Antiviral heterocyclic compounds

1. A compound represented by Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is selected from the group consisting of:

1) optionally substituted aryl; and

2) optionally substituted heteroaryl;

B is O;

R 1 and R 2 are each hydrogen;

Z is hydrogen;

W is

optionally substituted —C 1 -C 6 alkyl;

G is

—C(O)NR 11 R 12 ;

n is 1;

Y is O;

E is optionally substituted aryl;

R 3 is hydroxy or fluorine;

R 4 is selected from the group consisting of

optionally substituted —C 1 -C 6 alkyl and

optionally substituted —C 3 -C 8 cycloalkyl;

R 11 at each occurrence is independently selected from the group consisting of:

1) hydrogen;

2) optionally substituted —C 1 -C 8 -alkyl;

3) optionally substituted —C 3 -C 8 -cycloalkyl;

4) optionally substituted 3- to 8-membered heterocyclic;

5) optionally substituted aryl;

6) optionally substituted arylalkyl;

7) optionally substituted heteroaryl; and

8) optionally substituted heteroarylalkyl; and

R 12 at each occurrence is independently selected from the group consisting of:

1) hydrogen;

2) optionally substituted —C 1 -C 8 -alkyl;

3) optionally substituted —C 3 -C 8 -cycloalkyl;

4) optionally substituted 3- to 8-membered heterocyclic;

5) optionally substituted aryl;

6) optionally substituted arylalkyl;

7) optionally substituted heteroaryl; and

8) optionally substituted heteroarylalkyl;

alternatively, R 11 and R 12 are taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered heterocyclic ring.

2. The compound of claim 1 , wherein G is —C(O)NH 2 .

3. The compound of claim 1 , wherein E is selected from the groups set forth below:

4. The compound of claim 1 , wherein A is selected from the groups set forth below by removal of a hydrogen atom:

wherein each of these groups is optionally substituted.

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

wherein R 21 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; m is 0, 1, 2, 3, 4 or 5; and A, W, R 3 , R 4 , R 11 , and R 12 are as defined in claim 1 .

6. The compound of claim 1 , represented by Formula (X-1), or a pharmaceutically acceptable salt thereof:

wherein R 21 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; m′ is 0, 1 or 2; and A, W, R 11 , and R 12 are as defined in claim 1 .

7. The compound of claim 1 , represented by Formula (X-1a), or a pharmaceutically acceptable salt thereof:

wherein R 21 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; m′ is 0, 1 or 2; and A, W, R 11 , and R 12 are as defined in claim 1 .

8. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

9. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 .

10. The method of claim 9 , further comprising the step of administering to the subject an anti-RSV agent.

11. The method of claim 9 , further comprising administering to the subject a steroid anti-inflammatory compound.

12. A method of treating RSV and influenza in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 and a therapeutically effective amount of an anti-influenza agent.

13. The method of claim 10 , wherein the compound and the anti-RSV agent are co-formulated.

14. The method of claim 10 , wherein the compound and the anti-RSV agent are co-administered.

15. The method of claim 10 , wherein administering the compound allows for administering of the anti-RSV agent at a lower dose or frequency as compared to the administering of the anti-RSV agent alone that is required to achieve similar results in prophylactically treating an RSV infection in a subject in need thereof.

16. A method of treating an HMPV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds of claim 1 .

17. The method of claim 16 , further comprising the step of administering to the subject an anti-HMPV agent.

18. The method of claim 17 , wherein the compound and the anti-HMPV agent are co-formulated.