Salts of an epidermal growth factor receptor kinase inhibitor
The present invention provides a salt form and compositions thereof, which are useful as an inhibitor of EGFR kinases and which exhibits desirable characteristics for the same.
1. Compound 2:
wherein:
n is 1 or 2; and
X is hydrobromic acid, benzenesulfonic acid, camphor sulfonic acid, 1,2-ethane disulfonic acid, hydrochloric acid, maleic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, 1,5-naphthalene disulfonic acid, oxalic acid, 4-toluenesulfonic acid or 2,4,6-trihydroxybenzoic acid.
2. The compound of claim 1 , wherein X is hydrobromic acid.
3. The compound of claim 1 , wherein X is camphor sulfonic acid.
4. The compound of claim 1 , wherein X is 1,2-ethane disulfonic acid.
5. The compound of claim 1 , wherein X is hydrochloric acid.
6. The compound of claim 1 , wherein X is maleic acid.
7. The compound of claim 1 , wherein X is methanesulfonic acid.
8. The compound of claim 1 , wherein X is naphthalene-2-sulfonic acid.
9. The compound of claim 1 , wherein X is 1,5-naphthalene disulfonic acid.
10. The compound of claim 1 , wherein X is oxalic acid.
11. The compound of claim 1 , wherein X is 4-toluenesulfonic acid.
12. The compound of claim 1 , wherein X is 2,4,6-trihydroxybenzoic acid.
13. A method for selectively inhibiting at least one mutant of EGFR as compared to wild type (WT) EGFR, in a biological sample or in a patient, comprising contacting the biological sample with, or administering to the patient, a compound according to claim 1 , or a composition thereof.
14. The method according to claim 13 , wherein said compound is sparing for WT EGFR.
15. The method according to claim 13 , wherein the at least one mutant of EGFR is an activating mutant, a deletion mutant, a point mutation, or a mutant selected from T790M, delE746-A750, L858R, G719S.
16. The method of claim 13 , wherein the compound is a Form I hydrobromic acid salt characterized by one or more peaks in a powder X-ray diffraction pattern selected from those at about 17.39, about 19.45, about 21.41, about 23.56 and about 27.45 degrees 2-theta.
17. The method of claim 13 , wherein the compound is a Form III hydrobromic acid salt characterized by one or more peaks in a powder X-ray diffraction pattern selected from those at about 6.79, about 13.36, about 19.93, about 20.89, about 21.90, about 22.70, about 22.91 and about 26.34 degrees 2-theta.
18. The method of claim 13 , wherein the compound is a Form VIII hydrobromic acid salt characterized by one or more peaks in a powder X-ray diffraction pattern selected from those at about 8.79, about 11.13, about 19.97, about 21.31, about 21.56, about 25.30 and about 26.65 degrees 2-theta.
19. A method for treating a mutant EGFR-mediated disorder or condition in a patient, comprising administering to the patient a composition comprising a compound according to claim 1 .
20. The method of claim 19 , wherein the disorder or condition is a cancer.