Pyridyl reverse sulfonamides for HBV treatment

Patent metadata

Field	Value
Publication number	US-10428041-B2
Application number	US-201816191199-A
Country	US
Kind code	B2
Filing date	Nov 14, 2018
Priority date	Dec 30, 2014
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.

First claim

The invention claimed is:

1. A compound of Formula III:

or a pharmaceutically acceptable salt thereof;

wherein
ring A is heteroaryl;
two of G 1-4 are N and two of G 1-4 are CH;
each R 1 is independently selected from H and halo;
R 3 is halo; and
R 4 is C 3-7 -cycloalkyl.

2. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

3. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, further comprising at least one pharmaceutically acceptable carrier.

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

5. The method of claim 4 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of an HBV vaccine, HBV polymerase inhibitor, interferon, pegylated 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.

6. The method of claim 5 , wherein the pegylated interferon is pegylated interferon alpha (IFN-α), pegylated interferon lambda (IFN-λ), or pegylated interferon gamma (IFN-γ).

7. The method of claim 5 , 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.

8. The method of claim 5 , 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).

9. A composition comprising a compound according to claim 2 , or a pharmaceutically acceptable salt thereof, further comprising at least one pharmaceutically acceptable carrier.

10. A method of treating an HBV infection in an individual having an HBV infection, comprising administering to the individual a therapeutically effective amount of a compound according to claim 2 .

11. The method of claim 10 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of an HBV vaccine, HBV polymerase inhibitor, interferon, pegylated 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.

12. The method of claim 11 , wherein the pegylated interferon is pegylated interferon alpha (IFN-α), pegylated interferon lambda (IFN-λ), or pegylated interferon gamma (IFN-γ).

13. The method of claim 11 , 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.

14. The method of claim 11 , 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).

15. The compound of claim 1 , wherein ring A is selected from the group consisting of:

16. The compound of claim 1 , wherein R 3 is fluoro.

17. The compound of claim 16 , wherein each R 1 is independently selected from H and chloro.

18. The compound of claim 16 , wherein each R 1 is independently selected from H and fluoro.

19. The compound of claim 1 , wherein R 4 is cyclopropyl.

20. The compound of claim 1 , wherein R 4 is cyclohexyl.

Assignees

• Novira Therapeutics Inc

Inventors

• Clark Ryan C
• Truong Yen
• Stock Nicholas
• Jacintho Jason

Classifications

• C07D333/26 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D231/18

  One oxygen or sulfur atom · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D213/81

  Amides; Imides · CPC title