JAK1 and ALK2 inhibitors and methods for their use
Compounds having activity as inhibitors of ALK2 kinase and/or JAK2 kinase are disclosed. The compounds have the following structure (I): including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, z and A are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
1. A method for treating a solid tumor selected from the group consisting of breast cancer, prostate cancer, pancreatic cancer, ovarian cancer, head cancer, and neck cancer in a subject in need thereof, the method comprising:
administering an effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt thereof, to the subject.
2. The method of claim 1 , further comprising administering an effective amount of one or more chemotherapeutic agents.
3. The method of claim 1 , wherein the pharmaceutically acceptable salt is an acid addition salt.
4. The method of claim 3 , wherein the acid addition salt is a hydrochloric acid salt or a fumaric acid salt.
5. The method of claim 1 , wherein the solid tumor is ovarian cancer.
6. The method of claim 1 , wherein the solid tumor is prostate cancer.
7. The method of claim 1 , wherein the solid tumor is breast cancer.
8. The method of claim 1 , wherein the solid tumor is pancreatic cancer.
9. The method of claim 1 , wherein the solid tumor is head cancer.
10. The method of claim 1 , wherein the solid tumor is neck cancer.
11. The method of claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloric acid salt.