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-9814713-B2
Application number	US-201615152653-A
Country	US
Kind code	B2
Filing date	May 12, 2016
Priority date	Jan 30, 2014
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

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. A method for treating a condition treatable by inhibition of a kinase pathway, comprising administering to a subject having a condition treatable by inhibition of a kinase pathway an effective amount of a crystal form of Compound 1, or a tautomer thereof:

wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.55, 13.61, 17.20, 17.85, 18.04, 19.84, 22.90 and 24.36±0.2° 2θ, 9.80, 10.30, 14.62, 17.29, 18.23, 20.66, 21.74 and 30.55±0.2° 2θ, 9.83, 10.21, 12.16, 17.26, 17.61, 18.18, 20.46 and 21.86±0.2° 2θ, 10.37, 13.41, 17.54, 17.73, 19.52, 21.54, 22.47 and 23.92±0.2° 2θ, 9.92, 10.36, 11.97, 14.50, 17.29, 18.37, 20.10 and 21.81±0.2° 2θ, 8.07, 9.21, 12.06, 17.45, 17.79, 18.53, 20.85 and 21.10±0.2° 2θ, 9.51, 10.34, 16.94, 17.33, 17.90, 21.28, 28.83 and 31.22±0.2° 2θ, 9.74, 10.23, 14.64, 17.22, 18.04, 18.55, 21.76 and 24.18±0.2° 2θ, or 7.94, 10.50, 11.86, 16.00, 17.26, 18.27, 20.65 and 24.12±0.2° 2θ; and
wherein the condition treatable by inhibition of a kinase pathway is interstitial pulmonary fibrosis, systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, lupus, liver fibrotic disorder, diabetes or metabolic syndrome leading to a liver fibrotic disorder.

2. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.55, 13.61, 17.20, 17.85, 18.04, 19.84, 22.90 and 24.36±0.2° 2θ.

3. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.80, 10.30, 14.62, 17.29 18.23, 20.66, 21.74 and 30.55±0.2° 2θ.

4. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.83, 10.21 12.16, 17.26, 17.61, 18.18, 20.46 and 21.86±0.2° 2θ.

5. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.37, 13.41, 17.54, 17.73, 19.52, 21.54, 22.47 and 23.92±0.2° 2θ.

6. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.92, 10.36, 11.97, 14.50, 17.29, 18.37, 20.10 and 21.81±0.2° 2θ.

7. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 8.07, 9.21, 12.06, 17.45, 17.79, 18.53, 20.85 and 21.10±0.2° 2θ.

8. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.51, 10.34, 16.94, 17.33, 17.90, 21.28, 28.83 and 31.22±0.2° 2θ.

9. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.74, 10.23, 14.64, 17.22, 18.04, 18.55, 21.76 and 24.18±0.2° 2θ.

10. The method of claim 1 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 7.94, 10.50, 11.86, 16.00, 17.26, 18.27, 20.65 and 24.12±0.2° 2θ.

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

wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.55, 13.61, 17.20, 17.85, 18.04, 19.84, 22.90 and 24.36±0.2° 2θ, 9.80, 10.30, 14.62, 17.29, 18.23, 20.66, 21.74 and 30.55±0.2° 2θ, 9.83, 10.21, 12.16, 17.26, 17.61, 18.18, 20.46 and 21.86±0.2° 2θ, 10.37, 13.41, 17.54, 17.73, 19.52, 21.54, 22.47 and 23.92±0.2° 2θ, 9.92, 10.36, 11.97, 14.50, 17.29, 18.37, 20.10 and 21.81±0.2° 2θ, 8.07, 9.21, 12.06, 17.45, 17.79, 18.53, 20.85 and 21.10±0.2° 2θ, 9.51, 10.34, 16.94, 17.33, 17.90, 21.28, 28.83 and 31.22±0.2° 2θ, 9.74, 10.23, 14.64, 17.22, 18.04, 18.55, 21.76 and 24.18±0.2° 2θ, or 7.94, 10.50, 11.86, 16.00, 17.26, 18.27, 20.65 and 24.12±0.2° 2θ.

12. A method for treating a liver fibrotic disorder, diabetes, or metabolic syndrome leading to a liver fibrotic disorder, comprising administering to a subject having a liver fibrotic disorder, diabetes, or metabolic syndrome leading to a liver fibrotic disorder an effective amount a crystal form of Compound 1, or a tautomer thereof:

wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.55, 13.61, 17.20, 17.85, 18.04, 19.84, 22.90 and 24.36±0.2° 2θ, 9.80, 10.30, 14.62, 17.29, 18.23, 20.66, 21.74 and 30.55±0.2° 2θ, 9.83, 10.21, 12.16, 17.26, 17.61, 18.18, 20.46 and 21.86±0.2° 2θ, 10.37, 13.41, 17.54, 17.73, 19.52, 21.54, 22.47 and 23.92±0.2° 2θ, 9.92, 10.36, 11.97, 14.50, 17.29, 18.37, 20.10 and 21.81±0.2° 2θ, 8.07, 9.21, 12.06, 17.45, 17.79, 18.53, 20.85 and 21.10±0.2° 2θ, 9.51, 10.34, 16.94, 17.33, 17.90, 21.28, 28.83 and 31.22±0.2° 2θ, 9.74, 10.23, 14.64, 17.22, 18.04, 18.55, 21.76 and 24.18 ±0.2° 2θ, or 7.94, 10.50, 11.86, 16.00, 17.26, 18.27, 20.65 and 24.12 ±0.2° 2θ.

13. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.55, 13.61, 17.20, 17.85, 18.04, 19.84, 22.90 and 24.36±0.2° 2θ.

14. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.80, 10.30, 14.62, 17.29, 18.23, 20.66, 21.74 and 30.55±0.2° 2θ.

15. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.83, 10.21, 12.16, 17.26, 17.61, 18.18, 20.46 and 21.86±0.2° 2θ.

16. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 10.37, 13.41, 17.54, 17.73, 19.52, 21.54, 22.47 and 23.92±0.2° 2θ.

17. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.92, 10.36, 11.97, 14.50, 17.29, 18.37, 20.10 and 21.81±0.2° 2θ.

18. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 8.07, 9.21, 12.06, 17.45, 17.79, 18.53, 20.85 and 21.10±0.2° 2θ.

19. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.51, 10.34, 16.94, 17.33, 17.90, 21.28, 28.83 and 31.22±0.2° 2θ.

20. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 9.74, 10.23, 14.64, 17.22, 18.04, 18.55, 21.76 and 24.18±0.2° 2θ.

21. The method of claim 12 , wherein the crystal form has an X-ray powder diffraction pattern comprising peaks at 7.94, 10.50, 11.86, 16.00, 17.26, 18.27, 20.65 and 24.12±0.2° 2θ.

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

• C07D239/48 Primary

  Two nitrogen atoms · CPC title

• C07D239/42

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

• A61K31/505 Primary

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · 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

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title