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1. (WO2016123574) CRYSTALLINE FORMS OF C21H22CI2N4O2
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

What is claimed is:

1 . Crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide.

2. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide.

3. A crystalline free base of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 19.5° 2Θ.

4. A crystalline free base of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 9.1 and 19.5° 2Θ.

5. A crystalline free base of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 9.1 , 15.4, 19.5 and 21 .4° 2Θ.

6. A crystalline free base of a compound of formula:

having one or more XRPD 20-reflections (°) selected from the group consisting of about 9.1 , 12.5, 15.2, 15.4, 19.2, 19.5, 20.3, 20.5, 21 .4, 21 .7, 21 .9, 23.1 , 23.3, 23.6, and 24.3.

7. A crystalline free base of a compound of formula:


having an XRPD pattern substantially as shown in FIG. 1 .

8. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1603, 1533, 1487, 1080, 857, and 681 cm"1.

9. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having an FT-IR spectrum substantially as shown in FIG. 2.

10. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having (i) an XRPD pattern comprising one or more peaks at about 9.1 , 15.4, 19.5 and 21 .4° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1603, 1533, 1487, 1080, 857, and 681 cm"1.

1 1 . Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having a DSC thermogram with an endotherm having an onset temperature of approximately 184°C.

12. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having a DSC thermogram substantially as shown in FIG. 3.

13. A pharmaceutical composition comprising a crystalline compound according to claims 1 -12.

14. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 1 -12.

15. The method according to claim 14, wherein the subject is a mammal.

16. The method according to claim 15, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

17. The method according to claim 15, wherein the mammal is a human.

18. The method according to claim 14 further comprising administering to the subject at least one additional anti-cancer agent.

19. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 13.

20. The method according to claim 19, wherein the subject is a mammal.

21 . The method according to claim 20, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

22. The method according to claim 20, wherein the mammal is a human.

23. The method according to claim 19 further comprising administering to the subject at least one additional anti-cancer agent.

24. Crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI.

25. A crystalline hydrochloride salt of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 6.7° 2Θ.

26. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 6.7 and 1 1 .0° 2Θ.

27. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 6.7, 1 1 .0, 17.6 and 19.9° 2Θ.

28. A crystalline hydrochloride salt of a compound of formula:

having one or more XRPD 20-reflections (°) selected from the group consisting of about 6.1 , 6.7, 1 1 .0, 12.1 , 13.7, 15.2, 16.5, 17.6, 17.9, 18.4, 18.7, 19.6, 19.9, and 20.4.

29. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern substantially as shown in FIG. 4.

30. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1610, 1523, 1219, 1 141 , 1076, and 845 cm-1.

31 . Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having an FT-IR spectrum substantially as shown in FIG. 5.

32. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having (i) an XRPD pattern comprising one or more peaks at about 6.7, 1 1 .0, 17.6, and 19.9° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1610, 1523, 1219, 1 141 , 1076, and 845 cm"1.

33. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having a DSC thermogram with an endotherm having an onset temperature of approximately 239°C.

34. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having a DSC thermogram substantially as shown in FIG. 6.

35. A pharmaceutical composition comprising a crystalline compound according to any one of claims 24-34.

36. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 24-34.

37. The method according to claim 36, wherein the subject is a mammal.

38. The method according to claim 37, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

39. The method according to claim 37, wherein the mammal is a human.

40. The method according to claim 36 further comprising administering to the subject at least one additional anti-cancer agent.

41 . A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 35.

42. The method according to claim 41 , wherein the subject is a mammal.

43. The method according to claim 42, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

44. The method according to claim 42, wherein the mammal is a human.

45. The method according to claim 41 further comprising administering to the subject at least one additional anti-cancer agent.

46. Crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate.

47. A crystalline hydrochloride salt of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 10.5° 2Θ.

48. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 6.2 and 10.5° 2Θ.

49. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 6.2, 10.5, 22.4 and 28.5° 2Θ.

50. A crystalline hydrochloride salt of a compound of formula:

having one or more XRPD 20-reflections (°) selected from the group consisting of about 5.8, 5.9, 6.2, 10.5, 1 1 .8, 12.4, 15.9, 17.6, 17.8, 20.0, 20.4, 21 .1 , 21 .4, 21 .9, 22.4, 23.1 , 24.0, 24.2, 24.9, and 25.3.

51 A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern substantially as shown in FIG. 7.

52. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1573, 1237, 1 163, 946, and 790 cm"1.

53. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having an FT-IR spectrum substantially as shown in FIG. 8.

54. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having (i) an XRPD pattern comprising one or more peaks at about 6.2, 10.5, 22.4, and 28.5° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1573, 1237, 1 163, 946, and 790 cm"1.

55. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having a DSC thermogram substantially as shown in FIG. 9.

56. A pharmaceutical composition comprising a crystalline compound according to any one of claims 46-55.

57. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 46-55.

