Heterocyclic compounds as immunomodulators

• US 10,618,916 B2
• Filed: 05/10/2019
• Issued: 04/14/2020
• Est. Priority Date: 05/11/2018
• Status: Active Grant

• Current Assignee: Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Wu, Liangxing, Xiao, Kaijiong, Yao, Wenqing
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US16/409,026
• Publication Number:
  US 20190345170A1
• Time in Patent Office: 340 Days
• Field of Search: 546118, 514303
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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 4,4′

-(((((2-chloro-2′

-methyl-[1,1′

-biphenyl]-3,3′

-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid), or a pharmaceutically acceptable salt.

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

2. A compound, which is 4,4′

-(((((2-chloro-2′

-methyl-[1,1′

-biphenyl]-3,3′

-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid).

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

5. A compound, which is 4,4′

-(((((2,2′

-dichloro-[1,1′

-biphenyl]-3,3′

-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid), or a pharmaceutically acceptable salt.

6. The compound of claim 5, which is 4,4′

-(((((2,2′

-dichloro-[1,1′

-biphenyl]-3,3′

-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid.

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

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

9. A compound, which is 44243′

-(5-(2-(4-carboxybicyclo[2.2.1]heptan-1-yl)ethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2′

-dichloro-[1,1′

-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid, or a pharmaceutically acceptable salt.

10. The compound of claim 9, which is 4-((2-((3′

-(5-(2-(4-carboxybicyclo[2.2.1]heptan-1-yl)ethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2′

-dichloro-[1,1′

-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6, 7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid.

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

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

13. A compound, which is 4,4′

-(((((2-chloro-2′

-cyano-[1,1′

-biphenyl]-3,3′

-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid), or a pharmaceutically acceptable salt.

14. The compound of claim 13, which is 4,4′

-(((((2-chloro-2′

-cyano-[1,1′

-biphenyl]-3,3′

-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid).

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

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