Amine derivatives as potassium channel blockers

Abstract

The present invention relates to compounds useful in the modulation of potassium channel activity in cells, in particular the activity of Kv1.3 channels found in T cells. The invention also relates to the use of these compounds in the treatment or prevention of autoimmune and inflammatory diseases, including multiple sclerosis, pharmaceutical compositions containing these compounds and methods for their preparation.

1 - 113 . (canceled) 
     
     
         114 . A method of treating a condition selected from autoimmune disorders, immune-mediated disorders, inflammatory disorders, or other disorders, or conditions which benefit clinically from immunosuppressants, including multiple sclerosis, type-1 diabetes mellitus, type-2 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, contact dermatitis, obesity, graft-versus host disease, transplant rejection, and delayed type hypersensitivity, including the step of administering an effective amount of a compound according to Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         G 1  denotes a single bond, 
         G 2  denotes a CO group, 
         X is selected from a single bond, an alkylene group having 1 to 6 carbon atoms optionally substituted with 1 or 2 substituents selected from fluoro or C 1 -C 6 -alkyl, 
         Y is selected from an alkylene group having 1 to 6 carbon atoms optionally substituted one or two times with C 3 -C 8 -cycloalkyl or C 1 -C 3 -alkyl; or a 3-8-membered cycloalkylene group, 
         Q is selected from O, NH or a single bond, 
         W is selected from SO, SO 2  or a single bond, 
         U is cycloalkyl, cycloalkenyl, heterocyclyl or heteroaryl, each of the above groups being optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, —SO 2 —C 1 -C 6 -alkyl, —S—C 1 -C 6 -alkyl, NMe 2 , C 1 -C 6 -alkyl, —C(O)O—C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, or a 5-6-membered heteroaromatic group being optionally substituted by Hal, 
         V is an aryl group optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, SO 2 —C 1 -C 6  alkyl, NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, O—C 1 -C 6 -halo-alkyl or a 5-6-membered heteroaromatic group, 
         T denotes phenyl, triazolyl, thiazolyl, oxazolyl, oxadiazolyl, or pyrazolyl, 
         R 1  is Hal, —C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, cyano or —C 1 -C 6 -halo-alkyl, 
         R 2  and R 2′  are independently from one another H, Hal, —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, —C 1 -C 6 -halo-alkyl, or 
         R 1  and R 2  are linked to form with the ring T to which they are attached a 7-12-membered fused heterocyclyl or 7-12-membered fused cycloalkyl, each of which may be optionally substituted with 1 to 3 Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —O—C 1 -C 6 -alkyl, 
         R 3  is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —(CH 2 ) m —O—C 1 -C 6 -haloalkyl; a 3-8-membered cycloalkyl group, optionally substituted with 1 to 3 substituents independently selected from Hal, —C 1 -C 6 -halo-alkyl, or C 1 -C 6 -alkyl; or a 3-8-membered heterocyclic group, optionally substituted with 1 to 3 substituents independently selected from Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —O—C 1 -C 6 -halo-alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, 
         R 4  denotes H, C 1 -C 6 -alkyl, or forms together with R 3  a 3-8-membered cycloalkyl ring, optionally substituted with Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, 
         m is selected from 1, 2, 3 or 4, preferably 1 or 2, 
         Hal is F, Cl, Br, or I, 
         wherein -G 2 -Y—W together is at least 3 atoms in length, 
         or a pharmaceutically acceptable salts thereof, or an enantiomeric mixture of 2 enantiomers in all ratios, and/or as a mixture of diastereoisomers in all ratios. 
       
     
     
         115 . The method according to  claim 114  wherein V is a phenyl group optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, SO 2 —C 1 -C 6  alkyl, NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, O—C 1 -C 6 -halo-alkyl or a 5-6-membered heteroaromatic group. 
     
     
         116 . The method according to  claim 114  wherein U is a 5-6-membered cycloalkyl group, a 5-12-membered heterocyclyl or a 5-6 membered heteroaryl, each of the above groups being optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, SO 2 , NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C(O)O—C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -alkyl, —S—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, or a 5-6-membered heteroaromatic group being optionally substituted by Hal. 
     
