Imidazo (4,5-B) pyridine-derivatives as inducible no-synthase inhibitors

Abstract

The compounds of formula (I) in which R1, R2, R3, R4 and R11 have the meanings as given in the description are novel effective iNOS inhibitors.

1 - 11 . (canceled)  
     
     
         12 . A method for treating a chronic inflammatory disease of peripheral organs and the central nervous system (CNS) in a patient comprising administering to said patient a therapeutically effective amount of a compound of formula I  
       
         
           
           
               
               
           
         
       
       in which 
 R1 is hydrogen or 1-4C-alkyl,  
 R2 is hydrogen, halogen, hydroxyl, nitro, amino, 1-7C-alkyl, trifluoromethyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy, 1-4C-alkoxycarbonyl, mono- or di-1-4C-alkylaminocarbonyl, mono- or di-1-4C-alkylaminosulfonyl, 1-4C-alkylcarbonylamino, 1-4C-alkylsulfonylamino, phenyl, R21- and/or R211-substituted phenyl, phenyl-1-4C-alkyl, phenyl-1-4C-alkyl wherein the phenyl moiety is substituted by R22, phenyl-1-4C-alkoxy, pyridyl, pyridyl substituted by R23, pyridyl-1-4C-alkyl, or pyridyl-1-4C-alkyl wherein the pyridyl moiety is substituted by R24, in which  
 R21 is cyano, halogen, carboxyl, 1-4C-alkyl, 1-4C-alkoxy, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminosulfonyl, mono- or di-1-4C-alkylaminosulfonyl, amino, mono- or di-1-4C-alkylamino, trifluoromethyl, hydroxyl, phenylsulfonylamino or phenyl-1-4C-alkoxy,  
 R211 is halogen or 1-4C-alkoxy,  
 R22 is halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R23 is halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R24 is halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R3 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R4 is 1-4C-alkyl,  
 R11 is 1-4C-alkyl,  
 or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.  
 
     
     
         13 . The method according to  claim 12 , wherein 
 R1 is hydrogen or 1-4C-alkyl,    R2 is hydrogen,    R3 is hydrogen,    R4 is methyl,    R11 is 1-4C-alkyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         14 . The method according to  claim 12 , wherein 
 R1 is hydrogen,    R2 is hydrogen,    R3 is hydrogen,    R4 is methyl, and    R11 is methyl or ethyl,    or    R1 is methyl,    R2 is hydrogen,    R3 is hydrogen,    R4 is methyl, and    R11 is methyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         15 . The method according to  claim 12 , wherein 
 R4 is methyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         16 . The method according to  claim 12 , wherein 
 R1 is hydrogen, R4 is methyl and R11 is methyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         17 . A method for treating an acute inflammatory disease in a patient comprising administering to said patient a therapeutically effective amount of a compound of formula I  
       
         
           
           
               
               
           
         
       
       in which 
 R1 is hydrogen or 1-4C-alkyl,  
 R2 is hydrogen, halogen, hydroxyl, nitro, amino, 1-7C-alkyl, trifluoromethyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy, 1-4C-alkoxycarbonyl, mono- or di-1-4C-alkylaminocarbonyl, mono- or di-1-4C-alkylaminosulfonyl, 1-4C-alkylcarbonylamino, 1-4C-alkylsulfonylamino, phenyl, R21- and/or R211-substituted phenyl, phenyl-1-4C-alkyl, phenyl-1-4C-alkyl wherein the phenyl moiety is substituted by R22, phenyl-1-4C-alkoxy, pyridyl, pyridyl substituted by R23, pyridyl-1-4C-alkyl, or pyridyl-1-4C-alkyl wherein the pyridyl moiety is substituted by R24, in which  
 R21 is cyano, halogen, carboxyl, 1-4C-alkyl, 1-4C-alkoxy, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminosulfonyl, mono- or di-1-4C-alkylaminosulfonyl, amino, mono- or di-1-4C-alkylamino, trifluoromethyl, hydroxyl, phenylsulfonylamino or phenyl-1-4C-alkoxy,  
 R211 is halogen or 1-4C-alkoxy,  
 R22 is halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R23 is halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R24 is halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R3 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy,  
 R4 is 1-4C-alkyl,  
 R11 is 1-4C-alkyl,  
 or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.  
 
     
     
         18 . The method according to  claim 17 , wherein 
 R1 is hydrogen or 1-4C-alkyl,    R2 is hydrogen,    R3 is hydrogen,    R4 is methyl,    R11 is 1-4C-alkyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         19 . The method according to  claim 17 , wherein 
 R1 is hydrogen,    R2 is hydrogen,    R3 is hydrogen,    R4 is methyl, and    R11 is methyl or ethyl,    or    R1 is methyl,    R2 is hydrogen,    R3 is hydrogen,    R4 is methyl, and    R11 is methyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         20 . The method according to  claim 17 , wherein 
 R4 is methyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.    
     
     
         21 . The method according to  claim 17 , wherein 
 R1 is hydrogen, R4 is methyl and R11 is methyl,    or a pharmaceutically acceptable salt, N-oxide or a salt of an N-oxide thereof.