may comprise a hydroxy compounds of formula I according to the invention may be Substituent. divided into four embodiments. 0050 Most particularly preferred groups X are hydrogen, 0.045 According to a first embodiment relating to the cyano, methyl, ethyl, propyl, fluoromethyl, trifluoromethyl, group X, preferred compounds of formula I according to the cyanomethyl, 1-hydroxyethyl, 1-hydroxy-1-methylethyl, invention are those wherein the group X preferably denotes 2-hydroxyethyl, prop-2-enyl, prop-2-ynyl, methylcarbonyl, hydrogen, cyano, C6-alkyl, C2-alkynyl, C6-alkenyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocar C-7-cycloalkyl-C-alkyl, Cs 7-cycloalkenyl-C-alkyl, bonyl, methoxycarbonyl and ethoxycarbonyl. aryl-C-alkyl, heteroaryl-C-alkyl, aminocarbonyl, C alkylaminocarbonyl, C-alkylaminocarbonyl-C-alkyl, 0051. A selection of the most particularly preferred di-(C-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, pip groupS X includes methyl, ethyl, fluoromethyl and cyanom eridin-1-ylcarbonyl, morpholin-4-ylcarbonyl, C-alkylcar ethyl. US 2006/0035.841 A1 Feb. 16, 2006

0.052 According to a second embodiment relating to the 0060. The compounds according to this fourth embodi group X, preferred compounds of formula I according to the ment are particularly Suitable, in addition to their pharma invention are those wherein the group X preferably denotes ceutical activity as described above, as intermediate prod Co-alkoxy-methyl, C-7-cycloalkyloxy-methyl, Cs 7-cy ucts in the synthesis of compounds with an SGLT, preferably cloalkenyloxy-methyl, aryloxy-methyl or heteroaryloxy SGLT2 inhibiting activity, particularly in the synthesis of methyl, other compounds according to the invention. while the above-mentioned alkoxy, cycloalkyl and cycloalk 0061 Particularly preferred groups X according to this enyl groupS may be partly or totally fluorinated or mono- or embodiment are bromomethyl, iodomethyl, C-alkylsul disubstituted by identical or different Substituents selected phonyloxymethyl or phenylsulphonyloxymethyl, while the from chlorine, hydroxy, C-alkoxy and C-alkyl, and above-mentioned alkyl groups may be partly or completely fluorinated and the above-mentioned phenyl groups may be in the above-mentioned cycloalkyl and cycloalkenyl groups mono- or disubstituted by identical or different groups L, one or two methylene groups may be replaced independently while L is preferably Selected from among fluorine, chlorine, of one another by O, S, CO, SO or SO, and bromine and methyl. the terms aryland heteroaryl are as hereinbefore defined and 0062 Most particularly preferred is X representing tolyl aryl and heteroaryl groups independently of one another Sulphonyloxymethyl, phenylsulphonyloxymethyl, trifluo may be mono- or disubstituted by identical or different romethylsulphonyloxymethyl, bromomethyl or iodomethyl. groupS L. 0063 Preferred meanings of the Cy ring as hereinbefore 0.053 According to this embodiment preferred meanings defined are also given hereinafter. of the group X are C-alkyloxymethyl, C-7-cycloalky loxymethyl and aryloxymethyl, while by aryl is meant a 0064 Preferred meanings of the Cy ring are cyclopen phenyl or naphthyl group, particularly phenyl, which may be tane, cyclohexane, pyrrolidine, piperidine, piperazine, mor mono- or disubstituted by identical or different Substituents pholine, tetrahydrofuran, tetrahydropyran, 1,3-dioxane, 1,4- L. dioxane, tetrahydrothiophene, dithiolane and 1,3-dithiane, 0.054 Particularly preferred meanings of the group X are wherein a methylene group may be replaced by CO, and cyclopentyloxymethyl, isopropoxymethyl, ethoxymethyl which are substituted by R. R, R and R as specified hereinbefore, and wherein one or more H atoms bound to and methoxymethyl. carbon may be replaced by fluorine. 0.055 According to a third embodiment relating to the 0065. If in the above-mentioned cyclic groups a methyl group X preferred compounds of formula I according to the ene group is replaced by CO, preferred definitions of the invention are those wherein the group X preferably denotes group Cy are Selected from tetrahydrofuranon, tetrahydro arylsulphanylmethyl, C-alkylsulphanylmethyl or C-7-cy pyranone, piperidinone, piperazinone and morpholinone. cloalkylsulphanylmethyl, 0066 Moreover a double bond may be present in the while the above-mentioned alkyl groups may be partly or groupS Specified as being preferred for Cy. Preferred mean totally fluorinated or mono- or disubstituted by identical or ings of Such monounsaturated cyclic groups Cy are cyclo different Substituents Selected from chlorine, hydroxy, C.- pentene and cyclohexene. If substituents R, R, R and/or alkoxy and C-alkyl, and Rare joined together, this double bond may also be part of by aryl is meant a phenyl or naphthyl group, particularly an anellated cyclic System. phenyl, which may be mono- or disubstituted by identical or 0067 Particularly preferred meanings of the Cy ring are different Substituents L. cyclopentane, cyclohexane, pyrrolidine, piperidine, pipera Zine, tetrahydrofuran and 1,3-dioxane, which are Substituted 0056 According to this embodiment preferred meanings by R. R", RandR as stated hereinbefore, and wherein one of the group X are C-cycloalkylsulphanylmethyl and or more H atoms bound to carbon may be replaced by C-alkylsulphanylmethyl. fluorine. 0057 Particularly preferred meanings of the group X are 0068 The compounds of formula I according to the cyclopentylsulphanylmethyl, isopropylsulphanylmethyl and invention may be divided into two embodiments regarding methylsulphanylmethyl. Cy according to the number of ring atoms in the Cy ring. 0.058 According to a fourth embodiment relating to the 0069. According to a first embodiment preferred com group X preferred compounds of formula I according to the pounds of formula I according to the invention are those invention are those wherein the group X preferably denotes wherein the group Cy denotes a 6-membered Saturated or chloromethyl, bromomethyl, iodomethyl, C-alkylsulpho monounsaturated carbocycle, which may comprise in the nyloxymethyl, arylsulphonyloxymethyl or aryl-C-alkyl ring one, two or three, preferably one or two heteroatoms Sulphonyloxymethyl, selected independently of one another from N, O and S, and 0059) while the above-mentioned alkyl groups may be which is substituted by R', Rand R through a single bond partly or wholly fluorinated or mono- or dichlorinated and and by R through a single or double bond, and the above-mentioned aryl groups may be mono- or disub wherein a methylene group may be replaced by CO or a stituted by identical or different groups L., while L is Sulphanyl group may be replaced by SO or SO2, and preferably Selected from among fluorine, chlorine, bromine, iodine, C-alkyl, difluoromethyl, trifluoromethyl and wherein one or more H atoms bound to carbon may be cyano. replaced by fluorine, and US 2006/0035.841 A1 Feb. 16, 2006 wherein the other Substituents and groups have the meanings 0079. In the event that Cy denotes a 6-membered cyclic given hereinbefore and hereinafter. group, the group R is preferably in the 3- or 4-position to the bridge Z, particularly preferably in the 4-position to the 0070 Preferred Cy rings according to this embodiment bridge Z. are cyclohexane, piperidine, piperazine, morpholine, tet rahydropyran, 1,3-dioxane, 1,4-dioxane and 1,3-dithiane, 0080. In the event that Cy denotes a 5-membered cycle wherein a methylene group may be replaced by CO, and group, the group R is preferably in the 3-position to the which are substituted as specified hereinbefore by R. R", R bridge Z. and R, and wherein one or more H atoms bound to carbon 0081. Therefore, preferred compounds according to the may be replaced by fluorine. first embodiment, wherein Cy denotes a 6-membered cyclic 0.071) If in the above-mentioned cyclic groups a methyl group, are described by formulae I.1 and I.1": ene group is replaced by CO, preferred definitions of the group Cy are Selected from tetrahydropyranone, piperidi none, piperazinone and morpholinone. I.1 0.072 Moreover a double bond may be present in each case in the groupS Specified as being preferred for Cy. A preferred definition of Such monounsaturated Cy rings is cyclohexene. If substituents R. R", Rand/or Rare joined together, this double bond may also be part of an anellated cyclic System. 0.073 Particularly preferred Cy are cyclohexane, piperi dine, piperazine, tetrahydrofuran and 1,3-dioxane, which are I.1 substituted by R. R", Rand Ras stated hereinbefore, and wherein one or more H atoms bound to carbon may be replaced by fluorine. 0.074 According to a second embodiment regarding Cy, preferred compounds of formula I according to the invention are those wherein the group Cy denotes a 5-membered Saturated or monounsaturated carbocycle, which may com prise one, two or three, preferably one or two heteroatoms selected independently of one another from N, O and S, and which is substituted by R', Rand R through a single bond and by R through a single or double bond, and wherein wherein a methylene group may be replaced by CO or a V1,V2 independently of one another represent C or N, Sulphanyl group may be replaced by SO or SO2, and U1, U2, wherein one or more H atoms bound to carbon may be U3, U4 independently of one another represent C, N, O, CO replaced by fluorine, and or SO, wherein the remaining Substituents and groups have the with the proviso that in the ring formed by U and V there are meanings given hereinbefore and hereinafter. a maximum of 2 heteroatoms selected from N and O, which are not directly joined together, and there is at most one 0075 According to this embodiment preferred cycles Cy are cyclopentane, pyrrolidine, tetrahydrofuran, dithiolane group Selected from CO and SO2, and remaining free and tetrahydrothiophene, wherein a methylene group may be chemical bonds to C and Natoms are saturated with hydro replaced by CO, and which are substituted by R. R", Rand gen; and Ras stated hereinbefore, and wherein one or more H atoms wherein the remaining groups and Subsfituents have one of bound to carbon may be replaced by fluorine. the meanings given hereinbefore or hereinafter. 0.076 If in the above-mentioned cyclic groups a methyl 0082 Preferably in formulae I.1 and I.1" ene group is replaced by CO, a preferred definition of the group Cy is tetrahydrofuranone. V1,V2 independently of one another denote C or N, U1, U2, 0.077 Moreover in the groups specified hereinbefore as being preferred for Cy, a double bond may be present in each U3, U4 independently of one another denote C, N or O, case. A preferred meaning of Such monounsaturated cycles 0083 with the proviso that in the ring formed by the Cy is cyclopentene. If substituents R. R", Rand/or R are groupS U and V there are no, one or two heteroatoms joined together, this double bond may also be part of an selected from N and O, these heteroatoms not being directly anellated cyclic System. joined together, and remaining free chemical bonds to C and 0078 Particularly preferred Cy are cyclopentane, pyrro Natoms are Saturated with hydrogen. lidine and tetrahydrofuran, which are Substituted as Stated 0084. Moreover preferred compounds according to the hereinbefore with R. R", R and R, and wherein one or second embodiment, wherein Cy denotes a 5-membered more H atoms bound to carbon may be replaced by fluorine. cyclic group, may be described by formula I.2: US 2006/0035.841 A1 Feb. 16, 2006

