IP Library › Granted Patent US 8,119,643
Granted Patent B2
US 8,119,643 · App. 11/726,079 · Granted Feb 21, 2012

Benzoimidazolyl-pyrazine compounds for inflammation and immune-related uses

Assignee: Synta Pharmaceuticals Corp.
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Quick Facts
Patent No.
US 8,119,643
App. No.
11/726,079
Granted
Feb 21, 2012
Kind
B2
Abstract

Biologically active chemical compounds, namely benzoimidazolyl-pyrazine derivatives and structurally related compounds, are disclosed herein. Such compounds include those represented by structural formula (II): and as described in further detail within. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Claims (58)

1. A compound selected from the group consisting of:

2,6-Difluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-benzamide;

3,5-Difluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-isonicotinamide;

3-Fluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-isonicotinamide;

N-[5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-3-methyl-isonicotinamide;

2-Fluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-benzamide;

N-[5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-2-methyl -benzamide;

4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amide;

N-[5-(5-Ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-2,6-difluoro-benzamide;

N-[5-(5-Ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-3,5-difluoro-isonicotinamide;

N-[5-(5-Ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-3-fluoro-isonicotinamide;

N-[5-(5-Ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-3-methyl-isonicotinamide;

N-[5-(5-Ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-2-fluoro-benzamide;

N-[5-(5-Ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-2-methyl-benzamide;

4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(5-ethoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amide;

1-[5-(2,6-Difluoro-benzoylamino)-pyrazin-2-yl]-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(3,5-Difluoro-pyridine-4-carbonyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(3-Fluoro-pyridine-4-carbonyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(3-Methyl-pyridine-4-carbonyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-[5-(2-Fluoro-benzoylamino)-pyrazin-2-yl]-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-[5-(2-Methyl-benzoylamino)-pyrazin-2-yl]-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(4-Methyl- [1,2,3]thiadiazole-5-carbonyl) -amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

(2,6-Difluoro-benzyl)-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amine;

(3,5-Difluoro-pyridin-4-ylmethyl)-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amine;

(3-Fluoro-pyridin-4-ylmethyl)-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amine;

[5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(3-methyl-pyridin-4-ylmethyl)-amine;

(2-Fluoro-benzyl)-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amine;

[5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(2-methyl-benzyl)-amine;

[5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(4-methyl-[1,2,3]thiadiazol-5-ylmethyl)-amine;

1-[5-(2,6-Difluoro-benzylamino)-pyrazin-2-yl]-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(3,5-Difluoro-pyridin-4-ylmethyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(3-Fluoro-pyridin-4-ylmethyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5-[(3-Methyl-pyridin-4-ylmethyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-[5-(2-Fluoro-benzylamino)-pyrazin-2-yl]-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-[5-(2-Methyl-benzylamino)-pyrazin-2-yl]-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

1-{5[(4-Methyl-[1,2,3]thiadiazol-5-ylmethyl)-amino]-pyrazin-2-yl}-2-trifluoromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester;

2,6-Difluoro-N-[5-(6-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-benzamide;

N-[5-(6-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-3-methyl-isonicotinamide;

4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(6-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amide;

(2,6-Difluoro-benzyl)-[5-(6-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-amine;

[5-(6-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(3-methyl-pyridin-4-ylmethyl)-amine;

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 1 .

3. A method of inhibiting immune cell activation comprising administering to the cell a compound of claim 1 .

4. The method of claim 3 , wherein immune cell activation is inhibited in a subject by administering the compound to the subject.

5. The method of claim 4 , wherein the subject is human.

6. A method of inhibiting cytokine production in a cell, comprising administering to the cell a compound of claim 1 .

7. The method of claim 6 , wherein cytokine production is inhibited in a subject by administering the compound to the subject.

8. The method of claim 7 , wherein the subject is human.

9. The method of claim 7 , wherein the cytokine is selected from the group consisting of IL-2, IL-4, IL-5, IL-13, GM-CSF, IFN-α, TNF-α, and combinations thereof.

10. The method of claim 9 , wherein the cytokine is IL-2.

11. A method of modulating an ion channel in a cell, wherein the ion channel is involved in immune cell activation, comprising administering to the cell a compound of claim 1 .

12. The method of claim 11 , wherein the ion channel is in a subject and it is modulated by administering the compound to the subject.

13. The method of claim 12 , wherein the subject is human.

14. The method of claim 12 , wherein the ion channel is a Ca 2+ -release-activated Ca 2+ channel (CRAC).

15. A method of inhibiting mast cell degranulation, comprising administering to the cell a compound of claim 1 .

16. The method of claim 15 , wherein mast cell degranulation is inhibited in a subject by administering the compound to the subject.

17. The method of claim 16 , wherein the subject is human.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 5, 2007
From: CHEN, SHOUJUN; JIANG, JUN; ZHANG, JUNYI; XIE, YU
To: SYNTA PHARMACEUTICALS CORP.
Reel/Frame 019518/0267 →
Continuity (2)
Provisional Application 60784037 · Mar 20, 2006
Related Publication 20070249609A1 · Oct 25, 2007