Modulators of ror-gamma

Abstract

Provided are indole, benzoimidazole, pyrrolopyridine, and imidazopyridine derivatives and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by ROR . Such derivatives include e.g., those having the Formula II. as well as pharmaceutically acceptable salts thereof. The disclosed derivatives may be used for treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

1 - 25 . (canceled) 
     
     
         26 . A compound having the Formula (II): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
 A is N; 
 Y is CR 10 ; 
 L 2  is CH 2 , CH 2 CH 2 , CH(CH 3 ), O, C(═O), CH(OH), or OCH 2 , wherein the oxygen atom in CH 2 O can either be attached to Cy 2  or to the carbon atom on the center ring bridging NR 2  and A; 
 L 1  is absent or is CR 7 R 8 ; 
 Cy 1  is selected from aryl, heteroaryl, heterocyclyl, and cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl, and cycloalkyl are each substituted with 1, 2, or 3 independently selected R 5  substituents, and further wherein the heterocyclyl is optionally substituted with ═O; 
 Cy 2  is selected from aryl, heteroaryl, monocyclic cycloalkyl, and monocyclic heterocyclyl, wherein the aryl, heteroaryl, monocyclic cycloalkyl, and monocyclic heterocyclyl are each optionally substituted with 1, 2, or 3 independently selected R 6  substituents, and further wherein the heterocyclyl is optionally substituted with ═O; 
 R 2  is (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 1 -C 4 )haloalkyl, or monocyclic cycloalkyl; 
 R 5  and R 6  are each independently selected from halogen, —CN, —OR c , —NR d R e , —S(O) k R c , —NR c S(O) 2 R c , —S(O) 2 NR d R e , —C(═O)OR c , —OC(═O)OR c , —OC(═O)R c , —OC(═S)OR c , —C(═S)OR, —OC(═S)R c , —C(═O)NR d R e , —NR c C(═O)R c , —C(═S)NR d R e , —NR c C(═S)R c , —NR c C(═O)OR c , —OC(═O)NR d R e , —NR c (C═S)OR c , —OC(═S)NR d R e , —NR c C(═O)NR d R e , —NR c (C═S)NR d R e , —C(═S)R e , —C(═O)R c , (C 1 -C 6 )alkyl, cycloalkyl, —(CH 2 ) 1-4 -cycloalkyl, heterocyclyl, —(CH 2 ) 1-4 -heterocyclyl, aryl, —NHC(═O)-heterocyclyl, —NHC(═O)-cycloalkyl, —(CH 2 ) 1-4 -aryl, heteroaryl and —(CH 2 ) 1-4 -heteroaryl, 
 wherein the alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl portion present in each of said (C 1 -C 6 )alkyl, cycloalkyl, —(CH 2 ) 1-4 -cycloalkyl, heterocyclyl, —(CH 2 ) 1-4 -heterocyclyl, aryl, —(CH 2 ) 1-4 -aryl, heteroaryl and —(CH 2 ) 1-4 -heteroaryl substituent for R 6  are further optionally substituted with halogen, OR c , —NO 2 , —CN, —NR c C(═O)R c , —NR d R e , —S(O) k R c , —C(═O)OR c , —C(═O)NR d R e , —C(═O)R e , (C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkyl, or halo(C 1 -C 3 )alkoxy; 
 R 7  is H, OH, (C 1 -C 2 )alkyl, hydroxy(C 1 -C 3 )alkyl, —O(C 1 -C 3 )alkyl, —(C 1 -C 3 )alkyl-O—(C 1 -C 3 )alkyl, —(C 1 -C 3 )alkyl-NH 2 , —(C 1 -C 3 )alkyl-N-di(C 1 -C 3 )alkyl, (CH 2 ) 1-3 COOH, monocyclic heterocyclyl, —CO—(C 1 -C 3 )alkoxy, —(C 1 -C 3 )alkoxy-C(O)—NH 2 , —(C 1 -C 3 )alkoxy-O—(C 1 -C 3 )alkyl-C(O)—NH 2 , —(C 1 -C 3 )alkyl-C(O)—(C 1 -C 3 )alkoxy, —(C 1 -C 3 )alkyl-C(O)—NH 2 , halophenyl, —(C 1 -C 3 )alkyl-halophenyl, or quinolin-2(1H)-on-4-ylmethyl; 
 R 8  is H, OH, (C 1 -C 2 )alkyl, hydroxy(C 1 -C 3 )alkyl, —O(C 1 -C 3 )alkyl, —(C 1 -C 3 )alkyl-O—(C 1 -C 3 )alkyl, —(C 1 -C 3 )alkyl-NH 2 , —(C 1 -C 3 )alkyl-N-di(C 1 -C 3 )alkyl, (CH 2 ) 1-3 COOH, monocyclic heterocyclyl, —CO—(C 1 -C 3 )alkoxy, —(C 1 -C 3 )alkoxy-C(O)—NH 2 , —(C 1 -C 3 )alkoxy-O—(C 1 -C 3 )alkyl-C(O)—NH 2 , —(C 1 -C 3 )alkyl-C(O)—(C 1 -C 3 )alkoxy, —(C 1 -C 3 )alkyl-C(O)—NH 2 , halophenyl, —(C 1 -C 3 )alkyl-halophenyl, or quinolin-2(1H)-on-4-ylmethyl; 
 each R 9  is independently (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, —O(C 1 -C 4 )alkyl, or halogen; and 
 R 10  is H, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, —O(C 1 -C 4 )alkyl, or halogen; 
 each R c  is independently H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with 1, 2, or 3 halogens; 
 each R d  is H or (C 1 -C 6 )alkyl; 
 each R e  is H or (C 1 -C 6 )alkyl; 
 k is 0, 1 or 2; 
 n is 0, 1, 2, or 3; and 
 p is 0, 1, or 2. 
 
