Solid forms of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use

Patent metadata

Field	Value
Publication number	US-9365524-B2
Application number	US-201514608314-A
Country	US
Kind code	B2
Filing date	Jan 29, 2015
Priority date	Jan 30, 2014
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

Provided herein are formulations, processes, solid forms and methods of use relating to 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide.

First claim

What is claimed is:

1. Crystal Form A of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 10.55, 13.61 and 19.84° 2θ.

2. Crystal Form B of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 9.80, 17.29 and 21.74° 2θ.

3. Crystal Form C of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 9.83, 17.26 and 21.86° 2θ.

4. Crystal Form D of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 10.37, 13.41 and 19.52° 2θ.

5. Crystal Form E of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 9.92, 17.29 and 21.81° 2θ.

6. Crystal Form F of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 18.53, 20.85 and 21.10° 2θ.

7. Crystal Form G of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 9.51, 17.90 and 21.28° 2θ.

8. Crystal Form H of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 9.74, 17.22 and 21.76° 2θ.

9. Crystal Form I of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at approximately 7.94, 16.00 and 18.27° 2θ.

10. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 1 .

11. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 1 to a subject in need thereof.

12. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 1 to a subject in need thereof.

13. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 2 .

14. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 2 to a subject in need thereof.

15. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 2 to a subject in need thereof.

16. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 3 .

17. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 3 to a subject in need thereof.

18. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 3 to a subject in need thereof.

19. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 4 .

20. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 4 to a subject in need thereof.

21. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 4 to a subject in need thereof.

22. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 5 .

23. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 5 to a subject in need thereof.

24. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 5 to a subject in need thereof.

25. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 6 .

26. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 6 to a subject in need thereof.

27. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 6 to a subject in need thereof.

28. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting said cell with an effective amount of a crystal form of claim 7 .

29. A method for treating interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, or lupus, comprising administering an effective amount of a crystal form of claim 7 to a subject in need thereof.

30. A method for treating liver fibrotic disorders, diabetes, or metabolic syndrome leading to liver fibrotic disorders comprising administering an effective amount of a crystal form of claim 7 to a subject in need thereof.

31. A method of inhibiting a JNK1 or JNK2 kinase in a cell expressing said JNK1 or JNK2 kinase, comprising contacting

Assignees

• Signal Pharm Llc

Inventors

• Man Hon-Wah
• Xu Jean
• Beauchamps Marie Georges
• Kothare Mohit Atul
• Zou Nanfei
• Li Ying
• Huang Lianfeng
• Zou Daozhong

Classifications

• C07D239/42

  One nitrogen atom (nitro radicals C07D239/30) · CPC title

• A61K31/505 Primary

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• C07D239/48 Primary

  Two nitrogen atoms · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D239/28 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms · CPC title