Crystalline forms of a prolyl hydroxylase inhibitor
The present disclosure relates to crystalline solid forms of [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, the process of preparing the forms, and pharmaceutical compositions and methods of use thereof.
1. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid (Compound A Form A) characterized by an X-ray powder diffractogram comprising the following peaks: 8.5, 16.2, and 27.4° 2θ±0.2° 2θ.
2. Compound A Form A according to claim 1 , wherein the diffractogram further comprises peaks at 12.8, 21.6, and 22.9° 2θ±0.2° 2θ.
3. Compound A Form A according to claim 1 , wherein the diffractogram is substantially as shown in FIG. 1 .
4. Compound A Form A according to claim 1 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 223° C.
5. Compound A Form A according to claim 4 , wherein the DSC curve is substantially as shown in FIG. 2 .
6. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid hemihydrate (Compound A Form B) characterized by an X-ray powder diffractogram comprising the following peaks: 4.2, 8.3, and 16.6° 2θ±0.2° 2θ.
7. Compound A Form B according to claim 6 , wherein the diffractogram further comprises peaks at 12.5, 14.1, and 17.4° 2θ±0.2° 2θ.
8. Compound A Form B according to claim 6 , wherein the diffractogram is substantially as shown in FIG. 3 .
9. Compound A Form B according to claim 6 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 222° C.
10. Compound A Form B according to claim 9 , wherein the DSC curve is substantially as shown in FIG. 4 .
11. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid hexafluoropropan-2-ol solvate (Compound A Form C) characterized by an X-ray powder diffractogram comprising the following peaks: 4.5, 13.7, and 16.4° 2θ±0.2° 2θ.
12. Compound A Form C according to claim 11 , wherein the diffractogram further comprises peaks at 15.4, 15.5, and 20.6° 2θ±0.2° 2θ.
13. Compound A Form C according to claim 11 , wherein the diffractogram is substantially as shown in FIG. 5 .
14. Compound A Form C according to claim 11 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 222° C.
15. Compound A Form C according to claim 14 , wherein the DSC curve is substantially as shown in FIG. 6 .
16. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid DMSO:water solvate (Compound A Form D) characterized by an X-ray powder diffractogram comprising the following peaks: 8.4, 8.5, and 16.8° 2θ±0.2° 2θ.
17. Compound A Form D according to claim 16 , wherein the diffractogram further comprises peaks at 4.2, 12.6, and 28.4° 2θ±0.2° 2θ.
18. Compound A Form D according to claim 16 , wherein the diffractogram is substantially as shown in FIG. 7 .
19. Compound A Form D according to claim 16 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 222° C.
20. Compound A Form D according to claim 19 , wherein the DSC curve is substantially as shown in FIG. 8 .
21. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid sodium salt (Compound A sodium salt) characterized by an X-ray powder diffractogram comprising the following peaks: 5.3, 16.0, and 21.6° 2θ±0.2° 2θ.
22. Compound A sodium salt according to claim 21 , wherein the diffractogram further comprises peaks at 18.7, 19.2, and 24.0° 2θ±0.2° 2θ.
23. Compound A sodium salt according to claim 21 , wherein the diffractogram is substantially as shown in FIG. 9 .
24. Compound A sodium salt according to claim 21 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 314° C.
25. Compound A sodium salt according to claim 24 , wherein the DSC curve is substantially as shown in FIG. 10 .
26. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid L-arginine salt (Compound A L-arginine salt) characterized by an X-ray powder diffractogram comprising the following peaks: 20.8, 21.8, and 25.4° 2θ±0.2° 2θ.
27. Compound A L-arginine salt according to claim 26 , wherein the diffractogram further comprises peaks at 22.7, 23.4, and 26.4° 2θ±0.2° 2θ.
28. Compound A L-arginine salt according to claim 26 , wherein the diffractogram is substantially as shown in FIG. 11 .
29. Compound A L-arginine salt according to claim 26 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 210° C.
30. Compound A L-arginine salt according to claim 29 , wherein the DSC curve is substantially as shown in FIG. 12 .
31. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid L-lysine salt (Compound A L-lysine salt) characterized by an X-ray powder diffractogram comprising the following peaks: 19.8, 20.7, and 21.2° 2θ±0.2° 2θ.
32. Compound A L-lysine salt according to claim 31 , wherein the diffractogram further comprises peaks at 10.2, 16.9, and 18.4° 2θ±0.2° 2θ.
33. Compound A L-lysine salt according to claim 31 , wherein the diffractogram is substantially as shown in FIG. 13 .
34. Compound A L-lysine salt according to claim 31 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 237° C.
35. Compound A L-lysine salt according to claim 34 , wherein the DSC curve is substantially as shown in FIG. 14 .
36. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid ethanolamine salt (Compound A ethanolamine salt) characterized by an X-ray powder diffractogram comprising the following peaks: 21.8, 22.7, and 27.1° 2θ±0.2° 2θ.
37. Compound A ethanolamine salt according to claim 36 , wherein the diffractogram further comprises peaks at 21.1, 26.2, and 26.6° 2θ±0.2° 2θ.
38. Compound A ethanolamine salt according to claim 36 , wherein the diffractogram is substantially as shown in FIG. 15 .
39. Compound A ethanolamine salt according to claim 36 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 171° C.
40. Compound A ethanolamine salt according to claim 39 , wherein the DSC curve is substantially as shown in FIG. 16 .
41. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid diethanolamine salt (Compound A diethanolamine salt) characterized by an X-ray powder diffractogram comprising the following peaks: 16.9, 23.7, and 25.0° 2θ±0.2° 2θ.
42. Compound A diethanolamine salt according to claim 41 , wherein the diffractogram further comprises peaks at 19.6, 22.6, and 26.0° 2θ±0.2° 2θ.
43. Compound A diethanolamine salt according to claim 41 , wherein the diffractogram is substantially as shown in FIG. 17 .
44. Compound A diethanolamine salt according to claim 41 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 150° C.
45. Compound A diethanolamine salt according to claim 44 , wherein the DSC curve is substantially as shown in FIG. 18 .
46. Crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid tromethamine salt (Compound A tromethamine salt) characterized by an X-ray powder diffractogram comprising the following peaks: 10.1, 14.2, and 21.1° 2θ±0.2° 2θ.
47. Compound A tromethamine salt according to claim 46 , wherein the diffractogram further comprises peaks at 20.1, 25.7, and 28.4° 2θ±0.2° 2θ.
48. Compound A tromethamine salt according to claim 46 , wherein the diffractogram is substantially as shown in FIG. 19 .
49. Compound A tromethamine salt according to claim 46 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 176° C.
50. Compound A tromethamine salt according to claim 49 , wherein the DSC curve is substantially as shown in FIG. 20 .
51. A pharmaceutical composition comprising Compound A Form A according to claim 1 , and a pharmaceutically acceptable excipient.
52. The pharmaceutical composition of claim 51 , further comprising at least one additional therapeutic agent selected from the group consisting of vitamin B12, folic acid, ferrous sulfate, recombinant human erythropoietin, and an erythropoiesis stimulating agent (ESA).