Pyrimidine derivatives for the treatment of viral infections

Patent metadata

Field	Value
Publication number	US-10420767-B2
Application number	US-201815867041-A
Country	US
Kind code	B2
Filing date	Jan 10, 2018
Priority date	Apr 8, 2011
Publication date	Sep 24, 2019
Grant date	Sep 24, 2019

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.

First claim

The invention claimed is:

1. A compound of formula (I)

or a pharmaceutically acceptable salt, tautomer(s), solvate or polymorph thereof, wherein
R 1 is selected from the group consisting of hydrogen, C 1-4 alkyl, cyclopropyl, C 1-6 alkoxy, halogen, hydroxyl and trifluoromethyl;
R 2 is selected from the group consisting of C 1-8 alkyl, (C 1-4 )alkoxy-(C 1-4 )alkyl, C 3-7 cycloalkyl, C 4-7 heterocycle, aromatic, bicyclic heterocycle, arylalkyl, heteroaryl and heteroarylalkyl; and
R 3 is C 4-8 alkyl substituted with hydroxyl.

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

3. The compound of claim 1 , wherein R 2 is C 1-8 alkyl.

4. The compound of claim 3 , wherein R 2 is substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, amino, C 1-6 alkyl, di-(C 1-6 )alkylamino, C 1-6 alkylamino, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, carboxylic acid, carboxylic ester, carboxylic amide, heterocycle, aryl, alkenyl, alkynyl, arylalkyl, heteroaryl, heteroarylalkyl and nitrile.

5. The compound of claim 1 , wherein R 2 is C 1-3 alkyl 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 1-3 alkyl, alkoxy, carboxylic ester and carboxylic amide.

7. The compound of claim 1 , wherein R 2 is arylalkyl or heteroarylalkyl.

8. The compound of claim 7 , wherein R 2 substituted with at least one of the substitutents selected from the group consisting of C 1-3 alkyl, hydroxyl, alkoxy, nitrile, heterocycle or ester.

9. The compound of claim 7 , wherein R 2 is selected from the group consisting of

10. The compound of claim 1 , wherein R 3 is selected from the group consisting of

11. The compound of claim 1 , wherein
R 1 is hydrogen; and
R 2 is C 1-8 alkyl.

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.

Assignees

• Janssen Sciences Ireland Uc

Inventors

• Mcgowan David
• Raboisson Pierre Jean-Marie Bernard
• EMBRECHTS Werner
• Jonckers Tim Hugo Maria
• Last Stefaan Julien
• Pieters Serge Maria Aloysius
• Vlach Jaromir

Classifications

• C07D403/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61P31/12

  Antivirals · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title