CCR9 inhibitors and methods of use thereof

1. A compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

Y is C═O, S(O), or S(O) 2 ;

X 1 and X 2 are each independently CR;

R, for each occurrence, and R 1 are each independently H, an aliphatic group, 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 ; wherein R 11 , for each occurrence is, independently, H or an aliphatic group, and R 12 is an aliphatic group;

X 3 is CR 8 , wherein R 8 is halo, nitro, alkylcarbonyl, or trihaloalkyl;

R 6 is H, an aliphatic carbonyl group, or an aliphatic ester;

Ar 1 is a substituted or unsubstituted group selected from pyridyl, N-oxido pyridyl, pyrimidinyl, or pyrazinyl; and

Ar 2 is a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group.

2. The compound of claim 1 , wherein R 1 is H, R 6 is H, and Y is C═O, and the compound is represented by one of the following structural formulae:

wherein X 4 is N or N + —O − ;

ring A is optionally further substituted with one or more independent occurrences of 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 ; wherein R 11 , for each occurrence is, independently, H or an aliphatic group, and R 12 is an aliphatic group;

ring B is substituted or unsubstituted; and

Ar 2 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl group.

3. The compound of claim 2 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl, naphthyl, thienyl, or thianaphthenyl.

4. The compound of claim 2 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl or pyridyl.

5. The compound of claim 2 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl or thienyl.

6. The compound of claim 2 , wherein Ar 2 is unsubstituted or is substituted with one or more substituents selected from substituted or unsubstituted aliphatic, aryl, arylalkyl, substituted or unsubstituted alkoxy, aryloxy, aiylalkoxy, alkylthio, halo, nitro, cyano, S(O)-(aliphatic), S(O) 2 -(aliphatic), NR 11 S(O) 2 -(aliphatic), C(O)N(R 11 ) 2 , C(O)R 12 , N(R 11 ) 2 , NR 11 C(O) 2 ,R 12 , and NR 11 C(O)R 12 , wherein R 11 for each occurrence is independently H or an aliphatic group, and R 12 is an aliphatic group.

7. The compound of claim 2 , wherein Ar 2 is unsubstituted or is substituted with one or more substituents selected from aliphatic, alkoxy, or haloalkoxy.

8. The compound of claim 2 , wherein the compound is represented by the following structural formula:

9. The compound of claim 8 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl, naphthyl, thienyl, or thianaphthenyl.

10. The compound of claim 8 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl or pyridyl.

11. The compound of claim 8 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl or thienyl.

12. The compound of claim 8 , wherein Ar 2 is a substituted or unsubstituted phenyl ring and the compound is represented by the following structural formula

13. The compound of claim 12 , wherein the compound is represented by the following structural formula:

wherein

m and n are each, independently, 0 or an integer from 1 to 3;

each R 9 is, independently, 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 heteroatorns selected from N, O, and S;

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

aliphatic group; and

each R 10 is, independently, halo, aliphatic group, alkoxy, or haloalkyl; or two adjacent R 10 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.

14. The compound of claim 13 , wherein:

X 1 and X 2 are both CH;

m is 0; and

n is 1 and R 9 is para to the sulfonamide substituent and is an aliphatic, alkoxy, or haloalkoxy group.

15. The compound of claim 14 , wherin R 8 is Cl, Br, or NO 2 .

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

17. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and the compound of claim 13 .

18. A method of treating inflammatory bowel disease (lBD) in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1 or 13 .

19. The method of claim 18 , wherein the inflammatory bowel disease is selected from ulcerative colitis, Crohn's disease, ileitis, Celiac disease, nontropical Sprue, enteritis, enteropathy associated with seronegative arthropathies, microscopic or collagenous colitis, eosinophilic gastroenteritis, or pouchtis resulting after proctocolectomy, and ileoanal anastomosis.

20. The method of claim 19 , wherein the inflammatory disease is Crohn's disease or colitis.

21. The method of claim 19 , wherein the inflammatory disease is Celiac's disease.