Methods of treating or preventing autoimmune diseases with 2, 4-pyrimidinediamine compounds

• US 20050234049A1
• Filed: 07/30/2004
• Published: 10/20/2005
• Est. Priority Date: 07/30/2003
• Status: Active Grant

• Current Assignee: Rigel Pharmaceuticals, Inc.
• Original Assignee: Rigel Pharmaceuticals, Inc.
• Inventors: Clough, Jeffrey, Keim, Holger, Argade, Ankush, Carroll, David, Sylvain, Catherine, Bhamidipati, Somasekhar, Li, Hui, Singh, Rajinder
• Granted Patent: US 8,178,671 B2
• Time in Patent Office: Days
• US Class Current: 514/224.200
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/541 Non-condensed thiazines containing further heterocyclic rings
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 498/02 in which the condensed system contains two hetero rings
• CPC Class Codes: C07D 498/04 Ortho-condensed systems
• CPC Class Codes: C07D 498/06 Peri-condensed systems

Abstract

The present invention provides methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds, as well as methods of treating, preventing or ameliorating symptoms associated with such diseases. Specific examples of autoimmune diseases that can be treated or prevented with the compounds include rheumatoid arthritis and/or its associated symptoms, systemic lups erythematosis and/or its associated symptoms and multiple sclerosis and/or its associated symptoms.

Claims

1. A 2,4 pyrimidinediamine compound according to structure:

2. The compound of claim 1 in which R⁵ is fluoro.

3. The compound of claim 2 in which R⁶ is hydrogen.

4. The compound of claim 1 in which Y and Z are each, independently of one another, selected from the group consisting of O and NH.

5. The compound of claim 4 in which X is CH.

6. The compound of claim 5 in which Y and Z are each O.

7. The compound of claim 6 in which each R³⁵ is hydrogen.

8. The compound of claim 5 in which Y is O and Z is NH.

49. The compound of any one of claims 1-48 further comprising a pharmaceutically acceptable carrier, diluent or excipient.

50. A method of treating or preventing an autoimmune disease and/or one or more symptoms associated therewith, comprising the step of administering to a subject suffering from an autoimmune disease or at risk of developing an autoimmune disease an effective amount of a 2,4-pyrimidinediamine compound according to any one of claims 1-49.

9. A 2,4 pyrimidinediamine compound according to structure:

10. A compound according to the structural formula:

11. A compound according to the structural formula:

12. A compound according to the structural formula:

13. A compound according to the structural formula:

14. A 2,4-pyrimidinediamine compound according to structure:

15. The compound of claim 14 in which R² is a di or tri substituted phenyl group.

16. The compound of claim 15 in which one or more of the R⁸ groups are selected from the group consisting of halogens and alkoxy groups.

17. The compound of claim 16 in which the 2,4-pyrimidinediamine compound is 1256, 1257, 1258, 1259 or 1260.

18. A 2,4-pyrimidinediamine compound according to structure:

19. The compound of claim 18 in which R³⁵ is not a methyl group.

20. The compound of claim 18 in which the 2,4-pyrimidinediamine compound is 1000, 1001 or 1002.

21. A 2,4-pyrimidinediamine compound according to structure:

22. The compound of claim 21 in which Y is oxygen, Z is NH and one or more R³⁵ is an alkyl group.

23. The compound of claim 21 in which R⁴ is

24. The compound of claim 21 in which R⁴ is

25. The compound of claim 21 in which Y is oxygen, Z is NH.

26. The compound of claim 21 in which the 2,4-pyrimidinediamine compound is 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 1281, 1283, 1283, 1284, 1285, 1287, 1288, 1289, 1290 or 1291.

27. A 2,4-pyrimidinediamine compound according to structure:

28. The compound of claim 27 in which the 2,4-pyrimidinediamine compound is 1070, 1071, 1073, 1074, 1075, 1076, 1078, 1080, 1085, 1091 or 1092.

29. A 2, 4-pyrimidinediamine compound according to structure:

30. The compound of claim 29 in which R² is

31. The compound of claim 29 in which p1 R² is selected from the group consisting of

32. The compound of claim 31 in which R²² and R²³ or R²¹ and R²² or R²¹, R²² and R²³ are each methyl groups.

33. A 2, 4-pyrimidinediamine compound according to structure:

34. The compound of claim 33 in which R²⁸ is a methoxy.

35. The compound of claim 33 in which R²¹ is a methyl group.

36. The compound of claim 33 in which each R²⁸ is a chlorine.

37. The compound of claim 33 in which R²¹ is a methyl group and R²⁸ is a chlorine.

38. A 2, 4-pyrimidinediamine compound according to structure:

39. The compound of claim 38 in which R²¹ is a methyl group.

40. The compound of claim 38 in which each R²⁸ is a chlorine.

41. The compound of claim 38 in which R²¹ is a methyl group and R²⁸ is a chlorine.

42. The compound of claim 38 in which R⁵⁰ is —

CH₂CH₂OH.

43. The compound of claim 38 in which R⁵² is trifluoromethyl.

44. The compound of claim 38 in which R⁵⁰ is a methyl group.

45. The compound of claim 38 in which each R²⁸ is a chlorine.

46. The compound of claim 38 in which R⁵⁰ is a methyl group and R²⁸ is a chlorine.

47. A 2, 4-pyrimidinediamine compound according to structure:

48. The compound of claim 47 in which R²¹ is a methyl group.