CCR9 inhibitors and methods of use thereof

1. A compound represented by the following structural formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is aliphatic, haloalkyl, aryl, arylalkyl, alkoxy, cycloalkoxy, haloalkoxy, aryloxy, arylalkoxy, alkylthio, halo, nitro, cyano, hydroxy, NR 11 CO 2 R 12 , C(O)N(R 11 ) 2 , C(O)R 12 , CO 2 R 12 , OC(O)N(R 11 ) 2 , OC(O)R 12 , N(R 11 ) 12 , or NR 11 C(O)R 12 ; or two adjacent R 9 groups taken together with the atoms to which they are attached form a fused, saturated, unsaturated or partially unsaturated 5 to 7 membered ring having 0, 1, or 2 heteroatoms selected from N, O, and S; and

wherein each R 11 is, independently, selected from H or an aliphatic group; and R 12 is an aliphatic group.

2. The compound of claim 1 , wherein R 9 is an aliphatic, alkoxy, or haloalkoxy group.

3. The compound of claim 1 or 2 , wherein R 9 is in the para position relative to the sulfonamide.

4. A pharmaceutically acceptable salt of a compound represented by the following structural formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is aliphatic, haloalkyl, aryl, arylalkyl, alkoxy, cycloalkoxy, haloalkoxy, aryloxy, arylalkoxy, alkylthio, halo, nitro, cyano, hydroxy, NR 11 CO 2 R 12 , C(O)N(R 11 ) 2 , C(O)R 12 , CO 2 R 12 , OC(O)N(R 11 ) 2 , OC(O)R 12 , N(R 11 ) 2 , or NR 11 C(O)R 12 ; or two adjacent R 9 groups taken together with the atoms to which they are attached form a fused, saturated, unsaturated or partially unsaturated 5 to 7 membered ring having 0, 1, or 2 heteroatoms selected from N, O, and S; and

wherein each R 11 is, independently, selected from H or an aliphatic group; and R 12 is an aliphatic group.

5. The pharmaceutically acceptable salt of claim 4 , wherein in the compound R 9 is an aliphatic, alkoxy, or haloalkoxy group.

6. The pharmaceutically acceptable salt of claim 4 or 5 , wherein in the compound R 9 is in the para position relative to the sulfonamide.

7. The pharmaceutically acceptable salt of claim 4 which is a sodium salt.

8. A composition comprising a pharmaceutically acceptable carrier and a compound having the following structural formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is aliphatic, haloalkyl, aryl, arylalkyl, alkoxy, cycloalkoxy, haloalkoxy, aryloxy, arylalkoxy, alkylthio, halo, nitro, cyano, hydroxy, NR 11 CO 2 R 12 , C(O)N(R 11 ) 2 , C(O)R 12 , CO 2 R 12 , OC(O)N(R 11 ) 2 , OC(O)R 12 , N(R 11 ) 2 , or NR 11 C(O)R 12 ; or two adjacent R 9 groups taken together with the atoms to which they are attached form a fused, saturated, unsaturated or partially unsaturated 5 to 7 membered ring having 0, 1, or 2 heteroatoms selected from N, O, and S; and

wherein each R 11 is, independently, selected from H or an aliphatic group; and R 12 is an aliphatic group.

9. The composition of claim 8 , wherein in the compound R 9 is an aliphatic, alkoxy, or haloalkoxy group.

10. The composition of claim 8 or 9 , wherein in the compound R 9 is in the para position relative to the sulfonamide.

11. A composition comprising a pharmaceutically acceptable carrier and a pharmaceutically acceptable salt of a compound having the following structural formula:

wherein:

X i is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is aliphatic, haloalkyl, aryl, arylalkyl, alkoxy, cycloalkoxy, haloalkoxy, aryloxy, arylalkoxy, alkylthio, halo, nitro, cyano, hydroxy, NR 11 CO 2 R 12 , C(O)N(R 11 ) 2 , C(O)R 12 , CO 2 R 12 , OC(O)N(R 11 ) 2 , OC(O)R 12 , N(R 11 ) 2 , or NR 11 C(O)R 12 ; or two adjacent R 9 groups taken together with the atoms to which they are attached form a fused, saturated, unsaturated or partially unsaturated 5 to 7 membered ring having 0, 1, or 2 heteroatoms selected from N, O, and S; and

wherein each R 11 is, independently, selected from H or an aliphatic group; and R 12 is an aliphatic group.

12. The composition of claim 11 , wherein in the compound R 9 is an aliphatic, alkoxy, or haloalkoxy group.

13. The composition of claim 11 or 12 , wherein in the compound R 9 is in the para position relative to the sulfonamide.

14. The composition of claim 11 , wherein the pharmaceutically acceptable salt is a sodium salt.

15. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound or a pharmaceutically acceptable salt of a compound, wherein the compound has the following structural formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is aliphatic, haloalkyl, aryl, arylalkyl, alkoxy, cycloalkoxy, haloalkoxy, aryloxy, arylalkoxy, alkylthio, halo, nitro, cyano, hydroxy, NR 11 CO 2 R 12 , C(O)N(R 11 ) 2 , C(O)R 12 , CO 2 R 12 , OC(O)N(R 11 ) 2 , OC(O)R 12 , N(R 11 ) 2 , or NR 11 C(O)R 12 ; or two adjacent R 9 groups taken together with the atoms to which they are attached form a fused, saturated, unsaturated or partially unsaturated 5 to 7 membered ring having 0, 1, or 2 heteroatoms selected from N, O, and S; and

wherein each R 11 is, independently, selected from H or an aliphatic group; and R 12 is an aliphatic group.

16. The method of claim 15 , wherein in the compound R 9 is an aliphatic, alkoxy, or haloalkoxy group.

17. The method of claim 15 or 16 , wherein in the compound R 9 is in the para position relative to the sulfonamide.

18. The method of claim 15 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

19. A compound having the structure:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is isopropoxy.

20. A pharmaceutically acceptable salt of a compound having the formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is isopropoxy.

21. A composition comprising a pharmaceutically acceptable carrier and a compound having the formula:

wherein:

X i is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is isopropoxy.

22. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound having the formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is isopropoxy.

23. The method of claim 22 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

24. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a pharmaceutically acceptable salt of a compound having the formula:

wherein:

X 1 is CH;

X 4 is N + —O − ;

R 8 is Cl;

m is 0;

n is 1; and

R 9 is isopropoxy.