Prodrugs of Fluorinated Mevalonates to Inhibit the Mevalonate Pathway of Streptococcus pneumoniae

Abstract

Fluorinated prodrug compounds as can be used for selective streptococcal mevalonate pathway inhibition.

We claim: 
     
         1 . A compound of a formula 
       
         
           
           
               
               
           
         
         wherein X is selected from NH, O and S; R 1  is selected from mono- and polyfluoro-substituted methyl moieties; and R 2  is selected from alkyl, mono- and polyfluoro-substituted alkyl, alkanoyloxy, cycloalkyl, mono- and polyfluoro-substituted cycloalkyl, aryl, mono- and polyfluoro-substituted aryl, arylalkyl, and mono- and polyfluoro-substituted arylalkyl moieties; and hydrates and solvates thereof. 
       
     
     
         2 . The compound of  claim 1  wherein X is selected from NH and O; and R 1  is selected from fluoromethyl and trifluoromethyl moieties. 
     
     
         3 . The compound of  claim 2  wherein R 2  is selected from mono- and polyfluoro-substituted arylalkyl moieties. 
     
     
         4 . The compound of  claim 3  wherein R 2  is selected from mono- and difluoro-substituted benzyl moieties. 
     
     
         5 . The compound of  claim 1  in at least one of human plasma and contact with an enzyme in a streptococcal mevalonate biosynthetic pathway. 
     
     
         6 . A compound of a formula 
       
         
           
           
               
               
           
         
         wherein X is selected from NH, O and S; R 1  is selected from mono- and polyfluoro-substituted methyl moieties; and R 2  is selected from alkyl, mono- and polyfluoro-substituted alkyl, aryl, mono- and polyfluoro-substituted aryl, arylalkyl, and mono- and polyfluoro-substituted arylalkyl moieties; and hydrates and solvates thereof. 
       
     
     
         7 . The compound of  claim 6  wherein X is selected from NH and O; and R 1  is selected from fluoromethyl and trifluoromethyl moieties. 
     
     
         8 . The compound of  claim 7  wherein R 2  is selected from aryl, mono- and polyfluoroaryl, arylalkyl, mono- and polyfluoroarylalkyl moieties. 
     
     
         9 . The compound of  claim 8  wherein R 2  is selected from phenyl, mono- and polyfluorophenyl, benzyl, monofluorobenzyl and polyfluorobenzyl moieties. 
     
     
         10 . A compound of a formula 
       
         
           
           
               
               
           
         
         wherein X is selected from NH, O and S; R 1  is selected from mono- and polyfluoro-substituted methyl moieties; and R 2  is selected from alkyl, mono- and polyfluoro-substituted alkyl, aryl, mono- and polyfluoro-substituted aryl, arylalkyl, mono- and polyfluoro-substituted arylalkyl moieties; and R 3  and R 4  are independently selected from H, alkyl, alkoxyalkyl, aryl and arylalkyl moieties; and hydrates and solvates thereof. 
       
     
     
         11 . The compound of  claim 10  wherein X is selected from NH and O; and R 1  is independently selected from fluoromethyl and trifluoromethyl moieties. 
     
     
         12 . The compound of  claim 11  where R 2  is selected from arylalkyl, mono- and polyfluoro-substituted arylalkyl moieties. 
     
     
         13 . The compound of  claim 10  wherein R 3  and R 4  are independently selected from H and alkyl moieties. 
     
     
         14 . The compound of  claim 13  wherein at least one of R 3  and R 4  is methyl. 
     
     
         15 . A compound of a formula 
       
         
           
           
               
               
           
         
         wherein X is selected from NH, O and S; R 1  is selected from mono- and polyfluoro-substituted methyl moieties; R 2  is selected from alkyl, mono- and polyfluoro-substituted alkyl, aryl, mono- and polyfluoro-substituted aryl, arylalkyl, mono- and polyfluoro-substituted arylalkyl moieties; and R 3  and R 4  are independently selected from H, acetyl, propionyl and alkoxyalkyl moieties; and hydrates and solvates thereof. 
       
     
     
         16 . The compound of  claim 15  wherein X is selected from NH and O; and R 1  is selected from fluoromethyl and trifluoromethyl moieties. 
     
     
         17 . The compound of  claim 16  wherein R 2  is selected from alkyl, mono- and polyfluoro-substituted alkyl, aryl, mono- and polyfluoro-substituted aryl, arylalkyl, mono- and polyfluoro-substituted arylalkyl moieties. 
     
     
         18 . The compound of  claim 15  wherein X is O; R 2  is selected from alkyl, aryl and arylalkyl moieties; and R 3  and R 4  are independently selected from H and acetyl moieties. 
     
     
         19 . The compound of  claim 18  wherein at least one of R 3  and R 4  is acetyl. 
     
     
         20 . A compound of a formula 
       
         
           
           
               
               
           
         
         wherein R 1  is selected from mono- and polyfluoro-substituted methyl moieties; and R 2  is selected from acetyl, propionyl and alkoxyalkyl moieties; and hydrates and solvates thereof. 
       
     
     
         21 . The compound of  claim 20  wherein R 1  is selected from fluoromethyl and trifluoromethyl moieties. 
     
     
         22 . The compound of  claim 21  wherein R 2  is selected from acetyl and propionyl moieties. 
     
     
         23 . The compound of  claim 22  wherein R 2  is acetyl.