in N-heterocycloalkyl groups a methylene group may be replaced by CO or SO. I.2 0089. If the group R' denotes a cycloalkyl or cycloalk enyl group, wherein one or two methylene groups are replaced independently of one another by O, S, CO, SO or SO, preferred meanings of the group R are selected from among tetrahydrofuranyl, tetrahydrofuranonyl, tetrahy drothienyl, tetrahydropyranyl, tetrahydropyranonyl, dioxa nyl and trioxanyl. 0090. If the group R' denotes an N-heterocycloalkyl group wherein a methylene group is replaced by CO or SO2, preferred meanings of the group R are selected from among wherein pyrrolidinone, piperidinone, piperazinone and morpholi Oc. V1,V2 independently of one another represent C or N. 0.091 Particularly preferably R' denotes hydrogen, fluo U1, U2, rine, chlorine, bromine, iodine, C-alkyl, C-alkynyl, Co-alkenyl, C-7-cycloalkyl, Cs 7-cycloalkenyl, C-alky U3 independently of one another represent C, N, O, CO or loxy, C-7-cycloalkyloxy or cyano, while in cycloalkyl and SO, cycloalkenyl groups one or two methylene units may be with the proviso that in the ring formed by the groups U and replaced independently of one another by O or CO and alkyl, V there are a maximum of 2 heteroatoms selected from N alkenyl and alkynyl groupS may be partly or completely and O, these heteroatoms not being directly joined together, fluorinated. and there is at most one group Selected from CO and SO, 0092. Examples of the most particularly preferred groups and any remaining free chemical bonds to C and Natoms are R" are hydrogen, fluorine, chlorine, bromine, methyl, ethyl, Saturated with hydrogen; and isopropyl, trifluoromethyl, ethynyl, methoxy, cyclopenty wherein the remaining groups and Substituents have one of loxy and cyano. the meanings given hereinbefore or hereinafter. 0093 Preferred meanings of the group R are hydrogen, 0085 Preferably in formula I.2 fluorine, chlorine, bromine, methyl, hydroxy, methoxy, ethoxy, trifluoromethoxy, cyano, nitro and methyl Substi V1,V2 independently of one another represent C or N, tuted by 1 to 3 fluorine atoms. U1, U2, U3 independently of one another represent C, N or 0094) Particularly preferred meanings of the group R are O, hydrogen, fluorine, hydroxy, methoxy, ethoxy and methyl, particularly hydrogen and methyl. with the proviso that in the ring formed by the groups U and V there are no heteroatoms or one heteroatom Selected from 0.095. In the event that R and R are bound to two N and O, while any remaining free chemical bonds to C and adjacent C atoms of the phenyl ring, R' and R may be N atoms are Saturated with hydrogen. joined together such that R' and R together preferably form a C-alkylene or butadienylene bridge, wherein one or two 0.086 Some preferred definitions of the remaining groups methylene units may be replaced independently of one and Substituents in the novel compounds of general formula another by O, NRN or CO, and wherein in the case of a I, particularly of formulae I.1, I.1" and I.2, will now be given: butadienylene bridge a methyne group may be replaced by 0087 Preferably R' denotes hydrogen, fluorine, chlorine, an Natom. Preferably the groups R' and R joined together bromine, iodine, C6-alkyl, C6-alkynyl, C-alkenyl, form, with the phenyl ring to which they are attached, a Co-cycloalkyl, Cso-cycloalkenyl, C-alkylcarbonyl, bicyclic ring System Selected from indane, dihydroindole, aminocarbonyl, C-alkyl-aminocarbonyl, di-(C-alky dihydrobenzofuran, tetrahydroquinoline, dihydro-quinoli l)aminocarbonyl, C-alkoxycarbonyl, C-alkylamino, none, tetrahydroisoquinoline, dihydroisoquinolinone, tet di-(C-alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl, mor rahydronaphthalene, naphthalene, quinoline and isoquino pholina-yl, C-alkylcarbonylamino, C-alkyloxy, Co line. cycloalkyloxy, Co-cycloalkenyloxy, C-alkylsulphanyl, 0096) The substituent R has the meanings given herein C-alkylsulphonyl, Co-cycloalkylsulphanyl, Co-cy before. In the event that R is bound to an N atom, R cloalkylsulphonyl, Cs-o-cycloalkenylsulphanyl, Cso-cy preferably does not denote halogen or alkyl, cycloalkyl, cloalkenyl-Sulphonyl, hydroxy and cyano, cycloalkenyl or arylsulphanyl. 0088 while alkyl, alkenyl, alkynyl, cycloalkyl and 0097 As specified hereinbefore, the group R may be cycloalkenyl groups may be partly or completely fluorinated connected to the Cy ring via a single bond or a double bond. or may be mono- or disubstituted by identical or different The preferred definitions for the two variants are given Substituents Selected from chlorine, hydroxy, C-alkoxy below. and C-alkyl, and 0098) If the group R is bound to Cy through a single while in cycloalkyl- and cycloalkenyl groups one or two bond, R preferably denotes hydrogen, fluorine, chlorine, methylene groups may be replaced independently of one C6-alkyl, C2-alkynyl, C2-alkenyl, Co-cycloalkyl, another by O, S, CO, SO or SO, and Co-cycloalkyl-methyl, Cs-o-cycloalkenyl, Co-cy US 2006/0035.841 A1 Feb. 16, 2006 cloalkenyl-methyl, aryl, heteroaryl, C-alkylcarbonyl, cyclopentyloxy, methoxycarbonyl, N-pyrrolidinonyl, aminocarbonyl, C-alkylaminocarbonyl, di-(C-alky 1H-pyrazol-1-yl, 2H-tetrazol-5-yl and 2-methyl-2H-tetra l)aminocarbonyl, C-alkoxycarbonyl, di-(C-alky Zol-5-yl, and l)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, C-alkylcarbonylamino, C6-alkoxy, Co-cycloalkyloxy, in the event that R is bound to an N atom, R most Co-cycloalkenyl-oxy, aryloxy, heteroaryloxy, C-alkyl particularly preferably denotes hydrogen, methyl, ethyl, Sulphanyl, C-alkylsulphonyl, Co-cycloalkylsulphanyl, isopropyl, tert-butyl, 2-methylpropyl or methylcarbonyl. Co-cycloalkylsulphonyl, Cs-o-cycloalkenylsulphanyl, 0106). If the group R is bound to Cy through a double Co-cycloalkenylsulphonyl, hydroxy or cyano, and bond, R has a meaning selected from the group Y. 0099 in the event that R is bound to an N atom, R 0107 The group Y preferably denotes oxygen, meth preferably denotes hydrogen, cyano, C-alkyl, C-alky ylidene, fluoromethylidene, C-alkyl-methylidene, C.- nyl, C2-alkenyl, C-6-cycloalkyl, C-6-cycloalkyl-C-3- alkynyl-methylidene, C-alkenyl-methylidene, C-7-cy alkyl, Cse-cycloalkenyl, Cse-cycloalkenyl-C-alkyl, aryl, cloalkyl-methylidene or C-7-cycloalkylidene, heteroaryl, aryl-C-alkyl, heteroaryl-C-alkyl, C-alky 0.108 while the above-mentioned alkyl, alkenyl, alkynyl lcarbonyl, arylcarbonyl, heteroarylcarbonyl, C-alkylsul and cycloalkylidene groups may be partly or completely phonyl, arylsulphonyl or heteroarylsulphonyl, fluorinated and may be mono- or disubstituted indepen 0100 while alkyl, alkenyl, alkynyl, cycloalkyl and dently of one another by Substituents selected from chlorine, cycloalkenyl groups may be partly or completely fluorinated hydroxy, C-alkoxy and C-alkyl, and or may be mono- or disubstituted by identical or different the above-mentioned unsubstituted methylidene group or Substituents Selected from chlorine, hydroxy, C-alkoxy the above-mentioned monoSubstituted methylidene groups and C-3-alkyl, and may additionally be monosubstituted by fluorine, C-alkyl, in cycloalkyl and cycloalkenyl groups one or two methylene trifluoromethyl or cyano, and groups may be replaced independently of one another by O, a methylene group bound directly to the methylidene group S, CO, SO or SO, and may be replaced by CO, COO or CONR, and in N-heterocycloalkyl groups a methylene group may be in a cycloalkylidene group a methylene group may be replaced by CO or SO, replaced by O, S or NRS or an ethylene group may be while the terms aryl and heteroaryl are as hereinbefore replaced by -NRN-CO-, -CO-NRN-, -O-CO defined and aryland heteroaryl groups may independently of or-CO-O-. one another be mono- or disubstituted by identical or 0109. In the event that in a cycloalkylidene group a different groupS L. methylene group is replaced by O, S or NRS or an ethylene group is replaced by -NRS-CO-, -CO-NRN-, 0101) If the group R denotes a cycloalkyl or cycloalk O CO- or -CO-O-, the meaning of such a substi enyl group, wherein one or two methylene groups are tuted cycloalkylidene group is preferably Selected from replaced independently of one another by O, S, CO, SO or among dihydrofuranylidene, dihydropyranylidene, dihy SO, preferred definitions of the group R are selected from drothiophenylidene, pyrrolidinylidene, piperidinylidene, among tetrahydrofuranyl, dihydrofuranonyl, tetrahydrothie dihydrofuranonylidene, dihydropyranonylidene, pyrrolidi nyl, tetrahydropyranyl, tetrahydropyranonyl and dioxanyl. nonylidene, N-methylpyrrolidinonylidene, piperidi 0102) If the group R denotes an N-heterocycloalkyl nonylidene and N-methylpiperidinonylidene. group wherein a methylene group is replaced by CO or SO, 0110 Most particularly preferred definitions of the group preferred meanings of the group R are selected from among Y are oxygen, methylidene, fluoromethylidene, C-alkyl pyrrolidinone, piperidinone, piperazinone and morpholi methylidene, C-7-cycloalkyl-methylidene and C-7-cy OC. cloalkylidene, while the above-mentioned unsubstituted 0103 Particularly preferred meanings of R are hydro methylidene group or the above-mentioned monoSubstituted gen, cyano, C6-alkyl, C-alkynyl, C-alkyloxy, Co methylidene groups may additionally be monoSubstituted by cycloalkyl, Co-cycloalkyloxy, phenyl, C-alkylcarbo fluorine. nyl, C-alkyloxycarbonyl, C-7-cycloalkylmethyl, 0111 Examples of the most particularly preferred defi phenyloxy, C-7-cycloalkylsulphonyl, C-alkylsulphanyl, nitions of the group Y are oxygen, difluoromethylidene, pyrrolidinon-N-yl, pyrazolyl, tetrazolyl and hydroxy, and ethylidene, isobutylidene, cyclopentyl-methylidene and if R is bound to an N atom, R particularly preferably cyclopentylidene. denotes hydrogen, cyano, C-alkyl, C-6-cycloalkyl, aryl, 0112) If there are cycloalkyl or cycloalkenyl rings in the C-alkylcarbonyl or C-alkylsulphonyl, residues or groups X, Y, R' or R wherein two methylene groups are replaced by O or S or by CO, SO or SO, these 0104 while in the cycloalkyl groups one or two methyl methylene groups are preferably not joined together directly. ene units may be replaced independently of one another by If, however, two methylene groups are replaced by O and O or CO and alkyl groups may be partly or totally fluori CO, these may be joined together directly, So as to form a nated, and the phenyl group may be mono- or disubstituted -O-CO- or -CO-O-group. In the event that X, Y, by identical or different substituents L. R' or R is a cycloalkyl or cycloalkenyl group with one or 0105 Most particularly preferred groups R are hydro two methylene groups replaced according to the invention, gen, cyano, hydroxy, methyl, ethyl, isopropyl, tert-butyl, the relevant group X, Y, R or R preferably denotes a 2-methylpropyl, phenyl, methoxy, ethoxy, isopropyloxy, cycloalkyl or cycloalkenyl group wherein a methylene group US 2006/0035.841 A1 Feb. 16, 2006 is replaced by O, S, CO, SO or SO or an ethylene group is another by O, NRN or CO. Particularly preferably the replaced by -O-CO- or -CO-O-. attached groups R' and R together with Cy form a bicyclo 0113 Some meanings of other groups and Substituents 3.2.1]octane System. will now be given, which are to be regarded as preferred 0121) If in the above-mentioned bicyclic rings one or two according to general formula I, formulae I.1 and I.2 and the methylene units are replaced independently of one another embodiments described hereinbefore: by O, NRS or CO, preferred meanings include decahydro 0114) Preferred meanings of the group R" are hydrogen, quinoline, decahydroisoquinoline, octahydroquinolinone, methyl and fluorine, particularly hydrogen. In the event that octahydro-isoquinolinone, decahydroquinoxaline, octahyd R" is bound to an Natom, R preferably denotes hydrogen roquinoxalinone, octahydrobenzoxazine. or methyl. 0122) Preferred meanings of the group R are hydrogen, 0115) In the event that R and R' are bound to the same methyl and fluorine, particularly hydrogen. In the event that C atom of Cy, R and R' may be joined together such that R is bound to an Natom, R preferably denotes hydrogen R and R' together preferably form a Cis-alkylene bridge, or methyl. 0116 wherein one or two methylene units may be replaced independently of one another by O, NRN or CO. 0123. In the event that the groups R, R and R are Preferably the groups R and R' joined to one another joined together, together they preferably form a C-s-alkan together with the carbon atom of Cy to which they are etriyl bridge which together with the Cy ring forms a attached form a ring Selected from cyclopentane, tetrahy tricyclic System, while the alkanetriyl bridge may be mono drofuran, tetrahydrofuranone, pyrrolidine, pyrrolidinone, or polyfluorinated or mono- or disubstituted by identical or dioxolan, dithiolan, cyclohexane, piperidine, piperidinone, different Substituents Selected from chlorine, hydroxy, C.- tetrahydropyran, tetrahydropyranone, dithian and dioxane, alkoxy and C-alkyl, and wherein one or two methylene particularly dioxolane. groups may be replaced independently of one another by O, CO, SO or NRS. Preferably the Cis-alkanetriyl bridge 0117. In the event that R and R' are bound to two adjacent C atoms of the Cy ring, R and R may be joined together with the Cy ring forms a tricyclic System Selected together such that R and R' together with the two above from tricyclononane, tricyclodecane and tricycloundecane, mentioned adjacent atoms of the Cy ring preferably form an particularly preferably adamantane, which may be unsub anellated cyclohexane, benzene or cyclopentadiene ring, Stituted or mono- or polyfluorinated or mono- or disubsti wherein one or two methylene groups may be replaced tuted by identical or different substituents selected from independently of one another by O, S or NRN and/or one or chlorine, hydroxy, C-alkoxy and C-alkyl. two methyne groups may be replaced by N, and which may be mono- or polyfluorinated or mono- or disubstituted by 0.124 Preferred meanings of the group Z are -O-, identical or different Substituents selected from chlorine, CH-, -CF-,-C(CH)-, -CH=,-NRN-, and hydroxy, C-alkoxy and C-alkyl or in the case of an -CO-, particularly -O-, -CH2-, -CH= and aromatic anellated ring may be mono- or disubstituted by -CO-, most particularly preferably -CH-. identical or different Substituents L. 0125) The substituents R', R", R' independently of one 0118 Preferably the groups R and R' connected to one another preferably represent hydrogen, (Cis-alkyl)oxycar another form, together with the two above-mentioned adja bonyl, (C-alkyl)carbonyl, benzoyl, particularly hydrogen cent atoms of the Cy ring, an anellated cyclohexane, ben or (C6-alkyl)oxycarbonyl, (Cs-alkyl)carbonyl, particu Zene, furan, thiophene or pyrrole ring, particularly a cyclo larly preferably hydrogen, methoxycarbonyl, ethoxycarbo hexane or benzene ring, which may be mono- or nyl, methylcarbonyl or ethylcarbonyl. Most particularly polyfluorinated or mono- or disubstituted by identical or preferably R', R" and R' represent hydrogen. different Substituents Selected from chlorine, hydroxy, C.- alkoxy and C-alkyl or in the case of an aromatic anellated 0126) The compounds of formula I wherein R', R", R' ring Selected from benzene, furan, thiophene or pyrrole may and R' have a meaning according to the invention which is be mono- or disubstituted by identical or different substitu other than hydrogen, for example C-alkylcarbonyl, are ents L. preferably Suitable as intermediate products in the Synthesis of compounds of formula I wherein R', R", R' and R' 0119 Preferred meanings of the group R are hydrogen, represent hydrogen. methyl and fluorine, particularly hydrogen. In the event that R is bound to an Natom, R preferably denotes hydrogen 0127. The substituents L are preferably selected indepen or methyl. dently of one another from among fluorine, chlorine, bro mine, C-alkyl, difluoromethyl, trifluoromethyl, C I0120) In the event that R' and Rare joined together and alkoxy, difluoromethoxy, trifluoromethoxy and cyano, with 2, 3 or 4 atoms of the Cy ring form an anellated or particularly preferably from among fluorine, chlorine, bridged bicyclic group, R" and R together preferably rep methyl, trifluoromethyl, methoxy and difluoromethoxy. If resent a C-alkylene bridge, wherein one or two methylene the Substituent L is linked to an Natom, preferred meanings units may be replaced independently of one another by O, L are selected from C-alkyl, difluoromethyl and trifluo NR or CO. Preferably the groups R* and Rattached to one romethyl. another together with Cy form a bicyclic ring Selected from bicyclo2.2.1]heptane, bicyclo2.2.2]octane, bicyclo3.2.1 0128 Particularly preferred compounds of general for octane, octahydroindene and decalin, wherein one or two mula I are Selected from among formulae I.1a to I.1d and methylene units may be replaced independently of one I.2a to I.2d, particularly formula I.1c and I.2c: US 2006/0035.841 A1 Feb. 16, 2006 11

