Isoindolone derivatives

Abstract

The present invention provides for compounds of formula (I) wherein A, Y, J, R 1 , R 2 , and R 3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof,that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

1 . A compound of formula (I), or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
       
       wherein
 A is C(R 8 R 9 ); 
 Y is C(R 6 R 7 ); 
 J is C(R 4 R 5 ); 
 R 1  is hydrogen or C 1 -C 3  alkyl; 
 R 2  is hydrogen or C 1 -C 3  alkyl; 
 R 3  is heteroaryl, 9 to 12 membered bicyclic aryl, napthalen-1yl, unsubstituted phenyl, or X, wherein X is 
 
       
         
           
           
               
               
           
         
         wherein said heteroaryl, 9 to 12 membered bicyclic aryl, or napthalen-1-yl may be substituted with one to three substituents independently selected from the group consisting of NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, 50 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), —NH—C(O)—C 1 -C 3  alkyl, —NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; 
         wherein X is substituted as set out in (i) or (ii): 
         (i) four of R 10 , R 11 , R 12 , R 13 , and R 14  are hydrogen, and one of R 10 , R 11 , R 12 , R 13 , or R 14  is selected from the following groups:
 R 10  is NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3  alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkyleneC 3 -C 5  cycloalkyl, C 1 -C 3  alkyleneC 7 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; 
 R 11  is NR 16 R 18 , fluoro, iodo, bromo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 1 -C 3  alkyleneC 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; 
 R 12  is NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 2 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl,—O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; 
 R 13  and R 14  are NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; 
 
         (ii) wherein 5-n of R 10 , R 11 , R 12 , R 13 , and R 14  are hydrogen, and n of R 10 , R 11 , R 12 , R 13 , and R 14  are selected from the following groups:
 NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 16 -C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl,—O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; 
 wherein n is 2, 3, 4 or 5; 
 
         wherein any of said aryl groups of —O-aryl, —S-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl; said heterocycloalkyl; said heterocycloalkyl groups of —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl) and —O—C 1 -C 3  alkylene-heterocycloalkyl; said heteroaryl; said heteroaryl groups of —C(O)—NH(heteroaryl), NH—C(O)-heteroaryl, and —O—C 1 -C 3  alkylene-heteroaryl; and said cycloalkyl groups of —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkyleneC 3 -C 5  cycloalkyl, and —O—C 1 -C 3  alkyleneC 3 -C 14  cycloalkyl may be subsitituted with 1 to 3 subsitituents selected from the group consisting of:
 halo, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, CN, and NR 16 R 18 ; 
 
         R 4  and R 5  are each independently selected from hydrogen, aryl, and C 1 -C 4  alkyl; 
         R 6  and R 7  are each independently selected from hydrogen and C 1 -C 4  alkyl; 
         R 8  and R 9  are each independently selected from hydrogen and C 1 -C 4  alkyl; and 
         R 16  and R 18  are each independently selected from hydrogen and C 1 -C 3  alkyl. 
       
     
     
         2 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  and R 5  are hydrogen; and R 8  and R 9  are each hydrogen. 
     
     
         3 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2  is hydrogen. 
     
     
         4 . The compound of  claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 1  is C 1 -C 3  alkyl. 
     
     
         5 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1  is methyl. 
     
     
         6 . The compound of  claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 13  is NR 16 R 18 , NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, or NH—C(O)-heteroaryl. 
     
     
         7 . The compound of  claim 6 , or a pharmaceutically acceptable salt thereof, wherein R 13  is N 16 R 18 , —NR 16 —SO 2 —C 1 -C 3  alkyl, or —NH—SO 2 —C 1 -C 3  haloalkyl. 
     
     
         8 . The compound of  claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 3  is heteroaryl, 9 to 12 membered bicyclic aryl, or napthalen-1-yl. 
     
     
         9 . The compound of  claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 3  is indolyl, 1,3-benzodioxolyl, or benzimidazolyl. 
     
     
         10 . The compound of  claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 3  is X. 
     
