Crystalline forms of IRAK degraders
The present disclosure relates generally to various forms, salts and compositions of compounds useful for the modulation of one or more interleukin-1 receptor-associated kinases (“IRAK”) via ubiquitination and/or degradation and uses of the same in the treatment various diseases.
1. A crystalline solid form of compound 1:
wherein the crystalline solid form is selected from the group consisting of Form A of compound 1 and Form B of compound 1; and wherein:
Form A of compound 1 is characterized by three or more peaks in its X-ray powder diffraction pattern selected from those at about 6.0, about 16.5, about 17.2, about 23.0, and about 23.9 degrees 2-theta; and
Form B of compound 1 is characterized by three or more peaks in its X-ray powder diffraction pattern selected from those at about 3.2, about 16.2, about 16.5, about 17.1, and about 18.2 degrees 2-theta.
2. The crystalline solid form according to claim 1 , wherein said a crystalline solid form is Form A of compound 1 having at least about 95% by weight of Form A of compound 1.
3. The crystalline solid form according to claim 1 , wherein said crystalline solid form is Form A of compound 1 having at least about 99% by weight of Form A of compound 1.
4. The crystalline solid form according to claim 1 , wherein the crystalline solid form is Form A of compound 1.
5. The crystalline solid form according to claim 4 , having four or more peaks in its X-ray powder diffraction pattern selected from those at about 6.0, about 16.5, about 17.2, about 23.0, and about 23.9 degrees 2-theta.
6. The crystalline solid form according to claim 4 , having five peaks in its X-ray powder diffraction pattern at about 6.0, about 16.5, about 17.2, about 23.0, and about 23.9 degrees 2-theta.
7. The crystalline solid form according to claim 1 , wherein the crystalline solid form is Form B of compound 1.
8. The crystalline solid form according to claim 7 , having four or more peaks in its X-ray powder diffraction pattern selected from those at about 3.2, about 16.2, about 16.5, about 17.1, and about 18.2 degrees 2-theta.
9. The crystalline solid form according to claim 7 , having five peaks in its X-ray powder diffraction pattern at about 3.2, about 16.2, about 16.5, about 17.1, and about 18.2 degrees 2-theta.
10. A crystalline salt form of compound 1:
selected from the group consisting of:
and
wherein:
the crystalline salt form of compound 2 is Form A of compound 2;
the crystalline salt form of compound 3 is Form A of compound 3;
the crystalline salt form of compound 4 is Form A of compound 4; and
wherein:
Form A of compound 2 is characterized by three or more peaks in its X-ray powder diffraction pattern selected from those at about 14.1, about 17.0, about 17.3, about 19.0, about 21.0, about 21.2 and about 23.3 degrees 2-theta;
Form A of compound 3 is characterized by three or more peaks in its X-ray powder diffraction pattern selected from those at about 6.4, about 11.9, about 16.2, about 17.2, and about 20.9 degrees 2-theta; and
Form A of compound 4 is characterized by three peaks in its X-ray powder diffraction pattern at about 3.3, about 6.4, and about 16.7 degrees 2-theta.
11. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of compound 2 having at least about 95% by weight of Form A of compound 2.
12. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of compound 2 having at least about 99% by weight of Form A of compound 2.
13. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of Compound 2.
14. The crystalline salt form according to claim 13 , having four or more peaks in its X-ray powder diffraction pattern selected from those at about 14.1, about 17.0, about 17.3, about 19.0, about 21.0, about 21.2 and about 23.3 degrees 2-theta.
15. The crystalline salt form according to claim 13 , having five or more peaks in its X-ray powder diffraction pattern selected from those at about 14.1, about 17.0, about 17.3, about 19.0, about 21.0, about 21.2 and about 23.3 degrees 2-theta.
16. The crystalline salt form according to claim 13 , having six or more peaks in its X-ray powder diffraction pattern selected from those at about 14.1, about 17.0, about 17.3, about 19.0, about 21.0, about 21.2 and about 23.3 degrees 2-theta.
17. The crystalline salt form according to claim 13 , having seven peaks in its X-ray powder diffraction pattern at about 14.1, about 17.0, about 17.3, about 19.0, about 21.0, about 21.2 and about 23.3 degrees 2-theta.
18. The crystalline salt form according to claim 13 , having the XRPD pattern as depicted in FIG. 3 A wherein each peak is within +/−0.2 degrees 2-theta.
19. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of compound 3 having at least about 95% by weight of Form A of compound 3.
20. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of compound 3 having at least about 99% by weight of Form A of compound 3.
21. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of Compound 3.
22. The crystalline salt form according to claim 21 , having ene four or more peaks in its X-ray powder diffraction pattern selected from those at about 6.4, about 11.9, about 16.2, about 17.2, and about 20.9 degrees 2-theta.
23. The crystalline salt form according to claim 21 , having five peaks in its X-ray powder diffraction pattern at about 6.4, about 11.9, about 16.2, about 17.2, and about 20.9 degrees 2-theta.
24. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of compound 4 having at least about 95% by weight of Form A of compound 4.
25. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of compound 4 having at least about 99% by weight of Form A of compound 4.
26. The crystalline salt form according to claim 10 , wherein said crystalline salt form is Form A of Compound 4.
27. A composition comprising a crystalline salt form according to claim 10 and a pharmaceutically acceptable carrier or excipient.
28. A method of degrading IRAK4 protein kinase in a patient or biological sample comprising administering to said patient, or contacting said biological sample with a crystalline salt form according to claim 10 , or a pharmaceutical composition thereof.
29. A method of treating an IRAK4-mediated disorder, disease, or condition in a patient comprising administering to said patient a crystalline salt form according to claim 10 , or a pharmaceutical composition thereof.