Salts and crystal forms of omecamtiv mecarbil

Patent metadata

Field	Value
Publication number	US-11465969-B2
Application number	US-201917263224-A
Country	US
Kind code	B2
Filing date	Aug 16, 2019
Priority date	Aug 17, 2018
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

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 free base crystalline form which is any one of the following forms:
i) an omecamtiv mecarbil free base crystalline form III, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.50, 19.06, and 23.01±0.2° 2θ using Cu Kα radiation;
ii) an omecamtiv mecarbil free base crystalline form IV, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.18, 10.35, 14.84, 15.54, 18.10, and 19.92±0.2° 2θ using Cu Kα radiation;
iii) an omecamtiv mecarbil free base crystalline form V, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.38, 8.56, 9.14, and 18.28±0.2° 2θ using Cu Kα radiation;
iv) an omecamtiv mecarbil free base crystalline form VI, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.07, 16.67, 18.18, 19.70, 20.89, and 21.28±0.2° 2θ using Cu Kα radiation; or
v) an omecamtiv mecarbil free base crystalline form VII, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.40, 8.71, 13.08, 15.66, and 19.61±0.2° 2θ using Cu Kα radiation.

2. The omecamtiv mecarbil free base crystalline form of claim 1 , wherein the crystalline form is omecamtiv mecarbil free base crystalline form III, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.50, 19.06, and 23.01±0.2° 2θ using Cu Kα radiation.

3. The omecamtiv mecarbil free base crystalline form III of claim 2 , further characterized by XRPD pattern peaks at 14.27, 15.25, 16.10, 17.78, and 23.87±0.2° 2θ using Cu Kα radiation.

4. The omecamtiv mecarbil free base crystalline form III of claim 2 , further characterized by XRPD pattern peaks at 7.91, 20.65, 28.11, 31.01, 31.95, and 32.34±0.2° 2θ using Cu Kα radiation.

5. The omecamtiv mecarbil free base crystalline form III of claim 2 , having an XRPD pattern substantially as shown in FIG. 1 .

6. The omecamtiv mecarbil free base crystalline form III of claim 2 , having an endothermic transition at 175° C. to 190° C., as measured by differential scanning calorimetry.

7. The omecamtiv mecarbil free base crystalline form III of claim 6 , wherein the endothermic transition is at 186° C.±3° C.

8. The omecamtiv mecarbil free base crystalline form III of claim 2 , having a thermogravimetric analysis (TGA) substantially as shown in FIG. 3 .

9. The omecamtiv mecarbil free base crystalline form of claim 5 , wherein the crystalline form is omecamtiv mecarbil free base crystalline form IV, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.18, 10.35, 14.84, 15.54, 18.10, and 19.92±0.2° 2θ using Cu Kα radiation.

10. The omecamtiv mecarbil free base crystalline form IV of claim 9 , further characterized by XRPD pattern peaks at 14.21, 20.62, 20.77, 22.86, 24.05, 24.36, 27.81, and 29.42±0.2° 2θ using Cu Kα radiation.

11. The omecamtiv mecarbil free base crystalline form IV of claim 9 , further characterized by XRPD pattern peaks at 7.42, 7.70, 21.70, 22.40, 23.09, 25.20, 25.72, 27.40, 28.18, 28.63, 28.98, and 30.51±0.2° 2θ using Cu Kα radiation.

12. The omecamtiv mecarbil free base crystalline form IV of claim 9 , having an XRPD pattern substantially as shown in FIG. 4 .

13. The omecamtiv mecarbil free base crystalline form IV of claim 9 , having an endothermic transition at 175° C. to about 190° C., as measured by differential scanning calorimetry.

14. The omecamtiv mecarbil free base crystalline form IV of claim 13 , wherein the endothermic transition is at 185° C.±3° C.

15. The omecamtiv mecarbil free base crystalline form IV of claim 9 , having a thermogravimetric analysis (TGA) as shown in FIG. 6 .

