Crystalline forms of (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide

• US 10,577,350 B2
• Filed: 08/25/2016
• Issued: 03/03/2020
• Est. Priority Date: 08/28/2015
• Status: Active Grant

• Current Assignee: Constellation Pharmaceuticals Incorporated (Morphosys Ag)
• Original Assignee: Constellation Pharmaceuticals Incorporated (Morphosys Ag)
• Inventors: Albrecht, Brian K., Arrigo, Alisha, Corson, Donald, Gehling, Victor S., Hache, Bruno Patrice, Harmange, Jean-Christophe, Lane, Jonathan
• Primary Examiner(s): Jarrell, Noble E
• Application Number:
  US15/755,854
• Publication Number:
  US 20180327386A1
• Time in Patent Office: 1,286 Days
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 401/14 containing three or more hetero rings

Abstract

The present disclosure relates to a crystalline Forms A, B, and C of (R)—N-((4-methoxy-6-methyl-2-oxo-1,2-di-hydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide, each of which are useful as modulators the activity of histone methyl modifying enzymes. The present disclosure also provides pharmaceutically acceptable compositions comprising the crystalline forms and methods of using said compositions in the treatment of various disorders.

Claims

1. Crystalline Form C of a compound having the formula

2. The crystalline Form C of claim 1, characterized by at least four X-ray powder diffraction peaks at 2Θ

angles selected from 7.56°

, 10.24°

, 14.18°

, 14.38°

, 16.26°

, 18.04°

, 19.60°

, and 21.52°

.

3. The crystalline Form C of claim 2, characterized by at least five X-ray powder diffraction peaks at 2Θ

angles selected from 7.56°

, 10.24°

, 14.18°

, 14.38°

, 16.26°

, 18.04°

, 19.60°

, and 21.52°

.

4. The crystalline Form C of claim 3, characterized by at least six X-ray powder diffraction peaks at 2Θ

angles selected from 7.56°

, 10.24°

, 14.18°

, 14.38°

, 16.26°

, 18.04°

, 19.60°

, and 21.52°

.

5. The crystalline Form C of claim 4, characterized by at least seven X-ray powder diffraction peaks at 2Θ

angles selected from 7.56°

, 10.24°

, 14.18°

, 14.38°

, 16.26°

, 18.04°

, 19.60°

, and 21.52°

.

6. The crystalline Form C of claim 5, characterized by X-ray powder diffraction peaks at 2Θ

angles selected from 7.56°

, 10.24°

, 14.18°

, 14.38°

, 16.26°

, 18.04°

, 19.60°

, and 21.52°

.

7. The crystalline Form C of claim 6, characterized by X-ray powder diffraction peaks at 2Θ

angles selected from 7.56°

, 9.94°

, 10.24°

, 14.18°

, 14.38°

, 16.26°

, 17.14°

, 17.63°

, 18.04°

, 18.54°

, 19.60°

, 20.28°

, 21.52°

, 22.32°

, 24.16°

, 24.46°

, 25.00°

, and 27.88°

.

8. The crystalline Form C of claim 1, wherein the crystalline form is at least 75% pure by weight.

9. A pharmaceutical composition comprising the crystalline Form C of claim 1, and a pharmaceutically acceptable carrier or diluent.

10. A method of treating a disease or disorder selected from pancreatic cancer, renal cancer, prostate cancer, bladder cancer, breast cancer, colorectal cancer, and non-small lung cancer in a patient in need thereof, comprising the step of administering to said patient the crystalline Form C of claim 1.

13. The crystalline Form C of claim 1, wherein the crystalline form is at least 90% pure by weight.

14. The crystalline Form C of claim 1, wherein the crystalline form is at least 95% pure by weight.

15. The crystalline Form C of claim 1, wherein the crystalline form is at least 98% pure by weight.

11. A process for preparing crystalline Form C of a compound having the formula

12. The process of claim 11, wherein the mixture is agitated at a temperature of about 65°

C.