       
     
     
         27 . The compound of  claim 26 , wherein the compound is of Formula (III): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof. 
       
     
     
         28 . The compound of  claim 27 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein L 2  is CH 2 , CH(CH 3 ), O, or C(O). 
     
     
         29 . The compound of  claim 28 , wherein the compound is of Formula (IV) or Formula (V): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof. 
       
     
     
         30 . The compound of  claim 29 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7  is H, (C 1 -C 2 )alkyl, (C 1 -C 3 )alkylOH, —(C 1 -C 3 )alkylNH 2 , —(C 1 -C 3 )alkyl-N-di(C 1 -C 3 )alkyl, or —O(C 1 -C 3 )alkyl-C(O)—NH 2 ; and R 8  is hydrogen. 
     
     
         31 . The compound of  claim 30 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7  is (C 1 -C 3 )OH. 
     
     
         32 . The compound of  claim 31 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2  is (C 1 -C 4 )alkyl or cyclopropyl. 
     
     
         33 . The compound of  claim 32 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Cy 1  is aryl or heteroaryl, each substituted with 1 to 3 groups independently selected from R 5 . 
     
     
         34 . The compound of  claim 33 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Cy 1  is phenyl or pyridyl, each substituted with 1 to 3 groups independently selected from R 5 . 
     
     
         35 . The compound  claim 34 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein at least 1 R 5  is S(O) 2 (C 1 -C 3 )alkyl. 
     
     
         36 . The compound of  claim 35 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Cy 1  is pyridyl substituted with 1 to 3 groups independently selected from R 5 , wherein at least 1 R 5  is S(O) 2 (C 1 -C 3 )alkyl. 
     
     
         37 . The compound of  claim 35 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Cy 2  is phenyl, pyridyl, cyclohexyl, tetrahydropyranyl, cyclopropyl, or cyclobutyl, each optionally substituted with 1, 2, or 3 independently selected R 6  substituents. 
     
     
         38 . The compound of  claim 37 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Cy 2  is phenyl, pyridyl, cyclohexyl, or tetrahydropyranyl, each optionally substituted with 1, 2, or 3 independently selected R 6  substituents. 
     
