Solid state forms of substituted pyrazolopyrimidines and uses thereof
The present disclosure relates to: a) solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); b) pharmaceutical compositions comprising one or more solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III), and optionally, a pharmaceutically acceptable carrier or diluent; c) methods of treating tumors or cancers by administering one or more solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III) to a subject in need thereof; and d) methods for the preparation of solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III).
1. A solid state form of 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II):
or a pharmaceutically acceptable salt thereof.
2. The solid state form of claim 1 , wherein the solid state form is a pharmaceutically acceptable co-crystal formed between 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II) and a pharmaceutically acceptable acid.
3. The solid state form of claim 2 , wherein the pharmaceutically acceptable acid is gentisic acid.
4. The solid state form of claim 3 , wherein the gentisic acid co-crystal is crystalline Form 2 characterized by an XRPD pattern having peaks at 16.6±0.2, 18.7±0.2, and 22.5±0.2 degrees two theta.
5. The solid state form of claim 3 , characterized by an endothermic peak at about 186.0° C., as determined by DSC.
6. The solid state form of claim 3 , characterized by an about 3.17 wt % loss between room temperature and about 170° C., as determined by TGA.
7. The solid state form of claim 3 , characterized by at least one of the following:
a) an XRPD pattern as shown in FIG. 9 ;
b) a DSC profile as shown in FIG. 10 ; or
c) a TGA profile as shown in FIG. 10 .
8. A mixture comprising the solid state form of claim 3 and a second solid state form of 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II).
9. The solid state form of 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II) of claim 2 selected from the group consisting of:
a) crystalline Form A, wherein Form A is characterized by an XRPD pattern having peaks at 14.3±0.2, 21.5±0.2, and 21.8±0.2 degrees two theta;
b) crystalline Form C, wherein Form C is characterized by an XRPD pattern having peaks at 14.2±0.2, 17.0±0.2, and 19.1±0.2 degrees two theta;
c) crystalline Form D, wherein Form D is characterized by an XRPD pattern having peaks at 13.9±0.2, 15.2±0.2, and 19.3±0.2 degrees two theta;
d) crystalline Form E, wherein Form E is characterized by an XRPD pattern having peaks at 10.6±0.2, 18.7±0.2, and 20.9±0.2 degrees two theta; and
e) crystalline Form F, wherein Form F is characterized by an XRPD pattern having peaks at 10.7±0.2, 14.3±0.2, and 21.8±0.2 degrees two theta;
or combinations thereof.
10. The solid state form of claim 9 , wherein the solid state form is crystalline Form A, and
wherein the solid state form is characterized by at least one of the following:
a) an XRPD pattern as shown in FIG. 1 ;
b) an endothermic peak at about 165° C., as determined by DSC;
c) a DSC profile as shown in FIG. 2 ;
d) an about 0.93 wt % loss between room temperature and about 150° C., as determined by TGA; or
e) a TGA profile as shown in FIG. 2 .
11. The solid state form of claim 9 , wherein the solid state form is crystalline Form C, and
wherein the solid state form is characterized by an XRPD pattern as shown in FIG. 3 .
12. The solid state form of claim 9 , wherein the solid state form is crystalline Form D, and
wherein the solid state form is characterized by an XRPD pattern as shown in FIG. 4 .
13. The solid state form of claim 9 , wherein the solid state form is crystalline Form E, and
wherein the solid state form is characterized by at least one of the following:
a) an XRPD pattern as shown in FIG. 5 ;
b) an endothermic peak at about 107° C., as determined by DSC;
c) a DSC profile as shown in FIG. 6 ;
d) an about 13.5 wt % loss between room temperature and about 200° C., as determined by TGA; or
e) a TGA profile as shown in FIG. 6 .
14. The solid state form of claim 9 , wherein the solid state form is crystalline Form F, and
wherein the solid state form is characterized by one of the following:
a) an XRPD pattern as shown in FIG. 25 ;
b) an endothermic peak at about 157° C., as determined by DSC; or
c) a DSC profile as shown in FIG. 26 .
15. The solid state form of claim 1 , wherein the solid state form is a pharmaceutically acceptable salt formed between 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II) and a pharmaceutically acceptable acid.
16. The solid state form of claim 15 , wherein the pharmaceutically acceptable salt is a hydrochloric acid salt; and wherein the hydrochloric acid salt is crystalline Form 1 characterized by an XRPD pattern having peaks at 12.5±0.2, 22.4±0.2, and 23.9±0.2 degrees two theta.
17. The solid state form of claim 2 , wherein the pharmaceutically acceptable acid is benzoic acid, and
wherein the benzoic acid co-crystal is crystalline Form 8 characterized by an XRPD pattern having peaks at 12.1±0.2, 14.2±0.2, and 16.5±0.2 degrees two theta.
18. The solid state form of claim 2 , wherein the pharmaceutically acceptable acid is salicylic acid, and
wherein the salicylic acid co-crystal is crystalline Form 9 characterized by an XRPD pattern having peaks at 11.0±0.2, 16.5±0.2, 17.3±0.2 and 25.3±0.2 degrees two theta.
19. A pharmaceutical composition comprising the solid state form of claim 1 and one or more pharmaceutically acceptable carriers or diluents.
20. A pharmaceutical composition comprising the solid state form of claim 3 and one or more pharmaceutically acceptable carriers or diluents.
21. A pharmaceutical composition comprising the solid state form of claim 4 and one or more pharmaceutically acceptable carriers or diluents.
22. The pharmaceutical composition of claim 19 , which is an oral solid dosage form.
23. The pharmaceutical composition of claim 22 , wherein the solid dosage form is selected from a tablet, a capsule, a pill, granules, a powder, a sachet, a chewable, and a film.
24. The pharmaceutical composition of claim 20 , which is an oral solid dosage form.
25. The pharmaceutical composition of claim 24 , wherein the solid dosage form is selected from a tablet, a capsule, a pill, granules, a powder, a sachet, a chewable, and a film.
26. The pharmaceutical composition of claim 21 , which is an oral solid dosage form.
27. The pharmaceutical composition of claim 26 , wherein the solid dosage form is selected from a tablet, a capsule, a pill, granules, a powder, a sachet, a chewable, and a film.