     
         11 . The compound of  claim 10 , or a pharmaceutically acceptable salt thereof, wherein four of R 10 , R 11 , R 12 , R 13 , and R 14  are hydrogen, and one of R 10 , R 11 , R 12 , R 13 , or R 14  is selected from the following groups:
 R 10  is NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkyleneC 3 -0 5  cycloalkyl, C 1 -C 3  alkyleneC 7 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl;   R 11  is NR 16 R 18 , fluoro, iodo, bromo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 1 -C 3  alkyleneC 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl;   R 12  is NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 2 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl,—O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl;   R 13  and R 14  are NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl, —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl; and   
       wherein any of said aryl groups of —O-aryl, —S-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl; said heterocycloalkyl; said heterocycloalkyl groups of —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl) and —O—C 1 -C 3  alkylene-heterocycloalkyl; said heteroaryl and said heteroaryl groups of —C(O)—NH(heteroaryl), NH—C(O)-heteroaryl, and —O—C 1 -C 3  alkylene-heteroaryl; and said cycloalkyl groups of —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkyleneC 3 -C 5  cycloalkyl, and —O—C 1 -C 3  alkyleneC 3 -C 14  cycloalkyl may be subsitituted with 1 to 3 subsitituents selected from the group consisting of:
 halo, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, CN, and NR 16 R 18 . 
 
     
     
         12 . The compound of  claim 10 , or a pharmaceutically acceptable salt thereof, wherein 5-n of R 10 , R 11 , R 12 , R 13 , and R 14  are hydrogen, and n of R 10 , R 11 , R 12 , R 13 , and R 14  are selected from the following groups:
 NR 16 R 18 , halo, hydroxyl, C 1 -C 3  alkyl, —O-aryl, C 1 -C 3  alkylene-aryl, C 1 -C 3  alkylene-O-aryl, —S-aryl, —O—C 1 -C 3  alkylene-aryl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —O—C 1 -C 3  alkyl, —C(O)—O—C 1 -C 3  alkyl, —C(O)—OH, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, NH—C(O)-heteroaryl, heterocycloalkyl, —O—C 1 -C 3  alkylene-heterocycloalkyl,—O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-heteroaryl, or heteroaryl;   wherein n is 2, 3, 4 or 5;   
       wherein any of said aryl groups of —O-aryl, —S-aryl, C 1 -C 3  alkylene-O-aryl; said heterocycloalkyl groups of —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl) and —O—C 1 -C 3  alkylene-heterocycloalkyl; said heteroaryl and said heteroaryl groups of —C(O)—NH(heteroaryl), NH—C(O)-heteroaryl, and —O—C 1 -C 3  alkylene-heteroaryl; and said cycloalkyl groups of —O—C 3 -C 14  cycloalkyl, —O—C 1 -C 3  alkylene-C 3 -C 5  cycloalkyl, and —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl may be subsitituted with 1 to 3 subsitituents selected from the group consisting of: halo, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, CN, and NR 16 R 18 . 
     
     
         13 . The compound of  claim 12 , or a pharmaceutically acceptable salt thereof, wherein n is 3. 
     
     
         14 . The compound of  claim 12 , or a pharmaceutically acceptable salt thereof, wherein n is 2. 
     
     
         15 . The compound of  claim 14 , or a pharmaceutically acceptable salt thereof, wherein R 13  is NR 16 R 18 , —NR 16 —SO 2 —NR 18 —C 1 -C 3  alkyl, —NR 16 —SO 2 —NR 18 —C 1 -C 3  haloalkyl, —NR 16 —SO 2 —C 1 -C 3  alkyl, —NR 16 —SO 2 —C 1 -C 3  haloalkyl, SO 2 —NR 16 R 18 , SO 2 —C 1 -C 3 alkyl, —C(O)—NR 16 R 18 , —C(O)—NH(C 1 -C 3  haloalkyl), —C(O)—NH(C 1 -C 3  alkylene-heterocycloalkyl), —C(O)—NH(heteroaryl), NH—C(O)—C 1 -C 3  alkyl, or NH—C(O)-heteroaryl. 
     
     
         16 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 13  is NR 16 R 18 , —NR  16 —SO 2 —C 1 -C 3  SO 2 —C 1 -C 3  alkyl, or —NH—SO 2 —C 1 -C 3  haloalkyl. 
     
     
         17 . The compound of  claim 16 , or a pharmaceutically acceptable salt thereof, wherein R 10  is O-aryl. 
     