     
         39 . The compound of  claim 38 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Cy 2  is phenyl or cyclohexyl, each optionally substituted with 1, 2, or 3 independently selected R 6  substituents. 
     
     
         40 . The compound of  claim 39 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein;
 Cy 1  is phenyl substituted with 1 to 3 groups independently selected from R 5 , wherein at least 1 R 5  is S(O) 2 (C 1 -C 3 )alkyl; and   Cy 2  is cyclohexyl substituted with 1, 2, or 3 independently selected R 6  substituents.   
     
     
         41 . The compound of  claim 39 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
 R 5  is halogen, —CN, —OR c , —NR d R e , —NR c S(O) 2 R c , —S(O) 2 NR d R e , —C(═O)OR c , —C(═O)NR d R e , —NR c C(═O)R c , —NR c C(═O)OR c , —OC(═S)NR d R e , —C(═O)R c , —S(O) 2 (C 1 -C 3 )alkyl, or (C 1 -C 4 )alkyl; and   R 6  is halogen, —CN, —OR c , —NR d R e , —NR c S(O) 2 R c , —S(O) 2 NR d R e , —C(═O)OR c , —OC(═O)OR c , —OC(═O)R c , —C(═O)NR d R e , —NR c C(═O)R c , —C(═S)NR d R e , —NR c C(═S)R c , —NR c C(═O)OR, —OC(═O)NR d R e , —NR c (C═S)OR c , —OC(═S)NR d R e , —NR c C(═O)NR d R e , —NR c (C═S)NR d R e , —C(═S)R e , —C(═O)R c , S(O) 2 (C 1 -C 3 )alkyl, or (C 1 -C 4 )alkyl, wherein the (C 1 -C 4 )alkyl is optionally substituted with halogen.   
     
     
         42 . The compound of  claim 41 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
 R 5  is S(O) 2 (C 1 -C 3 )alkyl;   R 6  is halogen, —OR c , or (C 1 -C 4 )alkyl, wherein the (C 1 -C 4 )alkyl is optionally substituted with halogen; and   R c  is (C 1 -C 4 )alkyl, wherein the (C 1 -C 4 )alkyl is optionally substituted with 1, 2, or 3 halogen.   
     
     
         43 . The compound of  claim 42 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 6  is CF 3 . 
     
     
         44 . The compound of  claim 42 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 6  is —OCF 3 . 
     
