Pyrimidine prodrugs for the treatment of viral infections and further diseases

Abstract

This invention relates to pyrimidine prodrug derivatives, processes for their preparation, pharmaceutical compositions, and their use in therapy.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate or polymorph thereof, wherein 
         R 1A  is hydrogen or a substituted or unsubstituted C 1-3  alkyl; 
         R 1B  is selected from a substituted or unsubstituted C 1-3  alkyl, heterocycle, or a substituted or unsubstituted phosphoramidate; and 
         R 2  is a C 1-8  alkyl optionally substituted by a hydroxyl group, —OSi(C 1-4  alkyl) 3 , or an organophosphate group. 
       
     
     
         2 . A compound according to  claim 1  wherein R 1B  is a substituted or unsubstituted phosphoramidate and wherein R 2  is a C 1-6  alkyl substituted by a hydroxyl group. 
     
     
         3 . A compound according to  claim 1  wherein R 1A  or R 1B  are methyl and wherein R 2  is a C 6 -alkyl substituted by a hydroxyl group. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . A compound according to  claim 1 , wherein R 1A  and R 1B  are methyl and wherein R 2  is a C 6 -alkyl substituted by a hydroxyl group. 
     
     
         8 . A compound according to  claim 1 , wherein R 2  is a C 1-8  alkyl optionally substituted by a hydroxyl group, —OTBDMS, or —OP(═O)(OEt) 2 . 
     
     
         9 . A compound according to  claim 8 , wherein R 2  is a C 1-8  alkyl optionally substituted by a hydroxyl group or R 2  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt, solvate or polymorph thereof, together with one or more pharmaceutically acceptable excipients, diluents or carriers. 
     
     
         11 . A method for treating a viral infection, comprising administering to a subject in need thereof the compound according to  claim 1  in an effective amount to treat the viral infection. 
     
     
         12 . The method of  claim 11 , wherein the viral infection is a hepatitis B infection. 
     
     
         13 . A method for treating an immune disorder, comprising administering to a subject in need thereof the compound according to  claim 1  in an effective amount to treat the immune disorder. 
     
     
         14 . A method for treating cancer, comprising administering to a subject in need thereof the compound according to  claim 1  in an effective amount to treat the cancer. 
     
     
         15 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         16 . A pharmaceutical composition comprising the compound according to  claim 15 , or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, diluents or carriers. 
     
     
         17 . A method for treating a viral infection, comprising administering to a subject in need thereof the compound according to  claim 15  in an effective amount to treat the viral infection. 
     
     
         18 . The method of  claim 17 , wherein the viral infection is a hepatitis B infection. 
     
     
         19 . A method for treating an immune disorder, comprising administering to a subject in need thereof the compound according to  claim 15  in an effective amount to treat the immune disorder. 
     
     
         20 . A method for treating cancer, comprising administering to a subject in need thereof the compound according to  claim 15  in an effective amount to treat the cancer.