BIS-ARYL SULFONAMIDES

1 . A modulator of the formula (I) or a salt or N-oxide thereof:

L is —C(O)—, —S—, —S(O)— or —S(O)2-;

X represents from 1 to 5 substituents independently selected from the group consisting of halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, —CN, —NO2, —C(O)R1, —CO2R1, —C(O)NR1R2, —OR1, —OC(O)R1, —OC(O)NR1R2, —NO2, —NR3C(O)R1, —NR3C(O)NR1R2, —NR1R2, —NR3CO2R1, —NR3S(O)2R1, —SR1, —S(O)R1, —S(O)2R1, —S(O) 2 NR1R2, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl;

substituted C 1-8 alkyl, substituted C 2-8 alkenyl, or substituted C 2-8 alkynyl may have from 1-5 substituents independently selected from the group consisting of halogen, —OH, —CN, —NO 2 , ═O, —OC(O)R 1 , —OR 1 , —C(O)R 1 , —C(O)NR 1 R 2 , —OC(O)NR 1 R 2 , —NR 2 C(O)R 1 , —NR 1 C(O)NR 2 R 3 , —CO 2 R 1 , —NR 1 R 2 , —NR 2 CO 2 R 1 , —SR 1 , —S(O)R 1 , —S(O) 2 R 1 , —S(O) 2 NR 1 R 2 , —NR 1 S(O) 2 R 2 , unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heterocyclyl;

substituted C 6-10 aryl, substituted 5- to 10-membered heteroaryl, or substituted 3- to 10-membered heterocyclyl, may have from 1-4 substituents independently selected from the group consisting of halogen, unsubstituted C 1-8 alkyl, unsubstituted C 1-8 haloalkyl, unsubstituted 4- to 7-membered heterocycle, —CN, —NO 2 , —OR 1 , ═O, —OC(O)R 1 , —CO 2 R 1 , —C(O)R 1 , —C(O)NR 1 R 2 , —OC(O)NR 1 R 2 , —NR 2 C(O)R 1 , —NR 1 C(O)NR 2 R 3 , —NR 1 R 2 , —NR 2 CO 2 R 1 , —SR 1 , —S(O)R 1 , —S(O) 2 R 1 , —S(O) 2 NR 1 R 2 , and —NR 1 S(O) 2 R, with the proviso that if X represents a heterocycle, suitable substituents preferably do not include another heterocycle;

R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, aryl-C 1-4 alkyl, aryloxy-C 1-4 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, or where R 1 and R 2 , or R 3 and R 2 , or R 1 and R 3 , may together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring;

and where the aliphatic and aromatic portions of R 1 , R 2 and R 3 are optionally further substituted with from 1 to 3 substituents selected from the group consisting of halogen, —OH, —OR m , —OC(O)NHR m , —OC(O)NR m R n , —SH, —SR m , —S(O)R m , —S(O) 2 R m , —S(O) 2 NH 2 , —S(O) 2 NHR m , —S(O) 2 NR m R n , —NHS(O) 2 R m , —NR m S(O) 2 R n , —C(O)NH 2 , —C(O)NHR m , —C(O)N(R m ) 2 , —C(O)R m , —NHC(O)R m , —NR m C(O)R n , —NHC(O)NH 2 , —NR m C(O)NH 2 , —NR m C(O)NHR n , —NHC(O)NHR m , —NR o C(O)NR m R n , —NHC(O)N(R m ) 2 , —CO 2 H, —CO 2 R m , —NHCO 2 R m , —NR m CO 2 R n , —CN, —NO 2 , —NH 2 , —NHR n , —NR m R n , —NR m S(O)NH 2 and —NR m S(O) 2 NHR n , where R m , R n , and R o are each independently unsubstituted C 1-6 alkyl;

Y represents from 1 to 4 substituents, each independently selected from the group consisting of halogen, —CN, —NO 2 , —OR 4 , —C(O)R 4 , —CO2R4, —SR4, —S(O)R4, —S(O)2R4, and unsubstituted or substituted C1-4 alkyl;

substituted C 1-4 alkyl may have from 1 to 3 substituents independently selected from the group consisting of halogen, —OR 4 , —CN, —NO 2 , ═O, —OC(O)R 4 , —CO 2 R 4 , —C(O)R 4 , —CONR 4 R 5 , —OC(O)NR 4 R 5 , —NR 4 C(O)R 5 , —NR 4 C(O)NR 5 R 6 , —NR 4 R 5 , —NR 4 CO 2 R 5 , —SR 4 , —SOR 4 , —SO 2 R 4 , —SO 2 NR 4 R 5 , and —NR 4 SO 2 R 5 ;

