Compositions useful for treating disorders related to kit
Compounds and compositions useful for treating disorders related to mutant KIT are described herein.
1. A compound which is:
2. A compound which is:
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprising a compound which is:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
4. A method of treating a condition selected from gastrointestinal stromal tumor (GIST), mastocytosis, and acute myeloid leukemia (AML) in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a compound which is
or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the condition is GIST.
6. The method of claim 5 , wherein the patient has a D842V mutation in PDFGRα in Exon 18.
7. The method of claim 5 , wherein the patient has a mutation in Exon 17 in KIT.
8. The method of claim 5 , wherein the patient is refractory to treatment with imatinib, sunitinib, and/or regorafenib.
9. The method of claim 7 , wherein the patient has a D816 mutation in KIT in Exon 17.
10. The method of claim 9 , wherein the D816 mutation is D816V.
11. The method of claim 5 , wherein the patient has unresectable GIST.
12. The method of claim 4 , wherein the condition is mastocytosis.
13. The method of claim 12 , wherein the mastocytosis is systemic mastocytosis (SM) or cutaneous mastocytosis (CM).
14. The method of claim 13 , wherein the systemic mastocytosis (SM) is selected from indolent (ISM), smoldering (SSM), aggressive (ASM), SM with associated hematologic non-mast cell lineage disease (SM-AHNMD), and mast cell leukemia (MCL).
15. The method of claim 13 , wherein the systemic mastocytosis is aggressive (ASM).
16. The method of claim 13 , wherein the systemic mastocytosis is systemic mastocytosis-associated hematologic non-mast cell disease (SM-AHNMD).
17. The method of claim 13 , wherein the systemic mastocytosis is mast cell leukemia (MCL).
18. The method of claim 12 , wherein the patient has a mutation in Exon 17 in KIT.
19. The method of claim 18 , wherein the patient has a D816 mutation in KIT in Exon 17.
20. The method of claim 19 , wherein the D816 mutation is D816V.
21. The method of claim 4 , wherein the condition is acute myeloid leukemia (AML).
22. The method of claim 21 , wherein the patient has a mutation in Exon 17 in KIT.
23. The method of claim 22 , wherein the patient has a D816 mutation in KIT in Exon 17.
24. The method of claim 23 , wherein the D816 mutation is D816V.