Solid state forms of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide and uses thereof
The present disclosure relates to: a) solid state forms of hydrobromide salts of Compound 1; b) pharmaceutical compositions comprising one or more solid state forms of hydrobromide salts of Compound 1, and, optionally, a pharmaceutically acceptable carrier; c) methods of treating tumors or cancers by administering one or more solid state forms of hydrobromide salts of Compound 1 to a subject in need thereof; and d) methods for the preparation of solid state forms of Compound 1.
1. A crystalline form of a hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol -4-yl)pentanamide of Formula (I)
selected from the group consisting of:
a) crystalline Form A, wherein Form A is characterized by an XRPD pattern having peaks at 8.8±0.2, 9.8±0.2, and 23.3±0.2 degrees two theta;
b) crystalline Form B, wherein Form B is characterized by an XRPD pattern substantially as shown in FIG. 4 ;
c) crystalline Form D, wherein Form D is characterized by an XRPD pattern substantially as shown in FIG. 11 ;
d) crystalline Form E, wherein Form E is characterized by an XRPD pattern substantially as shown in FIG. 14 ;
e) crystalline Form F, wherein Form F is characterized by an XRPD pattern substantially as shown in FIG. 17 ;
f) crystalline Form F′, wherein Form F′ is characterized by an XRPD pattern substantially as shown in FIG. 18 ;
g) crystalline Form G, wherein Form G is characterized by an XRPD pattern substantially as shown in FIG. 21 ;
h) crystalline Form H, wherein Form H is characterized by an XRPD pattern substantially as shown in FIG. 22 ;
i) crystalline Form H′, wherein Form H′ is characterized by an XRPD pattern substantially as shown in FIG. 23 ;
j) crystalline Form J, wherein Form J is characterized by an XRPD pattern substantially as shown in FIG. 24 ;
k) crystalline Form K, wherein Form K is characterized by an XRPD pattern substantially as shown in FIG. 25 ;
1 ) crystalline Form L, wherein Form L is characterized by an XRPD pattern substantially as shown in FIG. 26 ;
m) crystalline Form M, wherein Form M is characterized by an XRPD pattern substantially as shown in FIG. 29 ; and
n) crystalline Form N, wherein Form N is characterized by an XRPD pattern substantially as shown in FIG. 30 .
2. The crystalline form of claim 1 , wherein the crystalline form is crystalline Form B, wherein Form B is characterized by an XRPD pattern substantially as shown in FIG. 4 .
3. The crystalline form of claim 1 , wherein the crystalline form is crystalline Form D, wherein Form D is characterized by an XRPD pattern substantially as shown in FIG. 11 .
4. The crystalline form of claim 1 , wherein the crystalline form is Form E, wherein Form E is characterized by an XRPD pattern substantially as shown in FIG. 14 .
5. The crystalline form of claim 1 , wherein the crystalline form is Form F, wherein Form F is characterized by an XRPD pattern substantially as shown in FIG. 17 .
6. The crystalline form of claim 1 , wherein the crystalline form is Form F′, wherein Form F′ is characterized by an XRPD pattern substantially as shown in FIG. 18 .
7. The crystalline form of claim 1 , wherein the crystalline form is Form G, wherein Form G is characterized by an XRPD pattern substantially as shown in FIG. 21 .
8. The crystalline form of claim 1 , wherein the crystalline form is Form H, wherein Form H is characterized by an XRPD pattern substantially as shown in FIG. 22 .
9. The crystalline form of claim 1 , wherein the crystalline form is Form H′, wherein Form H′ is characterized by an XRPD pattern substantially as shown in FIG. 23 .
10. The crystalline form of claim 1 , wherein the crystalline form is Form J, wherein Form J is characterized by an XRPD pattern substantially as shown in FIG. 24 .
11. The crystalline form of claim 1 , wherein the crystalline form is Form K, wherein Form K is characterized by an XRPD pattern substantially as shown in FIG. 25 .
12. The crystalline form of claim 1 , wherein the crystalline form is Form L, wherein Form L is characterized by an XRPD pattern substantially as shown in FIG. 26 .
13. The crystalline form of claim 1 , wherein the crystalline form is Form M, wherein Form M is characterized by an XRPD pattern substantially as shown in FIG. 29 .
14. The crystalline form of claim 1 , wherein the crystalline form is Form N, wherein Form N is characterized by an XRPD pattern substantially as shown in FIG. 30 .
15. A composition comprising a crystalline form of claim 1 , wherein the crystalline form has one or more of a D[V,0.10] particle size between 0.5 μm and 15 μm, a D[V,0.50] particle size between 2 μm and 30 μm, a D[V,0.90] particle size between 8 μm and 600 μm, or a D[4,3] particle size of 5 μm to 200 μm.
16. A pharmaceutical composition comprising a crystalline form or composition of claim 1 and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is a tablet.
18. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises 25 mg to 400 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl -1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.
19. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises 50 mg of the hydrobromide salt of (S)-2-(((S)-6, 8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-y1)-1H-imidazol-4-yl)pentanamide.
20. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises 100 mg of the hydrobromide salt of (S)-2-(((S)-6, 8-difluoro-1,2,3 ,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-y1)-1Himidazol-4-yl)pentanamide.
21. A method of treating desmoid tumors comprising administering to a subject in need of such treatment a pharmaceutical composition of claim 16 .
22. The method of claim 21 , wherein the subject is administered 50 mg to 500 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol -4-yl)pentanamide daily.
23. The method of claim 21 , wherein the subject is administered 100 mg to 400 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol -4-yl)pentanamide daily.
24. The method of claim 21 , wherein the subject is administered 300 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide daily.
25. The method of claim 21 , wherein the subject is administered 200 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide daily.
26. The method of claim 21 , wherein the subject is administered a total daily dose provided as two separate doses.
27. The method of claim 26 , wherein the total daily dose is provided as two separate doses of 150 mg.
28. The method of claim 26 , wherein the total daily dose is provided as two separate doses of 100 mg.