Prodrugs of phosphonate nucleotide analogues

Abstract

A novel method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided.

1 . A nucleotide analog compound according to structure (Ia):  
       
         
           
           
               
               
           
         
       
       and/or a salt and/or solvate thereof, wherein: 
 R 6a  is selected from hydrogen and phenyl;  
 R 6b  is selected from hydrogen, methyl, ethyl and isopropyl; and  
 R 7  is selected from methyl, ethyl and benzyl, and which comprises at least about 60% by weight a diastereomer according to structure (Ib):  
                     
 
     
     
         2 . The nucleotide analog compound, salt and/or solvate of  claim 1  which comprises at least about 80% by weight the diastereomer of structure (Ib).  
     
     
         3 . The nucleotide analog compound, salt and/or solvate of  claim 1  which comprises at least about 95% by weight the diastereomer of structure (Ib).  
     
     
         4 . The nucleotide analog compound, salt and/or solvate of  claim 1  which is substantially free of the diastereomer of structure (Ic):  
       
         
           
           
               
               
           
         
       
     
     
         5 . The nucleotide analog compound, salt and/or solvate of  claim 4  in which R 6a  is hydrogen.  
     
     
         6 . The nucleotide analog compound, salt and/or solvate of  claim 5  in which R 6b  is hydrogen.  
     
     
         7 . The nucleotide analog compound, salt and/or solvate of  claim 4  in which R 6a  is phenyl.  
     
     
         8 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 7  is hydrogen.  
     
     
         9 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 7  is methyl.  
     
     
         10 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 7  is ethyl.  
     
     
         11 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 7  is benzyl.  
     
     
         12 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is methyl.  
     
     
         13 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is ethyl.  
     
     
         14 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is isopropyl.  
     
     
         15 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is methyl and R 7  is methyl.  
     
     
         16 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is methyl and R 7  is benzyl.  
     
     
         17 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is ethyl and R 7  is methyl.  
     
     
         18 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is ethyl and R 7  is hydrogen.  
     
     
         19 . The nucleotide analog compound, salt and/or solvate of  claim 7  in which R 6b  is ethyl and R 7  is ethyl.  
     
     
         20 . The nucleotide analog compound, salt and/or solvate of  claim 1  which is in the form of a salt.