Aryl sulfonamides

Abstract

The present invention relates to compounds that modulate various chemokine receptors. These compounds are useful for treating inflammatory and immune diseases.

1 . A compound of the formula (I), or a salt thereof: 
       
         
           
           
               
               
           
         
       
       where
 R a  and R b  are each independently hydrogen, halogen, substituted or unsubstituted C 1-8  alkyl, substituted or unsubstituted C 2-8  alkenyl, substituted or unsubstituted C 2-8  alkynyl, —CN, —OR 1 , —NR 1 R 2 , —NHC(O)R 1 , —NHSO 2 R 1 , —S(O)R 1 , or —S(O) 2 R 2 ; or where R a  and R b , together with the atom to which they are attached, form a substituted or unsubstituted C 3-8  cycloalkyl or substituted or unsubstituted 3- to 10-membered heterocyclic ring;
 where 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, C 6-10  aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, or when R 1  and R 2  are attached to the same nitrogen atom, can be combined with the nitrogen atom to form a 5- or 6-membered heterocyclyl; and 
 where the aliphatic and aromatic portions of R 1 , R 2 , R a  and R b  can be 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; 
 
 Ar 1  is a substituted or unsubstituted C 6-10  aryl or substituted or unsubstituted 5- to 10-membered heteroaryl; each having 0 to 5 substituents selected from the group consisting of halogen, substituted or unsubstituted C 1-8  alkyl, substituted or unsubstituted C 2-8  alkenyl, substituted or unsubstituted C 2-8  alkynyl, —CN, ═O, —C(O)R 3 , —CO 2 R 3 , —C(O)NR 3 R 4 , —OR 3 , —OC(O)R 3 , —OC(O)NR 3 R 4 , —NO 2 , —NR 5 C(O)R 3 , —NR 5 C(O)NR 3 R 4 , —NR 3 R 4 , —NR 5 CO 2 R 3 , —NR 5 S(O) 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl;
 suitable 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 3 , —OR 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —CO 2 R 3 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , —NR 3 S(O) 2 R 4 , unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heterocyclyl; 
 suitable 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, —CN, —NO 2 , —OR 3 , ═O, —OC(O)R 3 , —CO 2 R 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , and —NR 3 S(O) 2 R 4 ; 
 where R 3 , R 4 , and R 5  are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, or where R 3  and R 4 , together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring; 
 where the aliphatic and aromatic portions of R 3 , R 4  and R 5  can be 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 1 , Y 2 , Y 3 , and Y 4  are each independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-4  alkyl, —CN, —C(O)R 6 , —CO 2 R 6 , —OR 6 , —NO 2 , —SR 6 , —S(O)R 6 , and —S(O) 2 R 6 ;
 where substituted C 1-4  alkyl can have from 1 to 3 substituents independently selected from the group consisting of halogen, —OH, —OR 6 , —CN, —NO 2 , ═O, —OC(O)R 6 , —CO 2 R 6 , —C(O)R 6 , —C(O)NR 6 R 13 , —OC(O)NR 6 R 13 , —NR 13 C(O)R 6 , —NR 6 C(O)NR 13 R 14 , —NR 6 R 13 , —NR 13 CO 2 R 6 , —SR 6 , —S(O)R 6 , —S(O) 2 R 6 , —S(O) 2 NR 6 R 13 , and —NR 13 S(O) 2 R 6 ; where R 6 , R 13 , and R 14  are 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; and 
 where the aliphatic and aromatic portions of R 6 , R 13 , and R 14  can be 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; 
 
 Ar 2  is a substituted or unsubstituted C 6-10  aryl, a substituted or unsubstituted 5- to 10-membered heteroaryl, or a substituted or unsubstituted 3- to 10-membered heterocyclyl; each having 0 to 4 substituents selected from the group consisting of 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 7 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 8 R 9 , —OC(O)NR 8 R 9 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 8 R 9 , —NR 7 CO 2 R 8 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —S(O) 2 NR 8 R 9 , —NR 7 S(O) 2 R 8 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;
 suitable substituted C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OH, —OR 7 , —CN, —NO 2 , ═O, —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted or substituted phenyl, unsubstituted or substituted C 5-6  heteroaryl, or unsubstituted or substituted C 3-6  heterocyclyl; 
 suitable substituted aryl, heteroaryl and heterocyclyl substituents 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 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted C 3-6  heterocyclyl, unsubstituted C 1-8  alkyl, and unsubstituted C 1-8  haloalkyl; 
 where 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 , R 8  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 
 where the aliphatic and aromatic portions of R 7 , R 8  and R 9  can be 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 compound of the formula (III), or a salt thereof: 
       
