Therapeutically active compounds and their methods of use

Patent metadata

Field	Value
Publication number	US-9694013-B2
Application number	US-201514868283-A
Country	US
Kind code	B2
Filing date	Sep 28, 2015
Priority date	Sep 29, 2014
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).

First claim

The invention claimed is:

1. A method of treating a solid tumor characterized by the presence of a mutant allele of isocitrate dehydrogenase 2 (IDH2) comprising administering to a subject in need thereof a therapeutically effective dose of an inhibitor of a mutant IDH2, wherein the inhibitor is 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 or 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 therapeutically effective dose is from about 30 mg to about 300 mg.

2. The method of claim 1 , wherein the solid tumor is glioma, melanoma, chondrosarcoma, or cholangiocarcinoma.

3. A method of treating angioimmunoblastic T-cell lymphoma (AITL) characterized by the presence of a mutant allele of isocitrate dehydrogenase 2 (IDH2) comprising administering to a subject in need thereof a therapeutically effective dose of an inhibitor of a mutant IDH2, wherein the inhibitor is 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 or 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 therapeutically effective dose is from about 30 mg to about 300 mg.

4. The method of claim 1 , wherein the inhibitor is 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 or a crystalline form thereof.

5. The method of claim 1 , wherein the inhibitor is 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 or a crystalline form thereof.

6. The method of claim 3 , wherein the inhibitor is 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 or a crystalline form thereof.

7. The method of claim 3 , wherein the inhibitor is 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 or a crystalline form thereof.

8. The method of claim 1 , wherein 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 or 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 is administered orally.

9. The method of claim 1 , wherein the therapeutically effective dose is from about 30 mg to about 200 mg.

10. The method of claim 9 , wherein the therapeutically effective dose is from about 30 mg to about 150 mg.

11. The method of claim 1 , wherein the therapeutically effective dose is about 30 mg, or about 50 mg, or about 75 mg, or about 100 mg, or about 125 mg, or about 150 mg, or about 175 mg, or about 200 mg, or about 225 mg, or about 250 mg or about 275 mg, or about 300 mg.

12. The method of claim 8 , wherein the 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 or 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 is administered in a 50 mg, a 100 mg, a 150 mg, or a 200 mg oral dosage form.

13. The method of claim 3 , wherein 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 or 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 is administered orally.

14. The method of claim 13 , wherein the therapeutically effective dose is from about 30 mg to about 200 mg.

15. The method of claim 14 , wherein the therapeutically effective dose is from about 30 mg to about 150 mg.

16. The method of claim 13 , wherein the therapeutically effective dose is about 30 mg, or about 50 mg, or about 75 mg, or about 100 mg, or about 125 mg, or about 150 mg, or about 175 mg, or about 200 mg, or about 225 mg, or about 250 mg or about 275 mg, or about 300 mg.

17. The method of claim 13 , wherein the 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 or 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 is administered in a 50 mg, a 100 mg, a 150 mg, or a 200 mg oral dosage form.

Assignees

• Agios Pharmaceuticals Inc

Inventors

• Agresta Samuel V

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/185

  Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327) · CPC title