Indolyl-substituted phenylacetic acid derivatives

Abstract

The indolyl-substituted phenylacetic acid derivatives are prepared by reacting the corresponding phenylacetic acids with the required amines. The indolyl-substituted phenylacetic acid derivatives are suitable as active compounds in medicaments, in particular in antiarteriosclerotic medicaments.

1 . Indolyl-substituted phenylacetic acid derivatives of the general formula (I)  
       
         
           
           
               
               
           
         
       
       in which 
 D represents a radical of the formula  
                     
  wherein 
 T denotes a nitrogen atom or the —CH group,  
 R 6 , R 7 , R 10  and R 11  are identical or different and denote hydrogen, trifluoromethyl, halogen or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms,  
 R 5 , R 8  and R 9  are identical or different and denote hydrogen, cycloalkyl having 3 to 6 carbon atoms, phenyl, straight-chain or branched alkoxycarbonyl having up to 6 carbon atoms or straight-chain or branched alkyl having up to 6 carbon atoms, which is optionally substituted by halogen,  
 or, in the case where T represents a nitrogen atom, R 5  can also denote benzyl,  
 
 E and L are identical or different and represent hydrogen, halogen, trifluoromethyl, hydroxyl or carboxyl, or represent straight-chain or branched alkyl, alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms,  
 R 1  represents cycloalkyl having 3 to 10 carbon atoms, or represents straight-chain or branched alkyl having 1 to 10 carbon atoms, or represents phenyl, which is optionally substituted up to twice in an identical or different manner by halogen, cyano, hydroxyl or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,  
 R 2  represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms,  
 R 3  represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or represents cycloalkyl having 3 to 7 carbon atoms, or represents phenyl, or represents a 5- to 7-membered aromatic heterocyclic radical having up to 3 heteroatoms from the series consisting of S, N and/or O, each of which is optionally substituted up to 3 times in an identical or different manner by halogen, nitro, phenyl, hydroxyl or by straight-chain or branched alkyl or alkoxy having up to 6 carbon atoms,  
 R 4  represents hydrogen, or represents a group of the formula —CH 2 —OH or CH 2 O—CO—R 12 ,  
 wherein 
 R 12  denotes hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or phenyl, which is optionally substituted up to 3 times in an identical or different manner by halogen, hydroxyl, cyano or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,  
 
 and salts thereof.  
 
     
     
         2 . Indolyl-substituted phenylacetic acid derivatives of the formula according to  claim 1 , in which 
 D represents a radical of the formula                           wherein 
 T denotes a nitrogen atom or the —CH group,  
 R 6 , R 7 , R 10  and R 11  are identical or different and denote hydrogen, trifluoromethyl, fluorine, chlorine, bromine or straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms,  
 R 5 , R 8  and R 9  are identical or different and denote hydrogen, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms or straight-chain or branched alkyl having up to 5 carbon atoms, which is optionally substituted by fluorine, chlorine or bromine,  
 or, in the case where T represents a nitrogen atom, R 5  can also denote benzyl,  
   E and L are identical or different and represent hydrogen, fluorine, chlorine, bromine, trifluoromethyl, hydroxyl or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,    R 1  represents cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, or represents straight-chain or branched alkyl having up to 7 carbon atoms, or represents phenyl, which is optionally substituted by fluorine, chlorine, bromine, cyano, hydroxyl or straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms,    R 2  denotes hydrogen or methyl,    R 3  represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, cyclopropyl, cyclopentyl or cyclohexyl, or represents phenyl, pyridyl, thienyl or furyl, each of which is optionally substituted up to twice in an identical or different manner by fluorine, chlorine, bromine, phenyl, nitro, hydroxyl or by straight-chain or branched alkyl or alkoxy having up to 4 carbon atoms,    R 4  represents hydrogen, or represents a group of the formula —CH 2 —OH or —CH 2 O—CO—R 12 ,    wherein 
 R 12  denotes hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms or phenyl, which is optionally substituted up to twice in an identical or different manner by fluorine, chlorine, bromine, cyano, hydroxyl or straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms,  
   and salts thereof    
     
