Glucopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture

Abstract

Glucopyranosyl-substituted benzene derivatives of general formula I where the groups R 1 to R 6 as well as R 7a , R 7b , R 7c are defined herein and the tautomers, the stereoisomers thereof, the mixtures thereof and the salts thereof. The compounds according to the invention are suitable for the treatment of metabolic disorders.

1 . Glucopyranosyl-substituted benzene derivatives of general formula I 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is selected from the definitions of the group A and
 if R 3  is selected from the definitions of the group B, R 1  may additionally also be selected from the meanings hydrogen, fluorine, chlorine, bromine, iodine, C 1-4 -alkyl, C 2-4 -alkenyl-C 1-4 -alkyl, C 2-4 -alkynyl-C 1-4 -alkyl, C 2-4 -alkenyl-C 1-4 -alkoxy, C 2-4 -alkynyl-C 1-4 -alkoxy, C 3-7 -cycloalkyl-C 1-4 -alkyl, C 5-7 -cycloalkenyl-C 1-4 -alkyl, a methyl group substituted by 1 to 3 fluorine atoms, an ethyl group substituted by 1 to 5 fluorine atoms, C 1-4 -alkoxy, a methoxy group substituted by 1 to 3 fluorine atoms, an ethoxy group substituted by 1 to 5 fluorine atoms, a C 1-4 -alkyl group substituted by a hydroxy or C 1-3 -alkoxy group, a C 2-4 -alkoxy group substituted by a hydroxy or C 1-3 -alkoxy group, C 3-6 -cycloalkyl-C 1-3 -alkoxy or hydroxy, 
 while in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O or CO, and 
 
 R 2  denotes hydrogen, fluorine, chlorine, bromine, hydroxy, C 1-4 -alkyl, C 1-4 -alkoxy, cyano or nitro, while the alkyl or alkoxy group may be mono- or polysubstituted by fluorine, and 
 R 3  is selected from the definitions of the group B and
 if R 1  is selected from the definitions of the group A, R 3  may additionally also be selected from the meanings hydrogen, fluorine, chlorine, bromine, iodine, C 1-6 -alkyl, C 2-4 -alkenyl-C 1-4 -alkyl, C 2-4 -alkynyl-C 1-4 -alkyl, C 2-4 -alkenyl-C 1-4 -alkoxy, C 2-4 -alkynyl-C 1-4 -alkoxy, C 3-7 -cycloalkyl, C 5-7 -cycloalkenyl, C 3-7 -cycloalkyl-C 1-4 -alkyl, C 6-7 -cycloalkenyl-C 1-4 -alkyl, C 3-6 -cycloalkylidenmethyl, hydroxy, C 1-6 -alkoxy, C 3-6 -cycloalkyl-C 1-3 -alkoxy, aryl, aryl-C 1-3 -alkyl, heteroaryl, heteroaryl-C 1-3 -alkyl, aryloxy, aryl-C 1-3 -alkyl-oxy, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, a C 2-4 -alkyl or C 2-4 -alkoxy group substituted by 1 to 5 fluorine atoms, a C 1-4 -alkyl group substituted by a cyano group, a C 1-4 -alkyl group substituted by a hydroxy or C 1-3 -alkyloxy group, cyano, carboxy, C 1-3 -alkoxycarbonyl, aminocarbonyl, (C 1-3 -alkylamino)carbonyl, di-(C 1-3 -alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-yl-carbonyl, 4-(C 1-3 -alkyl)-piperazin-1-ylcarbonyl, (C 1-4 -alkyl)carbonylamino, C 1-4 -alkyl-sulphonylamino, C 1-4 -alkylsulphanyl, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, arylsulphonylamino, aryl-C 1-3 -alkylsulphonylamino or arylsulphonyl, 
 
