PKM2 modulators and methods for their use
View Patent ↗Compounds having activity as PKM2 activators 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 and R 6 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 compound selected from:
and pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition, comprising:
a compound selected from:
and pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier, diluent or excipient.
7. The pharmaceutical composition of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
9. The pharmaceutical composition of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
10. The pharmaceutical composition of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
11. A method for treating a cancer in a subject in need thereof, the method comprising:
administering an effective amount of a compound selected from:
and pharmaceutically acceptable salts thereof to the subject, wherein the cancer is lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy, wherein the subject has the cancer.
12. The method of claim 11 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13. The method of claim 11 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
14. The method of claim 11 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15. The method of claim 11 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
16. The method of claim 11 , wherein the cancer is lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, or ovarian cancer.
17. The method of claim 16 , wherein the cancer is lung cancer.
18. The method of claim 17 , wherein the lung cancer is non-small cell lung cancer (NSCLC).
19. The method of claim 11 , wherein the cancer is a hematological malignancy.
20. The method of claim 11 , further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.