Phenyl-Substituted Pyrazolopyrimidines

Abstract

The invention relates to novel phenyl-substituted pyrazolopyrimidines, process for their preparation, and their use for producing medicaments for improving perception, concentration, learning and/or memory.

1 . A compound of the formula 
       
         
           
           
               
               
           
         
         in which 
         R 1  is phenyl which is substituted by 1 to 5 substituents independently of one another selected from the group of halogen, C 1 -C 6 -alkyl, trifluoromethyl, trifluoroethoxy, cyano, hydroxy, nitro and C 1 -C 6 -alkoxy, 
         R 2  is pentan-3-yl, C 4 -C 6 -cycloalkyl, 
         X is oxygen or sulfur, 
         and the salts, solvates and/or solvates of the salts thereof. 
       
     
     
         2 . A compound as claimed in  claim 1 , where
 R 1  is phenyl which is substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, chlorine, bromine, C 1 -C 4 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 4 -alkoxy,   R 2  is pentan-3-yl, C 5 -C 6 -cycloalkyl,   X is oxygen or sulfur,   and the salts, solvates and/or solvates of the salts thereof.   
     
     
         3 . A compound as claimed in  claims 1  and  2  of the formula 
       
         
           
           
               
               
           
         
         in which 
         R 3  is hydrogen or chlorine, 
         R 4  is fluorine, chlorine, bromine, methyl, trifluoromethyl, 
         R 2  is pentan-3-yl, cyclopentyl, 
         X is oxygen or sulfur, 
         and the salts, solvates and/or solvates of the salts thereof, 
       
     
     
         4 . A compound as claimed in  claims 1  to  3  of the formula (Ia), where
 R 3  is hydrogen or chlorine, 
 R 4  is fluorine, chlorine, bromine, methyl, trifluoromethyl, 
 R 2  is pentan-3-yl, cyclopentyl, 
 X is oxygen, 
 and the salts, solvates and/or solvates of the salts thereof. 
 
     
     
         5 . A process for preparing compounds as claimed in  claim 1 , characterized in that
 [A] compounds of the formula   
       
         
           
           
               
               
           
         
         
           in which 
           R 2  has the meanings indicated in  claim 1 , 
         
         are converted by reaction with a compound of the formula
   R 1 —CH 2 —C(O)—Z   (IIIa),
 
 in which 
 R 1  has the meanings indicated in  claim 1 , 
 and 
 is chlorine or bromine, 
 initially in the presence of a base into compounds of the formula 
 
       
       
         
           
           
               
               
           
         
         
           in which 
           R 1  and R 2  have the meanings indicated in  claim 1 , 
           then cyclized in the presence of a base t© compounds of the formula 
         
       
       
         
           
           
               
               
           
         
         
           in which 
           R 1  and R 2  have the meanings indicated in  claim 1 , 
         
         or 
         [B] compounds of the formula (II) are reacted with direct cyclization to (Ib) with a compound of the formula
   R 1 —CH 2 —C(O)—OR 5    (IIIb),
 
 in which 
 R 1  has the meanings indicated in  claim 1 , 
 and 
 R 5  is methyl or ethyl, 
 in the presence of a base, 
 
         or 
         [C] compounds of the formula 
       
       
         
           
           
               
               
           
         
         
           in which 
           R 2  has the meanings indicated in  claim 1 , 
           are converted initially by reaction with a compound of the formula (IIIa) in the presence of a base into compounds of the formula 
         
       
       
         
           
           
               
               
           
         
         
           in which 
           R 1  and R 2  have the meanings indicated in  claim 1 , 
           and the latter are cyclized in a second step in the presence of base and of an oxidizing agent to (Ib), 
         
         and the compounds of the formula (Ib) are then converted where appropriate by reaction with a sulfurizing agent such as, for example, diphosphorus pentasulfide into the thiono derivatives of the formula 
       
       
         
           
           
               
               
           
         
         in which 
         R 1  and R 2  have the meanings indicated in  claim 1 , 
         and the resulting compounds of the formula (I) are reacted where appropriate with the appropriate (i) solvents and/or (ii) bases or acids to give the solvates, salts and/or solvates of the salts thereof. 
       
     
     
         6 . A compound as claimed in any of  claims 1  to  4  for the treatment and/or prophylaxis of diseases, 
     
     
         7 . A medicament comprising at least one of the compounds as claimed in any of  claims 1  to  4  and at least one pharmaceutically acceptable, essentially non-toxic carrier or excipient. 
     
     
         8 . The use of the compounds as claimed in any of  claims 1  to  4  for producing a medicament for the prophylaxis and/or treatment of impairments of perception, concentration, learning and/or memory. 
     
     
         9 . The use as claimed in  claim 8 , where the impairment is a consequence of Alzheimer's disease, 
     
     
         10 . The use of the compounds as claimed in any of  claims 1  to  4  for producing a medicament for improving perception, concentration, learning and/or memory. 
     
     
         11 . A method for controlling impairments of perception, concentration, learning and/or memory in humans or animals by administering an effective amount of the compounds from  claims 1  to  4 . 
     
     
         12 . The method as claimed in  claim 11 , where the impairment is a consequence of Alzheimer's disease.