 R 4 , R 5  independently of one another denote hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, C 1-3 -alkyl, C 1-3 -alkoxy, methyl or methoxy substituted by 1 to 3 fluorine atoms, 
 A denotes C 2-6 -alkyn-1-yl, C 2-6 -alken-1-yl, C 3-7 -cycloalkyl, C 6-7 -cycloalkenyl, aryl, heteroaryl, C 1-4 -alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C 1-4 -alkylaminocarbonyl, di-(C 1-3 -alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C 1-4 -alkyl)piperazin-1-ylcarbonyl, arylamino-carbonyl, heteroarylaminocarbonyl, C 1-4 -alkoxycarbonyl, aryl-C 1-3 -alkoxycarbonyl, heteroaryl-C 1-3 -alkoxycarbonyl, amino, C 1-4 -alkylamino, di-(C 1-3 -alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C 1-3 -alkyl)piperazin-1-yl, C 1-4 -alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, C 3-7 -cycloalkyloxy, C 5-7 -cycloalkenyloxy, aryloxy, heteroaryloxy, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, C 3-7 -cycloalkylsulphanyl, C 3-7 -cycloalkylsulphinyl, C 3-7 -cycloalkylsulphonyl, C 5-7 -cycloalkenylsulphanyl, C 5-7 -cycloalkenylsulphinyl, C 5-7 -cycloalkenylsulphonyl, arylsulphanyl, arylsulphinyl, arylsulphonyl, heteroarylsulphanyl, heteroarylsulphinyl, heteroarylsulphonyl, cyano or nitro,
 while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and 
 the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1, and 
 the above-mentioned cycloalkyl and cycloalkenylrings independently of one another may be mono- or disubstituted by substituents selected from fluorine and C 1-3 -alkyl, and 
 in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SC 2  or NR N , 
 
 B denotes tri-(C 1-4 -alkyl)silyl-C 1-6 -alkyl, C 2-6 -alkyn-1-yl, C 2-6 -alken-1-yl, amino, C 1-3 -alkylamino, di-(C 1-3 -alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C 1-3 -alkyl)piperazin-1-yl, arylcarbonylamino, heteroarylcarbonylamino, nitro, C 3-10 -cycloalkyloxy, C 5-10 -cycloalkenyloxy, C 3-10 -cycloalkylsulphanyl, C 3-10 -cycloalkylsulphinyl, C 3-10 -cycloalkylsulphonyl, C 5-10 -cycloalkenylsulphanyl, C 5-10 -cycloalkenylsulphinyl, C 5-10 -cycloalkenyl-sulphonyl, arylsulphanyl, arylsulphinyl, heteroarylsulphanyl or heteroarylsulphinyl,
 while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and 
 the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1; 
 while the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C 1-3 -alkyl, and 
 in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SC 2  or NR N , 
 
 R N  denotes H, C 1-4 -alkyl, C 1-4 -alkylcarbonyl or C 1-4 -alkylsulphonyl, 
 L1 independently of one another are selected from among hydroxy, cyano, nitro, C 3-7 -cycloalkyl, aryl, heteroaryl, C 1-4 -alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C 1-4 -alkylaminocarbonyl, di-(C 1-3 -alkyl)-aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, C 1-4 -alkoxycarbonyl, aryl-C 1-3 -alkoxycarbonyl, heteroaryl-C 1-3 -alkoxycarbonyl, C 1-4 -alkyloxy, aryloxy, heteroaryloxy, C 1-4 -alkylsulphanyl, arylsulphanyl, heteroarylsulphanyl, C 1-4 -alkylsulphinyl, arylsulphinyl, heteroarylsulphinyl, C 1-4 -alkylsulphonyl, arylsulphonyl and heteroarylsulphonyl; and 
 L2 independently of one another are selected from among fluorine, chlorine, bromine, iodine, C 1-3 -alkyl, difluoromethyl, trifluoromethyl, C 1-3 -alkoxy, difluoromethoxy, trifluoromethoxy and cyano; and 
 R 6 , R 7a , 
 R 7b , R 7c  independently of one another have a meaning selected from among hydrogen, (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, arylcarbonyl and aryl-(C 1-3 -alkyl)-carbonyl, 
 while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by identical or different groups L2; and 
 by the heteroaryl groups mentioned in the definition of the above groups are meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl, isoquinolinyl or tetrazolyl group, 
 or is meant a pyrrolyl, furanyl, thienyl or pyridyl group, wherein one or two methyne groups are replaced by nitrogen atoms, 
 or is meant an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, wherein one to three methyne groups are replaced by nitrogen atoms, 
 while the above-mentioned heteroaryl groups independently of one another may be mono- or disubstituted by identical or different groups L2; 
 while, unless otherwise stated, the above-mentioned alkyl groups may be straight-chain or branched, 
 the tautomers, the stereoisomers thereof, the mixtures thereof and the salts thereof. 
 
