Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors
The present invention relates to imidazo[1,2-b][1,2,4]triazines that are inhibitors of c-Met and are useful in the treatment of c-Met associated diseases including cancer.
1. A method of treating a hematopoietic malignancy, ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer, or melanoma associated with dysregulation of the HGF/c-MET signaling pathway in a patient, comprising administering to said patient a therapeutically effective amount of a compound, selected from
2-fluoro-N-[(2R)-2-hydroxypropyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide; and
2-chloro-N-[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide;
or a pharmaceutically acceptable salt of any of the aforementioned.
2. The method of claim 1 , wherein the compound is 2-fluoro-N -[(2R)-2-hydroxypropyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide.
3. The method of claim 1 , wherein the compound is 2-chloro-N -[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide.
4. The method of claim 1 , wherein said treatment is for a hematopoietic malignancy.
5. The method of claim 1 , wherein said treatment is for ovarian cancer, pancreatic cancer, prostate cancer, or thyroid cancer.
6. The method of claim 1 , wherein said treatment is for melanoma.
7. A method of treating a hematopoietic malignancy, ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer or melanoma in a patient comprising administering to said patient a therapeutically effective amount of a compound selected from
2-fluoro-N-[(2R)-2-hydroxypropyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide; and
2-chloro-N-[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]3-3-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide;
or a pharmaceutically acceptable salt of any of the aforementioned.
8. The method of claim 7 , wherein the compound is 2-fluoro-N -[(2R)-2-hydroxypropyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide.
9. The method of claim 7 , wherein the compound is 2-chloro-N -[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide.
10. The method of claim 7 , wherein said treatment is for a hematopoietic malignancy.
11. The method of claim 7 , wherein said treatment is for ovarian cancer, pancreatic cancer, prostate cancer, or thyroid cancer.
12. The method of claim 7 , wherein said treatment is for melanoma.
13. A method of treating a hematopoietic malignancy, ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer or melanoma in a patient comprising administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising a compound selected from
2-fluoro-N-[(2R)-2-hydroxypropyI]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide; and
2-chloro-N-[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]3-3-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide;
or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
14. The method of claim 13 , wherein the compound is 2-fluoro-N -[(2R)-2-hydroxypropyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide.
15. The method of claim 13 , wherein the compound is 2-chloro-N -[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide.
16. The method of claim 13 , wherein said treatment is for a hematopoietic malignancy.
17. The method of claim 13 , wherein said treatment is for ovarian cancer, pancreatic cancer, prostate cancer, or thyroid cancer.
18. The method of claim 13 , wherein said treatment is for melanoma.