-continued

wherein V1,V2 independently of one another represent C or N, U1, U2, U3, U4 independently of one another represent C, N, O, CO or SO, with the proviso that in the ring formed by the groupSU and V there are a maximum of 2 heteroatoms selected from N and O, which are not directly joined together, and there is a

maximum of one group Selected from CO and SO2, and remaining free chemical bonds to C and N atoms are Saturated with hydrogen; and wherein R to R, X, Z, R7 R7 R7 are as hereinbefore defined. 0129. Preferably in formulae I.1a to I.1d V1,V2 independently of one another represent C or N, U3, U4 independently of one another represent C, N or O, 0.130 with the proviso that in the ring formed by the groupS U and V there are no, one or two heteroatoms selected from N and O, these heteroatoms not being directly joined together, and any remaining free chemical bonds to C and N atoms are Saturated with hydrogen. 0131 Preferably in formula 1.2a to 1.2d V1,V2 independently of one another represent C or N, U1, U2, U3 independently of one another represent C, N or O, with the proviso that in the ring formed by the groupSU and V there are no heteroatoms or one heteroatom Selected from N and O, while any remaining free chemical bonds to C and Natoms are Saturated with hydrogen. 0132 Most particularly preferred are those compounds of formulae I.1a, I.1b, I.1c and I.1d, particularly of formula I.1c, wherein the groups U1, U2, U3, U4, V1 and V2 represent carbon, i.e. the cyclic group formed by the groups U and V denotes cyclohexane. US 2006/0035.841 A1 Feb. 16, 2006

0.133 Most particularly preferred are those compounds of aryl, C-alkylcarbonyl or C-alkylsulphonyl, while in formulae I.1a to I.1d or I.2a to I.2d, particularly of formula the cycloalkyl groups one or two methylene units are I.1c and I.2c, wherein the groups X, Z, R' to R, R', R", replaced independently of one another by O or CO and R" have the meanings given hereinbefore as being pre alkyl groups may be partly or totally fluorinated, and the ferred, particularly wherein phenyl group may be mono- or disubstituted by identical 0134 X according to a first embodiment denotes hydro or different substituents L.; particularly preferably R gen, cyano, C-alkyl, C2-alkynyl, C2-alkenyl, C denotes hydrogen, cyano, hydroxy, methyl, ethyl, isopro alkylcarbonyl, C-alkoxycarbonyl, aminocarbonyl, pyl, tert-butyl, 2-methylpropyl, phenyl, methoxy, ethoxy, C-alkylaminocarbonyl, di-(C-alkyl)aminocarbonyl, isopropyloxy, cyclopentyloxy, methoxycarbonyl, N-pyr C-alkylsulphonylamino-C-alkyl or C-alkylsul rolidinonyl, 1 H-pyrazol-1-yl, 2H-tetrazol-5-yl and 2-me phonyl-C-alkyl, while alkyl groups may be mono- or thyl-2H-tetrazol-5-yl, and in the event that R is bound to polyfluorinated or monoSubstituted by chlorine or cyano an Natom, R most particularly preferably denotes hydro and X representing alkyl with 2 or more C atoms may gen, methyl, ethyl, isopropyl, tert-butyl, 2-methylpropyl comprise a hydroxy Substituent, particularly or methylcarbonyl; or preferably X denotes hydrogen, cyano, methyl, ethyl, pro (2) denotes pyl, fluoromethyl, trifluoromethyl, cyanomethyl, 1-hy droxyethyl, 1-hydroxy-1-methylethyl, 2-hydroxyethyl, prop-2-enyl, prop-2-ynyl, methylcarbonyl, aminocarbo nyl, methylaminocarbonyl, dimethylaminocarbonyl, YE s and methoxycarbonyl or ethoxycarbonyl; or according to a Second embodiment denotes C-alkyloxym ethyl, C-7-cycloalkyloxymethyl or aryloxymethyl, while by aryl is meant a phenyl or naphthyl group, particularly 0137 Y (1) denotes oxygen; or phenyl, which may be mono- or disubstituted by identical (2) denotes methylidene, fluoromethylidene, C6-alkyl-me or different substituents L, particularly preferably X thylidene, C-alkynyl-methylidene, C-alkenyl-meth denotes cyclopentyloxymethyl, isopropoxymethyl, ylidene, C-7-cycloalkyl-methylidene or C-7-cycloalky ethoxymethyl or methoxymethyl; or lidene, according to a third embodiment denotes C-alkylsulpha nylmethyl or C-cycloalkylsulphanylmethyl, particu while the above-mentioned alkyl, alkenyl, alkynyl and larly preferably X denotes methylsulphanylmethyl, iso cycloalkylidene groups may be partly or totally fluori propylsulphanylmethyl or cyclopentylsulphanylmethyl, nated and mono- or disubstituted independently of one another by Substituents Selected from chlorine, hydroxy, O C-3-alkoxy and C-3-alkyl, according to a fourth embodiment denotes bromomethyl, iodomethyl, C-alkylsulphonyloxymethyl or phenylsul while the above-mentioned unsubstituted methylidene group phonyloxymethyl, while the above-mentioned alkyl or the above-mentioned monosubstituted methylidene groups may be partly or completely fluorinated and the groups may additionally be monoSubstituted by fluorine, above-mentioned phenyl groups may be mono- or disub C-alkyl, trifluoromethyl or cyano, and stituted by identical or different groups L., while L is preferably Selected from among fluorine, chlorine, bro while a methylene group bound directly to the methylidene mine and methyl, particularly preferably X denotes tolyl group may be replaced by CO, COO or CON, and Sulphonyloxymethyl, phenylsulphonyloxymethyl, trifluo in a cycloalkylidene group a methylene group may be romethylsulphonyloxymethyl, bromomethyl O replaced by O, S or NRS or an ethylene group may be iodomethyl; replaced by -NRN CO-, -CO-NRN-, -O-CO 0135) R' denotes hydrogen, fluorine, chlorine, bromine, or -CO-O-, C6-alkyl, C2-alkynyl, C2-alkenyl, C-7-cycloalkyl, particularly preferably Y denotes methylidene, fluorometh Cs-7-cycloalkenyl, C6-alkyloxy, C-7-cycloalkyloxy or ylidene, C-alkyl-methylidene, C-7-cycloalkyl-meth cyano, while in cycloalkyl and cycloalkenyl groups one or two methylene units may be replaced independently of ylidene or C-7-cycloalkylidene, while the above-men one another by O or CO and alkyl, alkenyl and alkynyl tioned unsubstituted methylidene group or the above groups may be partly or totally fluorinated; particularly mentioned monoSubstituted methylidene groups may preferably denotes hydrogen, fluorine, chlorine, bromine, additionally be monosubstituted by fluorine; methyl, ethyl, isopropyl, trifluoromethyl, ethynyl, meth 0138) R' denotes hydrogen, fluorine, chlorine, bromine, Oxy, cyclopentyloxy or cyano; and methyl, hydroxy, methoxy, ethoxy, trifluoromethoxy, 0136 R. (1) denotes hydrogen, cyano, Cisalkyl, Co cyano, nitro or methyl substituted by 1 to 3 fluorine atoms, alkynyl, C-alkyloxy, C-7-cycloalkyl, C-7-cycloalkyl particularly preferably denotes hydrogen, fluorine, methyl, C-7-cycloalkyloxy, phenyl, phenyloxy, C-7-cy hydroxy, methoxy, ethoxy or methyl, particularly hydro cloalkylsulphonyl, C-alkylcarbonyl, C1-a- gen or methyl, and alkyloxycarbonyl, C-alkylsulphanyl, pyrrolidinone-N- yl, pyrazolyl, tetrazolyl and hydroxy, and in the event that 0139) R' R, R is bound to an N atom, R particularly preferably 0140) R' in each case independently of one another denotes hydrogen, cyano, C-alkyl, C-6-cycloalkyl, denote hydrogen, methyl or fluorine, particularly hydro US 2006/0035.841 A1 Feb. 16, 2006

gen, and in the event that the Substituent is bound to an N 0155 (h) 1-chloro-4-(6-deoxy-6-methylsulphanyl-B-D- atom, independently denote hydrogen or methyl in each glucopyranoS-1-yl)-2-(4-methoxy-cyclohexylmethyl)- CaSe, Or benzene the groups R", R and R are joined together, forming a 0156 (i) 1-chloro-4-(6-deoxy-6-methoxy-f-D-glucopy Cis-alkanetriyl bridge and together with the Cy ring form ranos-1-yl)-2-(4-methoxy-cyclohexylmethyl)-benzene a tricyclic System Selected from tricyclononane, tricyclo decane and tricycloundecane, particularly preferably ada including the tautomers, the Stereoisomers and the mixtures mantane, which is unsubstituted or may be mono- or thereof. polyfluorinated or mono- or disubstituted by identical or O157 Some terms used above and hereinafter to describe different substituents selected from chlorine, hydroxy, the compounds according to the invention will now be C-alkoxy and C-alkyl, defined more closely. 0141 Z denotes -O-, -CH2-, -CH= or -CO-; 0158. The term halogen denotes an atom selected from most particularly preferably denotes -O- or -CH-, the group consisting of F, Cl, Brand I, particularly F, Cland and Br. 0142) 0159. The phrases “may be partly or completely fluori 0143 R' independently of one another represent hydro nated” and “may be mono- or polyfluorinated” which are gen, (Cs-alkyl)oxycarbonyl, (C-s-alkyl)carbonyl or used interchangeably indicate that the group thus designated benzoyl, particularly hydrogen or (Calkyl)oxycarbo is not fluorinated or comprises one or more fluorine Sub nyl, (C-alkyl)carbonyl, particularly preferably repre Stituents, and this also includes total fluorination of the Sent hydrogen, methoxycarbonyl, ethoxycarbonyl, meth group indicated. ylcarbonyl or ethylcarbonyl, most particularly preferably 0160 The term C-alkyl, wherein n may have a value of hydrogen, and 1 to 18, denotes a Saturated, branched or unbranched hydro carbon group with 1 to n C atoms. Examples of Such groups 0144) RN independently of one another denote H or include methyl, ethyl, n-propyl, iso-propyl, butyl, iso-butyl, C-alkyl, Sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert 014.5 L independently of one another represent fluorine, pentyl, n-hexyl, iso-hexyl, etc. chlorine, bromine, C-alkyl, difluoromethyl, trifluorom 0161 The term methylene denotes a -CH2-group and ethyl, C-alkoxy, difluoromethoxy, trifluoromethoxy the term methyne denotes a CH group. and cyano, and if L is bound to an N atom, they denote independently of one another C-alkyl, difluoromethyl 0162 The term methylidene denotes a group of the or trifluoromethyl; partial formula including the tautomers, the Stereoisomers, the mixtures thereof and the Salts thereof, particularly the physiologi cally acceptable Salts thereof. 0146 According to a variant of the embodiments described above, compounds wherein the cyclic group Cy which carries the substituent R comprises at least one other substituent R' and/or R which is different from hydrogen are also preferred. According to this variant, compounds attached by a attached bond. which comprise a Substituent R" representing methyl or 0163 The term C-alkyl-methylidene denotes a meth fluorine are also preferred. ylidene group wherein a hydrogen atom is Substituted by a 0147 Particularly preferred compounds of general for C-alkyl group. mula I are Selected from among: 0164. The term methanylylidene denotes a CH bridge of 0148 (a) 1-chloro-4-(6-deoxy-6-fluoro-B-D-glucopyra the partial formula noS-1-yl)-2-(4-methoxy-cyclohexyloxy)-benzene, 0149 (b) 1-chloro-4-(6-deoxy-6-fluoro-B-D-glucopyra noS-1-yl)-2-(4-methoxy-cyclohexylmethyl)-benzene, O150 c) 1-chloro4-(6-d1-cniorO4-O-deoxy-p-L-glucopyranoS-1-yl)-2- D-gl 1-vl)-2 (4-methoxy-cyclohexyloxy)-benzene, 0151 (d) 1-chloro-4-(6-deoxy-f-D-glucopyranos-1-yl)- 2-(4-methoxy-cyclohexylmethyl)-benzene attached via a Single bond and a double bond. 0152 (e) 1-chloro-4-(6-deoxy-6-cyano-B-D-glucopyra 0.165. The term “butadienylene' denotes the group noS-1-yl)-2-(4-methoxy-cyclohexyloxy)-benzene 0153 (f) 1-chloro4-(6-deoxy-6-cyano-B-D-glucopyra noS-1-yl)-2-(4-methoxy-cyclohexylmethyl)-benzene 0154 (g) 1-chloro-4-(6-deoxy-6-methylsulphanyl-B-D- glucopyranos-1-yl)-2-(4-methoxy-cyclohexyloxy)-ben ZCC US 2006/0035.841 A1 Feb. 16, 2006

