1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase
AssigneeIncyte Corporation
InventorsAndrew P. Combs, Eddy W. Yue, Richard B. Sparks, Wenyu Zhu, Jiacheng Zhou, Qiyan Lin, Lingkai Weng, Tai-Yuen Yue, Pingli Liu
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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.
Claims68
A method of suppressing immunosuppression or treating a disease selected from breast cancer, ovarian cancer, 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 in a patient, comprising administering to said patient a therapeutically effective amount of a compound of Formula I or Formula F28:
- or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting the disease or ameliorating the disease;
- wherein:
- R1 is NH2 or CH3;
- R2 is Cl, Br, CF3, CH3, or CN;
- R3 is H or F;
- R4 is F, Cl, Br, or I;
- and
- n is 1 or 2.
A method of suppressing immunosuppression or treating a disease selected from breast cancer, ovarian cancer, 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 in a patient, comprising administering to said patient 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, wherein said treating refers to inhibiting the disease or ameliorating the disease.
A method of suppressing immunosuppression or treating a disease selected from breast cancer, ovarian cancer, 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 in a patient, comprising administering to said patient a therapeutically effective amount of 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-[(4-bromo-2-furyl)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide, or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting the disease or ameliorating the disease.
A process for preparing a compound of Formula F15:
- or a salt thereof, wherein R2 is Cl, Br, CF3, CH3, or CN;
- R3 is H or F;
- and n is 1 or 2, comprising:
- a) reacting a compound of Formula F12:
- or a salt thereof, with sulfamide and an organic base to afford a compound of Formula F14:
- or a salt thereof, and
- b) reacting said compound of Formula F14, or a salt thereof, with a base to afford said compound of Formula F15.
A process for preparing a compound of Formula F15:
- or a salt thereof, wherein R2 is Cl, Br, CF3, CH3, or CN;
- R3 is H or F;
- and n is 1 or 2, comprising:
- a) reacting a compound of Formula F13:
- or a salt thereof, wherein Pg1 is an amino protecting group, with an amino deprotecting agent to afford a compound of Formula F14:
- or a salt thereof;
- and
- b) reacting said compound of Formula F14 with a base to afford said compound of Formula F15.
Dependencies are inferred from the claim text.