         
           
           
               
               
           
         
       
       where
 Ar 1  is a substituted or unsubstituted C 6-10  aryl or substituted or unsubstituted 5- to 10-membered heteroaryl; each having 0 to 5 substituents selected from the group consisting of halogen, substituted or unsubstituted C 1-8  alkyl, substituted or unsubstituted C 2-8  alkenyl, substituted or unsubstituted C 2-8  alkynyl, —CN, ═O, —C(O)R 3 , —CO 2 R 3 , —C(O)NR 3 R 4 , —OR 3 , —OC(O)R 3 , —OC(O)NR 3 R 4 , —NO 2 , —NR 5 C(O)R 3 , —NR 5 C(O)NR 3 R 4 , —NR 3 R 4 , —NR 5 CO 2 R 3 , —NR 5 S(O) 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; 
 suitable 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 3 , —OR 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —CO 2 R 3 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , —NR 3 S(O) 2 R 4 , unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heterocyclyl; 
 suitable 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, —CN, —NO 2 , —OR 3 , ═O, —OC(O)R 3 , —CO 2 R 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , and —NR 3 S(O) 2 R 4 ; 
 where R 3 , R 4 , and R 5  are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, or where R 3  and R 4 , together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring; 
 where the aliphatic and aromatic portions of R 3 , R 4  and R 5  can be 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 1 , Y 2 , Y 3 , and Y 4  are each independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-4  alkyl, —CN, —C(O)R 6 , —CO 2 R 6 , —OR 6 , —NO 2 , —SR 6 , —S(O)R 6 , and —S(O) 2 R 6 ; 
 where substituted C 1-4  alkyl can have from 1 to 3 substituents independently selected from the group consisting of halogen, —OH, —OR 6 , —CN, —NO 2 , ═O, —OC(O)R 6 , —CO 2 R 6 , —C(O)R 6 , —C(O)NR 6 R 13 , —OC(O)NR 6 R 13 , —NR 13 C(O)R 6 , —NR 6 C(O)NR 13 R 14 , —NR 6 R 13 , —NR 13 CO 2 R 6 , —SR 6 , —S(O)R 6 , —S(O) 2 R 6 , —S(O) 2 NR 6 R 13 , and —NR 13 S(O) 2 R 6 ; where R 6 , R 13 , and R 14  are 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; and 
 where the aliphatic and aromatic portions of R 6 , R 13 , and R 14  can be 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; 
 Ar 2  is a substituted or unsubstituted C 6-10  aryl, a substituted or unsubstituted 5- to 10-membered heteroaryl, or a substituted or unsubstituted 3- to 10-membered heterocyclyl; each having 0 to 4 substituents selected from the group consisting of 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 7 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 8 R 9 , —OC(O)NR 8 R 9 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 8 R 9 , —NR 7 CO 2 R 8 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —S(O) 2 NR 8 R 9 , —NR 7 S(O) 2 R 8 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl; 
 suitable substituted C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OH, —OR 7 , —CN, —NO 2 , ═O, —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted or substituted phenyl, unsubstituted or substituted C 5-6  heteroaryl, or unsubstituted or substituted C 3-6  heterocyclyl; 
 suitable substituted aryl, heteroaryl and heterocyclyl substituents 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 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted C 3-6  heterocyclyl, unsubstituted C 1-8  alkyl, and unsubstituted C 1-8  haloalkyl; 
 where 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 , R 8  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 
 where the aliphatic and aromatic portions of R 7 , R 8  and R 9  can be 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. 
 
     
     
         3 . A compound of the formula (VI), or a salt thereof: 
       
         
           
           
               
               
           
         
       
       where:
 R c  is hydrogen, substituted or unsubstituted C 1-8  alkyl, —C(O)R 1 , —C(O) 2 R 1 , or —S(O) 2 R 1 ;
 where R 1  is 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; and 
 where the aliphatic and aromatic portions of R 1  can be 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; 
 