0166 The term C-alkynyl, wherein n has a value of 3 and which may additionally comprise another optionally to 6, denotes a branched or unbranched hydrocarbon group Substituted imino group or an O or Satom in the ring. By an with 2 to n Catoms and a C=C triple bond. Examples of such imino group is meant the group -NH-. Examples of Such groups include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, N-heterocycloalkyl groups are pyrrolidine, piperidine, pip 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, erazine, N-alkyl-piperazine and morpholine. 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 0177) If alkyl radicals occurring in groups, for example in 5-hexynyl, 4-methyl-pent-2-yl etc. Unless Stated otherwise, X, R' or R, may be substituted, e.g. fluorinated, this alkynyl groups are linked to the rest of the molecule via the encompasses not only alkyl radicals in the groups which C atom in position 1. Therefore, terms Such as 1-propynyl, represent alkyl directly but also in other definitions which 2-propynyl, 1-butynyl, etc. are equivalent to the terms include alkyl groups, Such as for example alkoxy, alkylcar 1-propyn-1-yl, 2-propyn-1-yl, 1-butyn-1-yl, etc. This also bonyl, alkoxyalkyl, etc. Thus, for example X, R' and R applies analogously to C2-alkenyl groups. representing alkoxy, wherein the alkyl groups may be partly 0167 The term C-alkoxy or C-alkyloxy denotes a or totally fluorinated, also include difluoromethoxy and C-alkyl-O-group, wherein C -alkyl is as hereinbefore trifluoromethoxy. defined. Examples of Such groups include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, Sec-butoxy, 0.178 The style used above and hereinafter, in which a tert-butoxy, n-pentoxy, iso-pentoxy, neo-pentoxy, tert-pen bond of a Substituent in a cyclic group, for example a phenyl toxy, n-heXOXy, iso-heXOXy etc. group or in the group Cy, is shown towards the centre of the phenyl ring, denotes, unless otherwise Stated, that this Sub 0168 The term C-alkylcarbonyl denotes a C-alkyl Stituent may be bound to any free position of the cyclic C(=O) group, wherein C-alkyl is as hereinbefore group bearing an H atom. Thus, two Substituents may also defined. Examples of Such groups include methylcarbonyl, be bound to a methylene group of the cyclic group. ethylcarbonyl, n-propylcarbonyl, iso-propylcarbonyl, n-bu tylcarbonyl, iso-butylcarbonyl, Sec-butylcarbonyl, tert-bu 0179 The compounds according to the invention may be tylcarbonyl, n-pentylcarbonyl, iso-pentylcarbonyl, neo-pen obtained using methods of Synthesis known in principle. tylcarbonyl, tert-pentylcarbonyl, n-hexylcarbonyl, iso Preferably the compounds are obtained by the following methods according to the invention which are described in hexylcarbonyl, etc. more detail hereinafter. 0169. The term C-cycloalkyl denotes a saturated mono-, bi-, tri- or spirocarbocyclic group with 3 to n C 0180. The D-xylose derivatives described hereinafter atoms. Examples of Such groups include cyclopropyl, may be Synthesised from D-gluconolactone or a derivative cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooc thereof by addition of the desired aryl group in the form of tyl, cyclononyl, cyclododecyl, decalin, bicyclo3.2.1.loctyl, an organometallic compound (Diagram 1). Spiro4.5decyl, norpinyl, norbonyl, norcaryl, adamantyl, etc. Preferably the term C 7-cycloalkyl denotes Saturated monocyclic groups. Diagram 1: Addition of an organometallic compound to a gluconolactone 0170 The term C-cycloalkyloxy denotes a C-cy cloalkyl-O-group, wherein C-cycloalkyl is as herein Xs R4 before defined. Examples of Such groups include cyclopro pyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, etc. 0171 The term Cs-n-cycloalkenyl denotes a C-cy cloalkyl group which is as hereinbefore defined and addi halo selecane tionally comprises at least one unsaturated C=C double metal organyl bond. 0172 The term C-cycloalkylcarbonyl denotes a Can cycloalkyl-C(=O) group wherein C-cycloalkyl is as hereinbefore defined. 0173 The term tri-(C-alkyl)silyl comprises silyl groups which comprise identical alkyl groups or two or three different alkyl groups. 0174 The term di-(C-alkyl)amino comprises amino groups which have identical alkyl groups or two different alkyl groups. 0.175. The term cyclo-C-alkyleneimino denotes a 4- to 7-membered ring which comprises 3 to 6 methylene units as well as an imino group, the bond to the remainder of the 0181. The reaction according to Diagram 1 is best carried molecule being via the imino group. Examples of Such out Starting from aromatic groups Substituted with chlorine, cyclo-C-alkyleneimino groups are N-pyrrolidinyl and bromine or iodine. The corresponding organometallic com N-piperidinyl. pound may be prepared therefrom either by a So-called 0176) The term N-heterocycloalkyl denotes a saturated halogen-metal eXchange or by inserting the metal into the carbocyclic ring which comprises an imino group in the ring, carbon-halogen bond. The halogen-metal eXchange may be US 2006/0035.841 A1 Feb. 16, 2006 carried out for example with an organolithium compound independently of one another represent for example acetyl, Such as e.g. n-, Sec. or tert-butyllithium and thereby yields pivaloyl, benzoyl, tert-butoxycarbonyl, benzyloxycarbonyl, the corresponding lithiated aromatic group. The analogous trialkylsilyl, benzyl or substituted benzyl, magnesium compound may also be generated by a halogen metal eXchange with a Suitable Grignard compound Such as is reacted with a reducing agent in the presence of an acid. e.g. iSopropylmagnesium bromide or diisopropylmagne 0185 Suitable reducing agents for the reaction include sium. The reactions are preferably carried out between 0 and for example Silanes, Such as triethyl-, tripropyl-, triisopro -100° C., particularly preferably between -30 and -80 C. pyl- or diphenylsilane, Sodium borohydride, Sodium in Solvents Such as for example ether, tetrahydrofuran, cyanoborohydride, Zinc borohydride, borane, lithium alu toluene, hexane or methylene chloride. The magnesium or minium hydride, diisobutylaluminium hydride or Samarium lithium compounds thus obtained may be transmetallated iodide. The reductions are preferably carried out in the with metal Salts. Such as e.g. cerium trichloride, to produce presence of a Suitable acid, Such as e.g. hydrochloric acid, other organometal compounds Suitable for the addition. toluenesulphonic acid, trifluoroacetic acid, acetic acid, Alternatively the organometallic compounds may also be boron trifluoride etherate, trimethylsilyltriflate, titanium tet prepared by inserting a metal in the carbon-halogen bond of rachloride, tin tetrachloride, Scandium triflate or Zinc iodide. an aryl chloride, bromide or iodide. Suitable metals for this Depending on the reducing agent and the acid the reaction purpose are e.g. lithium or magnesium. The addition of the may be carried out in a Solvent, Such as for example organometallic compounds to the gluconolactone or deriva methylene chloride, chloroform, acetonitrile, toluene, heX tives thereof is preferably carried out at temperatures ane, diethyl ether, tetrahydrofuran, dioxane, ethanol, water between 0 and -100° C., particularly preferably at -30 to or mixtures thereof at temperatures between -60° C. and -80 C. Suitable solvents include e.g. ethers, toluene, meth 120° C. A particularly suitable combination of reagents ylene chloride, hexane, tetrahydrofuran or mixtures thereof consists for example of triethylsilane and boron trifluoride (see M. Schlosser, Organometallics in Synthesis, John Wiley etherate, which is conveniently used in acetonitrile or & Sons, Chichester/New York/Brisbane/Toronto/Singapore, dichloromethane at temperatures of -60° C. and 60° C. 1994). Moreover, hydrogen may be used in the presence of a 0182. The methods of synthesising the aromatic groups transition metal catalyst Such as e.g. palladium on charcoal are Standard transformations in organic chemistry and are or Raney nickel, in Solvents Such as tetrahydrofuran, ethyl part of the general knowledge in the art or are at least known acetate, methanol, ethanol, water or acetic acid, for the from the specialist literature as methods in organic synthesis transformation described. and would readily be available to the skilled man with 0186 Alternatively, in order to prepare compounds of respect to the compounds according to the invention (see general formula I according to method b) of the invention, inter alia J. March, Advanced Organic Reactions, Reactions, in a compound of general formula III Mechanisms, and Structure, 4th Edition, John Wiley & Sons, Chichester/New York/Brisbane/Toronto/Singapore, 1992 and literature cited therein). III 0183 The D-xylose derivatives to be used as educts in the methods of synthesis described above may be obtained from D-glucose by replacement of the 6-hydroxy group or suitable derivatisation of the 6-hydroxy group followed by Substitution with the desired group. Such transformations are within the general capabilities of the skilled man or are at least known from the Specialist literature as methods used in organic Synthesis and may readily be applied to the compounds according to the invention by anyone skilled in the art. wherein Cy, X, Z and R' to R are as hereinbefore defined 0184. In order to prepare compounds of general formula and R, R and R denotes one of the protective groups I according to process a) of the invention, a compound of defined hereinbefore, Such as e.g. an acyl, arylmethyl, acetal, general formula II ketal or Silyl group, the protective groups are cleaved. 0187 Any acyl, acetal or ketal protecting group used is II cleaved, for example, hydrolytically in an aqueous Solvent, e.g. in water, isopropanol/water, acetic acid/water, tetrahy drofuran/water or dioxane/water, in the presence of an acid Such as trifluoroacetic acid, hydrochloric acid or Sulphuric acid or in the presence of an alkali metal base Such as lithium hydroxide, Sodium hydroxide or potassium hydroxide or aprotically, e.g. in the presence of iodotrimethylsilane, at temperatures between 0 and 120° C., preferably at tempera tures between 10 and 100° C. A trifluoroacetyl group is preferably cleaved by treatment with an acid Such as hydro chloric acid, optionally in the presence of a Solvent Such as wherein X, Z, Cy and R', R' to R are as hereinbefore acetic acid, at temperatures between 50 and 120° C. or by defined and R, R and Rare as hereinbefore defined and treatment with Sodium hydroxide Solution, optionally in the US 2006/0035.841 A1 Feb. 16, 2006 presence of a Solvent Such as tetrahydrofuran or methanol, ochemistry”, Vol. 6, Wiley Interscience, 1971) into their at temperatures between 0 and 50° C. optical antipodes and compounds of general formula I with at least 2 asymmetric carbon atoms may be resolved into 0188 A trimethylsilyl group is cleaved for example in their diastereomers on the basis of their physical-chemical water, an aqueous Solvent mixture or a lower alcohol Such as differences using methods known per se, e.g. by chroma methanol or ethanol in the presence of a base Such as lithium tography and/or fractional crystallisation, and, if these com hydroxide, Sodium hydroxide, potassium carbonate or pounds are obtained in racemic form, they may Subsequently Sodium methoxide. In acqueous or alcoholic Solvents, acids Such as e.g. hydrochloric acid, trifluoroacetic acid or acetic be resolved into the enantiomers as mentioned above. acid are also Suitable. Fluoride reagents, Such as e.g. tet 0198 The enantiomers are preferably separated by col rabutylammonium fluoride, are also Suitable for cleaving in umn Separation on chiral phases or by recrystallisation from organic Solvents, Such as for example diethyl ether, tetrahy an optically active Solvent or by reacting with an optically drofuran or dichloromethane. active Substance which forms Salts or derivatives Such as e.g. esters or amides with the racemic compound, particularly 0189 A benzyl, methoxybenzyl or benzyloxycarbonyl acids and the activated derivatives or alcohols thereof, and group is advantageously cleaved hydrogenolytically, e.g. Separating the diastereomeric mixture of Salts or derivatives with hydrogen in the presence of a catalyst Such as palla thus obtained, e.g. on the basis of their differences in dium/charcoal, in a Suitable Solvent Such as methanol, solubility, whilst the free antipodes may be released from the ethanol, ethyl acetate or glacial acetic acid, optionally with pure diastereomeric Salts or derivatives by the action of the addition of an acid Such as hydrochloric acid, at tem Suitable agents. Optically active acids in common use are peratures between 0 and 100° C., but preferably at ambient e.g. the D- and L-forms of tartaric acid or dibenzoyltartaric temperature between 20 and 60° C., and under a hydrogen acid, di-o-tolyltartaric acid, malic acid, mandelic acid, cam pressure of 1 to 7 bar, but preferably from 3 to 5 bar. phorSulphonic acid, glutamic acid, aspartic acid or quinic However, a 2,4-dimethoxybenzyl group is preferably acid. An optically active alcohol may be for example (+) or cleaved in trifluoroacetic acid in the presence of anisole. (-)-menthol and an optically active acyl group in amides, for 0190. A tert-butyl or tert-butyloxycarbonyl group is pref example, may be a (+)-or (-)-menthyloxycarbonyl. erably cleaved by treatment with an acid Such as trifluoro 0199 Furthermore, the compounds of formula I obtained acetic acid or hydrochloric acid or by treatment with iodot may be converted into the Salts thereof, particularly for rimethylsilane, optionally using a Solvent Such as methylene pharmaceutical use into the physiologically acceptable Salts chloride, dioxane, methanol or diethyl ether. with inorganic or organic acids. Acids which may be used 0191 In the reactions described hereinbefore, any reac for this purpose include for example hydrochloric acid, tive groups present Such as ethynyl, hydroxy, amino, alky hydrobromic acid, Sulphuric acid, methaneSulphonic acid, lamino or imino groups may be protected during the reaction phosphoric acid, fumaric acid, Succinic acid, lactic acid, by conventional protecting groups which are cleaved again citric acid, tartaric acid or maleic acid. after the reaction, e.g. as described above. 0200 Moreover, the compounds obtained may be con 0.192 For example the trimethylsilyl or triisopropyl verted into mixtures, for example 1:1 or 1:2 mixtures with group may be used as a protective group for an ethynyl amino acids, particularly with alpha-amino acids Such as group. The 2-hydroxisoprop-2-yl group may also be used as proline or phenylalanine, which may have particularly a protective group. favourable properties Such as a high crystallinity. 0193 For example, a protecting group for a hydroxy 0201 The compounds of general formulae II and III used group may be a trimethylsilyl, acetyl, trityl, benzyl or as Starting materials are partly known from the literature or tetrahydropyranyl group. may be obtained by methods known from the literature and also analogously to the methods described in the Examples, 0194 Examples of protecting groups for an amino, alky optionally with the additional inclusion of protecting groups. lamino or imino group include the formyl, acetyl, trifluoro acetyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycar 0202) The compounds according to the invention may bonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl advantageously also be obtained by the methods described grOup. in the following Examples, which may also be combined with methods known to the skilled man from the literature, 0.195. Furthermore, the compounds of general formula I for example, particularly the methods described in WO thus obtained may be selectively derivatised at a hydroxy 98/31697, WO 01/27128, WO 02/083066, WO 03/099836, group or the hydroxy group itself may be Substituted. WO 04/063209 and WO 04/76470. 0196) Moreover, the compounds of general formula I 0203 As already mentioned hereinbefore, the com obtained may be resolved into their enantiomers and/or pounds of general formula I according to the invention and diastereomers, as mentioned hereinbefore. Thus, for the physiologically acceptable Salts thereof have valuable example, cis/trans mixtures may be resolved into their cis pharmacological properties, particularly an inhibitory effect and trans isomers, and compounds with at least one optically on the Sodium-dependent glucose cotransporter SGLT, pref active carbon atom may be separated into their enantiomers. erably SGLT2. 0.197 Thus, for example, the cis/trans mixtures may be 0204. The biological properties of the new compounds resolved by chromatography into the cis and trans isomers may be investigated as follows: thereof, the compounds of general formula I obtained which occur as racemates may be separated by methods known per 0205 The ability of the substances to inhibit the SGLT2 se (cf. Allinger N. L. and Eliel E. L. in “Topics in Stere activity may be demonstrated in a test Set-up in which a US 2006/0035.841 A1 Feb. 16, 2006