     
         18 . The compound of  claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 10  is O-phenyl or is O-phenyl which is substituted with 1 to 3 independently groups independently selected from the group consisting of halo. 
     
     
         19 . The compound of  claim 18 , or a pharmaceutically acceptable salt thereof, wherein R 10  is —O-2,4-difluoro-phenyl. 
     
     
         20 . The compound of  claim 16 , or a pharmaceutically acceptable salt thereof, wherein R 10  is —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, which may be substituted with 1 to 3 groups independently selected from the group consisting of halo and C 1 -C 3  alkyl. 
     
     
         21 . The compound of  claim 20 , or a pharmaceutically acceptable salt thereof, wherein R 10  is —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, which is substituted with 1 to 3 groups independently selected from the group consisting of halo and C 1 -C 3  alkyl. 
     
     
         22 . The compound of  claim 21 , or a pharmaceutically acceptable salt thereof, wherein R 10  is —O—C 1 -C 3  alkylene-C 3 -C 14  cycloalkyl, which is substituted with 1 to 3 groups independently selected from the group consisting of halo. 
     
     
         23 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 3. 
     
     
         24 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 2 and R 11 , R 12 , and R 14  are hydrogen. 
     
     
         25 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of:
 3-methyl-1-phenyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-(2-phenoxyphenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(2-aminophenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-(4-methylphenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   4-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)benzenesulfonamide;   1-(2-methoxyphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1(3,4,5-trimethoxyphenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[4-(methylsulfonyl)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)benzamide;   1-(1H-indol-4-yl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(4-methoxyphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(3,4-dimethylphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(4-chlorophenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[3-(benzyloxy)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(2-chlorophenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(3,5-dimethylphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(3-methoxyphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-(2-{[3-(trifluoromethyl)phenoxy]methyl}phenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(phenoxymethyl)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-{2-[(2-methylphenoxy)methyl]phenyl}-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[2-(furan-2-yl)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(2-hydroxyphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(tetrahydrofuran-3-ylmethoxy)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[2-(cyclopentylmethoxy)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(tetrahydrofuran-2-ylmethoxy)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(tetrahydro-2H-pyran-4-ylmethoxy)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-{2-[2-(morpholin-4-yl)ethoxy]phenyl}-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(pyridin-2-ylmethoxy)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(quinolin-8-ylmethoxy)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[2-(1-benzothiophen-7-ylmethoxy)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-[2-(pyridin-3-ylmethoxy)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[2-(1H-indazol-5-ylmethoxy)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(5-amino-2-phenoxyphenyl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-[3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxyphenyl]methanesulfonamide;   N-[3-(2,3-dimethyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxyphenyl]methanesulfonamide;   N-[3-(2,3-dimethyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxyphenyl]acetamide;   1-[5-amino-2-(phenylsulfanyl)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-[3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-(phenylsulfanyl)phenyl]methanesulfonamide;   1-[5-amino-2-(2,4-difluorophenoxy)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-[4-(2,4-difluorophenoxy)-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]methanesulfonamide;   N-[4-(2,4-difluorophenoxy)-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]ethanesulfonamide;   N-[4-(2,4-difluorophenoxy)-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]-2,2,2-trifluoro ethanesulfonamide;   N′-[4-(2,4-difluorophenoxy)-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]-N,N-dimethylsulfuric diamide;   N-[4-(2,4-difluorophenoxy)-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]acetamide;   N-[4-(2,4-difluorophenoxy)-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]-1H-pyrrole-2-carboxamide;   N-{4-[(4,4-difluorocyclohexyl)oxy]-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl }ethanesulfonamide;   methyl 3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxybenzoate;   3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxybenzoic acid;   N-ethyl-3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxybenzamide;   3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxy-N-(tetrahydrofuran-2-ylmethyl)benzamide;   3-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxy-N-(1,3-thiazol-2-yl)benzamide;   3,6,6-trimethyl-1-phenyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(2,5-dimethylphenyl)-3,6,6-trimethyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3,6,6-trimethyl-1-[2-(morpholin-4-yl)phenyl]-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[2-(benzyloxy)phenyl]-3,6,6-trimethyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3,6,6-trimethyl-1-(2-phenoxyphenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-[3-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)phenyl]methanesulfonamide;   3,6-dimethyl-1-(2-phenoxyphenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(5-amino-2-phenoxyphenyl)-3,6-dimethyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-[3-(3,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxyphenyl]methanesulfonamide;   3-methyl-6-(2-methylpropyl)-1-(2-phenoxyphenyl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-{3-[3-methyl-6-(2-methylpropyl)-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl]-4-phenoxyphenyl}methanesulfonamide;   3-methyl-1-(2-phenoxyphenyl)-6-(propan-2-yl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   N-{3-[3-methyl-4-oxo-6-(propan-2-yl)-4,5,6,7-tetrahydro-2H-isoindol-1-yl]-4-phenoxyphenyl}methanesulfonamide;   N-[3-(3-methyl-4-oxo-6-phenyl-4,5,6,7-tetrahydro-2H-isoindol-1-yl)-4-phenoxyphenyl]methanesulfonamide; and   1-[2-(cyclopropylmethoxy)-5-(methylsulfonyl)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one.   
     
