Heterocyclic compounds as immunomodulators

• US 10,669,271 B2
• Filed: 03/29/2019
• Issued: 06/02/2020
• Est. Priority Date: 03/30/2018
• Status: Active Grant

• Current Assignee: Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Wu, Liangxing, Li, Jingwei, Yao, Wenqing
• Primary Examiner(s): Coleman, Brenda L
• Application Number:
  US16/369,654
• Publication Number:
  US 20190300524A1
• Time in Patent Office: 431 Days
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

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.

Claims

1. A compound, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carb oxylic acid.

3. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

4. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable excipient or carrier.

5. A compound, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-(((R)-3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-(((R)-3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid.

7. A pharmaceutical composition comprising a compound of claim 5, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

8. A pharmaceutical composition comprising a compound of claim 6 and a pharmaceutically acceptable excipient or carrier.

9. A compound, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-(((R)-3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)-3-methylpyrrolidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-(((R)-3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)-3-methylpyrrolidine-3-carboxylic acid.

11. A pharmaceutical composition comprising a compound of claim 9, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

12. A pharmaceutical composition comprising a compound of claim 10 and a pharmaceutically acceptable excipient or carrier.

13. A compound, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-((3-hydroxy-3-methylpyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

14. The compound of claim 13, which is (R)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-((3-hydroxy-3-methylpyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid.

15. A pharmaceutical composition comprising a compound of claim 13, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

16. A pharmaceutical composition comprising a compound of claim 14 and a pharmaceutically acceptable excipient or carrier.

17. A compound, which is (S)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-((3-hydroxy-3-methylpyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

18. The compound of claim 17, which is (S)-1-((7-cyano-2-(3′

-(2-(difluoromethyl)-7-((3-hydroxy-3-methylpyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-ylamino)-2,2′

-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid.

19. A pharmaceutical composition comprising a compound of claim 17, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

20. A pharmaceutical composition comprising a compound of claim 18 and a pharmaceutically acceptable excipient or carrier.