     
     
         2 . Glucopyranosyl-substituted benzene derivatives of general formula I.2 
       
         
           
           
               
               
           
         
         wherein the groups R 1  to R 6  and R 7a , R 7b  and R 7c  are defined as in  claim 1 . 
       
     
     
         3 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group A denotes C 2-6 -alkyn-1-yl, C 2-6 -alken-1-yl, C 3-7 cycloalkyl, C 5-7 -cycloalkenyl, C 1-4 -alkylcarbonyl, aminocarbonyl, C 1-4 -alkylaminocarbonyl, di-(C 1-3 -alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C 1-4 -alkyl)piperazin-1-ylcarbonyl, C 1-4 -alkoxycarbonyl, amino, C 1-4 -alkylamino, di-(C 1-3 -alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C 1-3 -alkyl)piperazin-1-yl, C 1-4 -alkylcarbonylamino, C 3-7 cycloalkyloxy, C 5-7 -cycloalkenyloxy, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, C 3-7 -cycloalkyl-sulphanyl, C 3-7 -cycloalkylsulphinyl, C 3-7 -cycloalkylsulphonyl, C 5-7 -cycloalkenylsulphanyl, C 5-7 -cycloalkenylsulphinyl, C 5-7 -cycloalkenylsulphonyl, cyano or nitro,
 while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and   the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1, and the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C 1-3 -alkyl, and   in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SC 2  or NR N , and   L1 and R N  are defined as in  claim 1 .   
     
     
         4 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group B denotes tri-(C 1-4 -alkyl)silyl-C 1-6 -alkyl, C 2-6 -alkyn-1-yl, C 2-6 -alken-1-yl, amino, C 1-3 -alkylamino, di-(C 1-3 -alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C 1-3 -alkyl)piperazin-1-yl, nitro, C 3-7 -cycloalkyloxy, C 5-7 -cycloalkenyloxy, C 3-7 -cycloalkylsulphanyl, C 3-7 -cycloalkylsulphinyl, C 3-7 -cycloalkylsulphonyl, C 5-7 -cycloalkenylsulphanyl, C 5-7 -cycloalkenylsulphinyl or C 5-7 -cycloalkenylsulphonyl,
 while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and   the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1;   the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C 1-3 -alkyl, and   in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SC 2  or NR N , and   L1 and R N  are defined as in  claim 1 .   
     
     
         5 . Glucopyranosyl-substituted benzene derivatives according to  claim 1  characterised in that the group R 3  is selected from the definitions of the group B according to  claim 1 . 
     
     
         6 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group R 1  is selected from among hydrogen, fluorine, chlorine, bromine, iodine, C 1-4 -alkyl, C 2-6 -alkynyl, C 1-4 -alkoxy, C 2-4 -alkenyl-C 1-4 -alkoxy, C 2-4 -alkynyl-C 1-4 -alkoxy, methyl substituted by 1 to 3 fluorine atoms, ethyl substituted by 1 to 5 fluorine atoms, methoxy substituted by 1 to 3 fluorine atoms, ethoxy substituted by 1 to 5 fluorine atoms, C 1-4 -alkyl substituted by a hydroxy or C 1-3 -alkoxy group, C 2-4 -alkoxy substituted by a hydroxy or C 1-3 -alkoxy group, C 2-6 -alkenyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-3 -alkyl, C 3-7 -cycloalkyloxy, C 3-6 -cycloalkyl-C 1-3 -alkoxy, C 6-7 -cycloalkenyloxy, hydroxy, amino, nitro or cyano, while in the C 6-6 -cycloalkyl groups a methylene group may be replaced by O. 
     