     
         117 . The method according to  claim 114  wherein T is phenyl, triazolyl, or oxadiazolyl. 
     
     
         118 . The method according to  claim 114  wherein R 1  is O—C 1 -C 6 -alkyl, Hal, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, or cyano, in which m is 1. 
     
     
         119 . The method according to  claim 114  wherein R 2  and R 2′  are H or Hal. 
     
     
         120 . The method according to  claim 114  wherein R 2  is H or Hal and R 2′  is H. 
     
     
         121 . The method according to  claim 114  wherein R 1  is O—C 1 -C 6 -alkyl, Hal, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, or cyano, in which m is 1, R 2  is H or Hal and R 2′  is H. 
     
     
         122 . The method according to  claim 114  wherein R 1  and R 2  are linked to form with the ring T to which they are attached a dihydrobenzofuranyl, an indanyl, 
       
         
           
           
               
               
           
         
          each of these groups being optionally substituted with 1 to 3 Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —O—C 1 -C 6 -alkyl. 
       
     
     
         123 . The method according to  claim 114  wherein R 4  is H and R 3  is C 1 -C 6  alkyl, cyclopropyl, or a 3-8-membered heterocyclic group. 
     
     
         124 . The method according to  claim 114  wherein R 4  is H and R 3  is C 1 -C 6  alkyl or cyclopropyl. 
     
     
         125 . The method according to  claim 114  wherein R 4  is H and R 3  is cyclopropyl. 
     
     
         126 . The method according to  claim 114  wherein R 4  is H and R 3  is ethyl. 
     
     
         127 . The method according to  claim 114  wherein R 3  and R 4  are independently C 1 -C 3 -alkyl. 
     
     
         128 . The method according to  claim 127  wherein R 3  and R 4  are both methyl. 
     
     
         129 . The method according to  claim 114  wherein the compound of formula (I) is represented by formula (Ia): 
       
         
           
           
               
               
           
         
         wherein: 
         X is selected from a single bond, an alkylene group having 1 to 6 carbon atoms optionally substituted with 1 or 2 substituents selected from fluoro or C 1 -C 6 -alkyl, 
         Y is selected from an alkylene group having 1 to 6 carbon atoms optionally substituted one or two times with C 3 -C 8 -cycloalkyl or C 1 -C 3 -alkyl; or a 3-8-membered cycloalkylene group, 
         Q is selected from O, NH or a single bond, 
         V is an aryl group optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, SO 2 —C 1 -C 6  alkyl, NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, O—C 1 -C 6 -halo-alkyl or a 5-6-membered heteroaromatic group, 
         U is cycloalkyl, cycloalkenyl, heterocyclyl or heteroaryl, each of the above groups being optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, —SO 2 —C 1 -C 6 -alkyl, —S—C 1 -C 6 -alkyl, NMe 2 , C 1 -C 6 -alkyl, —C(O)O—C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, or a 5-6-membered heteroaromatic group being optionally substituted by Hal, 
         T denotes phenyl, triazolyl, thiazolyl, oxazolyl, oxadiazolyl, or pyrazolyl. 
         R 1  is Hal, —C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, cyano or —C 1 -C 6 -halo-alkyl, 
         R 2  and R 2′  are independently from one another H, Hal, —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, —C 1 -C 6 -halo-alkyl, or 
         R 1  and R 2  are linked to form with the ring T to which they are attached a 7-12-membered fused heterocyclyl or 7-12-membered fused cycloalkyl, each of which may be optionally substituted with 1 to 3 Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —O—C 1 -C 6 -alkyl, 
         R 3  is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —(CH 2 ) m —O—C 1 -C 6 -haloalkyl; a 3-8-membered cycloalkyl group, optionally substituted with 1 to 3 substitutents independently selected from Hal, —C 1 -C 6 -halo-alkyl, or C 1 -C 6 -alkyl; or a 3-8-membered heterocyclic group, optionally substituted with 1 to 3 substitutents independently selected from Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —O—C 1 -C 6 -halo-alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, 
         R 4  denotes H, C 1 -C 6 -alkyl, or forms together with R 3  a 3-8-membered cycloalkyl ring, optionally substituted with Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, and 
         each m is independently selected from 1, 2, 3, or 4 preferably 1 or 2; 
         or a pharmaceutically acceptable salts thereof. 
       
