1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase

Patent metadata

Field	Value
Publication number	US-9789094-B2
Application number	US-201615093420-A
Country	US
Kind code	B2
Filing date	Apr 7, 2016
Priority date	Jul 8, 2008
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

The present invention is directed to 1,2,5-oxadiazole derivatives, and compositions of the same, which are inhibitors of indoleamine 2,3-dioxygenase and are useful in the treatment of cancer and other disorders, and to the processes and intermediates for making such 1,2,5-oxadiazole derivatives.

First claim

What is claimed is:

1. A method of suppressing immunosuppression; or inhibiting or ameliorating a disease in a patient, wherein the disease is selected from breast cancer, ovarian cancer, lung cancer, head and neck cancer, pancreatic cancer, renal cancer, melanoma, HIV infection, HCV infection, depression, Alzheimer's disease, Huntington's disease, trauma, age-related cataracts, organ transplant rejection, asthma, rheumatoid arthritis, multiple sclerosis, allergic inflammation, inflammatory bowel disease, psoriasis, and systemic lupus erythematosus, said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, in combination with an anti-cancer vaccine, wherein:
R 1 is NH 2 or CH 3 ;
R 2 is Cl, Br, CF 3 , CH 3 , or CN;
R 3 is H or F; and
n is 1 or 2.

2. The method of claim 1 , wherein the disease is ovarian cancer.

3. The method of claim 1 , wherein the disease is lung cancer.

4. The method of claim 1 , wherein the disease is head and neck cancer.

5. The method of claim 1 , wherein the disease is pancreatic cancer.

6. The method of claim 1 , wherein the disease is renal cancer.

7. The method of claim 1 , wherein the disease is melanoma.

8. A method of suppressing immunosuppression; or inhibiting or ameliorating a disease in a patient, wherein the disease is selected from breast cancer, ovarian cancer, lung cancer, head and neck cancer, pancreatic cancer, renal cancer, melanoma, HIV infection, HCV infection, depression, Alzheimer's disease, Huntington's disease, trauma, age-related cataracts, organ transplant rejection, asthma, rheumatoid arthritis, multiple sclerosis, allergic inflammation, inflammatory bowel disease, psoriasis, and systemic lupus erythematosus, said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of Formula F28:

or a pharmaceutically acceptable salt thereof, in combination with an anti-cancer vaccine, wherein:
R 4 is F, Cl, Br, or I; and
n is 1 or 2.

9. The method of claim 8 , wherein the disease is ovarian cancer.

10. The method of claim 8 , wherein the disease is lung cancer.

11. The method of claim 8 , wherein the disease is head and neck cancer.

12. The method of claim 8 , wherein the disease is pancreatic cancer.

13. The method of claim 8 , wherein the disease is renal cancer.

14. The method of claim 8 , wherein the disease is melanoma.

15. A method of suppressing immunosuppression; or inhibiting or ameliorating a disease in a patient, wherein the disease is selected from breast cancer, ovarian cancer, lung cancer, head and neck cancer, pancreatic cancer, renal cancer, melanoma, HIV infection, HCV infection, depression, Alzheimer's disease, Huntington's disease, trauma, age-related cataracts, organ transplant rejection, asthma, rheumatoid arthritis, multiple sclerosis, allergic inflammation, inflammatory bowel disease, psoriasis, and systemic lupus erythematosus, said method comprising administering to the patient in need thereof a therapeutically effective amount of 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide or a pharmaceutically acceptable salt thereof in combination with an anti-cancer vaccine.

16. The method of claim 15 , wherein the patient is administered a therapeutically effective amount of 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide in combination with an anti-cancer vaccine.

17. The method of claim 15 , wherein the patient is administered a therapeutically effective amount of a pharmaceutically acceptable salt of 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide in combination with an anti-cancer vaccine.

18. The method of claim 15 , wherein the disease is ovarian cancer.

19. The method of claim 15 , wherein the disease is lung cancer.

20. The method of claim 15 , wherein the disease is head and neck cancer.

21. The method of claim 15 , wherein the disease is pancreatic cancer.

22. The method of claim 15 , wherein the disease is renal cancer.

23. The method of claim 15 , wherein the disease is melanoma.

Assignees

• Incyte Corp
• Incyte Holdings Corp

Inventors

• Combs Andrew P
• Yue Eddy W
• Sparks Richard B
• Zhu Wenyu

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title