CHO-KL cell line (ATCC No. CCL 61) or alternatively an Suitable for preventing beta-cell degeneration Such as e.g. HEK293 cell line (ATCC No. CRL-1573), which is stably apoptosis or necrosis of pancreatic beta cells. The Substances transfected with an expression vector p7eoSV (Invitrogen, are also Suitable for improving or restoring the functionality EMBL accession number L36849), which contains the of pancreatic cells, and also for increasing the number and cDNA for the coding Sequence of the human Sodium glucose Size of pancreatic beta cells. The compounds according to cotransporter 2 (Genbank Acc. No.NM 00304.1) (CHO the invention may also be used as diuretics or antihyperten hSGLT2 or HEK-hSGLT2). These cell lines transport 'C- Sives and are Suitable for the prevention and treatment of labelled alpha-methyl-glucopyranoside ("C-AMG, Amer acute renal failure. Sham) into the interior of the cell in Sodium-dependent 0211. In particular, the compounds according to the C. invention, including the physiologically acceptable Salts thereof, are suitable for the prevention or treatment of 0206. The SGLT2 assay is carried out as follows: diabetes, particularly type 1 and type 2 diabetes mellitus, 0207 CHO-hSGLT2 cells are cultivated in Ham's F12 and/or diabetic complications. Medium (BioWhittaker) with 10% foetal calf serum and 250 0212. The dosage required to achieve the corresponding ug/ml Zeocin (Invitrogen), and HEK293-hSGLT2 cells are activity for treatment or prevention usually depends on the cultivated in DMEM medium with 10% foetal calf serum compound which is to be administered, the patient, the and 250 ug/ml Zeocin (Invitrogen). The cells are detached nature and gravity of the illness or condition and the method from the culture flasks by washing twice with PBS and and frequency of administration and is for the patient's Subsequently treating with trypsin/EDTA. After the addition doctor to decide. Expediently, the dosage may be from 1 to of cell culture medium the cells are centrifuged, resuspended 100 mg, preferably 1 to 30 mg, by intravenous route, and 1 in culture medium and counted in a Casy cell counter. Then to 1000 mg, preferably 1 to 100 mg, by oral route, in each 40,000 cells per well are seeded into a white, 96-well plate case administered 1 to 4 times a day. For this purpose, the coated with poly-D-lysine and incubated overnight at 37 C., compounds of formula I prepared according to the invention 5% CO. The cells are washed twice with 250 ul of assay may be formulated, optionally together with other active buffer (Hanks Balanced Salt Solution, 137 mM NaCl, 5.4 Substances, together with one or more inert conventional mM KC1, 2.8 mM CaCl, 1.2 mM MgSO and 10 mM carriers and/or diluents, e.g. with corn Starch, lactose, glu HEPES (pH7.4), 50 tug/ml of gentamycin). 250 ul of assay cose, microcrystalline cellulose, magnesium Stearate, poly buffer and 5ul of test compound are then added to each well Vinylpyrrolidone, citric acid, tartaric acid, water, water/ and the plate is incubated for a further 15 minutes in the ethanol, water/glycerol, water/Sorbitol, water/polyethylene incubator. 5 ul of 10% DMSO are used as the negative glycol, propylene glycol, cetylstearyl alcohol, carboxymeth control. The reaction is started by adding 5 ul of "C-AMG ylcellulose or fafty Substances Such as hard fat or Suitable (0.05 uCi) to each well. After 2 hours incubation at 37 C., mixtures thereof, to produce conventional galenic prepara 5% CO, the cells are washed again with 250 ul of PBS (20° tions Such as plain or coated tablets, capsules, powders, C.) and then lysed by the addition of 25ul of 0.1 N NaOH Solutions, Suspensions or Suppositories. (5 min. at 37° C). 200 ul of MicroScint20 (Packard) are added to each well and incubation is continued for a further 0213 The compounds according to the invention may 20 min at 37 C. After this incubation the radioactivity of the also be used in conjunction with other active Substances, 'C-AMG absorbed is measured in a Topcount (Packard) particularly for the treatment and/or prevention of the dis using a "C Scintillation program. eases and conditions mentioned above. Other active Sub stances which are Suitable for Such combinations include, in 0208 To determine the selectivity with respect to human particular, those which potentiate the therapeutic effect of an SGLT1 an analogous test is set up in which the cDNA for SGLT inhibitor according to the invention with respect to hSGLT1 (Genbank Acc. No. NM000343) instead of one of the indications mentioned and/or which allow the hSGLT2 cDNA is expressed in CHO-K1 or HEK293 cells. dosage of an SGLT inhibitor according to the invention to be 0209 The compounds of general formula I according to reduced. Therapeutic agents which are Suitable for Such a combination include, for example, antidiabetic agents Such the invention may for example have EC50 values of less as mefformin, Sulphonylureas (e.g. glibenclamide, tolbuta than 1000 nM, particularly less than 200 nM, particularly mide, glimepiride), nateglinide, repaglinide, thiazolidinedi preferably less than 50 nM. ones (e.g. rosiglitaZone, pioglitaZone), PPAR-gamma-ago 0210. In view of their ability to inhibit the SGLTactivity, nists (e.g. GI 262570) and antagonists, PPAR-gamma/alpha the compounds of general formula I according to the inven modulators (e.g. KRP 297), alpha-glucosidase inhibitors tion and the corresponding pharmaceutically acceptable (e.g. acarbose, voglibose), DPPIV inhibitors (e.g. LAF237, salts thereof are theoretically suitable for the treatment MK-431), alpha2-antagonists, insulin and insulin analogues, and/or preventative treatment of all those conditions or GLP-1 and GLP-1 analogues (e.g. exendin-4) or amylin. diseases which may be affected by the inhibition of the Other active Substances which are Suitable as combination SGLT activity, particularly the SGLT2 activity. Therefore, partners include inhibitors of protein tyrosinephosphatase 1, compounds according to the invention are particularly Suit Substances that affect deregulated glucose production in the able for the prevention or treatment of diseases, particularly liver, Such as e.g. inhibitors of glucose-6-phosphatase, or metabolic disorders, or conditions Such as type 1 and type 2 fructose-1,6-bisphosphatase, glycogen phosphorylase, glu diabetes mellitus, complications of diabetes (such as e.g. cagon receptor antagonists and inhibitors of phosphoenol retinopathy, nephropathy or neuropathies, diabetic foot, pyruvate carboxykinase, glycogen Synthase kinase or pyru ulcers, macroangiopathies), metabolic acidosis or ketosis, Vate dehydrokinase, lipid lowering agents Such as for reactive hypoglycaemia, hyperinsulinaemia, glucose meta example HMG-CoA-reductase inhibitors (e.g. Simvastatin, bolic disorder, insulin resistance, metabolic Syndrome, dyS atorvastatin), fibrates (e.g. beZafibrate, fenofibrate), nico lipidaemias of different origins, atherosclerosis and related tinic acid and the derivatives thereof, PPAR-alpha agonists, diseases, obesity, high blood pressure, chronic heart failure, PPAR-delta agonists, ACAT inhibitors (e.g. avasimibe) or oedema and hyperuricaemia. These Substances are also cholesterol absorption inhibitorS Such as, for example, US 2006/0035.841 A1 Feb. 16, 2006

eZetimibe, bile acid-binding Substances Such as, for 0221) Thus, for example, a pharmaceutical composition example, cholestyramine, inhibitors of ileac bile acid trans according to the invention comprises a combination of a port, HDL-increasing compounds such as CETP inhibitors compound of formula I according to the invention or a or ABC1 regulators or active Substances for treating obesity, physiologically acceptable Salt of Such a compound and at Such as Sibutramine or tetrahydrolipostatin, dexfenflu least one angiotensin II receptor antagonist optionally ramine, axokine, antagonists of the cannabinoid1 receptor, together with one or more inert carriers and/or diluents. MCH-1 receptor antagonists, MC4 receptor agonists, NPY5 or NPY2 antagonists or B3-agonists such as SB-418790 or 0222. The compound according to the invention, or a AD-9677 and agonists of the 5HT2c receptor. physiologically acceptable Salt thereof, and the additional active substance to be combined therewith may both be 0214) Moreover, combinations with drugs for influencing present together in one formulation, for example a tablet or high blood pressure, chronic heart failure or atherOSclerosis capsule, or Separately in two identical or different formula such as e.g. A-II antagonists or ACE inhibitors, ECE inhibi tions, for example as a So-called kit-of-parts. tors, diuretics, B-blockers, Ca-antagonists, centrally acting antihypertensives, antagonists of the alpha-2-adrenergic 0223) In the foregoing and following text, H atoms of receptor, inhibitors of neutral endopeptidase, thrombocyte hydroxyl groups are not explicitly shown in every case in aggregation inhibitors and others or combinations thereof structural formulae. The Examples that follow are intended are Suitable. Examples of angiotensin II receptor antagonists to illustrate the present invention without restricting it: are candesartan cileXetil, potassium losartan, eprosartan 0224 Preparation of the Starting Compounds: mesylate, Valsartan, telmisartan, irbesartan, EXP-3174, L-158809, EXP-3312, olmesartan, medoxomil, tasosartan, KT-3-671, GA-0113, RU-64276, EMD-90423, BR-9701, EXAMPLE I etc. Angiotensin II receptor antagonists are preferably used for the treatment or prevention of high blood pressure and 0225) complications of diabetes, often combined with a diuretic Such as hydrochlorothiazide. C 0215. A combination with uric acid synthesis inhibitors or uricOSuricS is Suitable for the treatment or prevention of O gout. 0216 A combination with GABA-receptor antagonists, Na-channel blockers, topiramate, protein-kinase C inhibi tors, advanced glycation end product inhibitors or aldose Br reductase inhibitors may be used for the treatment or pre vention of complications of diabetes. 0217. The dosage for the combination partners men 5-bromo-2-chloro-phenol tioned above is usefully /s of the lowest dose normally 0226 96 ml of a 1 M solution of boron tribromide in recommended up to /1 of the normally recommended dose. dichloromethane are added to an ice-cooled Solution of 20 g 0218. Therefore, in another aspect, this invention relates 5-bromo-2-chloro-anisol in 300 ml dichloromethane. The to the use of a compound according to the invention or a reaction Solution is stirred for 14 h at ambient temperature physiologically acceptable Salt of Such a compound com and then cooled in the ice bath. The cooled solution is bined with at least one of the active Substances described combined with aqueous Saturated potassium carbonate Solu above as a combination partner, for preparing a pharmaceu tion, the aqueous phase is acidified with 1 M hydrochloric tical composition which is Suitable for the treatment or acid and extracted with dichloromethane. The combined prevention of diseases or conditions which can be affected organic phases are dried over Sodium Sulphate and the by inhibiting the Sodium-dependent glucose cotransporter Solvent is eliminated completely. SGLT. These are preferably metabolic diseases, particularly one of the diseases or conditions listed above, most particu Yield: 17.9 g (96% of theory) larly diabetes or diabetic complications. Mass spectrum (ESI): m/z=205/207/209 (bromine-chlo 0219. The use of the compound according to the inven rine) M+H" tion, or a physiologically acceptable Salt thereof, in combi nation with another active Substance may take place Simul EXAMPLE II taneously or at Staggered times, but particularly within a Short Space of time. If they are administered Simultaneously, 0227 the two active Substances are given to the patient together; while if they are used at Staggered times the two active Substances are given to the patient within a period of leSS than or equal to 12 hours, but particularly less than or equal to 6 hours. 0220 Consequently, in another aspect, this invention relates to a pharmaceutical composition which comprises a -> compound according to the invention or a physiologically acceptable Salt of Such a compound and at least one of the Br active Substances described above as combination partners, optionally together with one or more inert carriers and/or diluents. 4-bromo-1-chloro-2-(tri-isopropyl-silyloxy)-benzene US 2006/0035.841 A1 Feb. 16, 2006

