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 I of a compound of Formula (I):
characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.1, 13.8, 18.6, 20.1, 23.0, and 24.8 degrees 2θ (±0.2 degrees 2θ).
2. The crystalline Form I of claim 1 , wherein the XRPD pattern further comprises one or more peaks at 11.6, 14.7, 15.4, 16.6, 17.0, 19.3, 21.3, 22.1, 24.8, 26.6, 27.3, and 29.1 degrees 2θ (±0.2 degrees 2θ).
3. The crystalline Form I of claim 1 , characterized by an X-ray powder diffraction pattern that is substantially in accordance with FIG. 1 .
4. The crystalline Form I of claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 163.9° C.
5. The crystalline Form I of claim 1 , further characterized by a melting point onset of about 155.1° C. as determined by a differential scanning calorimetry thermogram (DSC).
6. The crystalline Form I of claim 4 , wherein the DSC thermogram is substantially in accordance with FIG. 2 .
7. Crystalline Form II of a compound of Formula (I):
characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 16.5, 22.8, and 24.6 degrees 2θ (±0.2 degrees 2θ).
8. The crystalline Form II of claim 7 , wherein the XRPD pattern further comprises one or more peaks at 10.1, 10.8, 12.8, 13.7, 17.7, and 19.0 degrees 2θ (±0.2 degrees 2θ).
9. The crystalline Form II of claim 7 , characterized by an X-ray powder diffraction pattern that is substantially in accordance with FIG. 3 .
10. The crystalline Form II of claim 7 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 166.5° C.
11. The crystalline Form II of claim 7 , further characterized by a melting point onset of about 157.4° C. as determined by a differential scanning calorimetry thermogram (DSC).
12. The crystalline Form II of claim 10 , wherein the DSC thermogram is substantially in accordance with FIG. 4 .
13. Crystalline Form V of a compound of Formula (I):
characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 15.8, 16.3, 16.8, 18.5, 19.1, 21.7, 22.1, and 23.0 degrees 2θ (±0.2 degrees 2θ).
14. The crystalline Form V of claim 13 , wherein the XRPD pattern further comprises one or more peaks at 10.4, 15.1, 19.7, and 23.6 degrees 2θ (±0.2 degrees 2θ).
15. The crystalline Form V of claim 13 , characterized by an X-ray powder diffraction pattern that is substantially in accordance with FIG. 8 .
16. The crystalline Form V of claim 13 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 150.4° C.
17. The crystalline Form V of claim 13 , further characterized by a melting point onset of about 135.8° C. as determined by a differential scanning calorimetry thermogram (DSC).
18. The crystalline Form V of claim 16 , wherein the DSC thermogram is substantially in accordance with FIG. 9 .
19. A pharmaceutical composition comprising a crystalline form of any one of claim 1 , 7 , or 13 , and a pharmaceutically acceptable excipient.
20. 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 claim 1 , 7 , or 13 , to a subject in need thereof.
21. The method of claim 20 , wherein the disease, disorder, or condition is cancer.
22. The method of claim 21 , 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.
23. 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 claim 1 , 7 , or 13 , and at least one additional therapeutic agent.