The method according to claim 57, wherein the subject is a mammal.

59. The method according to claim 58, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

60. The method according to claim 58, wherein the mammal is a human.

61 . The method according to claim 57 further comprising administering to the subject at least one additional anti-cancer agent.

62. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 56.

63. The method according to claim 62, wherein the subject is a mammal.

64. The method according to claim 63, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

65. The method according to claim 63, wherein the mammal is a human.

66. The method according to claim 62 further comprising administering to the subject at least one additional anti-cancer agent.

67. A crystalline hydrochloride salt of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 10.7° 2Θ.

68. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 10.7 and 18.1 ° 2Θ.

69. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 6.0, 10.7, 12.7, and -\ 8Α ° 2Θ.

70. A crystalline hydrochloride salt of a compound of formula:


having one or more XRPD 20-reflections (°) selected from the group consisting of about 6.0, 6.3, 10.7, 12.0, 12.7, 15.6, 16.2, 16.3, 16.7, 17.9, 18.1 , and 21 .4.

71 . A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern substantially as shown in FIG. 10.

72. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1537, 1471 , 1239, 1 163, 1067, and 946 cm"1.

73. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having an FT-IR spectrum substantially as shown in FIG. 1 1 .

74. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having (i) an XRPD pattern comprising one or more peaks at about 6.0, 12.7, and 18.1 ° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1537, 1471 , 1239, 1 163, 1067, and 946 cm"1.

75. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having a DSC thermogram substantially as shown in FIG. 12.

76. A pharmaceutical composition comprising a crystalline compound according to any one of claims 67-75.

77. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 67-75.

78. The method according to claim 77, wherein the subject is a mammal.

79. The method according to claim 78, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

80. The method according to claim 78, wherein the mammal is a human.

81 . The method according to claim 77 further comprising administering to the subject at least one additional anti-cancer agent.

82. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 76.

83. The method according to claim 82, wherein the subject is a mammal.

84. The method according to claim 83, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

85. The method according to claim 83, wherein the mammal is a human.

86. The method according to claim 82 further comprising administering to the subject at least one additional anti-cancer agent.

AMENDED CLAIMS

received by the International Bureau on 25th May 2016 (25.05.2016)

What is claimed is:

1 . Crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 19.5° 2Θ, 6.7° 2Θ, 10.5° 2Θ, or 10.7° 2Θ.

2. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide.

3. A crystalline free base of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 19.5° 2Θ.

4. A crystalline free base of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 9.1 and 19.5° 2Θ.

5. A crystalline free base of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 9.1 , 15.4, 19.5 and 21 .4° 2Θ.

6. A crystalline free base of a compound of formula:

having one or more XRPD 20-reflections (°) selected from the group consisting of about 9.1 , 12.5, 15.2, 15.4, 19.2, 19.5, 20.3, 20.5, 21.4, 21.7, 21.9, 23.1 , 23.3, 23.6, and 24.3.

7. A crystalline free base of a compound of formula:


having an XRPD pattern substantially as shown in FIG. 1.

8. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)- H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1603, 1533, 1487, 1080, 857, and 681 cm"1.

9. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having an FT-IR spectrum substantially as shown in FIG. 2.

10. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having (i) an XRPD pattern comprising one or more peaks at about 9.1 , 15.4, 9.5 and 21.4° 20; and (ii) a FT-IR spectrum comprising one or more peaks at about 1603, 1533, 1487, 1080, 857, and 681 cm"1.

1 1 . Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having a DSC thermogram with an endotherm having an onset temperature of approximately 184°C.

12. Crystalline free base 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 2 having a DSC thermogram substantially as shown in FIG. 3.

13. A pharmaceutical composition comprising a crystalline compound according to any one of claims 1 -12.

14. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 1 -12.

15. The method according to claim 14, wherein the subject is a mammal.

16. The method according to claim 15, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

17. The method according to claim 15, wherein the mammal is a human.

18. The method according to claim 14 further comprising administering to the subject at least one additional anti-cancer agent.

19. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 13.

20. The method according to claim 19, wherein the subject is a mammal.

21. The method according to claim 20, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

22. The method according to claim 20, wherein the mammal is a human.

23. The method according to claim 19 further comprising administering to the subject at least one additional anti-cancer agent.

24. Crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 6.7° 2Θ.

25. A crystalline hydrochloride salt of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 6.7° 20.

26. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 6.7 and 1 1 .0° 2Θ.

27. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 6.7, 1 1 .0, 17.6 and 19.9° 2Θ.

28. A crystalline hydrochloride salt of a compound of formula:

having one or more XRPD 20-reflections (°) selected from the group consisting of about 6.1 , 6.7, 11.0, 12.1 , 13.7, 15.2, 16.5, 17.6, 17.9, 18.4, 18.7, 19.6, 19.9, and 20.4.

29. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern substantially as shown in FIG. 4.

30. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)- H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1610, 1523, 1219, 1141 , 1076, and 845 cm-1.

31. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having an FT-IR spectrum substantially as shown in FIG. 5.

32. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having (i) an XRPD pattern comprising one or more peaks at about 6.7, 1 .0, 7.6, and 19.9° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1610, 1523, 1219, 1 141 , 1076, and 845 cm"1.

33. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having a DSC thermogram with an endotherm having an onset temperature of approximately 239°C.

34. Form C crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide mono HCI according to claim 24 having a DSC thermogram substantially as shown in FIG. 6.

35. A pharmaceutical composition comprising a crystalline compound according to any one of claims 24-34.

36. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 24-34.

37. The method according to claim 36, wherein the subject is a mammal.

38. The method according to claim 37, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

39. The method according to claim 37, wherein the mammal is a human.

40. The method according to claim 36 further comprising administering to the subject at least one additional anti-cancer agent.

41. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 35.

42. The method according to claim 41 , wherein the subject is a mammal.

43. The method according to claim 42, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

44. The method according to claim 42, wherein the mammal is a human.

45. The method according to claim 41 further comprising administering to the subject at least one additional anti-cancer agent.

46. Crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate.

47. A crystalline hydrochloride salt of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 10.5° 2Θ.

48. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 6.2 and 10.5° 20.

49. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 6.2, 10.5, 22.4 and 28.5° 20.

50. A crystalline hydrochloride salt of a compound of formula:

having one or more XRPD 20-reflections (°) selected from the group consisting of about 5.8, 5.9, 6.2, 10.5, 1 1.8, 12.4, 15.9, 17.6, 17.8, 20.0, 20.4, 21.1 , 21.4, 21.9, 22.4, 23.1 , 24.0, 24.2, 24.9, and 25.3.

51 A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern substantially as shown in FIG. 7.

52. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1573, 1237, 1 163, 946, and 790 cm"1.

53. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having an FT-IR spectrum substantially as shown in FIG. 8.

54. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having (i) an XRPD pattern comprising one or more peaks at about 6.2, 10.5, 22.4, and 28.5° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1573, 1237, 1 163, 946, and 790 cm"1.

55. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI hydrate according to claim 46 having a DSC thermogram substantially as shown in FIG. 9.

56. A pharmaceutical composition comprising a crystalline compound according to any one of claims 46-55.

57. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 46-55.

The method according to claim 57, wherein the subject is a mammal.

59. The method according to claim 58, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

60. The method according to claim 58, wherein the mammal is a human.

61. The method according to claim 57 further comprising administering to the subject at least one additional anti-cancer agent.

62. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 56.

63. The method according to claim 62, wherein the subject is a mammal.

64. The method according to claim 63, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

65. The method according to claim 63, wherein the mammal is a human.

66. The method according to claim 62 further comprising administering to the subject at least one additional anti-cancer agent.

67. A crystalline hydrochloride salt of a compound of formula:


having an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 10.7° 20.

68. A crystalline hydrochloride salt of a compound of formula:


having an XRPD pattern comprising characteristic peaks at about 10.7 and 18.1 ° 2Θ.

69. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern comprising characteristic peaks at about 6.0, 10.7, 12.7, and 18.1° 20.

70. A crystalline hydrochloride salt of a compound of formula:


having one or more XRPD 20-reflections (°) selected from the group consisting of about 6.0, 6.3, 10.7, 12.0, 12.7, 15.6, 16.2, 16.3, 16.7, 17.9, 18.1 , and 21.4.

71. A crystalline hydrochloride salt of a compound of formula:

having an XRPD pattern substantially as shown in FIG. 10.

72. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having a Fourier transform infrared spectroscopy (FT-IR) spectrum comprising one or more peaks at about 1537, 1471 , 1239, 1 163, 1067, and 946 cm" .

73. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)- H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having an FT-IR spectrum substantially as shown in FIG. 1 1 .

74. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having (i) an XRPD pattern comprising one or more peaks at about 6.0, 12.7, and 18.1 ° 2Θ; and (ii) a FT-IR spectrum comprising one or more peaks at about 1537, 471 , 1239, 1 163, 1067, and 946 cm"1.

75. Form D crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide HCI according to claim 24 having a DSC thermogram substantially as shown in FIG. 12.

76. A pharmaceutical composition comprising a crystalline compound according to any one of claims 67-75.

77. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 67-75.

78. The method according to claim 77, wherein the subject is a mammal.

79. The method according to claim 78, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

80. The method according to claim 78, wherein the mammal is a human.

81. The method according to claim 77 further comprising administering to the subject at least one additional anti-cancer agent.

82. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 76.

83. The method according to claim 82, wherein the subject is a mammal.

84. The method according to claim 83, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

85. The method according to claim 83, wherein the mammal is a human.

86. The method according to claim 82 further comprising administering to the subject at least one additional anti-cancer agent.