0228 9.2 g triisopropylsilyl chloride in 20 ml dichlo EXAMPLE IV romethane and then 0.5 g 4-dimethylaminopyridine are 0231) added to an ice-cooled solution of 9.2 g 5-bromo-2-chloro phenol and 9.4 ml triethylamine in 120 ml dichloromethane. The reaction is stirred for 18 h at ambient temperature and then diluted with 100 ml dichloromethane. The diluted Br Cl solution is washed with 1 M hydrochloric acid and aqueous Sodium hydrogen carbonate Solution, dried over Sodium sulphate and the solvent is removed. The residue is purified -O-y on Silica gel (cyclohexane/ethyl acetate 9:1-> 1:1). Yield: 9.4 g (59% of theory) (CSO Mass spectrum (ESI): m/z=363/365/367 (bromine-chlo rine) M+H" 1-bromo-3-cis-4-(tert-butyl-diphenyisilyloxy)-cyclohexy EXAMPLE III loxyl-4-chloro-benzene 0229) 0232 4.8 g of 5-bromo-2-chloro-phenol, 4.5 g triph enylphosphine and 3.3 ml diisopropyl azodicarboxylate are added to a solution of 1.85g trans-4-(tert-butyl-diphenylsi lyloxy)-cyclohexanol in 20 ml dry tetrahydrofuran in the order stated. The solution is stirred for 48 h at 55 C. and then combined with aqueous potassium carbonate Solution. - Si C - C Then the mixture is extracted with ethyl acetate, dried over Sodium Sulphate and the Solvent is removed. The residue is o1 O O purified on silica gel (cyclohexane/ethyl acetate 4:1). Yield: 3.5 g (72% of theory) Mass spectrum (ESI"): m/z=543/545/547 (bromine and O i. chlorine) M+H" EXAMPLE V cis-4-(tert-butyl-diphenYlsilyloxy)-cyclohexanol and trans4-(tert-butvl-diphenylsilyloxv)-cyclohexanol 0233 0230. A solution of 29.4 g tert-butylidiphenylsilyl chlo ride in 20 ml of dimethylformamide is added dropwise to an ice-cooled Solution of 10.0 g 1,4-cyclohexanediol (cis/trans Br Cl mixture approx. 1:1) and 14.6 g imidazole in 15 ml dry dimethylformamide and 20 ml dry tetrahydrofuran. The reaction Solution is stirred for 1 h in the ice bath and then -O- combined with 100 ml aqueous sodium chloride solution. The organic phase is separated off and the aqueous phase is extracted with ethyl acetate. The combined organic phases 0234 1-bromo-4-chloro-3-(cis-4-hydroxy-cyclohexy are dried over Sodium Sulphate, and the Solvent is eliminated loxy)-benzene totally. The residue is purified by chromatography and 0235 8.8 ml of a 1 M solution of tetrabutylammonium resolved into the two isomeric products (ethyl acetate/ fluoride in tetrahydrofuran are added to an ice-cooled Solu cyclohexane 1:1). tion of 4.8g 1-bromo-3-cis-4-(tert-butyl-diphenylsilyloxy)- cis-4-(tert-butyl-diphenylsilyloxy)-cyclohexanol: cyclohexyloxy4-chloro-benzene in 25 ml dry tetrahydrofu ran. The solution is stirred for 14 h at ambient temperature Yield: 4.9 g (16% of theory) and then combined with water. Then the mixture is extracted with ethyl acetate, dried over Sodium Sulphate and the Mass spectrum (ESI): m/z=355 M+H" Solvent is removed. The residue is purified on Silica gel (cyclohexane/ethyl acetate 1:0->3:2). trans-4-(tert-butyl-diphenylsilyloxy)-cyclohexanol: Yield: 2.1 g (79% of theory) Yield: 4.8 g (16% of theory) Mass spectrum (ESI): m/z=327/329/331 (bromine and Mass spectrum (ESI): m/z=355 M+H" chlorine) M+Na" US 2006/0035.841 A1 Feb. 16, 2006

EXAMPLE VI EXAMPLE VIII 0236 0240

Br

1-bromo-4-chloro-3-(cis-4-methoxy-cyclohexyloxy)-ben ZCC 0237 Under an argon atmosphere 0.28 g sodium hydride (60% in mineral oil) are added to an ice-cooled solution of 1-chloro-4-(2,3,4,6-tetra-O-acetyl-1-methoxy-D-glucoVra 2.1 g 1-bromo-4-chloro-3-(cis-4-hydroxy-cyclohexyloxy)- noS-1-yl)-2-(tri-isopropyl-silyloxy)-benzene benzene in 10 ml dry tetrahydrofuran. The solution is stirred for 30 min in the ice bath and then 0.44 ml methyl iodide are 0241) A solution of 5.0 g 1-bromo-4-chloro-3-(tri-isopro added. The reaction Solution is stirred for 6 h at ambient pyl-silyloxy)-benzene in 60 ml dry diethyl ether is cooled to temperature and then combined with water. Then the mix -80 C. under argon. 17.7 ml of a 1.7 M solution of ture is extracted with ethyl acetate, dried over Sodium tertbutyllithium in pentane are added dropwise to the cooled sulphate and the solvent is removed. The residue is purified Solution. The solution is stirred for 30 min at -80 C. and on Silica gel (cyclohexane/ethyl acetate 1:0-> 1:1). then added dropwise through a preSSure needle to a Solution of 7.3 g 2,3,4,6-tetrakis-O-(trimethylsilyl)-D-glucopyra Yield: 1.8 g (80% of theory) none in 40 ml diethyl ether cooled to -80 C. The resulting Solution is stirred for 4 hat -78 C. Then a solution of 3 ml Mass spectrum (ESI"): m/z=319/321/323 (bromine and methanesulphonic acid in 80 ml of methanol is added and chlorine) M+H" the Solution is stirred for 16 h at ambient temperature. The Solution is then neutralised with ethyldiisopropylamine and EXAMPLE VII evaporated down. The residue is taken up in toluene and evaporated down again. Then the residue is dissolved in 36 0238) ml of toluene and 3.4 ml ethylduisopropylamine are added to the Solution. The Solution-is cooled in the ice bath and

then 6.3 ml acetic anhydride and 0.17 g 4-dimethylaminopy ridine are added. The Solution is stirred for 6 h at ambient temperature and then combined with aqueous Sodium hydro gen carbonate Solution. The organic phase is separated off and the aqueous phase is extracted with ethyl acetate. After drying the combined organic extracts through Sodium Sul phate and eliminating the Solvent the residue is chromato graphed on Silica gel (cyclohexanelethyl acetate 6:1-> 1:1). Yield: 5.8 g (65% of theory) Mass spectrum (ESI): m/z=662/664 (chlorine) M+NH" 0242. The following compound is obtained analogously 2,3,4,6-tetrakis-O-(trimethylsilyl)-D-glucopyranone to Example VIII: 0239 A solution of 20 g of D-glucono-1,5-lactone and (1) 1-chloro-4-(2,3,4,6-tetra-O-acetyl-1-methoxy-D-glu 98.5 ml N-methylmorpholine in 200 ml of tetrahydrofuran is copyranos-1-yl)-2-(cis-4-methoxy-cyclohexyloxy)-benzene

cooled to -5° C. Then 85 ml trimethylsilyl chloride are added dropwise in Such a way that the temperature does not exceed 5 C. The solution is then stirred for 1 h at ambient temperature, for 5 h at 35 C. and for a further 14 h at ambient temperature. After the addition of 300 ml of toluene the Solution is cooled in the ice bath, and 500 ml of water are added so that the temperature does not exceed 10° C. The organic phase is then Separated off and washed once each with aqueous Sodium dihydrogen phosphate Solution, water and Saturated aqueous Sodium chloride Solution. The Solvent is removed, the residue is taken up in 250 ml of toluene and the Solvent is again eliminated totally. Yield: 52.5 g (approx. 90% pure) Mass spectrum (ESI): m/z=467 M+H" Mass spectrum (ESI); m/z=618/620 (chlorine) M+NH US 2006/0035.841 A1 Feb. 16, 2006 21

EXAMPLE IX EXAMPLE X 0243) 0246

1-chloro-4-(2,3,4,6-tetra-O-acetyl-3-D-glucopyranos-1-yl)- 1-chloro-4-(2,3,4,6-tetra-O-acetyl-f-D-glucopyranos-1-yl)- 2-hydroxy-benzene 2-(tri-isodropyl-silvloxy)-benzene 0247 5 ml of a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran are added to an ice-cooled Solu 0244. A solution of 5.83 g 1-chloro-4-(2,3,4,6-tetra-O- tion of 4.80 g 1-chloro-4-(2,3,4,6-tetra-O-acetyl-B-D-glu acetyl-1-methoxy-D-glucopyranos-1-yl)-2-(tri-isopropyl-Si copyranos-1-yl)-2-(tri-isopropyl-silyloxy)-benzene in 25 ml lyloxy)-benzene in 100 ml acetonitrile and 0.22 ml of water dry tetrahydrofuran. The solution is stirred for 14 h at is cooled in the ice bath. Then 7 ml triethylsilane and 1.5 ml ambient temperature and then combined with water. It is extracted with ethyl acetate, dried over Sodium Sulphate and boron trifluoride etherate are added. The Solution is stirred the solvent is removed. The residue is stirred in cyclohex for 1 h in the ice bath and then at ambient temperature. After ane/ethyl acetate (5:1) and then dried. 5 h a further 6 ml triethylsilane and 1.2 ml boron trifluoride etherate are added. After another 5 h Stirring at ambient Yield: 1.70 g (86% of theory) temperature aqueous Sodium hydrogen carbonate Solution is Mass spectrum (ESI): m/z=476/478 (chlorine) M+NH added, the mixture is stirred for 0.5 h and then extracted with EXAMPLE XI ethyl acetate. The organic phase is dried over Sodium 0248 Sulphate and evaporated to dryneSS.

Yield: 4.80 g (86% of theory) Mass spectrum (ESI): m/z=637/639 (chlorine) M+Na" 0245. The following compound is obtained analogously to Example IX: (1)1-chloro-4-(2,3,4,6-tetra-O-acetyl-B-D-glucopyranos-1- yl)-2-(cis-4-methoxy-cyclohexyloxy)-benzene

1-chloro-4-(2,3,4,6-tetra-O-acetyl-3-D-glucopyranos-1-yl)- 2-(4-methoxy-cyclohexyloxy)-benzene 0249 0.08 g 4-methoxycyclohexanol, 0.16 g triph enylphosphine and 0.12 ml diisopropyl azodicarboxylate are added to a solution of 0.25 g 1-chloro-4-(2,3,4,6-tetra-O- acetyl-f-D-glucopyranoS-1-yl)-2-hydroxy-benzene in 3 ml of tetrahydrofuran, in the order stated. The solution is stirred for 14 h at ambient temperature and then combined with aqueous potassium carbonate Solution. Then it is extracted with ethyl acetate, dried over Sodium Sulphate and the Solvent is removed. The residue is purified on Silica gel (cyclohexane/ethyl acetate 7:3->1:1). Mass spectrum (ESI): m/z=589/591 (chlorine) M+NH Yield: 0.05 g (16% of theory) US 2006/0035.841 A1 Feb. 16, 2006 22

EXAMPLE XII 1-chloro-2-(4-methoxy-benzyl)-4-(1-?3-D-glucopyranosyl)- 0250) benzene in 2.5 ml dichloromethane cooled to -40° C. The solution is left to come up to 0 C. in the cooling bath and then stirred for 2 h at this temperature. Then the solution is cooled to -50 C. and combined with 2 ml of methanol. After heating to ambient temperature the Solution is evapo rated down and the residue is chromatographed on Silica gel (dichloromethane/methanol 1:0->8:1). 0255 The following compound is obtained analogously to Example 1: 1-chloro-4-3-D-glucopyranos-1-yl-2-(4-methoxy-cyclo (1) 1-chloro-4-f-D-glucopyranoS-1-yl-2-(cis-4-methoxy hexyloxy)-benzene cyclohexyloxy)-benzene 0251 0.13 ml of 4M potassium hydroxide solution are added to a solution of 0.05 g 1-chloro-4-(2,3,4,6tetra-O- acetyl-f-D-glucopyranoS-1-yl)-2-(4-methoxy-benzyl)-ben Zene in 3 ml of methanol. The Solution is stirred for 3 hat ambient temperature and then neutralised with 1 M hydro chloric acid. The Solution is freed from methanol, combined with aqueous Sodium chloride Solution and extracted with ethyl acetate. The organic phase is dried over Sodium sulphate and the solvent is removed. The residue is purified on silica gel (dichloromethane/methanol 1:0->3:1). Yield: 0.01 g (28% of theory) Mass spectrum (ESI): m/z=420/422 (chlorine) M+NH Mass spectrum (ESI): m/z=405/407 (chlorine) M+H" 0252. The following compound is obtained analogously to Example XII: 0256 The following compounds are also prepared analo (1) 1-chloro-4-f-D-glucopyranoS-1-yl-2-(cis-4-methoxy gously to the foregoing Examples and other methods known cyclohexyloxy)-benzene from the literature:

Bsp. Structure

C O

Mass spectrum (ESI): m/z=403/405 (chlorine) M+H" Preparation of the End Compounds: (2) EXAMPLE 1. 0253)

(3)

1-chloro-2-(4-methoxy-cyclohexyloxy)-4-(6-desoxy-6- fluoro-f-D-glucopyranoS-1-yl)-benzene 0254 0.20 ml diethylaminosulphur trifluoride in 0.5 ml dichloromethane are added dropwise to a solution of 0.10 g US 2006/0035.841 A1 Feb. 16, 2006 23

-continued -continued

Bsp. Structure Bsp. Structure C (4) Cl

(5)

(6)

(7)

(8)

O (15) N (9) US 2006/0035.841 A1 Feb 16, 2006 24

-continued -continued

Bsp. Structure Bsp. Structure (21) (16)