16. The omecamtiv mecarbil free base crystalline form of claim 1 , wherein the crystalline form is omecamtiv mecarbil free base crystalline form V, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.38, 8.56, 9.14, and 18.28±0.2° 2θ using Cu Kα radiation.

17. The omecamtiv mecarbil free base crystalline form V of claim 16 , further characterized by XRPD pattern peaks at 8.93, 10.03, 10.73, 11.71, 13.69, 15.08, 16.85, 17.85, 18.86, 20.05, 20.72, 21.74, 23.56, 24.03, 26.23, and 27.62±0.2° 2θ using Cu Kα radiation.

18. The omecamtiv mecarbil free base crystalline form V of claim 16 , further characterized by XRPD pattern peaks at 5.40, 16.04, 22.83, 25.45, 26.23, 27.62, 28.58, 29.85, 32.10, and 33.37±0.2° 2θ using Cu Kα radiation.

19. The omecamtiv mecarbil free base crystalline form V of claim 16 , having an XRPD pattern substantially as shown in FIG. 7 .

20. The omecamtiv mecarbil free base crystalline form V of claim 16 , having an endothermic transition at 175° C. to 190° C., as measured by differential scanning calorimetry.

21. The omecamtiv mecarbil free base crystalline form V of claim 20 , wherein the endothermic transition is at 185° C.±3° C.

22. The omecamtiv mecarbil free base crystalline form V of claim 16 , having a thermogravimetric analysis (TGA) as shown in FIG. 9 .

23. The omecamtiv mecarbil free base crystalline form of claim 1 , wherein the crystalline form is omecamtiv mecarbil free base crystalline form VI, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.07, 16.67, 18.18, 19.70, 20.89, and 21.28±0.2° 2θ using Cu Kα radiation.

24. The omecamtiv mecarbil free base crystalline form VI of claim 23 , further characterized by XRPD pattern peaks at 15.88, 17.81, 18.80, 23.72, 24.26, 26.80, 27.59, and 29.82±0.2° 2θ using Cu Kα radiation.

25. The omecamtiv mecarbil free base crystalline form VI of claim 23 , further characterized by XRPD pattern peaks at 14.28, 20.23, 26.19, and 28.90±0.2° 2θ using Cu Kα radiation.

26. The omecamtiv mecarbil free base crystalline form VI of claim 23 , having an XRPD pattern substantially as shown in FIG. 10 .

27. The omecamtiv mecarbil free base crystalline form VI of claim 23 , having an endothermic transition at 175° C. to 190° C., as measured by differential scanning calorimetry.

28. The omecamtiv mecarbil free base crystalline form VI of claim 27 , wherein the endothermic transition is at 185° C.±3° C.

29. The omecamtiv mecarbil free base crystalline form of claim 1 , wherein the crystalline form is omecamtiv mecarbil free base crystalline form VII, characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.40, 8.71, 13.08, 15.66, and 19.61±0.2° 2θ using Cu Kα radiation.

30. The omecamtiv mecarbil free base crystalline form VII of claim 29 , further characterized by XRPD pattern peaks at 4.37, 16.83, 18.92, 20.32, 20.49, 22.26, 24.21, and 25.41±0.2° 2θ using Cu Kα radiation.

31. The omecamtiv mecarbil free base crystalline form VII of claim 29 , further characterized by XRPD pattern peaks at 7.84, 10.81, 21.61, 23.22, 23.46, 27.58, 29.53, 30.13, and 31.32±0.2° 2θ using Cu Kα radiation.

32. The omecamtiv mecarbil free base crystalline form VII of claim 29 , having an XRPD pattern substantially as shown in FIG. 12 .

Assignees

• Amgen Inc
• Cytokinetics 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 Ailsa
• MORGAN Bradley
• Peterson Matthew
• Eberlin Alex
• Oblezov Alexander

Classifications

• 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

• C07C309/08

  containing hydroxy groups bound to the carbon skeleton · CPC title

• C07C65/10

  Salicylic acid · CPC title

• C07C309/35

  Naphthalene sulfonic acids · CPC title

• C07C57/15

  Fumaric acid · CPC title