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 , X 2 , and X 3 are each independently N or CR, provided that at least one of X 1 , X 2 , or X 3 is 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;

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, and 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 Ar 1 is a substituted or unsubstituted group selected from pyrid-4-yl, N-oxido pyrid-4-yl, pyrimidinyl, and pyrazinyl.

3. The compound of claim 2 , 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 unsubstituted or is 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.

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

5. The compound of claim 3 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl and pyridyl.

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

7. The compound of claim 3 , wherein Ar 2 is unsubstituted or is substituted with one or more substituents selected from substituted aliphatic, unsubstituted aliphatic, aryl, arylalkyl, substituted alkoxy, unsubstituted alkoxy, aryloxy, arylalkoxy, 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.

8. The compound of claim 3 , wherein Ar 2 is unsubstituted or is substituted with one or more substituents selected from aliphatic, alkoxy, and haloalkoxy.

9. The compound of claim 3 , wherein one or both rings A and B are unsubstituted or are independently substituted with a substituent selected from halo, aliphatic, alkoxy, and haloalkyl.

10. The compound of claim 3 , wherein ring A is substituted para to the sulfonamide group with an electron withdrawing substituent selected from halo, haloalkyl, nitro, cyano, sulfonamide, sulfone, and sulfoxide.

11. The compound of claim 3 , wherein the compound is represented by the following structural formula:

wherein X 4 is N or N + —O − ;

ring A is unsubstituted or is 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.

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

13. The compound of claim 11 , wherein Ar 2 is a substituted or unsubstituted group selected from phenyl and pyridyl.

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

15. The compound of claim 11 , wherein Ar 2 is a substituted or unsubstituted phenyl ring and the compound is represented by the following structural formula

16. The compound of claim 15 , wherein ring A is substituted by R 8 and the compound is represented by the following structural formula:

wherein R 8 is H, halo, haloalkyl, nitro, cyano, sulfonamide, sulfone, or sulfoxide.

17. The compound of claim 16 , wherein the compound is represented by the following structural formula:

wherein

R 8 is H, halo, haloalkyl, nitro, cyano, sulfonamide, sulfone, or sulfoxide;

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 heteroatoms selected from N, O, and S;

wherein each R 11 is, independently, 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.

18. The compound of claim 17 , wherein:

R 8 is halo, nitro, alkylcarbonyl, or trihaloalkyl; and

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

19. The compound of claim 18 , wherein R 8 is Cl, Br, or NO 2 .

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

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