Salts and crystal forms of omecamtiv mecarbil

Patent metadata

Field	Value
Publication number	US-11926592-B2
Application number	US-202217929645-A
Country	US
Kind code	B2
Filing date	Sep 2, 2022
Priority date	Aug 17, 2018
Publication date	Mar 12, 2024
Grant date	Mar 12, 2024

Abstract

Provided herein are free base crystalline forms, crystalline salts, and an amorphous salts of omecamtiv mecarbil.

First claim

What is claimed:

1. An omecamtiv mecarbil fumarate crystalline salt form which is any one of the following forms:
i) an omecamtiv mecarbil bis-fumarate crystalline salt form A, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.64, 15.76, 22.03, and 23.87±0.2° 2θ using Cu Kα radiation;
ii) an omecamtiv mecarbil bis-fumarate crystalline salt form B, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.68, 6.11, 13.13, 18.08, and 22.47±0.2° 2θ using Cu Kα radiation;
iii) an omecamtiv mecarbil bis-fumarate crystalline salt form C, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.88, 18.79, 25.41, and 26.86±0.2° 2θ using Cu Kα radiation; or
iv) an omecamtiv mecarbil mono-fumarate crystalline salt form D, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.01, 15.20, and 20.02±0.2° 2θ using Cu Kα radiation.

2. The omecamtiv mecarbil fumarate crystalline salt form of claim 1 , wherein the crystalline salt form is omecamtiv mecarbil bis-fumarate crystalline salt form A, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.64, 15.76, 22.03, and 23.87±0.2° 2θ using Cu Kα radiation.

3. The omecamtiv mecarbil bis-fumarate crystalline salt form A of claim 2 , further characterized by XRPD pattern peaks at 16.80, 21.55, 21.87, 23.61, 23.87, 26.01, and 27.20±0.2° 2θ using Cu Kα radiation.

4. The omecamtiv mecarbil bis-fumarate crystalline salt form A of claim 2 , further characterized by XRPD pattern peaks at 10.80, 12.04, 15.76, 16.40, 17.94, 18.32, 19.87, 20.61, 22.88, 27.86, 32.73, and 36.54±0.2° 2θ using Cu Kα radiation.

5. The omecamtiv mecarbil bis-fumarate crystalline salt form A of claim 2 , having an XRPD pattern substantially as shown in FIG. 20 .

6. The omecamtiv mecarbil bis-fumarate crystalline salt form A of claim 2 , having a thermogravimetric analysis (TGA) as shown in FIG. 21 .

7. The omecamtiv mecarbil fumarate crystalline salt form of claim 1 , wherein the crystalline salt form is omecamtiv mecarbil bis-fumarate crystalline salt form B, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.68, 6.11, 13.13, 18.08, and 22.47±0.2° 2θ using Cu Kα radiation.

8. The omecamtiv mecarbil bis-fumarate crystalline salt form B of claim 7 , further characterized by XRPD pattern peaks at 9.69, 11.43, 12.92, 15.95, 20.81, 22.95, 26.04, 27.01, and 28.43±0.2° 2θ using Cu Kα radiation.

9. The omecamtiv mecarbil bis-fumarate crystalline salt form B of claim 7 , further characterized by XRPD pattern peaks at 19.52, 24.53, 31.37, 32.32, 34.89, 35.89, and 37.16±0.2° 2θ using Cu Kα radiation.

10. The omecamtiv mecarbil bis-fumarate crystalline salt form B of claim 7 , having an XRPD pattern substantially as shown in FIG. 22 .

11. The omecamtiv mecarbil bis-fumarate crystalline salt form B of claim 7 , having a thermogravimetric analysis (TGA) as shown in FIG. 23 .

12. The omecamtiv mecarbil fumarate crystalline salt form of claim 1 , wherein the crystalline salt form is omecamtiv mecarbil bis-fumarate crystalline salt form C, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.88, 18.79, 25.41, and 26.86±0.2° 2θ using Cu Kα radiation.

13. The omecamtiv mecarbil bis-fumarate crystalline salt form C of claim 12 , further characterized by XRPD pattern peaks at 12.74, 13.56, 17.15, 17.63, 20.29, 21.47, 21.77, 22.21, 22.92, 23.58, 24.15, 25.41, 26.78, and 27.83±0.2° 2θ using Cu Kα radiation.

14. The omecamtiv mecarbil bis-fumarate crystalline salt form C of claim 12 , having an XRPD pattern substantially as shown in FIG. 24 .

15. The omecamtiv mecarbil bis-fumarate crystalline salt form C of claim 12 , having a thermogravimetric analysis (TGA) as shown in FIG. 25 .

16. The omecamtiv mecarbil fumarate crystalline salt form of claim 1 , wherein the crystalline salt form is omecamtiv mecarbil mono-fumarate crystalline salt form D, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.01, 15.20, and 20.02±0.2° 2θ using Cu Kα radiation.

17. The omecamtiv mecarbil mono-fumarate crystalline salt form D of claim 16 , further characterized by XRPD pattern peaks at 12.11, 12.67, 14.46, 16.01, 16.57, 17.04, 17.63, 20.51, 21.75, 22.86, 24.25, 24.97, 25.84, 26.17, 27.10, 27.97, and 29.21±0.2° 2θ using Cu Kα radiation.

18. The omecamtiv mecarbil mono-fumarate crystalline salt form D of claim 16 , having an XRPD pattern substantially as shown in FIG. 26 .

19. The omecamtiv mecarbil mono-fumarate crystalline salt form D of claim 16 , having an endothermic transition at 110° C. to 130° C., as measured by differential scanning calorimetry.

20. The omecamtiv mecarbil mono-fumarate crystalline salt form D of claim 16 , wherein the endothermic transition is at 125° C.±3° C.

21. The omecamtiv mecarbil mono-fumarate crystalline salt form D of claim 16 , having a thermogravimetric analysis (TGA) as shown in FIG. 28 .

Assignees

• Amgen Inc

Inventors

• Morrison Henry
• Cui Sheng
• Quasdorf Kyle
• Yanez Evelyn
• Quan Bin Peter
• Kelly Ron C
• Caille Sebastien
• Xiao Lingyun
• Pearson David
• Raeburn Jaclyn
• Golightly Alisa

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D213/75 Primary

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07C309/04

  containing only one sulfo group · CPC title

• C07C57/15

  Fumaric acid · CPC title