Therapeutically active compounds and their methods of use

Patent metadata

Field	Value
Publication number	US-9738625-B2
Application number	US-201414909451-A
Country	US
Kind code	B2
Filing date	Aug 1, 2014
Priority date	Aug 2, 2013
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

Provided are isocitrate dehydrogenase 2 (IDH2) inhibitor compounds useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof a compound described herein. Also provided are polymorphic forms of the IDH2 inhibitor compounds characterized by X Ray powder diffraction patterns, having improved physicochemical properties that influence in vivo dissolution rate for formulation purposes.

First claim

The invention claimed is:

1. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, wherein the isolated crystalline form is Form 16, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 6.8, 10.6, 13.6, 14.2, and 19.2°±0.2°.

2. The isolated crystalline form of claim 1 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 34 .

3. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, wherein the isolated crystalline form is Form 1, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 8.9, 13.0, 18.9, 23.8, and 28.1°±0.2°.

4. The isolated crystalline form of claim 3 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 1 .

5. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, wherein the isolated crystalline form is Form 2, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 12.7, 17.1, 19.2, 23.0, and 24.2°±0.2°.

6. The isolated crystalline form of claim 5 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 2 .

7. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate, wherein the isolated crystalline form is Form 3, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 7.5, 9.3, 14.5, 18.8, 21.3, and 24.8°±0.2°.

8. The isolated crystalline form of claim 7 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 5 .

9. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate, wherein the isolated crystalline form is Form 7, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 14.1, 19.1, 21.8, 23.5, and 25.7°±0.2°.

10. The isolated crystalline form of claim 9 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 15 .

11. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate, wherein the isolated crystalline form is Form 8, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 9.0, 9.2, 21.9, 22.1, 24.2, and 24.6°±0.2°.

12. The isolated crystalline form of claim 11 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 17 .

13. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate, wherein the isolated crystalline form is Form 9, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 6.5, 19.6, 20.1, and 21.6°±0.2°.

14. The isolated crystalline form of claim 13 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 19 .

15. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, wherein the isolated crystalline form is Form 17, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 7.2, 13.6, 18.5, 19.3, 21.9, and 23.5°±0.2°.

16. The isolated crystalline form of claim 15 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 37 .

17. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, wherein the isolated crystalline form is Form 18, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 6.4, 8.4, 9.8, 17.8, and 19.7°±0.2°.

18. The isolated crystalline form of claim 17 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 38 .

19. An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl] amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, wherein the isolated crystalline form is Form 19, characterized by an X-ray powder diffraction pattern having peaks at 2θ angles of 8.1, 14.1, 16.4, 17.3, 20.5, and 24.1°±0.2°.

20. The isolated crystalline form of claim 19 , characterized by an X-ray powder diffraction pattern substantially similar to FIG. 39 .

Assignees

• Agios Pharmaceuticals Inc

Inventors

• Agresta Samuel V
• Gu Chong-Hui
• Schenkein David
• Yang Hua
• Guo Liting
• Tang Zhen
• Wang Jianming
• Zhang Yanfeng
• Zhou Yan

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title