Aryl sulfonamides

Abstract

Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.

1 - 85 . (canceled) 
   
   
       86 . A compound of formula (I) or a pharmaceutically acceptable salt thereof: 
     
       
         
         
             
             
         
       
       wherein X represents —OR 1 ; 
       R 1  is selected from the group consisting of hydrogen, C 1-6  haloalkyl, C 1-6  alkyl, C 3-6  cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, 5- to 10-membered heteroaryl, aryl-C 1-4  alkyl, and aryloxy-C 1-4  alkyl; 
       L is C(O); 
       Z is 4-(1-oxy)pyridyl; and 
       Y is halogen. 
     
   
   
       87 . A composition comprising at least one compound or a pharmaceutically acceptable salt thereof of  claim 86 . 
   
   
       88 . A method of treating inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound or a pharmaceutically acceptable salt thereof of  claim 86 . 
   
   
       89 . A compound of formula (I) or a pharmaceutically acceptable salt thereof: 
     
       
         
         
             
             
         
       
     
     wherein
 X represents —OR 1 ; 
 R 1  is selected from the group consisting of hydrogen, linear or branched C 1-6  haloalkyl, linear or branched C 1-6  alkyl, C 3-6  cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, 5- to 10-membered heteroaryl, aryl-C 1-4  alkyl, and aryloxy-C 1-4  alkyl; 
 L is C(O); 
 Z is 4-(1-oxy)pyridyl which is unsubstituted or substituted with unsubstituted C 1-8  alkyl; and 
 Y is halogen. 
 
   
   
       90 . The compound of  claim 89 , wherein Z is 4-(1-oxy)pyridyl which is unsubstituted or substituted with methyl. 
   
   
       91 . The compound of  claim 90 , wherein Z is 4-(1-oxy)pyridyl which is substituted with methyl at the 2-position. 
   
   
       92 . The compound of  claim 90 , wherein Z is 4-(1-oxy)pyridyl which is unsubstituted. 
   
   
       93 . The compound of  claim 92 , wherein Y is chloro. 
   
   
       94 . The compound of  claim 93 , wherein Y is 4-chloro. 
   
   
       95 . The compound of  claim 94 , wherein X is para to the sulfonamide group. 
   
   
       96 . The compound of  claim 95 , wherein R 1  is a linear or branched C 1-6  haloalkyl or linear or branched C 1-6  alkyl. 
   
   
       97 . The compound of  claim 96 , wherein R 1  is linear or branched C 1-6  alkyl. 
   
   
       98 . The compound of  claim 97 , wherein R 1  is a linear alkyl. 
   
   
       99 . The compound of  claim 98 , wherein R 1  is methyl or ethyl. 
   
   
       100 . The compound of  claim 97 , wherein R 1  is branched alkyl. 
   
   
       101 . The compound of  claim 100 , wherein R 1  is isopropyl. 
   
   
       102 . A composition comprising at least one compound or a pharmaceutically acceptable salt thereof of  claim 89 . 
   
   
       103 . A method of treating inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound or a pharmaceutically acceptable salt thereof of  claim 89 .