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

Patent metadata

Field	Value
Publication number	US-11207302-B2
Application number	US-202016849610-A
Country	US
Kind code	B2
Filing date	Apr 15, 2020
Priority date	Jul 8, 2008
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

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 treating cervical cancer in a patient, comprising administering to said patient a therapeutically effective amount of a compound, which is 4-({2-[(amino sulfonyl)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 antibody therapeutic, wherein the treating is inhibiting or ameliorating the cancer.

2. The method of claim 1 , wherein the antibody therapeutic is an anti-PD-1 antibody.

3. The method of claim 1 , wherein the antibody therapeutic is an anti-CTLA-4 antibody.

4. A method of treating cervical cancer in a patient, comprising administering to said patient a therapeutically effective amount of a compound, which is 4-({2-[(amino sulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide in combination with an antibody therapeutic, wherein the treating is inhibiting or ameliorating the cancer.

5. The method of claim 4 , wherein the antibody therapeutic is an anti-PD-1 antibody.

6. The method of claim 4 , wherein the antibody therapeutic is an anti-CTLA-4 antibody.

7. The method of claim 4 , wherein the compound and the antibody therapeutic are administered simultaneously.

8. The method of claim 4 , wherein the compound and the antibody therapeutic are administered sequentially.

9. The method of claim 5 , wherein the compound and the antibody therapeutic are administered simultaneously.

10. The method of claim 5 , wherein the compound and the antibody therapeutic are administered sequentially.

11. The method of claim 6 , wherein the compound and the antibody therapeutic are administered simultaneously.

12. The method of claim 6 , wherein the compound, and the antibody therapeutic are administered sequentially.

13. A method of treating cervical cancer in a patient, comprising administering to said patient a therapeutically effective amount of a compound, which is 4-({2-[(amino sulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide, or a pharmaceutically acceptable salt thereof, or 4-({2-[(amino sulfonyl)amino]ethyl}amino)-N-[(4-bromo-2-furyl)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide, or a pharmaceutically acceptable salt thereof, in combination with an anti-cancer vaccine, wherein the treating is inhibiting or ameliorating the cancer.

14. The method of claim 13 , wherein the anti-cancer vaccine is selected from dendritic cells, a synthetic peptide, a DNA vaccine, and a recombinant virus.

15. A method of treating cervical cancer in a patient, comprising administering to said patient a therapeutically effective amount of a compound, which is 4-({2-[(amino sulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide or 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-[(4-bromo-2-furyl)methyl]-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide in combination with an anti-cancer vaccine, wherein the treating is inhibiting or ameliorating the cancer.

16. The method of claim 15 , wherein the anti-cancer vaccine is selected from dendritic cells, a synthetic peptide, a DNA vaccine, and a recombinant virus.

17. The method of claim 15 , wherein the compound and the anti-cancer vaccine are administered simultaneously.

18. The method of claim 15 , wherein the compound and the anti-cancer vaccine are administered sequentially.

19. The method of claim 16 , wherein the compound and the anti-cancer vaccine are administered simultaneously.

20. The method of claim 16 , wherein the compound and the anti-cancer vaccine are administered sequentially.

Assignees

• Incyte Corp
• Incyte Holdings Corp

Inventors

• Combs Andrew P
• Yue Eddy W
• Sparks Richard B
• Zhu Wenyu
• Zhou Jiacheng
• Lin Qiyan
• Weng Lingkai
• Yue Tai-Yuen
• Liu Pingli

Classifications

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• C07D307/04

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07D271/08 Primary

  1,2,5-Oxadiazoles; Hydrogenated 1,2,5-oxadiazoles · CPC title

• A61P31/18

  for HIV · CPC title