2,5-disubstituted arylsulfonamide ccr3 antagonists

Abstract

Provided herein are 2,5-disubstituted arylsulfonamide CCR3 antagonists, e.g., compounds of Formula I, and pharmaceutical compositions thereof: Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disorder, disease, or condition.

1 - 27 . (canceled) 
     
     
         28 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, or tautomer thereof; 
       wherein:
 X is S, SO, or SO 2 ; 
 Y is CH 2 , CHF, CHCH 3 , O, S, or SO 2 ; 
 Z is hydrogen or C 1-6  alkyl optionally substituted by aryl, hydroxy, carboxy, alkoxy, carbamoyl, or halo; 
 R 1  and R 2  are each independently halogen, C 1-6  alkyl, or C 1-6  haloalkyl; 
 R 3  is NO 2 ; and 
 R 4  is hydrogen or C 1-6  alkyl optionally substituted by aryl, hydroxy, carboxy, alkoxy, carbamoyl, or halo. 
 
     
     
         29 . The compound of  claim 28 , wherein X is S. 
     
     
         30 . A method for treating, preventing, or ameliorating one or more symptoms of a CCR3-related disorder, disease, or condition in a subject, comprising administering to the subject a therapeutically effective amount of the compound of  claim 28 . 
     
     
         31 . A method of  claim 30 , further comprising administering a second therapeutic agent. 
     
     
         32 . A method of  claim 30 , wherein the second therapeutic agent is administered simultaneously with compound of formula I. 
     
     
         33 . A method of  claim 30 , wherein the second therapeutic agent is administered after the compound of formula I. 
     
     
         34 . A method of  claim 30 , wherein the second therapeutic agent is administered prior to compound of formula I. 
     
     
         35 . A method of any of  claim 30 , wherein the weight ratio of compound of formula I to NSAID is from about 1,000:1 to about 1:1,000.