Dihydropyrrolopyridine inhibitors of ror-gamma

Abstract

Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I) and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

1 - 16 . (canceled) 
     
     
         17 . A compound of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 R 2  is (C 1 -C 3 )alkyl, hydroxy(C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, benzyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkyl, tetrahydropyranyl, or —CH 2 -tetrahydropyranyl; 
 R 3  and R 4  are each independently hydrogen or methyl; 
 Cy 1  is phenyl or pyridyl, each substituted with (C 1 -C 3 )alkylsulfonyl; and 
 Cy 2  is cyclohexyl or tetrahydropyranyl, each of which are optionally substituted with one or more groups selected from halo(C 1 -C 3 )alkyl and C 1 -C 3 (alkoxy). 
 
     
     
         18 . The compound of  claim 17 , wherein the compound is of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The compound of  claim 17 , wherein the compound is of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The compound of  claim 17 , wherein the compound is of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         21 . The compound of  claim 17 , wherein the compound is of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 X is CH or N; 
 Y 1  is O and Y 2  is CH 2 , Y 1  is CH 2  and Y 2  is O, or Y 1  and Y 2  are each CH 2 ; 
 R 9  is halo(C 1 -C 3 )alkyl; and 
 R 10  is (C 1 -C 3 )alkylsulfonyl. 
 
     
     
         22 . The compound of  claim 21 , wherein the compound is of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The compound of  claim 22 , wherein the compound is of the Formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         24 . The compound of  claim 17 , wherein R 2  is methyl, ethyl, benzyl, or isopropyl. 
     
     
         25 . The compound of  claim 17 , wherein R 2  is ethyl or isopropyl. 
     
     
         26 . The compound of  claim 21 , wherein R 9  is CF 3 ; and R 10  is SO 2 Et or SO 2 Me. 
     
     
         27 . A pharmaceutical composition comprising the compound of  claim 17 , or a pharmaceutical acceptable salt thereof; and a pharmaceutically acceptable carrier. 
     
     
         28 . A method of treating a disease or disorder selected from psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD), rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, ankylosing spondylitis, asthma, and dry eye in a subject, comprising administering to the subject a therapeutically effective amount of the compound of  claim 17 , or a pharmaceutical acceptable salt thereof. 
     
     
         29 . The method of  claim 28 , wherein the disease or disorder is dry eye.