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 .- 22 . (canceled) 
     
     
         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 Hal 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 . (canceled) 
     
     
         26 . Compound of general formula IV 
       
         
           
           
               
               
           
         
         wherein Hal 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 Hal 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 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, 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 .