Crystalline forms of a CD73 inhibitor and uses thereof
Crystalline forms of the compound of Formula (I), which modulates the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compound and methods for preparing the crystalline forms, are described herein. The use of such crystalline form of Formula (I) and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.
1. Crystalline Form III of a compound of Formula (I):
characterized by an XRPD pattern comprising peaks at 6.6, 10.9, 14.2, 16.1, 18.4, and 19.3 degrees 20 (±0.2 degrees 2θ).
2. The crystalline Form III of claim 1 , wherein the XRPD pattern further comprises one or more peaks at 20.2, 22.0, 24.7, and 28.1 degrees 2θ (±0.2 degrees 2θ).
3. The crystalline Form III of claim 1 , wherein the XRPD pattern further comprises three or more peaks at 20.2, 22.0, 24.7, and 28.1 degrees 2θ (±0.2 degrees 2θ).
4. The crystalline Form III of claim 1 , wherein the X-ray powder diffraction pattern is substantially in accordance with FIG. 5 .
5. The crystalline Form III of claim 1 , which is substantially free of other crystalline or amorphous forms of a compound of Formula (I).
6. The crystalline Form III of claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 161.8° C.
7. The crystalline Form III of claim 1 , further characterized by a melting point onset of about 149.6° C. as determined by a differential scanning calorimetry thermogram (DSC).
8. The crystalline Form III of claim 6 , wherein the DSC thermogram is substantially in accordance with FIGS. 6 .
9. Crystalline Form VI of a compound of Formula (I):
characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 19.4, 21.3, 22.4, and 24.4 degrees 2θ (±0.2 degrees 2θ) and further comprising three or more peaks at 5.8, 10.4, 27.5, and 31.1 degrees 2θ (±0.2 degrees 2θ).
10. The crystalline Form VI of claim 9 , wherein the X-ray powder diffraction pattern is substantially in accordance with FIG. 10 .
11. The crystalline Form VI of claim 9 , which is substantially free of other crystalline or amorphous forms of a compound of Formula (I).
12. The crystalline Form VI of claim 9 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 142.9° C.
13. The crystalline Form VI of claim 12 , wherein the DSC thermogram is substantially in accordance with FIG. 11 .
14. The crystalline Form VI of claim 9 , further characterized by a melting point onset of about 116.6° C. as determined by a differential scanning calorimetry thermogram (DSC).
15. A pharmaceutical composition comprising a crystalline form of any one of claims 1 or 9 , and a pharmaceutically acceptable excipient.
16. A method of treating a disease, disorder, or condition, mediated at least in part by CD73, said method comprising administering an effective amount of a crystalline form of the compound of any one of claims 1 or 9 , to a subject in need thereof.
17. The method of claim 16 , wherein the disease, disorder, or condition is cancer.
18. The method of claim 17 , wherein the cancer is selected from the group consisting of melanoma, colon cancer, pancreatic cancer, breast cancer, prostate cancer, lung cancer, leukemia, a brain tumor, lymphoma, ovarian cancer, and Kaposi's sarcoma.
19. A method of treating cancer in a subject, said method comprising administering to said subject an effective amount of a crystalline form of the compound of any one of claims 1 or 9 , and at least one additional therapeutic agent.