Use of 2-alkoxyphenyl-substituted imidazotriazinones

Abstract

The present invention relates to the use of known 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position and cGMP PDE-inhibitory properties for the treatment of cardiac insufficiency, cancer, bladder disorders, or prostate hyperplasia.

1 . A method for the treatment of cardiac insufficiency, cancer, bladder disorders, or prostate hyperplasia, comprising administering to a subject in need thereof an effective amount of one or more 2-phenyl-substituted imidazotriazinones of formula (I)  
       
         
           
           
               
               
           
         
         in which  
         R 1  represents methyl or ethyl,  
         R 2  represents ethyl or propyl,  
         R 3  and R 4  are identical or different and represent a straight-chain or branched alkyl chain having up to 5 carbon atoms, which is optionally up to disubstituted identically or differently by hydroxyl or methoxy,  
         or  
         R 3  and R 4  together with the nitrogen atom form a piperidinyl ring, morpholinyl ring, thiomorpholinyl ring or a radical of the formula  
         
           
             
             
                 
                 
             
           
           in which  
           R 5  denotes hydrogen, formyl, acyl or alkoxycarbonyl in each case having up to 3 carbon atoms, 
 or denotes straight-chain or branched alkyl having up to 3 carbon atoms, which is optionally mono- to disubstituted, identically or differently, by hydroxyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl in each case having up to 3 carbon atoms or by groups of the formula -(D) a NR 6 R 7  or —P(O)(OR 8 )(OR 9 ),  
 in which  
 a denotes a number 0 or 1,  
 D denotes a group of the formula —CO,  
 R 6  and R 7  are identical or different and denote hydrogen or methyl,  
 R 8  and R 9  are identical or different and denote hydrogen, methyl or ethyl,  
 or  
 
         
         R 5  denotes cyclopentyl,  
         and the heterocycles mentioned under R 3  and R 4 , formed together with the nitrogen atom, are optionally mono- to disubstituted, identically or differently, optionally also geminally, by hydroxyl, formyl, carboxyl, acyl or alkoxycarbonyl in each case having up to 3 carbon atoms or groups of the formula —P(O)(OR 10 )(OR 11 ) or —(CO) b NR 12 R 13 ,  
         in which  
         R 10  and R 11  are identical or different and denote hydrogen, methyl or ethyl,  
         b denotes a number 0 or 1,  
         and  
         R 12  and R 13  are identical or different and denote hydrogen or methyl  
         or the heterocycles mentioned under R 3  and R 4 , formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms, which is optionally mono- to disubstituted, identically or differently, by hydroxyl, carboxyl or by a radical of the formula P(O)OR 14 OR 5 ,  
         in which  
         R 14  and R 15  are identical or different and denote hydrogen, methyl or ethyl,  
         or the heterocycles mentioned under R 3  and R 4 , formed together with the nitrogen atom, are optionally substituted by piperidinyl or pyrrolidinyl linked via N,  
         and  
         R 16  represents ethoxy or propoxy,  
         or a salt, hydrate, or solvate thereof.  
       
     
     
         2 . The method according to  claim 1  wherein the compounds are of the general formula (Ia),  
       
         
           
           
               
               
           
         
         where R 1 , R 2 , R 3 , R 4  and R 16  have the meaning indicated in  claim 1 ,  
         or a salt, hydrate, or solvate thereof.  
       
     
     
         3 . The method according to  claim 1  or  2  wherein the 2-phenyl-substituted imidazotriazinones have the following structures:  
       
         
           
                 
               
                     
                 
                     
                 
                   Structure