     
         7 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group R 1  is selected from the definitions of the group A according to  claim 1 . 
     
     
         8 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group R 3  is selected from among hydrogen, fluorine, chlorine, bromine, hydroxy, cyano, C 1-6 -alkyl, trimethylsilylethyl, C 2-6 -alkenyl, C 2-6 -alkynyl, difluoromethyl, trifluoromethyl, C 3-7 -cycloalkyl, C 6-7 -cycloalkenyl, C 1-6 -alkyloxy, difluoromethoxy, trifluoromethoxy, pentafluorethoxy, C 3-7 -cycloalkyloxy, tetrahydrofuranyloxy, tetrahydrofuranonyloxy, C 1-6 -alkylsulphanyl, cyclopropylidenemethyl, aryl and heteroaryl. 
     
     
         9 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group R 2  denotes hydrogen, fluorine, chlorine, bromine, methyl, hydroxy, methoxy, ethoxy, trifluoromethoxy, cyano, nitro or methyl substituted by 1 to 3 fluorine atoms. 
     
     
         10 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the groups R 4  and/or R 5  independently of one another represent hydrogen or fluorine. 
     
     
         11 . Glucopyranosyl-substituted benzene derivatives according to  claim 1 , characterised in that the group R 6  denotes hydrogen, (C 1-8 -alkyl)oxycarbonyl, C 1-8 -alkylcarbonyl or benzoyl, preferably hydrogen. 
     
     
         12 . Glucopyranosyl-substituted benzene derivatives according to one or more of  claim 1 , characterised in that the groups R 7a , R 7b , R 7c  represent hydrogen. 
     
     
         13 . Physiologically acceptable salts of the compounds according  claim 1  with inorganic or organic acids. 
     
     
         14 . Pharmaceutical composition, containing a compound according to  claim 1  or a physiologically acceptable salt thereof, optionally together with one or more inert carriers and/or diluents. 
     
     
         15 . Process for preparing a pharmaceutical composition according to  claim 14 , comprised of the step of incorporating one or more inert carriers and/or diluents into said composition by a non-chemical method. 
     
     
         16 . A method of treating treatment diseases or conditions which can be influenced by inhibiting the sodium-dependent glucose cotransporter SGLT said method comprised of the steps of administering to a patient in need thereof an effective compound according to  claim 1  or a physiologically salt thereof. 
     
     
         17 . A method of treating metabolic disorders said method comprised of the steps of administering to a patient in need thereof an effective amount of a compound according to  claim 1 . 
     
     
         18 . The method of  claim 16  wherein the metabolic disorder is selected from the group consisting of type 1 and type 2 diabetes mellitus, complications of diabetes, metabolic acidosis or ketosis, reactive hypoglycaemia, hyperinsulinaemia, glucose metabolic disorder, insulin resistance, metabolic syndrome, dyslipidaemias of different origins, atherosclerosis and related diseases, obesity, high blood pressure, chronic heart failure, edema and hyperuricaemia. 
     
     
         19 . A method of treating a sodium dependent glucose co-transporter SGLT2 said method comprised of the steps of administering to a patient in need thereof an effective amount of a compound according to  claim 1  or a physiologically acceptable salt thereof. 
     
     
         20 . A method of preventing the degeneration of pancreatic beta cells and/or for improving and/or restoring the functionality of pancreatic beta cells said method comprised of the steps of administering to a patient in need thereof an effective amount of a compound according to  claim 1  or a physiologically acceptable salt thereof. 
     
     
         21 . A pharmaceutical composition for use as a diuretic or hypertensive, said composition comprised of a compound according to  claim 1  or a physiological salt thereof. 
     
