2,4,6-trisubstituted 1,3,5-triazines as modulators of CX3CR1

Patent metadata

Field	Value
Publication number	US-12404253-B2
Application number	US-202418783231-A
Country	US
Kind code	B2
Filing date	Jul 24, 2024
Priority date	Oct 19, 2022
Publication date	Sep 2, 2025
Grant date	Sep 2, 2025

Abstract

There are disclosed certain 2,4,6-trisubstituted 1,3,5-triazine compounds of Formula (I),

and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are modulators of CX 3 CR1 and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as non-ischemic dilated cardiomyopathy and heart failure.

First claim

The invention claimed is:

1. A compound selected from N-(4-((R)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide and N-(4-((S)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 which is N-(4-((R)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 which is N-(4-((S)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 2 which is N-(4-((R)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

5. The compound of claim 3 which is N-(4-((S)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

6. The pharmaceutically acceptable salt of claim 2 , which is a pharmaceutically acceptable salt of N-(4-((R)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

7. The pharmaceutically acceptable salt of claim 3 , which is a pharmaceutically acceptable salt of N-(4-((S)-2-(2,3-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide

8. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 .

9. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 2 .

10. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 3 .

11. A compound selected from N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide and N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((S)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 11 which is N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 11 which is N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((S)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 12 which is N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

15. The compound of claim 13 which is N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((S)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

16. The pharmaceutically acceptable salt of claim 12 , which is a pharmaceutically acceptable salt of N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

17. The pharmaceutically acceptable salt of claim 13 , which is a pharmaceutically acceptable salt of N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((S)-2-(6-methoxypyridin-3yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide:

18. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 11 .

19. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 12 .

20. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 13 .

21. A compound selected from N-(4-((R)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide and N-(4-((S)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

22. The compound of claim 21 which is N-(4-((R)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

23. The compound of claim 21 which is N-(4-((S)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

or a pharmaceutically acceptable salt thereof.

24. The compound of claim 22 which is N-(4-((R)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

25. The compound of claim 23 which is N-(4-((S)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

26. The pharmaceutically acceptable salt of claim 22 , which is a pharmaceutically acceptable salt of N-(4-((R)-2-(5-Fluoro-6-methoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide:

27. The pharmaceutically acceptable salt of claim 23 , which is a pharmaceutically a

Assignees

• Astrazeneca Ab

Inventors

• Nilsson Karolina
• Bauer Martin
• Halvarsson Maria Olwegard
• Brink Mikael
• Bergström Fredrik

Classifications

• C07D498/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D405/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title