Pyrimidine derivatives for the treatment of viral infections

• US 10,420,767 B2
• Filed: 01/10/2018
• Issued: 09/24/2019
• Est. Priority Date: 04/08/2011
• Status: Active Grant

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Inventors: McGowan, David, Raboisson, Pierre Jean-Marie Bernard, Embrechts, Werner, Jonckers, Tim Hugo Maria, Last, Stefaan Julien, Pieters, Serge Maria Aloysius, Vlach, Jaromir
• Primary Examiner(s): Pagano, Alexander R
• Assistant Examiner(s): Sackey, Ebenezer O
• Application Number:
  US15/867,041
• Publication Number:
  US 20180207155A1
• Time in Patent Office: 622 Days
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07D 239/48 Two nitrogen atoms
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

This invention relates to pyrimidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections such as HCV or HBV.

Claims

1. A compound of formula (I)

2. The compound of claim 1, wherein R₁ is hydrogen.

3. The compound of claim 1, wherein R₂ is C_1-8alkyl.

4. The compound of claim 3, wherein R₂ is substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, amino, C_1-6alkyl, di-(C_1-6)alkylamino, C_1-6alkylamino, C_1-6alkyl, C_1-6alkoxy, C_3-6cycloalkyl, carboxylic acid, carboxylic ester, carboxylic amide, heterocycle, aryl, alkenyl, alkynyl, arylalkyl, heteroaryl, heteroarylalkyl and nitrile.

5. The compound of claim 1, wherein R₂ is C_1-3alkyl substituted with at least one substituent selected from the group consisting of an aryl, heterocycle and heteroaryl.

6. The compound of claim 5, wherein the aryl, heterocycle or heteroaryl is further substituted with at least one of the subsitutents selected from the group consisting of C_1-3alkyl, alkoxy, carboxylic ester and carboxylic amide.

7. The compound of claim 1, wherein R₂ is arylalkyl or heteroarylalkyl.

8. The compound of claim 7, wherein R₂ substituted with at least one of the substitutents selected from the group consisting of C_1-3alkyl, hydroxyl, alkoxy, nitrile, heterocycle or ester.

9. The compound of claim 7, wherein R₂ is selected from the group consisting of

10. The compound of claim 1, wherein R₃ is selected from the group consisting of

11. The compound of claim 1, wherein

R₁ is hydrogen;

and

R₂ is C_1-8alkyl.

12. The compound of claim 1, wherein the compound is selected from the group consisting of

13. The compound of claim 1, wherein the compound is selected from the group consisting of

14. The compound of claim 1, wherein the compound is selected from the group consisting of

15. A pharmaceutical composition comprising a compound of claim 1 and at least one of pharmaceutically acceptable excipient.

16. A method of treating a condition susceptible to activation of human TLR7 and/or TLR8 in a subject comprising administering a therapeutically effective amount of a compound of claim 1 to said subject.

17. The method of claim 16, wherein the condition is a viral infection.

18. A method of inducing interferon to treat a viral infection in a subject comprising administering a therapeutically effective amount of a compound of claim 1 to said subject.