Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b] pyrazin-2(1H)-one

Patent metadata

Field	Value
Publication number	US-9359364-B2
Application number	US-201414254023-A
Country	US
Kind code	B2
Filing date	Apr 16, 2014
Priority date	Apr 17, 2013
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

Provided herein are formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one.

First claim

What is claimed is:

1. A crystal form of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at 9.8±0.2, 12.0±0.2 and 17.9±0.2° 2θ.

2. A pharmaceutical composition comprising the crystal form of claim 1 , and one or more pharmaceutically acceptable excipients or carriers, each independently selected from carboxymethyl cellulose, cellulose, lactose, magnesium stearate, starch, and stearic acid.

3. The crystal form of claim 1 which has an X-ray powder diffraction pattern further comprising peaks at 15.9±0.2, 25.2±0.2 and 27.1±0.2° 2θ.

4. The crystal form of claim 1 which has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at approximately 269.6° C. when heated from about 25° C. to about 300° C.

5. The crystal form of claim 1 which is substantially pure.

6. A crystal form of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at 7.5±0.2, 10.4±0.2 and 11.7±0.2° 2θ.

7. The crystal form of claim 6 which has an X-ray powder diffraction pattern further comprising peaks at 4.9±0.2, 8.6±0.2 and 17.9±0.2° 2θ.

8. The crystal form of claim 6 which has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at approximately 267.8° C. when heated from about 25° C. to about 300° C.

9. The crystal form of claim 6 which has a differential scanning calorimetry thermogram comprising an exotherm with a maximum at approximately 158.8° C. when heated from about 25° C. to about 300° C.

10. The crystal form of claim 6 which is substantially pure.

11. A pharmaceutical composition comprising the crystal form of claim 6 , and one or more pharmaceutically acceptable excipients or carriers, each independently selected from carboxymethyl cellulose, cellulose, lactose, magnesium stearate, starch, and stearic acid.

12. A crystal form of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at 9.3±0.2, 11.7±0.2 and 19.9±0.2° 2θ.

13. The crystal form of claim 12 which has an X-ray powder diffraction pattern further comprising peaks at 7.4±0.2, 17.3±0.2 and 23.7±0.2° 2θ.

14. The crystal form of claim 12 which has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at approximately 270.3° C. when heated from about 25° C. to about 300° C.

15. The crystal form of claim 12 which has a differential scanning calorimetry thermogram comprising an exotherm with a maximum at approximately 135.9° C. when heated from about 25° C. to about 300° C.

16. The crystal form of claim 12 which is substantially pure.

17. A pharmaceutical composition comprising the crystal form of claim 12 , and one or more pharmaceutically acceptable excipients or carriers, each independently selected from carboxymethyl cellulose, cellulose, lactose, magnesium stearate, starch, and stearic acid.

18. A crystal form of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at 11.0±0.2, 20.2±0.2 and 21.9±0.2° 2θ.

19. The crystal form of claim 18 which has an X-ray powder diffraction pattern further comprising peaks at 18.2±0.2, 19.6±0.2 and 23.4±0.2° 2θ.

20. The crystal form of claim 18 which has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at approximately 269.0° C. when heated from about 25° C. to about 300° C.

21. The crystal form of claim 18 which is substantially pure.

22. A pharmaceutical composition comprising the crystal form of claim 18 , and one or more pharmaceutically acceptable excipients or carriers, each independently selected from carboxymethyl cellulose, cellulose, lactose, magnesium stearate, starch, and stearic acid.

23. A crystal form of Compound 1, or a tautomer thereof:

which has an X-ray powder diffraction pattern comprising peaks at 9.3±0.2, 15.3±0.2 and 18.6±0.2° 2θ.

24. The crystal form of claim 23 which has an X-ray powder diffraction pattern further comprising peaks at 7.0±0.2, 10.5±0.2 and 23.2±0.2° 2θ.

25. The crystal form of claim 23 which has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at approximately 269.7° C. when heated from about 25° C. to about 300° C.

26. The crystal form of claim 23 which has a differential scanning calorimetry thermogram comprising an exotherm with a maximum at approximately 180.4° C. when heated from about 25° C. to about 300° C.

27. The crystal form of claim 23 which is substantially pure.

28. A pharmaceutical composition comprising the crystal form of claim 23 , and one or more pharmaceutically acceptable excipients or carriers, each independently selected from carboxymethyl cellulose, cellulose, lactose, magnesium stearate, starch, and stearic acid.

Assignees

• Signal Pharm Llc

Inventors

• Menon Anil
• Parikh Darshan K
• Visky Dora
• Kreilein Matthew Michael
• Boersen Nathan
• Lee Thomas
• Li Ying
• Xu Jean
• Liang Xiaozhang
• Leong William Wei-Hwa
• Cohen Benjamin

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K31/4985 Primary

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title