Solid forms of an epidermal growth factor receptor kinase inhibitor
The present invention provides a solid form and compositions thereof, which are useful as an inhibitor of EGFR kinases and which exhibit desirable characteristics for the same.
1. A solid form of Compound 1:
wherein Compound 1 is a free base.
2. The solid form of claim 1 , wherein the solid form is amorphous.
3. The solid form of claim 1 , wherein the solid form is crystalline.
4. The solid form of claim 3 , wherein Compound 1 is unsolvated.
5. The solid form of claim 4 , wherein the solid form is Form A.
6. The solid form of claim 5 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 6.73, about 18.30, about 18.96 and about 25.48 degrees 2-theta.
7. The solid form of claim 4 , wherein the solid form is Form B.
8. The solid form of claim 7 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 10.67, about 12.21, about 18.11, about 19.24 and about 21.53 degrees 2-theta.
9. The solid form of claim 3 , wherein Compound 1 is a dimethylformamide solvate.
10. The solid form of claim 9 , wherein the solid form is Form C.
11. The solid form of claim 10 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 16.32, about 18.82, about 20.26, about 22.58 and about 25.36 degrees 2-theta.
12. The solid form of claim 3 , wherein Compound 1 is a 1,4-dioxane solvate.
13. The solid form of claim 12 , wherein the solid form is Form D.
14. The solid form of claim 13 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 18.40, about 19.31, about 20.14, about 20.53 and about 25.25 degrees 2-theta.
15. The solid form of claim 3 , wherein Compound 1 is a methyl ethyl ketone solvate.
16. The solid form of claim 15 , wherein the solid form is Form E.
17. The solid form of claim 16 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 5.78, about 12.57, about 15.34, about 19.10 and about 24.80 degrees 2-theta.
18. The solid form of claim 3 , wherein Compound 1 is a N-methyl-2-pyrrolidone solvate.
19. The solid form of claim 18 , wherein the solid form is Form F.
20. The solid form of claim 19 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 15.51, about 16.86, about 18.80, about 20.97 and about 23.32 degrees 2-theta.
21. The solid form of claim 18 , wherein the solid form is Form G.
22. The solid form of claim 21 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 6.79, about 17.86, about 19.43, about 19.98 and about 22.35 degrees 2-theta.
23. The solid form of claim 3 , wherein Compound 1 is a hydrate.
24. The solid form of claim 23 , wherein the solid form is Form H.
25. The solid form of claim 24 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 10.82, about 11.08, about 18.45, about 22.85 and about 25.06 degrees 2-theta.
26. The solid form of claim 23 , wherein the solid form is Form I.
27. The solid form of claim 26 , having one or more peaks in its X-ray powder diffraction pattern selected from those at about 6.13, about 12.22, about 15.91, about 18.35, about 18.88, and about 21.90 degrees 2-theta.
28. A composition comprising the solid form of claim 1 and a pharmaceutically acceptable carrier or excipient.
29. A method for inhibiting at least one mutant of EGFR selectively as compared to wild type EGFR (WT EGFR), in a biological sample or in a patient, comprising contacting the biological sample with, or administering to the patient, a solid form according to claim 1 , or a composition thereof.
30. The method according to claim 29 , wherein said method is sparing for WT EGFR.
31. The method according to claim 29 , wherein the at least one mutant is an activating mutant, a deletion mutant, a point mutation, or a mutant selected from T790M, delE746-A750, L858R or G719S.
32. A method for treating a mutant EGFR-mediated disorder or condition in a patient, comprising administering to the patient a composition according to claim 28 .
33. The method of claim 32 , wherein the disorder or condition is a cancer.