Use of N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds for treating hepatitis virus infections

Abstract

Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immuno-stimulating agents.

1 - 84 . (canceled)  
     
     
         85 . A pharmaceutical composition, consisting essentially of an antiviral effective amount of at least one N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound of Formula I or a pharmaceutically acceptable salt thereof:  
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of straight chain alkyl having a chain length of C 7  to C 20 , branched chain alkyl having a chain length of C 3  to C 20  in the main chain, alkoxyalkyl, arylalkyl, and cycloalkylalkyl, and  
         wherein W, X, Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aroyl, and trifluoroalkanoyl; and  
         a pharmaceutically acceptable carrier, diluent, or excipient.  
       
     
     
         86 . The pharmaceutical composition of  claim 85 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y and Z are each hydrogen.  
     
     
         87 . The pharmaceutical composition of  claim 86 , wherein R is nonyl.  
     
     
         88 . The pharmaceutical composition of  claim 85 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y, and Z are each alkanoyl.  
     
     
         89 . The pharmaceutical composition of  claim 88 , wherein R is nonyl.  
     
     
         90 . The pharmaceutical composition of  claim 89 , wherein said alkanoyl is butanoyl.  
     
     
         91 - 92 . (canceled)  
     
     
         93 . A pharmaceutical composition, comprising an antiviral effective amount of at least one N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound of Formula I or a pharmaceutically acceptable salt thereof:  
       
         
           
           
               
               
           
         
         substantially free of a nucleoside, nucleotide, immunomodulator, or immunostimulant,  
         wherein R is selected from the group consisting of straight chain alkyl having a chain length of C 7  to C 20 , branched chain alkyl having a chain length of C 3  to C 20  in the main chain, alkoxyalkyl, arylalkyl, and cycloalkylalkyl, and  
         wherein W, X, Y, and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aroyl, and trifluoroalkanoyl; and  
         a pharmaceutically acceptable carrier, diluent, or excipient.  
       
     
     
         94 . The pharmaceutical composition of  claim 93 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y, and Z are each hydrogen.  
     
     
         95 . The pharmaceutical composition of  claim 93 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y, and Z are each alkanoyl.  
     
     
         96 . The pharmaceutical composition of  claim 93 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y, and Z are each alkanoyl.  
     
     
         97 . The pharmaceutical composition of  claim 96 , wherein R is nonyl.  
     
     
         98 . The pharmaceutical composition of  claim 97 , wherein said alkanoyl is butanoyl.  
     
     
         99 - 136 . (canceled)  
     
     
         137 . A salt, comprising an N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound of Formula I:  
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of straight chain alkyl having a chain length of C 7  to C 20 , branched chain alkyl having a chain length of C 3  to C 20  in the main chain, alkoxyalkyl, arylalkyl, and cycloalkylalkyl, and  
         wherein W, X, Y, and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aroyl, and trifluoroalkanoyl; and  
         a compound selected from the group consisting of a nucleoside having an acidic moiety and a nucleotide.  
       
     
     
         138 . The salt of  claim 137 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y, and Z are each hydrogen.  
     
     
         139 . The salt of  claim 138 , wherein R is nonyl.  
     
     
         140 . The salt of  claim 137 , wherein R is straight chain alkyl having a chain length of C 7  to C 20 , and W, X, Y, and Z are each alkanoyl.  
     
     
         141 . The salt of  claim 140 , wherein R is nonyl.  
     
     
         142 . The salt of  claim 141 , wherein said alkanoyl is butanoyl.  
     
     
         143 - 147 . (canceled)  
     
     
         148 . A method, comprising reacting N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol and (−)-2′-deoxy-3′-thiocytidine-5′-triphosphate under salt-forming conditions.  
     
     
         149 . A salt formed by the method of  claim 148.