 Ar 1  is a substituted or unsubstituted C 6-10  aryl or substituted or unsubstituted 5- to 10-membered heteroaryl; each having 0 to 5 substituents selected from the group consisting of halogen, substituted or unsubstituted C 1-8  alkyl, substituted or unsubstituted C 2-8  alkenyl, substituted or unsubstituted C 2-8  alkynyl, —CN, —NO 2 , ═O, —C(O)R 3 , —CO 2 R 3 , —C(O)NR 3 R 4 , —OR 3 , —OC(O)R 3 , —OC(O)NR 3 R 4 , —NR 5 C(O)R 3 , —NR 5 C(O)NR 3 R 4 , —NR 3 R 4 , —NR 5 CO 2 R 3 , —NR 5 S(O) 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl;
 suitable 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 3 , —OR 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —CO 2 R 3 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , —NR 3 S(O) 2 R 4 , unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heterocyclyl; 
 suitable 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, —CN, —NO 2 , —OR 3 , ═O, —OC(O)R 3 , —CO 2 R 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , and —NR 3 S(O) 2 R 4 ; 
 where R 3 , R 4 , and R 5  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 where R 3  and R 4 , together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring; 
 
 where the aliphatic and aromatic portions of R 3 , R 4  and R 5  can be 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 1 , Y 2 , Y 3 , and Y 4  are each independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-4  alkyl, —CN, —C(O)R 6 , —CO 2 R 6 , —OR 6 , —NO 2 , —SR 6 , —S(O)R 6 , and —S(O) 2 R 6 ;
 where substituted C 1-4  alkyl can have from 1 to 3 substituents independently selected from the group consisting of halogen, —OH, —OR 6 , —CN, —NO 2 , ═O, —OC(O)R 6 , —CO 2 R 6 , —C(O)R 6 , —C(O)NR 6 R 13 , —OC(O)NR 6 R 13 , —NR 13 C(O)R 6 , —NR 6 C(O)NR 13 R 14 , —NR 6 R 13 , —NR 13 CO 2 R 6 , —SR 6 , —S(O)R 6 , —S(O) 2 R 6 , —S(O) 2 NR 6 R 13 , and —NR 13 S(O) 2 R 6 ; where R 6 , R 13 , and R 14  are 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; and
 where the aliphatic and aromatic portions of R 6 , R 13 , and R 14  can be 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; 
 
 
 Ar 2  is a substituted or unsubstituted C 6-10  aryl, a substituted or unsubstituted 5- to 10-membered heteroaryl, or a substituted or unsubstituted 3- to 10-membered heterocyclyl; each having 0 to 4 substituents selected from the group consisting of 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 7 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 8 R 9 , —OC(O)NR 8 R 9 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 8 R 9 , —NR 7 CO 2 R 8 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —S(O) 2 NR 8 R 9 , —NR 7 S(O) 2 R 8 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;
 suitable substituted C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OH, —OR 7 , —CN, —NO 2 , ═O, —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted or substituted phenyl, unsubstituted or substituted C 5-6  heteroaryl, or unsubstituted or substituted C 3-6  heterocyclyl; 
 suitable substituted aryl, heteroaryl and heterocyclyl substituents 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 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted C 3-6  heterocyclyl, unsubstituted C 1-8  alkyl, and unsubstituted C 1-8  haloalkyl; 
 where 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 , R 8  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 
 
 where the aliphatic and aromatic portions of R 7 , R 8  and R 9  can be 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. 
 
     
     
         4 . A compound of the formula (VIII), or pharmaceutically acceptable salt or N-oxide thereof: 
       
         
           
           
               
               
           
         
       
       where:
 T is selected from the group consisting of ═CR d R e , ═NOR d , and ═NR d ;
 R d  and R e  are each independently selected from the group consisting of hydrogen, halogen (only for ═CR d R e ), substituted or unsubstituted C 1-8  alkyl, —CN, —OR 41  (only for ═CR d R e ), —C(O)R 41 , —C(O) 2 R 41 , —C(O)NR 41 R 42 , —SR 41  (only for ═CR d R e ); —NR 41 R 42  (only for ═CR d R e ), —S(O)R 41  (only for ═CR e R e ), and —S(O) 2 R 42  (only for ═CR d R e ); or where R e  and R e , together with the atom to which they are attached, form substituted or unsubstituted C 3-8  cycloalkyl or substituted or unsubstituted 3- to 10-membered heterocyclic ring (only for ═CR d R e ); 
 R 41  and R 42  are each independently hydrogen, C 1-8  alkyl, 5- to 10-membered heteroaryl, 3 to 10 membered heterocycle, or when attached to the same nitrogen atom, can be combined with the nitrogen atom to form a 5- or 6-membered heterocyclyl, and 
 substituted C 1-8  alkyl, substituted 3- to 10-membered heterocyclic ring, substituted 5- to 10-membered heteroaryl, and the aliphatic portions of R 41  and R 42  can be 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; 
 
