Novel compounds

Abstract

The present invention is directed to novel retinoid-related orphan receptor gamma (RORγ) modulators, processes for their preparation, pharmaceutical compositions containing these modulators, and their use in the treatment of inflammatory, metabolic and autoimmune diseases mediated by RORγ.

What is claimed is: 
     
         1 . A compound of formula (Ia), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group consisting of H, C 1-3 alkyl, C 1-3 alkoxy, CF 3 , and halo; 
         R 2 , R 3  and R 4  are H; 
         R 5  is C 1-3 alkyl; 
         R 6  is C 3-5 alkyl or —CH 2 C 3-4 cycloalkyl; 
         R 7  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         each R 8  is independently selected from the group consisting of halo, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, CN, OH, C(O)OH, C(O)OC 1-3 alkyl and CH 2 OH; 
         R 9  is the group —(CHR 10 ) s —(X) t —(CHR 10 ) u —R 11 ; 
         each R 10  is independently selected from H, CH 3 , OH and CH 2 OH; 
         X is CH 2 , NH or O; 
         R 11  is a heterocycloalkyl or C 3-6  cycloalkyl group which may be unsubstituted or substituted with one or more substituents independently selected from the group consisting of CH 3 , OMe, OH, CH 2 OH and halo; 
         r is 0, 1 or 2; 
         s is 0, 1 or 2; 
         t is 0 or 1; 
         u is 0, 1 or 2; 
         with the proviso that no more than two R 10  groups represent CH 3 , OH or CH 2 OH. 
       
     
     
         2 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  and R 5  are CH 3 . 
     
     
         3 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6  is selected from the group consisting of propyl, isobutyl, and —CH 2 cyclopropyl. 
     
     
         4 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7  is: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein r is 2. 
     
     
         6 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 8  is independently selected from the group consisting of CH 3 , OCH 3 , CH 2 OH, cyclopropyl, fluoro and chloro. 
     
     
         7 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein r is 0. 
     
     
         8 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein s is 1. 
     
     
         9 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein u is 2. 
     
     
         10 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein u is 0. 
     
     
         11 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein t is 0. 
     
     
         12 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11  is a heterocycloalkyl group selected from oxirane, oxetane, tetra hydrofuran, tetra hydro-2H-pyran, pyrrolidine, piperidine, morpholine, morpholin-3-one, and thiomorpholine 1,1-dioxide. 
     
     
         13 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11  is cyclohexane. 
     
     
         14 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, which is (S)-N-(4-ethylphenyl)-4-(1-hydroxy-2-morpholinoethyl)-3-(hydroxymethyl)-N-isobutylbenzenesulfonamide. 
     
     
         15 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, which is (R)-N-(4-ethylphenyl)-4-(1-hydroxy-2-morpholinoethyl)-3-(hydroxymethyl)-N-isobutylbenzenesulfonamide. 
     
     
         16 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, which is N-(4-ethylphenyl)-3-(hydroxymethyl)-N-isobutyl-4-((tetrahydro-2H-pyran-4-yl)methoxy)benzenesulfonamide. 
     
     
         17 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. 
     
     
         18 . A method of treating a disease in a subject in need thereof, comprising administering to said subject an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and wherein the disease is selected from asthma, chronic obstructive pulmonary disease, bronchitis, allergic rhinitis, atopic dermatitis, psoriasis, ulcerative colitis, Crohn's disease, inflammatory bowel disease, or inflammatory bowel syndrome. 
     
     
         19 . A method of treatment according to  claim 18 , wherein the disease is atopic dermatitis. 
     
     
         20 . A method of treatment according to  claim 18 , wherein the disease is psoriasis.