Prodrugs of fluorinated mevalonates to inhibit the mevalonate pathway of
Fluorinated prodrug compounds as can be used for selective streptococcal mevalonate pathway inhibition.
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.
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.
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, C 1 -C 2 alkoxyalkyl, aryl and arylalkyl moieties.
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 C 1 -C 2 alkoxyalkyl moieties, providing compound is not
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 C 1 -C 2 alkoxyalkyl moieties, providing said compound is not
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.