Pyridone derivatives for the treatment of viral infections and further diseases

• US 10,377,738 B2
• Filed: 05/23/2014
• Issued: 08/13/2019
• Est. Priority Date: 05/24/2013
• Status: Active Grant

• Current Assignee: Janssen Sciences Ireland Unlimited Company (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland Unlimited Company (Johnson & Johnson)
• Inventors: McGowan, David Craig, Raboisson, Pierre Jean-Marie Bernard
• Primary Examiner(s): Pagano, Alexander R
• Assistant Examiner(s): Sackey, Ebenezer O
• Application Number:
  US14/892,701
• Publication Number:
  US 20160108021A1
• Time in Patent Office: 1,908 Days
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

This invention relates to pyridone derivatives, processes for their preparation, phamaceutical compositions, and their use in therapy.

Claims

1. A compound of formula (I)

2. A compound of formula (I) according to claim 1 wherein R₁ is n-butyl and wherein R₂, R₃, R₄, and R₅ are hydrogen.

3. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt, solvate or polymorph thereof, together with one or more pharmaceutically acceptable excipients, diluents or carriers.

4. A method of treating a disorder in which the modulation activating TLR 7 and/or TLR 8 in a cell, comprising contacting said cell with a therapeutically effective amount of at least one compound of claim 1.

5. A method of inducing interferon production in a cell, comprising contacting said cell with a therapeutically effective amount of at least one compound of claim 1.

6. A compound of formula (I) according to claim 1, wherein R₁ is C_4-6alkyl.

7. A compound of formula (I) according to claim 1, wherein R₂, R₃, R₄ and R₅ are each hydrogen.

8. A compound of formula (I) according to claim 1, wherein R₂ and R₃ are each independently hydrogen or CH₃.

9. A compound of formula (I) according to claim 1, wherein R₄ is CF₃ or CH₃.

10. A compound of formula (I) according to claim 1, wherein R₅ is F or hydrogen.

11. A compound of formula (I) according to claim 1, wherein R₁ is C_4-6alkyl;

and R₂, R₃, R₄ and R₅ are each hydrogen.

12. A compound of formula (I) according to claim 1, wherein R₂ is CH₃;

and R₃, R₄ and R₅ are each hydrogen.

13. A compound of formula (I) according to claim 1, wherein R₂, R₄ and R₅ are each hydrogen;

and R₃ is CH₃.

14. A compound of formula (I) according to claim 1, wherein R₂, R₃ and R₅ are each hydrogen;

and R₄ is CF₃ or CH₃.

15. A compound of formula (I) according to claim 1, wherein R₂, R₃ and R₄ are each hydrogen;

and R₅ is F or hydrogen.

16. A compound of formula (I) according to claim 1, wherein R₁ is C_4-6 alkyl;

R₂ is CH₃, and R₃, R₄ and R₅ are each hydrogen.

17. A compound of formula (I) according to claim 1, wherein R₁ is C_4-6 alkyl;

R₂, R₄ and R₅ are each hydrogen; and

R₃ is CH₃.

18. A compound of formula (I) according to claim 1, wherein R₁ is C_4-6 alkyl;

R₂, R₃ and R₅ are each hydrogen; and

R₄ is CF₃ or CH₃.

19. A compound of formula (I) according to claim 1, wherein R₁ is C_4-6 alkyl;

R₂, R₃ and R₄ are each hydrogen; and

R₅ is F or hydrogen.

20. A compound of formula (I) according to claim 1, wherein R₁ is selected from the group consisting of n-butyl, n-pentyl and n-hexyl.

21. A compound of formula (I) according to claim 1, wherein R₁ is n-butyl, and R₂ is CH₃, and R₃, R₄ and R₅ are each hydrogen.

22. A compound of formula (I) according to claim 1, wherein R₁ is n-butyl;

R₂, R₄ and R₅ are each hydrogen; and

R₃ is CH₃.

23. A compound of formula (I) according to claim 1, wherein R₁ is n-butyl;

R₂, R₃ and R₅ are each hydrogen; and

R₄ is CF₃ or CH₃.

24. A compound of formula (I) according to claim 1, wherein R₁ is n-butyl;

R₂, R₃ and R₄ are each hydrogen; and

R₅ is F or hydrogen.

25. A compound according to claim 1, wherein said compound is selected from the group consisting of

26. A method of activating TLR 7 and/or TLR 8 in a cell, comprising contacting said cell with a therapeutically effective amount of at least one compound as claimed in claim 25.

27. A method of inducing interferon production in a cell, comprising contacting said cell with a therapeutically effective amount of at least one compound as claimed in claim 25.

28. The method of claim 4, wherein the cell is in a human subject.

29. The method of claim 5, wherein the cell is in a human subject.

30. The method of claim 26, wherein the cell is in a human subject.

31. The method of claim 27, wherein the cell is in a human subject.

32. A method of preparing a compound of formula (I), said method comprising reacting a compound of formula A

33. The method of claim 32, wherein the compound of formula B is reduced to form a compound of formula C