     
         45 . A compound selected from:
 1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide;   1-ethyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(4-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide;   (R)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide;   (S)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide;   (R)-2-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-indole-5-carboxamide;   (R)-2-(4-(difluoromethoxy)benzyl)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-indole-5-carboxamide;   (R)-2-(3-(difluoromethoxy)benzyl)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-indole-5-carboxamide;   (R)-2-(4-chlorobenzyl)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-indole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1H-indole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-indole-5-carboxamide;   (R)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-indole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-indole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N—((R)-1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N—((R)-1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(((1s,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1s,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-indole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzyl)-1H-indole-5-carboxamide;   (R)-2-(4-carbamoylbenzyl)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-indole-5-carboxamide;   (R)-2-(4-cyanobenzyl)-1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-indole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(5-(trifluoromethyl)picolinoyl)-1H-indole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(hydroxy(5-(trifluoromethyl)pyridin-2-yl)methyl)-1H-indole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;   1-cyclopropyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-(2-methylallyl)-2-(4-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;   1-cyclopropyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-isobutyl-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-isobutyl-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethoxy)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)—N-(2-(dimethylamino)-1-(4-(ethylsulfonyl)phenyl)ethyl)-1-ethyl-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)—N-(2-amino-1-(4-(ethylsulfonyl)phenyl)ethyl)-1-ethyl-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)-2-((4,4-difluorocyclohexyl)methoxy)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-2-((3,3-difluorocyclobutyl)methoxy)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)benzyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)benzyl)oxy)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-2-((4,4-difluorocyclohexyl)methoxy)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-2-(cyclopropylmethoxy)-1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-isobutyl-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-isobutyl-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((S)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N—((S)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((1r,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((S)-1-(4-(ethylsulfonyl)phenyl)-3-hydroxypropyl)-2-(((1r,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1-isobutyl-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1-isobutyl-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((R)-1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((S)-1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(((1r,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(methylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-((5-(N-methylsulfamoyl)pyridin-2-yl)methyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((R)-2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(N-methylsulfamoyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-methyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-(2,2,2-trifluoroethyl)-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclobutyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-neopentyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1-isopropyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-isobutyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   1-(tert-butyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1-isobutyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   rel-(R)—N-(1-(4-(ethylsulfonyl)phenyl)ethyl)-1-isobutyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-methoxycyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1s,4s)-4-methoxycyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethoxy)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-2-(4-(difluoromethoxy)benzyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   tert-butyl 4-((1-cyclopropyl-5-((4-(ethylsulfonyl)benzyl)carbamoyl)-1H-benzo[d]imidazol-2-yl)methyl)piperidine-1-carboxylate;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   2-((5-chloropyridin-2-yl)methyl)-1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-1-isobutyl-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   (S)-1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(1-(4-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((3S,6S)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((3R,6R)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((3R,6S)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(((3S,6R)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((3S,6S)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((3R,6R)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((3R,6S)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-ethyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(((3S,6R)-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   7-bromo-N-(4-(ethylsulfonyl)benzyl)-1-methyl-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   7-bromo-N-(4-(ethylsulfonyl)benzyl)-1-methyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   N-(4-(ethylsulfonyl)benzyl)-7-methoxy-1-methyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzoyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-1-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)piperidine-1-carbonyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((S)-hydroxy(trans-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((R)-hydroxy(trans-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)cyclohexane-1-carbonyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzoyl)-1H-benzo[d]imidazole-5-carboxamide;   (R)-2-(1-cyclopropyl-2-(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamido)-2-(4-(ethylsulfonyl)phenyl)ethyl carbamate;   (S)-2-(1-cyclopropyl-2-(((1r,4S)-4-(trifluoromethyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carboxamido)-2-(4-(ethylsulfonyl)phenyl)ethyl carbamate;   2-(4-(ethylsulfonyl)phenyl)-N-(1-isobutyl-2-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-5-yl)acetamide;   2-(4-(ethylsulfonyl)phenyl)-N-(1-isobutyl-2-((4-(trifluoromethyl)piperidin-1-yl)methyl)-1H-benzo[d]imidazol-5-yl)acetamide;   (R)-1-cyclopropyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)phenoxy)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((((1s,4S)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-1H-benzo[d]imidazole-5-carboxamide;   1-cyclopropyl-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((((1r,4R)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-1H-benzo[d]imidazole-5-carboxamide;   3-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxamide;   3-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(((1s,4s)-4-(trifluoromethyl)cyclohexyl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxamide;   3-cyclopropyl-N-(4-(methylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-b]pyridine-6-carboxamide; and   3-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-b]pyridine-6-carboxamide, or a pharmaceutically acceptable salt or stereoisomer of any of the foregoing.   
     
     
         46 . A pharmaceutical composition comprising a compound of  claim 26 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier. 
     
     
         47 . A pharmaceutical composition comprising a compound of  claim 45 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier. 
     
     
         48 . A method for modulating retinoic acid receptor-related orphan receptor gamma activity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of  claim 26 , or a pharmaceutically acceptable salt or stereoisomer thereof. 
     
