Hydrochloride salt of((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate
View Patent ↗Disclosed is a compound of formula (I): crystalline forms thereof, and solvates thereof; pharmaceutical compositions comprising a pharmaceutically effective amount of the compound of formula (I), or a crystalline form thereof, or a solvate thereof, and a pharmaceutically acceptable carrier or diluent; and the use of a compound of formula (I), or a crystalline form thereof, or a solvate thereof, for treating a patient suffering from, or subject to, a pathological condition capable of being ameliorated by inhibiting an E1 activating enzyme, particularly NAE, including, e.g., cancer.
1. A pharmaceutical composition comprising at least one crystalline form chosen from crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 1, Form 2, Form 3A, Form 3B, Form 3C, Form 5, and Form 7 and a pharmaceutically acceptable carrier or diluent.
2. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 1.
3. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 2.
4. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 3A.
5. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 3B.
6. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 3C.
7. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 5.
8. Crystalline ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate hydrochloride Form 7.
9. The compound of claim 2 , wherein Form 1 is characterized by an XRPD pattern having peaks at 2θ angles of 9.6°, 13.6° and 19.1°, wherein each 2θ angle value is ±0.2°.
10. The compound of claim 2 , wherein Form 1 is characterized by an XRPD pattern having peaks at 2θ angles of 9.6°, 13.6°, 14.5°, 19.1° and 23.7°, wherein each 2θ angle value is ±0.2°.
11. The compound of claim 2 , wherein Form 1 is characterized by at least two of (I-i)-(I-iv):
(I-i) an XRPD pattern having peaks at 2θ angles of 9.6°, 13.6° and 19.1°, wherein each 2θ angle value is ±0.2°;
(I-ii) a DSC profile as shown in FIG. 2 ;
(I-iii) a TGA profile as shown in FIG. 3 ; or
(I-iv) a solubility of about 7.8 mg/mL in water.
12. The compound of claim 3 , wherein Form 2 is characterized by an XRPD pattern having peaks at 2θ angles of 8.7°, 18.2° and 23.8°, wherein each 2θ angle value is ±0.2°.
13. The compound of claim 3 , wherein Form 2 is characterized by an XRPD pattern having peaks at 2θ angles of 8.7°, 18.2°, 19.4°, 23.8°, 24.3° and 27.5°, wherein each 2θ angle value is ±0.2°.
14. The compound of claim 3 , wherein Form 2 is characterized by at least two of (II-i)-(II-iii):
(II-i) an XRPD pattern having peaks at 2θ angles of 8.7°, 18.2° , and 23.8°, wherein each 2θ angle value is ±0.2°.
(II-ii) a DSC profile as shown in FIG. 5 ; or
(II-iii) a TGA profile as shown in FIG. 5 .
15. The compound of claim 4 , wherein Form 3 A is characterized by an XRPD pattern having peaks at 2θ angles of 10.9°, 14.6°, 19.5° and 24.0°, wherein each 2θ angle value is ±0.2°.
16. The compound of claim 4 , wherein Form 3 A is characterized by an XRPD pattern having peaks at 2θ angles of 10.9°, 14.6°, 19.5° and 24.0°, wherein each 2θ angle value is ±0.2°.
17. The compound of claim 4 , wherein Form 3 A is characterized by at least two of (III-i)-(III-iii):
(III-i) an XRPD pattern having peaks at b 2 θ angles of 10.9°, 14.6°, 19.5° and 24.0°, wherein each 2θ angle value is ±0.2°;
(III-ii) a DSC profile as shown in FIG. 7 ; or
(III-iii) a TGA profile as shown in FIG. 7 .
18. The compound of claim 5 , wherein Form 3 B is characterized by an XRPD pattern having peaks at 2θ angles of 10.8°, 16.9°, 23.7° and 24.0°, wherein each 2θ angle value is ±0.2°.
19. The compound of claim 5 , wherein Form 3 B is characterized by an XRPD pattern having peaks at 2θ angles of 10.8°, 14.5°, 16.9°, 19 . 3 °, 21 . 2 °, 23 . 7 °, 24 . 0 ° and 28.8°, wherein each 2θ angle value is ±0.2°.
20. The compound of claim 5 , wherein Form 3 B is characterized by at least two of (IV-i)-(IV-iii):
(IV-i) an XRPD pattern having peaks at 2θ angles of 10.8°, 16.9°, 23.7° and 24.0°, wherein each 2θ angle value is ±0.2°;
(IV-ii) a DSC profile as shown in FIG. 9 ; or
(IV-iii) a TGA profile as shown in FIG. 9 .
21. The compound of claim 6 , wherein Form 3 C is characterized by an XRPD pattern having peaks at 2θ angles of 11.0°, 12.2° and 24.4°, wherein each 2θ angle value is ±0.2°.
22. The compound of claim 6 , wherein Form 3 C is characterized by an XRPD pattern having peaks at 2θ angles of 11.0°, 12.2°, 14.9°, 19.8°, 24.0° and 24.4°, wherein each 2θ angle value is ±0.2°.
23. The compound of claim 6 , wherein Form 3 C is characterized by at least two of (V-i)-(V-iii):
(V-i) an XRPD pattern having peaks at 2θ angles of 11.0°, 12.2° and 24.4°, wherein each 2θ angle value is ±0.2°;
(V-ii) a DSC profile as shown in FIG. 11 ; or
(V-iii) a TGA profile as shown in FIG. 11 .
24. The compound of claim 7 , wherein Form 5 is characterized by an XRPD pattern having peaks at 2θ angles of 16.7° and 22.9°, wherein each 2θ angle value is ±0.2°.
25. The compound of claim 7 , wherein Form 5 is characterized by an XRPD pattern having peaks at 2θ angles of 16.7°, 17.2°, 18.1° and 22.9°, wherein each 2θ angle value is ±0.2°.
26. The compound of claim 7 , wherein Form 5 is characterized by at least two of (VI-i)-(VI-iv):
(VI-i) an XRPD pattern having peaks at 2θ angles of 16.7° and 22.9°, wherein each 2θ angle value is ±0.2°.
(VI-ii) a DSC profile as shown in FIG. 13 ; or
(VI-iii) a TGA profile as shown in FIG. 13 .
27. The compound of claim 8 , wherein Form 7 is characterized by an XRPD pattern having peaks at 2θ angles of 15.4°, 17.3°, 19.6° and 22.5°, wherein each 2θ angle value is ±0.2°.
28. The compound of claim 8 , wherein Form 7 is characterized by an XRPD pattern having peaks at 2θ angles of 10.0°, 15.4°, 16.6°, 17.3°, 18.0°, 18.3°, 19.6°, 22.0° and 22.5°, wherein each 2θ angle value is ±0.2°.
29. The compound of claim 8 , wherein Form 7 is characterized by at least two of (VII-i)-(VII-iii):
(VII-i) an XRPD pattern having peaks at 2θ angles of 15.4°, 17.3°, 19.6° and 22.5°, wherein each 2θ angle value is ±0.2°;
(VII-ii) a DSC profile as shown in FIG. 15 ; or
(VII-iii)a TGA profile as shown in FIG. 15 .