Salts and solid forms of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and compositions comprising and methods of using the same
Salts and solid forms of 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a stereoisomer thereof, are disclosed. Compositions comprising and methods of using the salts and solid forms are also disclosed.
1. A method of treating cancer, an immune-related disease or disorder, an inflammatory disease or disorder, or a symptom thereof in a subject, comprising administering to the subject a therapeutically effective amount of a solid form comprising a salt, hydrate, or solvate of Compound (I-S):
wherein the solid form is crystalline, wherein the solid form
comprises Compound (I-S) and water, having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees 2θ;
comprises Compound (I-S) and THF, having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees 2θ;
comprises a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96 degrees 2θ;
comprises a DMSO solvate of a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 16.88, 18.14, and 20.02 degrees 2θ;
comprises a D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and 25.86 degrees 2θ;
comprises a hemi D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.21, 12.91, and 16.32 degrees 2θ;
comprises a L-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32 degrees 2θ;
comprises a tosylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25 degrees 2θ; or
comprises a (+) camphorsulfonic acid salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.05, 14.61, and 16.82 degrees 2θ;
wherein the cancer, immune-related disease or disorder, or inflammatory disease or disorder is lupus, scleroderma, Sjögren syndrome, ANCA-induced vasculitis, anti-phospholipid syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), discoid lupus erythematosus (DLE), drug-induced lupus, or multiple myeloma.
2. The method of claim 1 , comprising Compound (I-S) and water having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees 2θ.
3. The method of claim 2 , wherein the XRPD pattern further comprises peaks at approximately 13.79, 17.15, and 26.00 degrees 2θ.
4. The method of claim 2 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 5 .
5. The method of claim 1 , comprising Compound (I-S) and THF having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees 2θ.
6. The method of claim 5 , wherein the XRPD pattern further comprises peaks at approximately 6.03 and 18.59 degrees 2θ.
7. The method of claim 5 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 8 .
8. The method of claim 1 , comprising a besylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96 degrees 2θ.
9. The method of claim 8 , wherein the XRPD pattern further comprises peaks at approximately 15.48 and 15.92 degrees 2θ.
10. The method of claim 8 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 11 .
11. The method of claim 1 , comprising a DMSO solvate of a besylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 16.88, 18.14, and 20.02 degrees 2θ.
12. The method of claim 11 , wherein the XRPD pattern further comprises peaks at approximately 7.31 and 24.49 degrees 2θ.
13. The method of claim 11 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 16 .
14. The method of claim 1 , comprising a D-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and 25.86 degrees 2θ.
15. The method of claim 14 , wherein the XRPD pattern further comprises peaks at approximately 19.25 and 21.25 degrees 2θ.
16. The method of claim 14 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 20 .
17. The method of claim 1 , comprising a hemi D-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 6.21, 12.91, and 16.32 degrees 2θ.
18. The method of claim 17 , wherein the XRPD pattern further comprises peaks at approximately 12.32 and 19.09 degrees 2θ.
19. The method of claim 17 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 23 .
20. The method of claim 1 , comprising a L-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32 degrees 2θ.
21. The method of claim 20 , wherein the XRPD pattern further comprises peaks at approximately 11.97, 14.41, and 17.08 degrees 2θ.
22. The method of claim 20 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 26 .
23. The method of claim 1 , comprising a tosylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25 degrees 2θ.
24. The method of claim 23 , wherein the XRPD pattern further comprises peaks at approximately 7.41 and 22.97 degrees 2θ.
25. The method of claim 23 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 29 .
26. The method of claim 1 , comprising a (+) camphorsulfonic acid salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 9.05, 14.61, and 16.82 degrees 2θ.
27. The method of claim 26 , wherein the XRPD pattern further comprises peaks at approximately 13.97, 15.34, and 16.35 degrees 2θ.
28. The method of claim 26 , wherein the XRPD pattern matches the XRPD pattern presented in FIG. 32 .
29. The method of claim 1 , wherein the immune-related or inflammatory disease or disorder is lupus, scleroderma, Sjögren syndrome, ANCA-induced vasculitis, anti-phospholipid syndrome, or myasthenia gravis.
30. The method of claim 1 , wherein the immune-related or inflammatory disease or disorder is scleroderma.
31. The method of claim 1 , wherein the immune-related or inflammatory disease or disorder is systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), discoid lupus erythematosus (DLE), or drug-induced lupus.
32. The method of claim 31 , wherein the immune-related or inflammatory disease or disorder is SLE.
33. The method of claim 31 , wherein the immune-related or inflammatory disease or disorder is CLE.
34. The method of claim 1 , wherein the cancer is multiple myeloma.