     
         22 . Process for preparing the compounds of general formula I according to  claim 1 , comprising the step of reacting a compound of general formula II 
       
         
           
           
               
               
           
         
       
       wherein
 R′ denotes H, C 1-4 -alkyl, (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, arylcarbonyl and aryl-(C 1-3 -alkyl)-carbonyl, wherein the alkyl or aryl groups may be mono- or polysubstituted by halogen; 
 R 8a , R 8b , 
 R 8c , R 8d  independently of one another have one of the meanings given for the groups R 6 , R 7a , R 7b , R 7c , denote a benzyl group or a R a R b R c Si group or a R 8b , R 8c , ketal or acetal group, while in each case two adjacent groups R 8a , R 8d  may form a cyclic ketal or acetal group or a 1,2-di(C 1-3 -alkoxy)-1,2-di(C 1-3 -alkyl)-ethylene bridge, while the above-mentioned ethylene bridge forms, together with two oxygen atoms and the two associated carbon atoms of the pyranose ring, a substituted dioxane ring, and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or C 1-3 -alkoxy and benzyl groups may also be substituted by a di-(C 1-3 -alkyl)amino group; and 
 R a , R b , R G  independently of one another denote C 1-4 -alkyl, aryl or aryl-C 1-3 -alkyl, wherein the aryl or alkyl groups may be mono- or polysubstituted by halogen; 
 while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, preferably phenyl groups; 
 and R 1  to R 5  and R 6 , R 7a , R 7b , R 7c  have the meanings given in  claim 1 , 
 with a reducing agent in the presence of a Lewis or Brφnsted acid, while any protective groups present are cleaved simultaneously or subsequently; 
 if desired converting a compound of general formula I thus obtained wherein R 6  denotes a hydrogen atom, is by acylation into a corresponding acyl compound of general formula I, and/or 
 if necessary cleaving any protective group used in the reactions described above 
 if desired a resolving said compound of general formula I thus obtained into its stereoisomers and/or 
 if desired converting a compound of general formula I thus obtained into the salts, particularly for pharmaceutical use into the physiologically acceptable salts thereof. 
 
     
     
         23 . Process for preparing compounds of general formula II 
       
         
           
           
               
               
           
         
       
       wherein
 R′ denotes H, C 1-4 -alkyl, (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, arylcarbonyl and aryl-(C 1-3 -alkyl)-carbonyl, wherein the alkyl or aryl groups may be mono- or polysubstituted by halogen; 
 R 8a , R 8b , 
 R 8c , R 8d  independently of one another have one of the meanings given for the groups R 6 , R 7a , R 7b , R 7c , denote a benzyl group or a R a R b R c Si group or a ketal or acetal group, while in each case two adjacent groups R 8a , R 8b , R 8c , R 8d  may form a cyclic ketal or acetal group or a 1,2-di(C 1-3 -alkoxy)-1,2-di(C 1-3 -alkyl)-ethylene bridge, while the above-mentioned ethylene bridge forms, together with two oxygen atoms and the two associated carbon atoms of the pyranose ring, a substituted dioxane ring, and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or C 1-3 -alkoxy and benzyl groups may also be substituted by a di-(C 1-3 -alkyl)amino group; and 
 R a , R b , R c  independently of one another denote C 1-4 -alkyl, aryl or aryl-C 1-3 -alkyl, wherein the aryl or alkyl groups may be mono- or polysubstituted by halogen; 
 while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, preferably phenyl groups; 
 and R 1  to R 5  and R 6 , R 7a , R 7b , R 7c  have the meanings given in  claims 1 ,
 wherein an organometallic compound (V) which may be obtained by halogen-metal exchange or by the insertion of a metal in the carbon-halogen bond of a halogen-benzylbenzene compound of general formula IV 
 
 
       
         
           
           
               
               
           
         
         
           wherein HaI denotes Cl, Br and I and R 1  to R 5  are as hereinbefore defined, and optionally subsequent transmetallation, is added to a gluconolactone of general formula VI 
         
       
       
         
           
           
               
               
           
         
         
           wherein R 8a , R 8b , R 8c , R 8d  are as hereinbefore defined, 
           and 
           then reacting the adduct obtained with water or an alcohol R′—OH, where R′ denotes optionally substituted C 1-4 -alkyl, in the presence of an acid and optionally the product obtained in the reaction with water wherein R′ denotes H is converted in a subsequent reaction with an acylating agent into the product of formula II wherein R′ denotes (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, arylcarbonyl or aryl-(C 1-3 -alkyl)-carbonyl, which may be substituted as specified. 
         