(22)

(17)

(23)

(18)

(24)

(19)

(25)

(20) (26) US 2006/0035.841 A1 Feb. 16, 2006 25

-continued -continued

Bsp. Structure Bsp. Structure (27) o-/ (32)

(33) (28) o-/

(34)

(29)

O

(35)

(30)

(36)

(31)

(37) US 2006/0035.841 A1 Feb. 16, 2006 26

-continued -continued

Bsp. Structure Bsp. Structure

(38) (44)

(39) (45)

(40) (46)

(41) (47)

(42) (48)

(49) (43) US 2006/0035.841 A1 Feb. 16, 2006 27

-continued -continued Bsp. Structure corn starch 40.0 mg colloidal silica 10.0 mg (50) polyvinylpyrrollidone 10.0 mg magnesium stearate 1.0 mg 300.0 mg

Preparation: 0264. The active substance mixed with lactose, corn Starch and Silica is moistened with a 20% aqueous polyvi nylpyrrollidone Solution and passed through a Screen with a mesh size of 1.5 mm. The granules, dried at 45 C., are passed through the Same Screen again and mixed with the 0257 The following are examples of formulations in Specified amount of magnesium Stearate. Tablets are pressed which the phrase “active Substance' denotes one or more from the mixture. compounds according to the invention, including the Salts thereof. 0265 Weight of tablet: 300 mg 0258. In the case of one of the combinations with one or 0266 die: 10 mm, flat more other active Substances the term “active Substance' also includes the additional active Substances. EXAMPLE C EXAMPLEA Hard Gelatine Capsules Containing 150 mg of Active Sub Stance Tablets Containing 100 mg of Active Substance 0267. 1 capsule contains: Composition: 0259 1 tablet contains: active substance 150.0 mg corn starch (dried approx. 180.0 mg lactose (powdered) approx. 87.0 mg active substance 100.0 mg magnesium stearate 3.0 mg lactose 80.0 mg corn starch 34.0 mg approx. 420.0 mg polyvinylpyrrollidone 4.0 mg magnesium stearate 2.0 mg 220.0 mg Preparation: 0268. The active substance is mixed with the excipients, passed through a Screen with a mesh size of 0.75 mm and Method of Preparation: homogeneously mixed using a Suitable apparatus. The fin 0260 The active substance, lactose and starch are mixed ished mixture is packed into Size 1 hard gelatine capsules. together and uniformly moistened with an aqueous Solution of the polyvinylpyrrollidone. After the moist composition has 0269 Capsule filling: approx. 320 mg been Screened (2.0 mm mesh size) and dried in a rack-type 0270 Capsule shell: size 1 hard gelatine capsule. drier at 50° C. it is screened again (1.5 mm mesh size) and the lubricant is added. The finished mixture is compressed to EXAMPLED form tablets. Suppositories Containing 150 mg of Active Substance 0261) Weight of tablet: 220 mg 0271 1 suppository contains: 0262 Diameter: 10 mm, biplanar, facetted on both Sides and notched on one side. active substance 150.0 mg EXAMPLEB polyethyleneglycol 1500 550.0 mg polyethyleneglycol 6000 460.0 mg Tablets Containing 150 mg of Active Substance polyoxyethylene sorbitan monostearate 840.0 mg Composition: 2,000.0 mg 0263. 1 tablet contains: Preparation: active substance 150.0 mg 0272. After the Suppository mass has been melted the powdered lactose 89.0 mg active Substance is homogeneously distributed therein and the melt is poured into chilled moulds. US 2006/0035.841 A1 Feb. 16, 2006 28

EXAMPLEE C-3-alkyl, C6-alkoxy-C-3-alkyl, C3-10 cycloalkyloxy-C-alkyl, Cso-cycloalkenyl-oxy-C- Ampoules Containing 10 mg Active Substance 3-alkyl, aryloxy-C-alkyl, heteroaryloxy-C-3-alkyl, 0273 Composition: C-alkylsulphanyl-C-alkyl, C-alkylsulphinyl, C-alkylsulphonyl, C-alkylsulphinyl-C-3-alkyl, C-alkylsulphonyl-C-alkyl, arylsulphanyl-C-a- alkyl, arylsulphonyl-C-alkyl, aryl-C-3-alkyl-Sul active substance 10.0 mg 0.01 N hydrochloric acid qis. phonyl-C-alkyl, C-alkylsulphonyloxy-C-3-alkyl, double-distilled water ad 2.0 ml arylsulphonyloxy-C-alkyl, aryl-C-alkyl-Sulpho nyloxy-C-alkyl, Co-cyclo-alkylsulphanyl-C-a- alkyl, Co-cycloaklylsulphinly, Co-cycloalkylsul Preparation: phinyl-C-3-alkyl, C-1o-cycloalkylsulphonyl, Cs-o- cycloalkylsulphonyl-C-alkyl, Cs-10'- 0274) The active substance is dissolved in the necessary cycloalkenylsulphanyl-C-alkyl, Cs-1o amount of 0.01 NHCl, made isotonic with common salt, cycloalkenylsulphinyl, Csocycloalkenyl-Sulphinyl filtered sterile and transferred into 2 ml ampoules. C-alkyl, Cso-cycloalkenylsulphonyl, Cs-10'- cycloalkenylsulphinyl-C-alkyl, bromomethyl, EXAMPLE F iodomethyl or cyano, Ampoules Containing 50 mg of Active Substance while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl 0275 Composition: groups may be partly or totally fluorinated or mono- or disubstituted by identical or different substituents selected from chlorine, cyano, hydroxy, mercapto, active substance 50.0 mg C-3-alkoxy and C-3-alkyl, and 0.01 N hydrochloric acid q.s. in cycloalkyl and cycloalkenyl groups one or two meth double-distilled water ad 10.0 ml ylene groups may be replaced independently of one another by O, S, CO, SO or SO, and Preparation: in N-heterocycloalkyl groups a methylene group may be 0276. The active substance is dissolved in the necessary replaced by CO or SO, and amount of 0.01 NHCl, made isotonic with common Salt, X representing hydroxymethyl is preferably excluded, filtered sterile and transferred into 10 ml ampoules. Cy denotes a 5- or 6-membered Saturated or monounsat 1. A compound comprised of a D-Xylopyranosyl-phenyl urated carbocyclic ring, which may comprise one, two substituted cyclic compound of general formula I or three heteratoms Selected independently of one another from N, O and S, and is substituted by R", Rand R through a single bond and by R through a single or double bond, and wherein one or two methylene groups may be replaced by CO or a sulphanyl group by SO or SO, and wherein one or more H atoms bound to carbon may be replaced by fluorine, Z denotes-O-, -CH2-, -CH=, -NRS-, -S-, -SO-or -SO-, while H atoms of the methylene or methanylylidene bridge may be substituted indepen dently of one another by CH or F; wherein denotes a single or double bond, and R" denotes hydrogen, fluorine, chlorine, bromine, iodine, X denotes hydrogen, C6-alkyl, C6-alkynyl, C6-alk C6-alkyl, C6-alkynyl, C2-6-alkenyl, C-10-cy enyl, Co-cycloalkyl, Co-cycloalkyl-C-3-alkyl, cloalkyl, Co-cycloalkyl-C-3-alkyl, Cs-o-cycloalk Cso-cycloalkenyl, Co-cycloalkenyl-C-alkyl, enyl, Cso-cycloalkenyl-C-alkyl, C-alkylcarbo aryl, aryl-C-alkyl, heteroaryl, heteroaryl-C-3-alkyl, nyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C-alkylcarbonyl, arylcarbonyl, aminocarbonyl, C-alkylaminocarbonyl, di-(C-3-alkyl)aminocarbo aminocarbonyl-C-alkyl, C-alkylaminocarbonyl, nyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, C-alkylaminocarbonyl-C-3-alkyl, di-(C-3-alky morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, l)aminocarbonyl, di-(C-alkyl)-aminocarbonyl-C- 4-(C-alkyl)piperazin-1-ylcarbonyl, C-alkoxycar alkyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, bonyl, amino, C-alkylamino, di-(C-alkyl)amino, morpholina-ylcarbonyl, hydroxycarbonyl, hydroxycar pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piper bonyl-C-alkyl, C-alkoxycarbonyl, C-alkoxy azin-1-yl, 4-(C-alkyl)piperazin-1-yl, C-alkylcar carbonyl-C-alkyl, C-alkylcarbonylamino-Cis bonylamino, C6-alkyloxy, Co-cycloalkyloxy, alkyl, N-(C1-alkylcarbonyl)-N-(C-3-alkyl)-amino Co-cycloalkenyloxy, aryloxy, C-alkylsulphanyl, C-3-alkyl, arylcarbonyl-amino-C3-alkyl, C-4- C-alkylsulphinyl, C-alkylsulphonyl, Co-cy alkylsulphonylamino-C-alkyl, arylsulphonylamino cloalkylsulphanyl, Cs-o-cycloalkylsulphinyl, C-1o US 2006/0035.841 A1 Feb. 16, 2006 29

cycloalkylsulphonyl, Cs-o-cycloalkenylsulphanyl, in N-heterocycloalkyl groups a methylene group may be Cs-o-cycloalkenylsulphinyl, Cs-o-cycloalkenylsul replaced by CO or SO, or phonyl, arylsulphanyl, arylsulphinyl, arylsulphonyl, hydroxy, cyano or nitro, R denotes a group Y connected to Cy through a double bond, while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups may be partly or totally fluorinated or mono- or R" denotes hydrogen, fluorine, chlorine, cyano, nitro, disubstituted by identical or different substituents amino, C-alkyl-amino, di-(C-3-alkyl)amino, Cis Selected from chlorine, hydroxy, C-alkoxy and C alkylcarbonylamino, C-alkyl, C-alkoxy, hydroxy alkyl, and carbonyl, C-alkoxycarbonyl or methyl or methoxy in cycloalkyl and cycloalkenyl groups one or two meth Substituted by 1 to 3 fluorine atoms, or ylene groups may be replaced independently of one in the event that R and R' are bound to the same C atom another by O, S, CO, SO or SO, and of the Cy ring, R and R' may be joined together such in N-heterocycloalkyl groups a methylene group may be that R and R' together form a C6-alkylene or Co replaced by CO or SO, and alkenylene bridge which may be partly or wholly fluorinated or mono- or disubstituted by identical or R denotes hydrogen, fluorine, chlorine, bromine, different Substituents selected from chlorine, hydroxy, hydroxy, C-alkyl, C-alkoxy, cyano or nitro, while C-alkoxy and C-alkyl and wherein one or two alkyl groups may be mono- or poly Substituted by methylene groups may be replaced independently of fluorine, or one another by O, S, CO, SO, SO or NRS, or in the event that R' and R are bound to two adjacent C atoms of the phenyl ring, R and R may be joined in the event that R and R are bound to two adjacent together Such that R' and R together form a Cas atoms of the Cy ring, RandR' may be joined together alkylene, C-alkenylene or butadienylene bridge, such that R and R' together with the two adjacent atoms of the Cy ring form an anellated Saturated or which may be partly or wholly fluorinated or mono- or mono- or polyunsaturated 5- or 6-membered carbocy disubstituted by identical or different substituents clic group wherein one or two methylene groups may Selected from chlorine, hydroxy, C-alkoxy and C be replaced independently of one another by O, S, CO, alkyl and wherein one or two methylene groups may be SO, SO or NRN and/or one or two methyne groups replaced independently of one another by O, S, CO, may be replaced by N, and may be mono- or polyflu SO, SO or NRS, and wherein in the case of a butadi orinated or mono- or disubstituted by identical or enylene bridge one or two methyne groups may be different Substituents selected from chlorine, hydroxy, replaced by an N atom, and C-alkoxy and C-alkyl or in the case of an aromatic R denotes hydrogen, fluorine, chlorine, bromine, Co anellated cyclic group may be mono- or disubstituted alkyl, C2-alkynyl, C2-alkenyl, Co-cycloalkyl, by identical or different substituents L, Co-cycloalkyl-C-3-alkyl, Cs-o-cycloalkenyl, Cs-o- cycloalkenyl-C-alkyl, aryl, heteroaryl, aryl-C- R denotes hydrogen, fluorine, chlorine, cyano, Cis alkyl, heteroaryl-C-alkyl, C-alkylcarbonyl, aryl alkyl, C-alkoxy or methyl or methoxy Substituted by carbonyl, heteroarylcarbonyl, aminocarbonyl, C 1 to 3 fluorine atoms, or alkylaminocarbonyl, di-(C-alkyl)aminocarbonyl, R" and Rare joined together so that R" and R together pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, mor form a C-alkylene or C-alkenylene bridge which pholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C- forms an anellated or bridged bicyclic group with 2, 3 alkyl)piperazin-1-ylcarbonyl, hydroxycarbonyl, C or 4 atoms of the Cy ring and may be partly or wholly alkoxycarbonyl, aryl-C-alkoxycarbonyl, C fluorinated or mono- or disubstituted by identical or alkylamino, di-(C-alkyl)amino, pyrrolidin-1-yl, different Substituents selected from chlorine, hydroxy, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-(C- C-alkoxy and C-alkyl, and wherein one or two alkyl)piperazin-1-yl, C-alkylcarbonylamino, aryl methylene groups may be replaced independently of carbonylamino, heteroarylcarbonylamino, C-alkyl Sulphonylamino, arylsulphonylamino, C-alkoxy, one another by O, S, CO, SO, SO or NRS, and Co-cycloalkyloxy, Cs-o-cycloalkenyloxy, aryloxy, R denotes hydrogen, C-3-alkyl or fluorine, or heteroaryloxy, C-alkylsulphanyl, C-alkylsulphi R, R and Rare joined together such that R", RandR nyl, C-alkylsulphonyl, Co-cycloalkylsulphanyl, together form a C-alkanetriyl bridge, which together Co-cycloalkylsulphinyl, Co-cycloalkylsulphonyl, with the Cy ring forms a bridged bicyclic or a tricyclic Cso-cycloalkenylsulphanyl, Cso-cycloalkenylsul System, while the alkanetriyl bridge may be mono- or phinyl, Cso-cycloalkenylsulphonyl, arylsulphanyl, polyfluorinated or mono- or disubstituted by identical arylsulphinyl, arylsulphonyl, amino, hydroxy, cyano or or different Substituents selected from chlorine, nitro, hydroxy, C-alkoxy and C-alkyl, and wherein one while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl or two methylene groups may be replaced indepen groups may be partly or totally fluorinated or mono- or dently of one another by O, CO, SO or NRS, and disubstituted by identical or different substituents Selected from chlorine, hydroxy, C-alkoxy and C 0 denotes oxygen, or alkyl, and methylidene, fluoromethylidene, chloromethylidene, in cycloalkyl and cycloalkenyl groups one or two meth Co-alkyl-methylidene, Co-alkenyl-methylidene, ylene groups may be replaced independently of one Co-alkynyl-methylidene, C-7-cycloalkyl-meth another by O, S, CO, SO or SO, and ylidene, C-7-cycloalkenyl-methylidene, C-7-cy US 2006/0035.841 A1 Feb. 16, 2006 30