     
     
         130 . The method according to  claim 114  wherein the compound of formula (I) is represented by formula (Ib) 
       
         
           
           
               
               
           
         
         wherein: 
         X is selected from a single bond, an alkylene group having 1 to 6 carbon atoms optionally substituted with 1 or 2 substituents selected from fluoro or C 1 -C 6 -alkyl, 
         Y is a 3-membered cycloalkylene group. 
         Q is selected from O, NH or a single bond, 
         V is an aryl group optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, SO 2 —C 1 -C 6  alkyl, NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, O—C 1 -C 6 -halo-alkyl or a 5-6-membered heteroaromatic group, 
         U is cycloalkyl, cycloalkenyl, heterocyclyl or heteroaryl, each of the above groups being optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, —SO 2 —C 1 -C 6 -alkyl, —S—C 1 -C 6 -alkyl, NMe 2 , C 1 -C 6 -alkyl, —C(O)O—C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, or a 5-6-membered heteroaromatic group being optionally substituted by Hal, 
         T denotes phenyl, triazolyl, thiazolyl, oxazolyl, oxadiazolyl, or pyrazolyl, 
         R 1  is Hal, —C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, cyano or —C 1 -C 6 -halo-alkyl, 
         R 2  and R 2′  are independently from one another H, Hal, —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, —C 1 -C 6 -halo-alkyl, or 
         R 1  and R 2  are linked to form with the ring T to which they are attached a 7-12-membered fused heterocyclyl or 7-12-membered fused cycloalkyl, each of which may be optionally substituted with 1 to 3 Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —O—C 1 -C 6 -alkyl, 
         R 3  is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —(CH 2 ) m —O—C 1 -C 6 -haloalkyl; a 3-8-membered cycloalkyl group, optionally substituted with 1 to 3 substituents independently selected from Hal, —C 1 -C 6 -halo-alkyl, or C 1 -C 6 -alkyl; or a 3-8-membered heterocyclic group, optionally substituted with 1 to 3 substituents independently selected from Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —O—C 1 -C 6 -halo-alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, 
         R 4  denotes H, C 1 -C 6 -alkyl, or forms together with R 3  a 3-8-membered cycloalkyl ring, optionally substituted with Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, and 
         each m is independently selected from 1, 2, 3 or 4, 
         or a pharmaceutically acceptable salts thereof, or an enantiomeric mixture of 2 enantiomers in all ratios, and/or as a mixture of diastereoisomers in all ratios. 
       
     
     
         131 . The method according to  claim 114  wherein the compound of formula (I) is represented by formula (Ic): 
       
         
           
           
               
               
           
         
         wherein: 
         X is selected from a single bond, an alkylene group having 1 to 6 carbon atoms optionally substituted with 1 or 2 substituents selected from fluoro or C 1 -C 6 -alkyl, 
         Y is an alkylene group having 1 to 6 carbon atoms, 
         Q is selected from O, NH or a single bond, 
         V is an aryl group optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, SO 2 —C 1 -C 6  alkyl, NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, O—C 1 -C 6 -halo-alkyl or a 5-6-membered heteroaromatic group, 
         U is cycloalkyl, cycloalkenyl, heterocyclyl or heteroaryl, each of the above groups being optionally substituted with 1 to 3 substituents selected from Hal, NO 2 , CN, —SO 2 —C 1 -C 6 -alkyl, —S—C 1 -C 6 -alkyl, NMe 2 , C 1 -C 6 -alkyl, —C(O)O—C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, or a 5-6-membered heteroaromatic group being optionally substituted by Hal, 
         T is a phenyl, triazolyl, thiazolyl, an oxazolyl, an oxadiazolyl, or pyrazolyl group, 
         R 1  is Hal, —C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, cyano or —C 1 -C 6 -halo-alkyl, 
         R 2  and R 2′  are independently from one another H, Hal, —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, —C 1 -C 6 -halo-alkyl, or 
         R 1  and R 2  are linked to form with the ring T to which they are attached a 7-12-membered fused heterocyclyl or 7-12-membered fused cycloalkyl, each of which may be optionally substituted with 1 to 3 Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —O—C 1 -C 6 -alkyl, 
         R 3  is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —(CH 2 ) m —O—C 1 -C 6 -haloalkyl; a 3-8-membered cycloalkyl group, optionally substituted with 1 to 3 substituents independently selected from Hal, —C 1 -C 6 -halo-alkyl, or C 1 -C 6 -alkyl; or a 3-8-membered heterocyclic group, optionally substituted with 1 to 3 substituents independently selected from Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —O—C 1 -C 6 -halo-alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, 
         R 4  denotes H, C 1 -C 6 -alkyl, or forms together with R 3  a 3-8-membered cycloalkyl ring, optionally substituted with Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —C(O)—C 1 -C 6 -alkyl, or —C(O)O—C 1 -C 6 -alkyl, 
         each m is independently selected from 1, 2, 3 or 4, 
         or a pharmaceutically acceptable salts thereof, or an enantiomeric mixture of 2 enantiomers in all ratios, and/or as a mixture of diastereoisomers in all ratios. 
       