R 4 , R 5 and R 6 are each independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; or where R 4 and R 5 , or R 6 and R 4 or R 5 and R 6 , together with the atom to which they are attached, form a substituted or unsubstituted 5-, 6- or 7-membered ring;

and the aliphatic and aromatic portions of R 4 , R 5 , and R 6 are optionally further substituted with from 1 to 3 substituents selected from the group consisting of halogen, —OH, —OR m , —OC(O)NHR m , —OC(O)NR m R n , —SH, —SR m , —S(O)R m , —S(O) 2 R m , —S(O) 2 NH 2 , —S(O) 2 NHR m , —S(O) 2 NR m R n , —NHS(O) 2 R m , —NR m S(O) 2 R n , —C(O)NH 2 , —C(O)NHR m , —C(O)N(R m ) 2 , —C(O)R m , —NHC(O)R m , —NR m C(O)R n , —NHC(O)NH 2 , —NR m C(O)NH 2 , —NR m C(O)NHR n , —NHC(O)NHR m , —NR o C(O)NR m R n , —NHC(O)N(R m ) 2 , —CO 2 H, —CO 2 R m , —NHCO 2 R m , —NR m CO 2 R n , —CN, —NO 2 , —NH 2 , —NHR n , —NR m R n , —NR m S(O)NH 2 and —NR m S(O) 2 NHR n , where R m , R n , and R o are each independently unsubstituted C 1-8 alkyl; and

Z represents from 0 to 5 substituents independently selected from the group consisting of halogen, unsubstituted or substituted C 1-8 alkyl, unsubstituted or substituted C 2-8 alkenyl, unsubstituted or substituted C 2-8 alkynyl, —CN, —NO 2 , —OR 7 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —CONR 7 R 8 , —OC(O)NR 7 R 8 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 7 R 8 , —NR 7 CO 2 R 8 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —SO 2 NR 7 R 8 , —NR 7 SO 2 R 8 , unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5- to 10-membered heteroaryl and unsubstituted or substituted 3- to 10-membered heterocyclyl;

substituted C 1-8 alkyl, C 2-8 alkenyl and C 2-8 alkynyl substituents on Z may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OR', —CN, —NO 2 , ═O, —CN, —NO 2 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —CONR 7 R 8 , —OC(O)NR 7 R 8 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 7 R 8 , —NR 7 CO 2 R 8 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —SO 2 NR 7 R 8 , —NR 7 SO 2 R 8 , unsubstituted or substituted phenyl, unsubstituted or substituted 5- or 6-membered heteroaryl, or unsubstituted or substituted 4- to 7-membered heterocyclyl;

substituted aryl, heteroaryl and heterocyclyl substituents on Z may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OR 7 , —CN, —NO 2 , ═O, —OC(O)R 7 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —CONR 7 R 8 , —OC(O)NR 7 R 8 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 7 R 8 , —NR 7 CO 2 R 8 , —SR 7 , —SOR 7 , —SO 2 R 7 , —SO 2 NR 7 R 8 , —NR 7 SO 2 R 8 , unsubstituted 4- to 7-membered heterocyclyl, unsubstituted C 1-8 alkyl and unsubstituted C 1-8 haloalkyl;

R 7 , R 8 and R 9 are each independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl, 5 to 10 membered heteroaryl and 3- to 10-membered heterocycle, or R 7 and R 8 , or R 8 and R 9 , or R 7 and R 9 , may together with the atom(s) to which they are attached, form a substituted or unsubstituted 5-, 6-, or 7-membered ring; and

the aliphatic and aromatic portions of R 7 , R 8 and R 9 are optionally further substituted with 1 to 3 substituents selected from the group consisting of halogen, —OH, —OR m , —OC(O)NHR m , —OC(O)NR m R n , —SH, —SR m , —S(O)R m , —S(O) 2 R m , —S(O) 2 NH 2 , —S(O) 2 NHR m , —S(O) 2 NR m R n , —NHS(O) 2 R m , —NR m S(O) 2 R n , —C(O)NH 2 , —C(O)NHR m , —C(O)N(R m ) 2 , —C(O)R m , —NHC(O)R m , —NR m C(O)R n , —NHC(O)NH 2 , —NR m C(O)NH 2 , —NR m C(O)NHR n , —NHC(O)NHR m , —NR o C(O)NR m R n , —NHC(O)N(R m ) 2 , —CO 2 H, —CO 2 R m , —NHCO 2 R m , —NR m CO 2 R n , —CN, —NO 2 , —NH 2 , —NHR n , —NR m R n , —NR m S(O)NH 2 and —NR m S(O) 2 NHR n , where R m , R n , and R o are each independently unsubstituted C 1-6 alkyl.

2 . A composition comprising a pharmaceutically acceptable carrier and a compound according to any of claim 1 .

3 . A method for treating a CCR9-mediated condition or disease comprising administering to a subject a safe and effective amount of the compound according to any of claim 1 .

4 . A method of modulating CCR9 function in a cell, comprising contacting the cell with a CCR9 modulating amount of the compound according to any of claim 1 .