Antiviral compounds

1. A compound of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein:

Base is

R 1A and R 2A are each independently:

(A) C 1-12 alkyl optionally substituted with 1 to 3 R 1B ,

(B) 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, wherein the 3 to 6 membered heterocyclyl is optionally substituted with 1 to 3 R 1C , or

(C) phenyl, wherein

each R 1B is independently —OH, —NH 2 , C 1-6 alkoxy, methoxyethoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, and

each R 1C is independently C 1-3 alkyl;

R 3 is —N(H)R 3A or —N═C(R 3B )(R 3C );

R 3A is H, —CH 2 OP(O)(OH) 2 , or —C(O)R 3D , wherein

R 3D is C 1-6 alkyl optionally substituted with 1 methoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C 1-3 alkyl;

R 3B is H or C 1-3 alkyl;

R 3C is —N(R 3C1 )(R 3C2 );

R 3C1 and R 3C2 are each independently H or C 1-6 alkyl; or

R 3C1 and R 3C2 together with the atom to which they are attached form a 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C 1-6 alkyl;

R 4A is O or S; and

R 4B and R 4C are each independently

(A) —OH;

(B) —OR 4B1 , wherein

R 4B1 is C 1-6 alkyl optionally substituted with 1 to 3 R 4B2 groups, or C 6-12 aryl, wherein

each R 4B2 group is independently C 1-6 alkoxy, —S—R 4B3 , or —S(O) 2 —R 4B3 , and

each R 4B3 group is independently C 1-6 alkyl;

(C)

 wherein

m is 0, 1, 2, 3, 4, or 5; and

each R 4D is independently C 1-3 alkyl optionally substituted with 1 to 3 R 4D1 groups, C 1-3 alkoxy optionally substituted with 1 to 3 R 4D2 groups, or —C(O)N(R 4D3 ) 2 , wherein

each R 4D1 group is independently —NH 2 or —C(O)OR 4D3 ,

each R 4D2 is independently C 1-3 alkoxy, and

each R 4D3 is independently C 1-3 alkyl;

(D)

 wherein

R 4E1 and R 4E2 are each independently H or C 1-6 alkyl,

R 4F1 and R 4F2 are each independently H or C 1-6 alkyl, or R 4F1 and R 4F2 together are oxo,

R 4G is C 1-12 alkyl optionally substituted with 1 to 3 R 4G1 , C 3-7 cycloalkyl optionally substituted with 1 to 3 R 4G2 , 3 to 8 membered heterocyclyl having 1 to 3 heteroatoms selected from N, O and S, optionally substituted with 1 to 3 R 4G3 , or —C(O)R 4G4 ,

each R 4G1 is independently —OH, C 1-6 alkyl, C 1-3 alkoxy, —(CH 2 OCH 2 ) 1-5 —CH 3 , —N(R 4G8 ) 2 , —OP(O)(OH) 2 , C 3-7 cycloalkyl optionally substituted with 1 to 3 R 4G9 , 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with 1 to 3 R 4G10 , or phenyl,

each R 4G2 is independently C 1-6 alkyl, C 1-3 haloalkyl, or —NH 2 ,

each R 4G3 is independently halogen or C 1-3 alkyl;

each R 4G4 is independently C 1-12 alkyl,

each R 4G8 is independently C 1-6 alkyl,

each R 4G9 is independently C 1-3 haloalkyl, or —NH 2 , and

each R 4G1 ° is independently C 1-3 haloalkyl; or

(E) —(OP(O)(OH)) 1-2 —OH; and

R 5A and R 5B are each C 1-6 alkyl substituted with —OP(O)(OH) 2 .

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1A and R 2A are C 1-12 alkyl optionally substituted with 1 to 3 R 1B .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1A and R 2A are each selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, and isopentyl, each optionally substituted with 1 to 3 R 1B .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein one of R 4B and R 4C is:

and

the other of R 4B and R 4C is:

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4F1 and R 4F2 together are oxo.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is C 1-12 alkyl optionally substituted with 1 to 3 R 4G1 .

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl or 2-ethyl-butyl, each optionally substituted with 1 to 3 R 4G1 .