 Ar 1  is a substituted or unsubstituted C 6-10  aryl or substituted or unsubstituted 5- to 10-membered heteroaryl; each having 0 to 5 substituents selected from the group consisting of halogen, substituted or unsubstituted C 1-8  alkyl, substituted or unsubstituted C 2-8  alkenyl, substituted or unsubstituted C 2-8  alkynyl, —CN, ═O, —C(O)R 3 , —CO 2 R 3 , —C(O)NR 3 R 4 , —OR 3 , —OC(O)R 3 , —OC(O)NR 3 R 4 , —NO 2 , —NR 5 C(O)R 3 , —NR 5 C(O)NR 3 R 4 , —NR 3 R 4 , —NR 5 CO 2 R 3 , —NR 5 S(O) 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl;
 suitable 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 3 , —OR 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —CO 2 R 3 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , —NR 3 S(O) 2 R 4 , unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heterocyclyl; 
 suitable 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, —CN, —NO 2 , —OR 3 , ═O, —OC(O)R 3 , —CO 2 R 3 , —C(O)R 3 , —C(O)NR 3 R 4 , —OC(O)NR 3 R 4 , —NR 4 C(O)R 3 , —NR 3 C(O)NR 4 R 5 , —NR 3 R 4 , —NR 4 CO 2 R 3 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , and —NR 3 S(O) 2 R 4 ; 
 where R 3 , R 4 , and R 5  are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, or where R 3  and R 4 , together with the atom(s) to which they are attached, form an substituted or unsubstituted 5-, 6-, or 7-membered ring; 
 
 where the aliphatic and aromatic portions of R 3 , R 4  and R 5  can be 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 1 , Y 2 , Y 3 , and Y 4  are each independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-4  alkyl, —CN, —C(O)R 6 , —CO 2 R 6 , —OR 6 , —NO 2 , —SR 6 , —S(O)R 6 , and —S(O) 2 R 6 ; and
 where substituted C 1-4  alkyl can have from 1 to 3 substituents independently selected from the group consisting of halogen, —OH, —OR 6 , —CN, —NO 2 , ═O, —OC(O)R 6 , —CO 2 R 6 , —C(O)R 6 , —C(O)NR 6 R 13 , —OC(O)NR 6 R 13 , —NR 13 C(O)R 6 , —NR 6 C(O)NR 13 R 14 , —NR 6 R 13 , —NR 13 CO 2 R 6 , —SR 6 , —S(O)R 6 , —S(O) 2 R 6 , —S(O) 2 NR 6 R 13 , and —NR 13 S(O) 2 R 6 ; where R 6 , R 13 , and R 14  are 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; and 
 where the aliphatic and aromatic portions of R 6 , R 13 , and R 14  can be 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; 
 
 Ar 2  is a substituted or unsubstituted C 6-10  aryl, a substituted or unsubstituted 5- to 10-membered heteroaryl, or a substituted or unsubstituted 3- to 10-membered heterocyclyl; each having 0 to 4 substituents selected from the group consisting of 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 7 , —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 8 R 9 , —OC(O)NR 8 R 9 , —NR 7 C(O)R 8 , —NR 7 C(O)NR 8 R 9 , —NR 8 R 9 , —NR 7 CO 2 R 8 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —S(O) 2 NR 8 R 9 , —NR 7 S(O) 2 R 8 , substituted or unsubstituted C 6-10  aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;
 suitable substituted C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl may have from 1 to 5 substituents independently selected from the group consisting of halogen, —OH, —OR 7 , —CN, —NO 2 , ═O, —OC(O)R 7 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted or substituted phenyl, unsubstituted or substituted C 5-6  heteroaryl, or unsubstituted or substituted C 3-6  heterocyclyl; 
 suitable substituted aryl, heteroaryl and heterocyclyl substituents 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 , —CO 2 R 7 , —C(O)R 7 , —C(O)NR 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 , —S(O) 2 NR 7 R 8 , —NR 7 S(O) 2 R 8 , unsubstituted C 3-6  heterocyclyl, unsubstituted C 1-8  alkyl, and unsubstituted C 1-8  haloalkyl; 
 where 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 , R 8  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 
 
 where the aliphatic and aromatic portions of R 7 , R 8  and R 9  can be 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. 
 
     
     
         5 . A composition comprising a pharmaceutically acceptable carrier and a compound of  claim 1 ,  2 ,  3 , or  4 . 
     
     
         6 . A method for treating a CCR9-mediated condition or disease comprising administering to a subject a safe and effective amount of the compound of  claim 1 ,  2 ,  3 , or  4 . 
     
     
         7 . A method of modulating CCR9 function in a cell, comprising contacting the cell with a CCR9 modulating amount of the compound of  claim 1 ,  2 ,  3 , or  4 .