Crystalline forms of a compound that inhibits bromodomain
Forms of 4-(1-(1,1-di(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the forms of Compound I.
1. A crystalline form of Compound I of Form B having the formula:
characterized by an X-ray powder diffractogram comprising the following peaks: 19.0, 21.0, and 24.8 °2θ±0.2 °2θ, as determined on a diffractometer using Cu-Kα radiation.
2. A method for treating a patient suffering from, or at risk of, a disease or condition mediated by a bromodomain, the method comprising administering to the patient in need thereof an effective amount of a crystalline form of claim 1 , wherein the disease or condition is selected from the group consisting of: rheumatoid arthritis, osteoarthritis, ulcerative colitis, and atherosclerosis.
3. The crystalline form of claim 1 , wherein the diffractogram further comprises one or more peaks at: 10.9, 17.2, or 18.0 °2θ±0.2 °2θ.
4. A crystalline form of Compound I of Form C having the formula:
characterized by an X-ray powder diffractogram comprising the following peaks: 8.8, 17.1, and 17.7 °2θ±0.2 °2θ (Compound I Form C), as determined on a diffractometer using Cu-Kα radiation.
5. The crystalline form of claim 4 , wherein the diffractogram further comprises one or more peaks at: 11.6 or 15.1 °2θ±0.2 °2θ.
6. A crystalline form of Compound I of Form D having the formula:
characterized by an X-ray powder diffractogram comprising the following peaks: 8.0, 16.1, and 20.2 °2θ±0.2 °2θ (Compound I Form D), as determined on a diffractometer using Cu-Kα radiation.
7. The crystalline form of claim 6 , wherein the diffractogram further comprises one or more peaks at: 13.5 or 22.2 °2θ±0.2 °2θ.
8. A crystalline form of Compound I of Form E having the formula:
characterized by an X-ray powder diffractogram comprising the following peaks: 4.7, 9.4, and 18.8 °2θ±0.2 °2θ (Compound I Form E), as determined on a diffractometer using Cu-Kα radiation.
9. The crystalline form of claim 8 , wherein the diffractogram further comprises one or more peaks at: 9.1, 14.1, or 18.2 °2θ±0.2 °2θ.
10. A pharmaceutical composition comprising a crystalline form of claim 1 , and one or more pharmaceutically acceptable carriers.
11. A pharmaceutical composition comprising a crystalline form of claim 4 , and one or more pharmaceutically acceptable carriers.
12. A pharmaceutical composition comprising a crystalline form of claim 6 , and one or more pharmaceutically acceptable carriers.
13. A pharmaceutical composition comprising a crystalline form of claim 8 , and one or more pharmaceutically acceptable carriers.
14. A method for treating a patient suffering from, or at risk of, a disease or condition mediated by a bromodomain, the method comprising administering to the patient in need thereof an effective amount of a crystalline form of claim 4 , wherein the disease or condition is selected from the group consisting of: rheumatoid arthritis, osteoarthritis, ulcerative colitis, and atherosclerosis.
15. A method for treating a patient suffering from, or at risk of, a disease or condition mediated by a bromodomain, the method comprising administering to the patient in need thereof an effective amount of a crystalline form of claim 6 , wherein the disease or condition is selected from the group consisting of: rheumatoid arthritis, osteoarthritis, ulcerative colitis, and atherosclerosis.
16. A method for treating a patient suffering from, or at risk of, a disease or condition mediated by a bromodomain, the method comprising administering to the patient in need thereof an effective amount of a crystalline form of claim 8 , wherein the disease or condition is selected from the group consisting of: rheumatoid arthritis, osteoarthritis, ulcerative colitis, and atherosclerosis.