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is C 3-7 cycloalkyl optionally substituted with 1 to 3 R 4G2 .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, each optionally substituted with 1 to 3 R 4G2 .

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms selected from N, O and S, optionally substituted with 1 to 3 R 4G3 .

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is a 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from N and O, optionally substituted with 1 to 3 R 4G3 .

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is oxetanyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each optionally substituted with 1 to 3 R 4G3 .

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5A and R 5B are each —CH 2 OP(O)(OH) 2 .

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIa):

wherein R 5A is —CH 2 OP(O)(OH) 2 .

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIb):

wherein R 5B is —CH 2 OP(O)(OH) 2 .

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1A and R 2A are each independently

methyl optionally substituted with methoxy, methoxyethoxy, or morpholinyl,

ethyl optionally substituted with methoxy,

n-propyl,

isopropyl,

n-butyl,

isobutyl optionally substituted with —OH or —NH 2 ,

tert-butyl,

isopentyl,

oxetanyl,

tetrahydropyranyl,

piperidinyl optionally substituted with methyl, or

phenyl;

R 3 is —N(H)R 3A or —N═C(R 3B ) (R 3C );

R 3A is H, —C(H) 2 OP(O)(OH) 2 , or —C(O)R 3D ;

R 3D is

methyl,

ethyl optionally substituted with methoxy,

isopropyl, or

piperidinyl optionally substituted with methyl;

R 3B is H or methyl;

R 3C is —N(R 3C1 )(R 3C2 );

R 3C1 and R 3C2 are independently H or methyl; or

R 3C1 and R 3C2 together with the atom to which they are attached form a piperazinyl optionally substituted with methyl;

R 4A is O or S; and

R 4B and R 4C are each independently

(A) —OH;

(B) —O—C 1-6 alkyl optionally substituted with methoxy, methylthio or methyl sulfonyl;

(C)

 wherein

m is 0, 1 or 2; and

each R 4D is independently C 1-3 alkyl optionally substituted with 1 R 4D1 group, C 1-3 alkoxy optionally substituted with methoxy, or —C(O)N(R 4D3 ) 2 wherein

each R 4D1 group is independently —NH 2 or —C(O)OR 4D3 , and

each R 4D3 is independently C 1-3 alkyl; or

(D)

 wherein

R 4E1 and R 4E2 are each independently H or methyl;

R 4F1 and R 4F2 are each independently H or methyl, or R 4F1 and R 4F2 together are oxo;

R 4G is

methyl optionally substituted with R 4G1 ,

ethyl optionally substituted with morpholinyl or —N(C 1-3 alkyl) 2 ,

n-propyl optionally substituted with methoxy or morpholinyl, isopropyl,

n-butyl optionally substituted with C 1-3 alkyl,

isobutyl optionally substituted with —OH or —OP(O)(OH) 2 ,

cyclopropyl,

cyclobutyl,

cyclopentyl,

cyclohexyl optionally substituted with 1 to 3 groups independently —NH 2 , C 1-6 alkyl, or C 1-3 haloalkyl,

oxetanyl,

pyrrolidinyl optionally substituted with 1 to 3 methyl,

piperidinyl optionally substituted with halogen or C 1-3 alkyl,

tetrahydrofuranyl,

tetrahydropyranyl, or

—C(O)C 1-6 alkyl; and

R 4G1 is

cyclopropyl,

cyclobutyl,

cyclohexyl optionally substituted with —NH 2 or C 1-3 haloalkyl,

oxetanyl,

piperidinyl optionally substituted with C 1-3 haloalkyl,

tetrahydropyranyl, or

phenyl.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIc):

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, is represented by Formula (IId):

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIe):

20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIf):

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIg):

wherein m is 0 or 1.

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIh):

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIi):

24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIj):

25. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIk):

26. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIm):

27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, represented by Formula (IIn):

28. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1A and R 2A are each methyl, ethyl, or isopropyl.

29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1A and R 2A are each isopropyl.

30. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl or 2-ethyl-butyl.

31. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4G is methyl.

32. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of

33. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

34. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

35. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

36. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

37. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

38. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

39. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

40. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

41. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

42. The compound of claim 33 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

43. A pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.