Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors

Patent metadata

Field	Value
Publication number	US-10472367-B2
Application number	US-201815969519-A
Country	US
Kind code	B2
Filing date	May 2, 2018
Priority date	Feb 3, 2010
Publication date	Nov 12, 2019
Grant date	Nov 12, 2019

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Incyte Holdings Corp
• Incyte Corp
• Incyte Inc

Inventors

• Zhuo Jincong
• He Chunhong
• Yao Wenqing

Classifications

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title