     
         3 . Indolyl-substituted phenylacetic acid derivatives of the formula according to  claim 1 , in which 
 D represents a radical of the formula                          wherein 
 T denotes a nitrogen atom or the —CH group,  
 R 6 , R 7 , R 10  and R 11  are identical or different and denote hydrogen, trifluoromethyl, chlorine or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,  
 R 5 , R 8  and R 9  are identical or different and denote hydrogen, cyclopropyl, cyclopentyl, cyclohexyl phenyl, straight-chain or branched alkoxycarbonyl having up to 4 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms, which is optionally substituted by chlorine,  
 or, in the case where T represents a nitrogen atom, R 5  can also denote benzyl,  
   E and L are identical or different and represent hydrogen, fluorine, chlorine, bromine or trifluoromethyl,    R 1  represents cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, or represents straight-chain or branched alkyl having up to 6 carbon atoms, or represents phenyl, which is optionally substituted by fluorine, chlorine, cyano, hydroxyl, methyl or methoxy,    R 2  represents hydrogen or methyl,    R 3  represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, cyclopropyl, cyclopentyl or cyclohexyl, or represents pyridyl, thienyl or phenyl, each of which is optionally substituted up to twice in an identical or different manner by fluorine, chlorine, bromine, nitro, phenyl, hydroxyl or by straight-chain or branched alkyl or alkoxy having up to 3 carbon atoms,    R 4  represents hydrogen, or represents a group of the formula —CH 2 —OH or —CH 2 O—CO—R 12 ,    wherein 
 R 12  denotes hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms or phenyl, which is optionally substituted up to twice in an identical or different manner by fluorine, chlorine, bromine, cyano, hydroxyl, methyl or methoxy,  
   and salts thereof.    
     
     
         4 . Indolyl-substituted phenylacetic acid derivatives according to  claim 1  wherein such compound is 2-(R)- and 2-(S)-2-[4-(2-phenyl-1H-benzimidazol-1-ylmethyl)-phenyl]-2-cyclopentyl-aceticacid (2-(R)-2-phenyl-glycinol)-amide of the formula  
       
         
           
           
               
               
           
         
       
       and salts thereof.  
     
     
         5 . Indolyl-substituted phenylacetic acid derivatives according to  claim 1  wherein such compound is 2-Cycloheptyl-N-(2-hydroxy-1-(R)-phenylethyl)-2-[4-(2,3-dimethylindol-1-yl-methyl)phenyl]acetamide of the fromula  
       
         
           
           
               
               
           
         
       
       and salts thereof.  
     
     
         6 . Indolyl-substituted phenylacetic acid derivatives according to  claim 1  wherein such compound is 2-(R) and 2(S)-cycloheptyl-N-(2-hydroxy-1-(R)-phenylethyl)-2-[4-(2-carboethoxyindol-1-ylmethyl)-phenyl]acetamide of the formula  
       
         
           
           
               
               
           
         
       
       and salts thereof.  
     
     
         7 . Indolyl-substituted phenylacetic acid derivatives according to  claim 1  wherein such compound is 2-(R) and 2(S)-cycloheptyl-N-(2-hydroxy-1-(R)-phenylethyl)-2-[4-(2-phenylindol-1-ylmethyl)-phenyl]acetamide of the formula  
       
         
           
           
               
               
           
         
       
       and salts thereof.  
     
     
         8 . Indolyl-substituted phenylacetic acid derivatives according to  claim 1  wherein such compound is 2-(R) and 2(S)-cyclopentyl-N-(2-hydroxy-1-(R)-phenylethyl)-2-[4-(2,5,7-trimethyl-imidazo[4,5-b]pyridin-3-ylmethyl)-phenyl]of the formula  
       
         
           
           
               
               
           
         
       
       and salts thereof.  
     
     
         9 . A composition for the treatment of arteriosclerosis comprising an amount effective therefore of a compound or salt thereof according to  claim 1  and a pharmacologically acceptable diluent.  
     
     
         10 . The method for treating arteriosclerosis in a patient in need thereof which comprises administering to such patient an amount effective therefor or a salt thereof according to claim  1 .