       
     
     
         24 . Process according to  claim 23 , wherein the organometallic compound (V) is a lithium or magnesium compound. 
     
     
         25 . Process for preparing the compounds of general formula I according to  claim 1 , wherein R 6 , R 7a , R 7b  and R 7c  represent hydrogen, characterised comprised of the steps of hydrolyzing a compound of general formula III 
       
         
           
           
               
               
           
         
       
       wherein
 R 8a , R 8b , 
 R 8c , R 8d  independently of one another have one of the meanings given for the groups R 6 , R 7a , R 7b , R 7c , but at least one of the groups R 8a , R 8b , R 8c , R 8d  does not denote hydrogen, or denotes a benzyl group or a R a R b R c Si group or a ketal or acetal group, while in each case two adjacent groups R 8a , R 8b , R 8c , R 8d  may form a cyclic ketal or acetal group or a 1,2-di(C 1-3 -alkoxy)-1,2-di(C 1-3 -alkyl)-ethylene bridge, while the above-mentioned ethylene bridge forms a substituted dioxane ring together with two oxygen atoms and the associated two carbon atoms of the pyranose ring, and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or C 1-3 -alkoxy and benzyl groups may also be substituted by a di-(Cl 1-3 -alkyl)amino group; and 
 R a , R b , R c  independently of one another represent C 1-4 -alkyl, aryl or aryl-C 1-3 -alkyl, while the alkyl or aryl groups may be mono- or polysubstituted by halogen; 
 while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, preferably phenyl groups; 
 and R 1  to R 5 , R 6 , R 7a , R 7b , R 7c  have the meanings given in  claim 1 , 
 and 
 if desired converting a compound of general formula I thus obtained wherein R 6  denotes a hydrogen atom by acylation into a corresponding acyl compound of general formula I, and/or 
 if necessary cleaving any protective group used in the reactions described above and/or if desired resolving a compound of general formula I thus obtained into its stereoisomers and/or 
 if desired converting a compound of general formula I thus into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts thereof. 
 
     
     
         26 . Compound of general formula IV 
       
         
           
           
               
               
           
         
         wherein HaI denotes chlorine, bromine or iodine and the groups R 1 , R 2 , R 3 , R 4  and R 5  are defined as in  claim 1 . 
       
     
     
         27 . Compound of formula IV according to  claim 26 , characterised by the formula 
       
         
           
           
               
               
           
         
       
       wherein HaI denotes chlorine, bromine or iodine and the groups R 1 , R 2 , R 4  and R 5  are defined according to  claim 1  and the group R 3  is selected from the group B according to  claim 26 . 
     
     
         28 . Compound of general formula II 
       
         
           
           
               
               
           
         
       
       wherein
 R′ denotes H, C 1-4 -alkyl, (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, arylcarbonyl and aryl-(C 1-3 -alkyl)-carbonyl, wherein the alkyl or aryl groups may be mono- or polysubstituted by halogen; 
 R 8a , R 8b , 
 R 8c , R 8d  independently of one another have one of the meanings given for the groups R 6 , R 7a , R 7b , R 7c , or denote a benzyl group or a R a R b R c Si group or a ketal or acetal group, while in each case two adjacent groups R 8a , R 8b , R 8c , R 8d  may forma cyclic ketal or acetal group or a 1,2-di(C 1-3 -alkoxy)-1,2-di(C 1-3 -alkyl)-ethylene bridge, while the above-mentioned ethylene bridge forms, together with two oxygen atoms and the two associated carbon atoms of the pyranose ring, a substituted dioxane ring, and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or C 1-3 -alkoxy and benzyl groups may also be substituted by a di-(C 1-3 -alkyl)amino group; and 
 R a , R b , R c  independently of one another denote C 1-4 -alkyl, aryl or aryl-C 1-3 -alkyl, while the alkyl or aryl groups may be mono- or polysubstituted by halogen; 
 while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, preferably phenyl groups; 
 and R 1  to R 5  are defined as in one or more of  claim 1 .