Sulfonamide-substituted indole modulators of RORC2 and methods of use thereof

Abstract

The present invention provides sulfonamide-substituted indoles and Methods of Use Thereof-substituted pyrrolopyridines, pharmaceutical compositions thereof methods of modulating RORy activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such indoles and pharmaceutical compositions thereof.

We claim: 
     
       1. A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein,
 X is phenyl or 5-membered heteroaryl, in each case optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CF 3 , —CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , 
 
       
         
           
           
               
               
           
         
       
       —F, —Cl, —Br and —CN;
 R 1  is —CH 3  or —CH 2 CH 3 ; 
 W is 
 
       
         
           
           
               
               
           
         
       
       optionally substituted with one, two, three, four or five —CH 3 ; and
 R 2  is (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, phenyl or isothiazolyl, optionally substituted with one, two, three, four or five substitutents independently selected for each occurrence from the group consisting of —F, —Cl, —Br, —OH, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl and (C 3 -C 10 )cycloalkyl. 
 
     
     
       2. The compound of  claim 1 , wherein R 1  is —CH 3 . 
     
     
       3. The compound of  claim 2 , wherein W is 
       
         
           
           
               
               
           
         
       
     
     
       4. The compound of  claim 2 , wherein W is 
       
         
           
           
               
               
           
         
       
     
     
       5. The compound of  claim 2 , wherein W is 
       
         
           
           
               
               
           
         
       
     
     
       6. The compound of  claim 5 , wherein X is phenyl substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CF 3 , —CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , 
       
         
           
           
               
               
           
         
       
       —F, —Cl, —Br and —CN. 
     
     
       7. The compound of  claim 5 , wherein X is 5-membered heteroaryl optionally substituted with one additional substituent selected from the group consisting of —CH 3 , —CF 3 , —CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , 
       
         
           
           
               
               
           
         
       
       —F, —Cl, —Br and —CN. 
     
     
       8. The compound of  claim 5 , wherein X is 
       
         
           
           
               
               
           
         
       
     
     
       9. The compound of  claim 8 , wherein R 2  is (C 1 -C 6 )alkyl. 
     
     
       10. The compound of  claim 8 , wherein R 2  is unsubstituted (C 3 -C 10 )cycloalkyl. 
     
     
       11. The compound of  claim 8 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
       12. The compound of  claim 1 , selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof. 
     
     
       13. A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, admixed with a pharmaceutically acceptable carrier, excipient or dilutant.