Granted Patent B2

US 11,465,969 · App. 17/263,224 · Granted Oct 11, 2022

Inventors: Henry Morrison (Thousand Oaks, CA); Sheng Cui (Thousand Oaks, CA); Kyle Quasdorf (Thousand Oaks, CA); Evelyn Yanez (Thousand Oaks, CA); Bin Peter Quan (Thousand Oaks, CA); Ron C. Kelly (Thousand Oaks, CA); Sebastien Caille (Thousand Oaks, CA); Lingyun Xiao (Thousand Oaks, CA); David Pearson (Berwickshire, GB); Jaclyn Raeburn (Milton Bridge, GB); Ailsa Golightly (Tranent, GB); Bradley Morgan (Moraga, CA); Matthew Peterson (San Diego, CA); Alex Eberlin (South San Francisco, CA); Alexander Oblezov (South San Francisco, CA)

Assignees: CYTOKINETICS, INC.; AMGEN INC.

C07D213/75C07B2200/13

Abstract

Claims (37)

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 .

Assignments (13)

Continuity (2)

Cited By (9)

US 12,194,039 US 12,221,417 US 12,264,133 US 12,269,811 US 12,275,704 US 12,295,952 US 12,442,027 US 12,583,821 US 12,612,366