Bis-aryl sulfonamides

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

where Ar 2 is selected from the group consisting of

each A is independently CZ′,

each E is independently selected from the group consisting of CZ′ and N;

each Z′ is independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-8 alkyl, substituted or unsubstituted C 2-8 alkenyl, substituted or unsubstituted C 2-8 alkynyl, —CN, ═O, —NO 2 , —OR 10 , —OC(O)R 10 , —CO 2 R 10 , —C(O)R 10 , —C(O)NR 11 R 12 , —OC(O)NR 11 R 12 , —NR 10 C(O)R 11 , —NR 10 C(O)NR 11 R 12 , —NR 11 R 12 , —NR 10 CO 2 R 11 , —SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 11 R 12 , —NR 10 S(O) 2 R 11 , substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;

R 10 , R 11 , and R 12 are each selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, aryl, or heteroaryl; or R 10 and R 11 , R 11 and R 12 , or R 10 and R 12 , together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring;

G is O, S, or NR 7 ;

X a and X b are each independently selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , —OR 1 , —C(O)R 1 , —CO 2 R 1 , —O(CO)R 1 , —OC(O)NR 1 R 2 , —SR 1 , —SOR 1 , —SO 2 R 1 , —NR 1 R 2 , —NR 1 C(O)R 2 , —NR 1 C(O) 2 R 2 , —NR 1 (CO)NR 1 R 2 , unsubstituted or substituted C 1-8 alkyl, unsubstituted or substituted C 2-8 alkenyl, unsubstituted or substituted C 2-8 alkynyl, unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5- or 6-membered heteroaryl, and unsubstituted or substituted 4- to 7-membered heterocyclyl;

R 1 and R 2 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 may together with the atom(s) to which they are attached, form a substituted or unsubstituted 5-, 6-, or 7-membered ring, and where the aliphatic and aromatic portions of R 1 and R 2 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 a and Y b are each independently selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , —OR 4 , —C(O)R 4 , —SR 4 , —CF 3 , —SOR 4 , and —SO 2 R 4 ; and

R 4 is 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 R 4 and R 5 , 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.

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