PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS

• US 20140045849A1
• Filed: 04/10/2012
• Published: 02/13/2014
• 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, Last, Stefaan Julien, Pieters, Serge Maria Aloysius, Raboisson, Pierr Jeane-Marie Bernar, Embrechts, Werner, Jonckers, Tim Hugo Maria, Vlach, Jaromir
• Granted Patent: US 9,422,250 B2
• Time in Patent Office: Days
• US Class Current: 514/235.8
• 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. A compound of formula (I) according to claim 1 wherein R₃ is butyl or pentyl.

3. A compound of formula (I) according to claim 1 wherein R₃ is C_4-8alkyl substituted with hydroxyl.

4. A compound of formula (I) according to claim 3 wherein R₃, is one of the following

5. A compound of formula (I) according to claim 1 wherein R₁ is hydrogen or —

CH₃.

6. A compound of formula (I) according to claim 1 wherein wherein R₂ is arylalkyl or heteroarylalkyl, substituted with C_1-3alkyl, hydroxyl, alkoxy, nitrile, heterocycle or ester.

7. A compound of formula (I) according to claim 1 wherein R₂ is C_1-3alkyl substituted by aryl, heterocycle, or heteroaryl which is further substituted by C_1-3alkyl, alkoxy, carboxylic ester or carboxylic amide.

8. A compound of formula (I) according to claim 1 wherein R₂ is

9. A compound according to claim 1 having the formula:

10. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt, tautomer(s), solvate or polymorph thereof according claim 1 together with one or more pharmaceutically acceptable excipients, diluents or carriers.

12. A method for the treatment of a disorder or disease in a subject in which the modulation of TLR7 and/or TLR8 is involved, said method comprising administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof according to claim 1.

13. A compound of claim 1 having the formula:

14. A compound of claim 1 having the formula:

15. A compound of claim 1 having the formula:

16. A pharmaceutical composition comprising the compound of claim 13 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

17. A pharmaceutical composition comprising the compound of claim 14 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

18. A pharmaceutical composition comprising the compound of claim 15 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

19. A method for the treatment of a disorder or disease in a subject in which the modulation of TLR7 and/or TLR8 is involved, said method comprising administering to the subject an effective amount of the compound of claim 13 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

20. A method for the treatment of a disorder or disease in a subject in which the modulation of TLR7 and/or TLR8 is involved, said method comprising administering to the subject an effective amount of the compound of claim 14 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

21. A method for the treatment of a disorder or disease in a subject in which the modulation of TLR7 and/or TLR8 is involved, said method comprising administering to the subject an effective amount of the compound of claim 15 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

22. A method for the treatment of viral infections in a subject comprising administering to the subject an effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt, tautomer, solvate or polymorph thereof.

11. (canceled)