Heterocyclic substituted 2-amino quinazoline derivatives for the treatment of viral infections

• US 10,723,707 B2
• Filed: 04/08/2019
• Issued: 07/28/2020
• Est. Priority Date: 11/16/2012
• Status: Active Grant

• Current Assignee: Janssen Sciences Ireland Unlimited Company (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland Unlimited Company (Johnson & Johnson)
• Inventors: Last, Stefaan Julien, McGowan, David Craig, Embrechts, Werner, Pieters, Serge Maria Aloysius, Jonckers, Tim Hugo Maria, Raboisson, Pierre Jean-Marie Bernard
• Primary Examiner(s): Ward, Paul V
• Application Number:
  US16/377,752
• Publication Number:
  US 20190330160A1
• Time in Patent Office: 477 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 239/84 Nitrogen atoms
• CPC Class Codes: C07D 239/95 with hetero atoms directly attached in positions 2 and 4
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 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 417/12 linked by a chain containing hetero atoms as chain links

Abstract

This invention relates to heterocyclic substituted 2-amino-quinazoline derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

Claims

1. A method of treating a viral infection in which the modulation of TLR7 and/or TLR8 is involved in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I)

2. The method of claim 1, wherein R₅ is CH₃, and R₉ and R₁₁ are each independently H or CH₃.

3. The method of claim 1, wherein R₁₃ is H, CH₃ or CH₂CH₃.

4. The method of claim 1, wherein R₁ is

5. The method of claim 4, wherein R₉ is CH₃.

6. The method of claim 4, wherein R₂ is OCH₃ or —

O—

C₂H₄—

O—

CH₃.

7. The method of claim 4, wherein:

R₃, R₄, R₁₃ and R₈ are each H;

R₉ is CH₃; and

R₂ is —

O—

(C_1-3)-alkyl-O—

(C_1-3)-alkyl.

8. The method of claim 4, wherein:

R₃, R₄, R₁₃ and R₈ are each H;

R₉ is CH₃; and

R₂ is OCH₃.

9. The method of claim 1, wherein R₁ is

10. The method of claim 9, wherein

R₅ is CH₃;

and

R₈, R₉, R₁₀ and R₁₁ are each H.

11. The method of claim 1, wherein R₁ is

12. The method of claim 11, wherein R₅ is CH₃ or CH₂OH.

13. The method of claim 1, wherein R₁ is

14. The method of claim 13, wherein:

R₅ is CH₃, and

R₈ and R₉ are each H.

15. The method of claim 1, wherein R₁ is

16. The method of claim 15, wherein

each R₅ is CH₃;

and

R₈ and R₉ are each H.

17. The method of claim 4, wherein R₁ is

18. The method of claim 17, wherein each R₁₃ is (C_1-3)-alkyl.

19. The method of claim 1, wherein R₁ is

20. The method of claim 19, wherein each R₁₃ is (C_1-3)-alkyl.

21. The method of claim 1, wherein the compound is selected from the group consisting of:

22. The method of claim 1, wherein the compound is together with one or more pharmaceutically acceptable excipients, diluents or carriers in a pharmaceutical composition.

23. The method of claim 1, wherein the treatment stimulates the innate immune system of the subject through activation of TLR7 and/or TLR8.

24. A method of modulating human TLR7 and/or TLR8 by contacting a cell with an effective amount of a compound of formula (I):

25. The method of claim 24, wherein the compound is selected from the group consisting of:

26. The method of claim 24, wherein the compound is together with one or more pharmaceutically acceptable excipients, diluents or carriers in a pharmaceutical composition.