Compounds and pharmaceutical compositions for the treatment of viral infections

1. A compound of the formula:

or a pharmaceutically acceptable salt, a stereoisomeric, or tautomeric form thereof, wherein:

R y is alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkenyl, amino, heterocyclyl or heteroaryl;

R a and R b are selected as follows:

i) R a and R b are each independently hydrogen, alkyl, carboxyalkyl, hydroxyalkyl, hydroxyarylalkyl, acyloxyalkyl, aminocarbonylalkyl, alkoxycarbonylalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl or heterocyclyl; or

ii) R a and R b together with the nitrogen atom on which they are substituted form a 3-7 membered heterocyclic or heteroaryl ring;

A is H, alkyl, alkenyl, alkynyl, azido, carboxylic acid, CO 2 -alkyl, cyano, or carboxamide; and

R L is independently H, carbamyl, alkyl; acyl; CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, a lipid, an amino acid or a carbohydrate.

2. The compound of claim 1 , wherein R L is hydrogen, R y is optionally substituted alkyl and R a and R b are each independently hydrogen, optionally substituted alkyl or optionally substituted benzyl.

3. The compound of claim 1 , wherein R L is hydrogen; R y is hydroxyalkyl, aminoalkyl, hydroxyaryl or aminoaryl; and R a and R b are each independently hydrogen, alkyl, hydroxyalkyl or aminoalkyl.

4. The compound of claim 1 , wherein R L is hydrogen; R y is hydroxyalkyl, aminoalkyl, hydroxyaryl, aminoaryl; and R a and R b are each independently hydrogen, benzyl, hydroxybenzyl or aminobenzyl.

5. The compound of claim 1 , wherein R L is hydrogen, and R a and R b are independently substituted alkyl.

6. The compound of claim 1 , wherein R y is selected from the group consisting of alkyl and hydroxyalkyl.

7. The compound of claim 1 having the formula:

8. The compound of claim 1 having the formula:

wherein R b1 is halo, alkoxy or haloalkyl.

9. The compound of claim 8 having the formula:

10. A compound of the formula:

or a pharmaceutically acceptable salt, a stereoisomeric, or tautomeric form thereof.

11. The compound of claim 1 having the formula:

12. A method for the treatment of a host infected with a Flaviviridae virus or hepatitis B virus, comprising administering an effective treatment amount of a compound of claim 1 or 10 .

13. A method for the treatment of a host infected with a Flaviviridae virus or hepatitis B virus, comprising contacting a cell infected with the virus with a compound of claim 1 or 10 .

14. The method of claim 12 , wherein the virus is hepatitis C.

15. The method of claim 12 , wherein the host is a human.

16. The method of claim 12 , wherein the compound is

or a pharmaceutically acceptable salt or stereoisomer thereof.

17. The method of claim 12 , wherein the compound is

or a pharmaceutically acceptable salt or stereoisomer thereof.

18. The method of claim 12 , wherein said administration directs a substantial amount of said compound or pharmaceutically acceptable salt or stereoisomer thereof to the liver of said host.

19. The method of claim 12 , wherein said compound or pharmaceutically acceptable salt or stereoisomer thereof is administered in combination or alternation with a second anti-viral agent optionally selected from the group consisting of an interferon, ribavirin, an interleukin, a NS3 protease inhibitor, a cysteine protease inhibitor, a phenanthrenequinone, a thiazolidine derivative, a thiazolidine, a benzanilide, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, a gliotoxin, a cerulenin, an antisense phosphorothioate oligodeoxynucleotide, an inhibitor of IRES-dependent translation, and a ribozyme.

20. The method of claim 19 , wherein the second agent is selected from the group consisting of pegylated interferon alpha 2a, interferon alphacon-1, natural interferon, albuferon, interferon beta-1a, omega interferon, interferon alpha, interferon gamma, interferon tau, interferon delta and interferon γ-1b.

21. The method of claim 19 , wherein said compound or pharmaceutically acceptable salt or stereoisomer thereof is administered in combination or alternation with ribavirin.

22. A pharmaceutical composition comprising a compound of claim 1 or 10 and a pharmaceutically acceptable excipient, carrier or diluent.

23. The composition of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt or stereoisomer thereof.

24. The composition of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt or stereoisomer thereof.

25. The composition of claim 23 , wherein the composition is an oral formulation.

26. The composition of claim 24 , wherein the composition is an oral formulation.

27. A compound of the formula:

or a pharmaceutically acceptable salt, a stereoisomeric or tautomeric form thereof, wherein:

R y is alkyl, alkenyl, alkynyl, aryl, aryl alkyl, cycloalkyl, cycloalkenyl, amino, aminoalkyl, hydroxyalkyl, heterocyclyl or heteroaryl, all optionally substituted;

R a and R b are selected as follows:

i) R a and R b are each independently hydrogen, alkyl, carboxyalkyl, hydroxyalkyl, hydroxyarylalkyl, acyloxyalkyl, aminocarbonylalkyl, alkoxycarbonylalkyl, aryl, aryl alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl, all optionally substituted; or

ii) R a and R b together with the nitrogen atom on which they are substituted form a 3-7 membered heterocyclic or heteroaryl ring; and

R L is independently H, carbamyl, alkyl; acyl; CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, a lipid, an amino acid or a carbohydrate.

28. The compound of claim 27 , wherein:

R L is hydrogen;

R y is —OR c , —C(R c ) 3 or —NHR c ;

each R c is independently alkyl, substituted alkyl, aryl or substituted aryl, for instance hydroxy- or amino-substituted alkyl or aryl; and

R a and R b are independently hydrogen, alkyl, substituted alkyl, benzyl or substituted benzyl.

29. The compound of claim 28 , wherein R y is —C(CH 3 ) 2 CH 2 OH.