     
         49 . The method of  claim 48 , wherein the subject has a disease or disorder selected from the group consisting of asthma, chronic obstructive pulmonary disease, bronchitis, allergic rhinitis, atopic dermatitis, contact dermatitis, acne, cystic fibrosis, allograft rejection, multiple sclerosis, scleroderma, arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Hashimoto's disease, pancreatitis, autoimmune diabetes, type I diabetes, autoimmune ocular disease, ulcerative colitis, Crohn's disease, regional enteritis, inflammatory bowel disease, inflammatory bowel syndrome, Sjögren's syndrome, optic neuritis, obesity, hepatosteatosis, adipose tissue-associated inflammation, insulin resistance, type II diabetes, myasthenia gravis, age related macular degeneration, dry eye, uveitis, Guillain-Barré syndrome, Graves' disease, scleritis, major depression, seasonal affective disorder, post-traumatic stress disorder, bipolar disorder, autism, epilepsy, Alzheimer's disease, a central nervous system disorder associated with altered sleep, a central nervous system disorders associated with circadian rhythms, endometriosis, obstructive sleep apnea syndrome, Behçet's disease, dermatomyositis, polymyocitis, graft versus host disease, primary biliary cirrhosis, liver fibrosis, non-alcoholic fatty liver disease, sarcoidosis, primary sclerosing cholangitis, autoimmune thyroid disease, autoimmune polyendocrine syndrome type I, autoimmune polyendocrine syndrome type II, celiac disease, neuromyelitis, systemic sclerosis, myocardial infarction, pulmonary hypertension, cutaneous leishmaniasis, sinonasal polyposis, and cancer. 
     
     
         50 . The method of  claim 49 , wherein the subject has a disease or disorder selected from the group consisting of atopic dermatitis, acne, Crohn's disease, regional enteritis, ulcerative colitis, Sjögren's syndrome, uveitis, Behçet's disease, dermatomyositis, multiple sclerosis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, psoriasis, psoriatic arthritis, steroid resistant asthma, neuromyelitis optica, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, and rheumatoid arthritis. 
     
     
         51 . A method for modulating retinoic acid receptor-related orphan receptor gamma activity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of  claim 45 , or a pharmaceutically acceptable salt or stereoisomer thereof. 
     
     
         52 . The method of  claim 51 , wherein the subject has a disease or disorder selected from the group consisting of asthma, chronic obstructive pulmonary disease, bronchitis, allergic rhinitis, atopic dermatitis, contact dermatitis, acne, cystic fibrosis, allograft rejection, multiple sclerosis, scleroderma, arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Hashimoto's disease, pancreatitis, autoimmune diabetes, type I diabetes, autoimmune ocular disease, ulcerative colitis, Crohn's disease, regional enteritis, inflammatory bowel disease, inflammatory bowel syndrome, Sjögren's syndrome, optic neuritis, obesity, hepatosteatosis, adipose tissue-associated inflammation, insulin resistance, type II diabetes, myasthenia gravis, age related macular degeneration, dry eye, uveitis, Guillain-Barré syndrome, Graves' disease, scleritis, major depression, seasonal affective disorder, post-traumatic stress disorder, bipolar disorder, autism, epilepsy, Alzheimer's disease, a central nervous system disorder associated with altered sleep, a central nervous system disorders associated with circadian rhythms, endometriosis, obstructive sleep apnea syndrome, Behçet's disease, dermatomyositis, polymyocitis, graft versus host disease, primary biliary cirrhosis, liver fibrosis, non-alcoholic fatty liver disease, sarcoidosis, primary sclerosing cholangitis, autoimmune thyroid disease, autoimmune polyendocrine syndrome type I, autoimmune polyendocrine syndrome type II, celiac disease, neuromyelitis, systemic sclerosis, myocardial infarction, pulmonary hypertension, cutaneous leishmaniasis, sinonasal polyposis, and cancer. 
     
     
         53 . The method of  claim 52 , wherein the subject has a disease or disorder selected from the group consisting of atopic dermatitis, acne, Crohn's disease, regional enteritis, ulcerative colitis, Sjögren's syndrome, uveitis, Behçet's disease, dermatomyositis, multiple sclerosis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, psoriasis, psoriatic arthritis, steroid resistant asthma, neuromyelitis optica, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, and rheumatoid arthritis.