Hepatitis B antiviral agents

1. A compound of Formula V:

or a pharmaceutically acceptable salt thereof;

wherein

R 4 is H or C 1 -C 6 alkyl;

G 1 is H or C 1 -C 6 alkyl;

each R 5 is independently selected at each occurrence from the group consisting of OH, C 1 -C 6 alkyl, halo, —CN, —NO 2 , C 1 -C 6 chloroalkyl, —C 1 -C 6 dichloroalkyl, —C 1 -C 6 trichloroalkyl, —C 1 -C 6 fluoroalkyl, —C 1 -C 6 difluoroalkyl and —C 1 -C 6 trifluoroalkyl;

R 2 is independently selected at each occurrence from the group consisting of halo, —OH, —CN, —NO 2 , —C 1 -C 6 alkyl, —C 1 -C 6 alkoxy, —C 1 -C 6 fluoroalkyl, —C 1 -C 6 heteroalkyl, and C(O)—C 1 -C 6 alkyl;

n is 1, 2, 3, 4, 5, or 6;

x is selected from the group consisting of 0, 1, 2, 3 and 4; and

y is selected from the group consisting of 1, 2, and 3.

2. The compound of claim 1 , wherein

each R 5 is independently selected at each occurrence from the group consisting of —OH, C 1 -C 6 alkyl, halo, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, and trichloromethyl;

R 2 is independently selected at each occurrence from the group consisting of —OH, halo, —CN, —NO 2 , —C 1 -C 6 alkyl, —C 1 -C 6 alkoxy, —C 1 -C 6 fluoroalkyl, —C 1 -C 6 heteroalkyl, and C(O)—C 1 -C 6 alkyl.

3. The compound of claim 1 , wherein

each R 5 is independently selected at each occurrence from the group consisting of —OH, C 1 -C 6 alkyl, halo, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, and trichloromethyl; and

each R 2 is independently selected at each occurrence from the group consisting of halo, —C 1 -C 6 alkyl, or —C 1 -C 6 alkoxy.

4. A composition comprising a compound according to claim 1 , or a salt, solvate or N-oxide thereof.

5. The composition of claim 4 , wherein the composition is pharmaceutical and further comprises at least one pharmaceutically acceptable carrier.

6. A method of treating an HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a compound according to claim 1 .

7. The method of claim 6 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, BAY 41-4109, reverse transcriptase inhibitor, a TLR-agonist, AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide), and AT-130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide), and a combination thereof.

8. The method of claim 7 , wherein the reverse transcriptase inhibitor is at least one of Zidovudine, Didanosine, Zalcitabine, ddA, Stavudine, Lamivudine, Abacavir, Emtricitabine, Entecavir, Apricitabine, Atevirapine, ribavirin, acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir, Tenofovir, Adefovir, cidofovir, Efavirenz, Nevirapine, Delavirdine, or Etravirine.

9. The method of claim 7 , wherein the TLR-agonist is selected from the group consisting of SM360320 (9-benzyl-8-hydroxy-2-(2-methoxy-ethoxy)adenine) and AZD 8848 (methyl [3-({[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl][3-(4-morpholinyl)propyl]amino}methyl)phenyl]acetate).

10. The method of claim 7 , wherein the compound and the at least one additional therapeutic agent are co-formulated.

11. The method of claim 7 , wherein the compound and the at least one additional therapeutic agent are co-administered.

12. The method of claim 7 , wherein before administering the therapeutically effective amount of the compound of formula (I) the individual is known to be refractory to a compound selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, HAP-1, BAY 41-4109, (E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide, and (E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide, and combination thereof.

13. The method of claim 7 , wherein the administering of the compound reduces viral load in the individual to a greater extent compared to the administering of a compound selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, HAP-1, BAY 41-4109, (E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide, and (E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide, and combination thereof.

14. The method of claim 7 , wherein the administering of the compound causes a lower incidence of viral mutation and/or viral resistance than the administering of a compound selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, HAP-1, BAY 41-4109, (E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide, and (E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide, and combination thereof.

15. The compound of claim 3 , wherein

R 4 is H;

each R 5 is independently selected at each occurrence from the group consisting of —OH, halo, fluoromethyl, difluoromethyl, and trifluoromethyl; and

each R 2 is independently selected at each occurrence from halo.

16. The compound of claim 1 , wherein the compound of Formula V is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 , wherein the compound of Formula V is

or a pharmaceutically acceptable salt thereof.

18. A compound having the formula

or a pharmaceutically acceptable salt thereof.