Bicyclic heterocycles as FGFR4 inhibitors
The present disclosure relates to bicyclic heterocycles of Formula (I′), and pharmaceutical compositions of the same, that are inhibitors of the FGFR3 and/or FGFR4 enzyme and are useful in the treatment of FGFR-associated diseases.
1. A method for treating cancer in a patient, said method comprising: administering to said patient in need thereof a therapeutically effective amount of a compound selected from:
3-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(1,3-dimethyl-1H-pyrazol-4-yl)-1-pyrimidin-4-yl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one, and
4-(3-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(1,3-dimethyl-1H-pyrazol-4-yl)-2-oxo-3,4-dihydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzonitrile,
or a pharmaceutically acceptable salt thereof;
and wherein the cancer is selected from the group consisting of hepatocellular cancer, liver cancer, bladder cancer, multiple myeloma, acute myelogenous leukemia, gastric cancer, lung cancer, breast cancer, pancreatic cancer, cervical cancer endometrial cancer, head and neck cancer, ovarian cancer, esophageal cancer, gall bladder cancer, and glioblastoma.
2. The method of claim 1 , wherein the compound is 3-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(1,3-dimethyl-1H-pyrazol-4-yl)-1-pyrimidin-4-yl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the compound is 4-(3-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(1,3-dimethyl-1H-pyrazol-4-yl)-2-oxo-3,4-dihydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzonitrile or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein said cancer is hepatocellular cancer.
5. The method of claim 1 , wherein said cancer is liver cancer.
6. The method of claim 1 , wherein said cancer is bladder cancer.
7. The method of claim 1 , wherein said cancer is multiple myeloma.
8. The method of claim 1 , wherein said cancer is acute myelogenous leukemia.
9. The method of claim 1 , wherein said cancer is gastric cancer.
10. The method of claim 1 , wherein said cancer is lung cancer.
11. The method of claim 1 , wherein said cancer is breast cancer.
12. The method of claim 1 , wherein said cancer is pancreatic cancer.
13. The method of claim 1 , wherein said cancer is cervical cancer.
14. The method of claim 1 , wherein said cancer is endometrial cancer.
15. The method of claim 1 , wherein said cancer is head and neck cancer.
16. The method of claim 1 , wherein said cancer is ovarian cancer.
17. The method of claim 1 , wherein said cancer is esophageal cancer.
18. The method of claim 1 , wherein said cancer is gall bladder cancer.
19. The method of claim 1 , wherein said cancer is glioblastoma.