Heterocyclic compounds as immunomodulators
Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
1. A method of treating lung cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound, wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1, 7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.
3. The method of claim 1 , wherein the lung cancer is selected from non-small cell lung cancer (NSCLC), small cell lung cancer, bronchogenic carcinoma, alveolar carcinoma, bronchial adenoma, chondromatous hamartoma, and mesothelioma.
4. The method of claim 1 , wherein the lung cancer is non-small cell lung cancer (NSCLC).
5. The method of claim 1 , wherein the lung cancer is small cell lung cancer.
6. A method of treating hepatic cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound, wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1, 7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.
8. The method of claim 6 , wherein the hepatic cancer is selected from hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, and hemangioma.
9. The method of claim 6 , wherein the hepatic cancer is hepatocellular carcinoma.
10. A method of treating skin cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound, wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
11. The method of claim 10 , wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1, 7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.
12. A method of treating cancer of the bladder comprising administering to a patient in need thereof a therapeutically effective amount of a compound, wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
13. The method of claim 12 , wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1, 7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.
14. The method of claim 12 , wherein the cancer of the bladder is selected from urothelial cancer, urothelial carcinoma, squamous cell carcinoma of the bladder, transition cell carcinoma of the bladder, and adenocarcinoma of the bladder.
15. A method of treating cancer of the urethra comprising administering to a patient in need thereof a therapeutically effective amount of a compound, wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1, 7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.
17. The method of claim 15 , wherein the cancer of the urethra is selected from squamous cell carcinoma of the urethra, transition cell carcinoma of the urethra, and adenocarcinoma of the urethra.
18. A method of treating renal cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound, wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
19. The method of claim 18 , wherein the compound is (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.
20. The method of claim 18 , wherein the renal cancer is selected from renal cell carcinoma, clear cell carcinoma, adenocarcinoma of the kidney, and Wilm's tumor.
21. The method of claim 18 , wherein the renal cancer is renal cell carcinoma.
22. The method of claim 10 , wherein the skin cancer is selected from melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, and keloids.
23. The method of claim 22 , wherein the skin cancer is melanoma.
24. The method of claim 23 , wherein the melanoma is selected from cutaneous malignant melanoma, intraocular malignant melanoma, metastatic malignant melanoma, and ocular melanoma.
25. The method of claim 22 , wherein the skin cancer is squamous cell carcinoma.