cloalkylidene, Cs 7-cycloalkenylidene, C-7-cy and by the N-heterocycloalkyl group mentioned in the cloalkyl-C-alkyl-methylidene, Cs cycloalkenyl-C- definition of the above-mentioned groups is meant a 3-alkyl-methylidene, cyclo-Cae-alkyleneimino-C- Saturated carbocyclic ring which comprises an imino alkyl-methylidene, arylmethylidene, group in the ring, and which may comprise another heteroarylmethylidene, aryl-C-alkyl-methylidene or optionally Substituted imino group or an O or Satom in heteroaryl-C-alkyl-methylidene, the ring, and while alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cyclo-C-alkyleneimino, cycloalkylidene and unless otherwise Stated the above-mentioned alkyl groups cycloalkenylidene groups may be partly or totally flu may be Straight-chain or branched, orinated or mono- or disubstituted by identical or the tautomers, the Stereoisomers, the mixtures thereof and different Substituents Selected from chlorine, cyano, physiologically acceptable Salts thereof. hydroxy, C-alkoxy, C-alkylsulphanyl and C alkyl, and 2. A compound according to claim 1, wherein the above-mentioned unsubstituted methylidene group or the Cy ring denotes cyclopentane, cyclohexane, pyrroli the above-mentioned monosubstituted methylidene dine, piperidine, piperazine, morpholine, tetrahydrofu groups may additionally be monoSubstituted by fluo ran, tetrahydropyran, 1,3-dioxane, 1,4-dioxane, tet rine, chlorine, C-alkyl, trifluoromethyl, C-alkoxy, rahydrothiophene, dithiolane or 1,3-dithiane, cyano or nitro, and wherein a methylene group may be replaced by CO, and a methylene bridge bound directly to the methylidene which is substituted by R, R and R as specified in group may be replaced by -CO-, -SO-, claim 1, and wherein additionally one or more H atoms COO-, -CO-NRN- or -SO-NRN-, and bound to carbon may be replaced by fluorine. in cycloalkyl, cycloalkenyl, cycloalkylidene and 3. A compound according to claim 1 further characterised cycloalkenylidene groups one or two methylene groups by formula I. 1 or I.1" may be replaced independently of one another by O, S, CO, SO, SO or NRN, or I.1 in cyclo-C-alkyleneimino groups a methylene group may be replaced by CO or SO; and RN independently of one another denote H or C-alkyl, L is Selected independently of one another from the group consisting of fluorine, chlorine, bromine, iodine, C alkyl, difluoromethyl, trifluoromethyl, C-alkoxy, dif luoromethoxy, trifluoromethoxy and cyano,

I.1 R" independently of one another have a meaning selected from among hydrogen, (C-1s-alkyl)carbonyl, (C-1s alkyl)oxycarbonyl, arylcarbonyl and aryl-(C-alkyl)- carbonyl, while by the aryl groups mentioned above in the defini tions of the above groups are meant phenyl or naphthyl groups, which may be mono- or disubstituted indepen dently of one another by identical or different groups L., and by the heteroaryl groups mentioned in the definitions of wherein the above-mentioned groups is meant a pyrrolyl, fura nyl, thienyl, imidazolyl, pyridyl, indolyl, benzofuranyl, V1,V2 independently of one another represent C or N, benzothio-phenyl, quinolinyl or isoquinolinyl group, U1, U2, or a pyrrolyl, furanyl, thienyl, imidazolyl or pyridyl group, wherein one or two methyne groups are replaced U3, U4 independently of one another represent C, N, O, by nitrogen atoms, CO or SO, with the proviso that in the ring formed by U and V there or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl are a maximum of 2 heteroatoms Selected from N and or isoquinolinyl group, wherein O, these heteroatoms not being directly joined together, one to three methyne groups are replaced by nitrogen and there is at most one group Selected from CO and atOmS, SO, and any remaining free chemical bonds to C and Natoms are Saturated with hydrogen; and while the above-mentioned heteroaryl groups may be mono- or disubstituted independently of one another by wherein R to R, X, Z, R", R", R' have the meanings identical or different groups L.; according to claim 1. US 2006/0035.841 A1 Feb. 16, 2006 31

4. A compound according to claim 1 further characterised while alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl by formula I.2 groups may be partly or totally fluorinated or mono- or disubstituted by identical or different substituents Selected from chlorine, hydroxy, C-alkoxy and C

I.2 alkyl, and in cycloalkyl and cycloalkenyl groups one or two meth ylene groups may be replaced independently of one another by O, S, CO, SO or SO, and in N-heterocycloalkyl groups a methylene group may be replaced by CO or SO, while the terms aryl and heteroaryl are defined according to claim 1 and aryland heteroaryl groups may be mono or disubstituted independently of one another by iden wherein tical or different groupS L, and L is defined according V1,V2 independently of one another represent C or N, to claim 1. 8. A compound according to claim 1 wherein R is bound U1, U2, to Cy by a double bond and denotes oxygen, methylidene, U3 independently of one another represent C, N, O, CO fluoromethylidene, C-alkyl-methylidene, C-alkynyl methylidene, C-alkenyl-methylidene, C7-cycloalkyl or SO, methylidene or C-7-cycloalkylidene, with the proviso that in the ring formed by U and V there are a maximum of 2 heteroatoms Selected from N and while the above-mentioned alkyl, alkenyl, alkynyl and O, these heteroatoms not being directly joined together, cycloalkylidene groups may be partly or totally fluori and there is at most one group Selected from CO and nated and mono- or disubstituted independently of one SO, and any remaining free chemical bonds to C and another by Substituents Selected from chlorine, Natoms are Saturated with hydrogen; and hydroxy, C-alkoxy and C-alkyl, and R" to R, X, Z, R', R", R'have the meanings according the above-mentioned unsubstituted methylidene group or to claim 1. the above-mentioned monosubstituted methylidene 5. A compound according to claim 1 wherein groups may additionally be monoSubstituted by fluo R" denotes hydrogen, fluorine, chlorine, bromine, iodine, rine, C-alkyl, trifluoromethyl or cyano, and C6-alkyl, C2-alkynyl, C2-alkenyl, C-7-cycloalkyl, Cs 7-cycloalkenyl, Calkyloxy, C-7-cycloalkyloxy or a methylene group bound directly to the methylidene cyano, while in cycloalkyl and cycloalkenyl groups one group may be replaced by CO, COO or CONRS, and or two methylene units are replaced independently of in a cycloalkylidene group a methylene group may be one another by O or CO and alkyl, alkenyl and alkynyl replaced by O, S or NRN or an ethylene group may be groups may be partly or totally fluorinated. replaced by -NRN S-CO, -CO-NRS, 6. A compound according to claim 1 wherein -O-CO- or -CO-O-, and R° denotes hydrogen, fluorine, chlorine, bromine, methyl, RN is defined as in claim 1. hydroxy, methoxy, ethoxy, trifluoromethoxy, cyano, 9. A compound according to claim 1 wherein nitro or methyl substituted by 1 to 3 fluorine atoms. 7. A compound according to claim 1 wherein R denotes X denotes hydrogen, cyano, C6-alkyl, C2-alkynyl, hydrogen, fluorine, chlorine, C6-alkyl, C2-alkynyl, C2-6- Co-alkenyl, C-alkylcarbonyl, C-alkoxycarbonyl, alkenyl, Co-cycloalkyl, Co-cycloalkyl-methyl, Cso aminocarbonyl, C-alkylaminocarbonyl, di-(C- cycloalkenyl, Co-cycloalkenyl-methyl, aryl, heteroaryl, alkyl)aminocarbonyl, C-alkylsulphonylamino-C- C-alkylcarbonyl, aminocarbonyl, C-alkylaminocarbo alkyl or C-alkylsulphonyl-C-alkyl, while alkyl nyl, di-(C-alkyl)aminocarbonyl, C-alkoxycarbonyl, groups may be mono- or polyfluorinated or monoSub di-(C-alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl, mor Stituted by chlorine or cyano and X representing alkyl pholina-yl, C-alkylcarbonylamino, C-alkoxy, Co-cy with 2 or more C atoms may comprise a hydroxy clo-alkyloxy, Cso-cycloalkenyloxy, aryloxy, heteroary Substituent. loxy, C-alkylsulphanyl, C-alkylsulphonyl, Co 10. A compound according to claim 1 wherein cycloalkylsulphanyl, Co-cycloalkylsulphonyl, Cs-o- cycloalkenylsulphanyl, Co-cycloalkenylsulphonyl, X denotes C-alkyloxymethyl, C-7-cycloalkyloxym hydroxy or cyano, and ethyl or aryloxymethyl, in the event that R is bound to an Natom, R preferably while by the aryl group is meant a phenyl or naphthyl denotes hydrogen, cyano, C-alkyl, C2-alkynyl, group, preferably a phenyl group, which may be mono Co-alkenyl, C-cycloalkyl, C-cycloalkyl-C- or disubstituted by identical or different groups L., and alkyl, C5-6-cycloalkenyl, C5-6-cycloalkenyl-C-3-alkyl, L is defined according to claim 1. aryl, heteroaryl, aryl-C-alkyl, heteroaryl-C-alkyl, 11. A compound according to claim 1 wherein C-alkylcarbonyl, arylcarbonyl, heteroaryl-carbonyl, C-alkylsulphonyl, arylsulphonyl or heteroarylsul X denotes C-cycloalkylsulphanylmethyl or C-alkyl phonyl, Sulphanylmethyl. US 2006/0035.841 A1 Feb. 16, 2006 32

12. A compound according to claim 1 wherein 20. A method of treating or preventing diseases or con X denotes chloromethyl, bromomethyl, iodomethyl, C ditions which can be influenced by inhibiting the sodium alkylsulphonyloxymethyl, arylsulphonyloxymethyl or dependent glucose cotransporter SGLT said method com aryl-C-alkyl-Sulphonyloxymethyl, prised of the Step of administering to a patient in need while the above-mentioned alkyl groups may be partly or thereof a therapeutically effective amount of a compound wholly fluorinated or mono- or dichlorinated and the according to claim 1. above-mentioned aryl groupS may be mono- or disub 21. A method of treating or preventing metabolic disor stituted by identical or different groups L., while L is derS Said method comprised of the Steps of administering to preferably Selected from among fluorine, chlorine, bro a patient in need thereof a therapeutically effective amount mine, iodine, C-alkyl, difluoromethyl, trifluorom of a compound according to claim 1. ethyl and cyano. 22. The method of claim 21 wherein the metabolic 13. A compound according to claim 1 wherein disorder is Selected from the group consisting of type 1 R", R and R independently of one another represent and/or type 2 diabetes mellitus, complications of diabetes, hydrogen, fluorine or methyl. metabolic acidosis or ketosis, reactive hypoglycaemia, 14. A compound according to claim 1 wherein the groups hyperinsulinaemia, glucose metabolic disorder, insulin R", RandR are joined together, forming a Cas-alkanetriyl resistance, metabolic Syndrome, dyslipidaemias of different bridge, and together with the Cy ring form a tricyclic System origins, atherOSclerosis and related diseases, obesity, high Selected from tricyclononane, tricyclodecane and tricy blood pressure, chronic heart failure, oedema and hyperu cloundecane, particularly preferably adamantane, which is ricaemia. unsubstituted or may be mono- or polyfluorinated or mono or disubstituted by identical or different substituents selected 23. Use of at least one compound according to claim 1 for from chlorine, hydroxy, C-alkoxy and C-alkyl. preparing a pharmaceutical composition for. inhibiting the 15. A compound according to claim 1 wherein Sodium-dependent glucose cotransporter SGLT. 24. A method for preventing the degeneration of pancre Z denotes -O-, -CH-, -CF-, -C(CH), atic cells and/or restoring the functionality of pancreatic beta -CH=, -NRN- or -CO cells Said method comprised of the Steps of administering to 16. A compound according to claim 1 wherein a patient in need thereof a therapeutically effective amount R", R", R' independently of one another represent of a compound according to claim 1. hydrogen, (C6-alkyl)oxycarbonyl, (Cis-alkyl)carbo 25. Use of a pharmaceutical compound according claim 1 nyl or benzoyl, preferably hydrogen. or a physiologically acceptable Salt preparing diuretics and/ 17. Physiologically acceptable Salts of a compound or antihypertensives. according to claim 1 with inorganic or organic acids. 18. Use of a compound according to claim 1 or a 26. A method for preparing a pharmaceutical composition physiologically acceptable Salt thereof as pharmaceutical according to claim 1 Said method comprised of the Steps of compositions. incorporating Said composition in one or more inert carriers 19. A pharmaceutical composition comprised of a com and/or diluents by a non-chemical method. pound according to claim 1 further comprised of one or more inert carriers and/or diluents.