     
         26 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of:
 1-(1,3-benzodioxol-5-yl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-[2-(benzyloxy)phenyl]-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   3-methyl-1-(naphthalen-1-yl)-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(1H-benzimidazol-4-yl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   1-(1H-indol-7-yl)-3-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one;   2-[2-(3-methyl-4-oxo-4,5,6,7-tetrahydro-2H-isoindol-1-yl)benzyl]-1H-isoindole-1,3(2H)-dione; and   1-(1,3-benzodioxol-5-yl)-3,6,6-trimethyl-2,5,6,7-tetrahydro-4H-isoindol-4-one.   
     
     
         27 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to  claim 1 , or a pharmaceutically acceptable acceptable salt thereof, in combination with a pharmaceutically acceptable carrier. 
     
     
         28 . A method for treating a disease in a subject comprising administering a therapeutically effective amount of a compound of formula (I) according to  claim 1 , or a pharmaceutically acceptable acceptable salt thereof, to a subject in need thereof, wherein said disease is selected from a disease in one of the following groups which consist of:
 cancer;   Addison's disease, acute gout, ankylosing spondylitis, asthma, atherosclerosis, Behcet's disease, bullous skin diseases, chronic obstructive pulmonary disease (COPD), Crohn's disease, dermatitis, eczema, giant cell arteritis, glomerulonephritis, hepatitis, hypophysitis, inflammatory bowel disease, Kawasaki disease, lupus nephritis, multiple sclerosis, myocarditis, myositis, nephritis, organ transplant rejection, osteoarthritis, pancreatitis, pericarditis, Polyarteritis nodosa, pneumonitis, primary biliary cirrhosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleritis, sclerosing cholangitis, sepsis, systemic lupus erythematosus, Takayasu's Arteritis, toxic shock, thyroiditis, type I diabetes, ulcerative colitis, uveitis, vitiligo, vasculitis, and Wegener's granulomatosis;   diabetic nephropathy, hypertensive nephropathy, HIV-associated nephropathy, glomerulonephritis, lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis, minimal change disease, polycystic kidney disease and tubular interstitial nephritis;   ischemia-reperfusion induced kidney disease, cardiac and major surgery induced kidney disease, percutaneous coronary intervention induced kidney disease, radio-contrast agent induced kidney disease, sepsis induced kidney disease, pneumonia induced kidney disease, and drug toxicity induced kidney disease;   AIDS;   obesity;   type II diabetes; and   obesity, dyslipidemia, hypercholesterolemia, Alzheimer's disease, metabolic syndrome, hepatic steatosis, type II diabetes, insulin resistance, diabetic retinopathy and diabetic neuropathy.   
     
     
         29 . The method of  claim 28  wherein the cancer is selected from the group consisting of: acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute t-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, leukemia, lymphoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenström's macroglobulinemia, testicular tumors, uterine cancer and Wilms' tumor. 
     
     
         30 . The method of  claim 28  or  29 , further comprising administering a therapeutically effective amount of at least one additional therapeutic agent. 
     
     
         31 . A method of contraception in a male subject comprising administering a therapeutically effective amount of a compound of formula (I) according to  claim 1  or a pharmaceutically acceptable acceptable salt thereof, to a subject in need thereof.