     
     
         132 . The method according to  claim 114  wherein the compound of formula (I) is represented by formula (II): 
       
         
           
           
               
               
           
         
         Wherein 
         G1 denotes a single bond, 
         G2 denotes a CO group, 
         X is selected from a single bond, an alkylene group having 1 to 6 carbon atoms optionally substituted with 1 or 2 substituents selected from fluoro or C 1 -C 6 -alkyl, 
         Y is selected from an alkylene group having 1 to 6 carbon atoms optionally substituted one or two times with C 3 -C 5 -cycloalkyl or C 1 -C 3 -alkyl; or a 3-8-membered cycloalkylene group, 
         Q is selected from O, NH or a single bond, 
         W is selected from SO, SO 2  or a single bond, 
         U is cycloalkyl, cycloalkenyl, heterocyclyl or heteroaryl, each of the above groups being optionally substituted with 1 to 3 substitutents selected from Hal, NO 2 , CN, —SO 2 —C 1 -C 6 -alkyl, —S—C 1 -C 6 -alkyl, NMe 2 , C 1 -C 6 -alkyl, —C(O)O—C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, or a 5-6-membered heteroaromatic group being optionally substituted by Hal, 
         V is an aryl group optionally substituted with 1 to 3 substitutents selected from Hal, NO 2 , CN, SO 2 —C 1 -C 6  alkyl, NMe 2 , C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, —C 1 -C 6 -halo-alkyl, O—C 1 -C 6 -halo-alkyl or a 5-6-membered heteroaromatic group, 
         T denotes phenyl, triazolyl, thiazolyl, oxazolyl, oxadiazolyl, or pyrazolyl, 
         R 1  is H, Hal, —C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, cyano or —C 1 -C 6 -halo-alkyl, 
         R 2  and R 2′  are independently from one another H, Hal, —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —(CH 2 ) m —O—C 1 -C 6 -alkyl, O—C 1 -C 6 -halo-alkyl, —(CH 2 ) m —O—C 1 -C 6 -halo-alkyl, —SO 2 —C 1 -C 6 -alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -alkyl, —SO 2 —C 1 -C 6 -halo-alkyl, —(CH 2 ) m —SO 2 —C 1 -C 6 -halo-alkyl, —SO 2 -3-8-cycloalkyl, —(CH 2 ) m —SO 2 -3-8-cycloalkyl, —C 1 -C 6 -halo-alkyl, or 
         R 1  and R 2  are linked to form with the ring T to which they are attached a 7-12-membered fused heterocyclyl or 7-12-membered fused cycloalkyl, and optionally substituted with 1 to 3 Hal, —C 1 -C 6 -halo-alkyl, NO 2 , CN, a linear or branched alkyl group having 1 to 6 carbon atoms, —(CH 2 ) m —O—C 1 -C 6 -alkyl, or —O—C 1 -C 6 -alkyl, 
         R 3  is C 1 -C 6 -alkyl, 
         R 4  is C 1 -C 6 -alkyl, 
         m is selected from 1, 2, 3 or 4, preferably 1 or 2, 
         Hal is F, Cl, Br, or I, 
         wherein -G 2 -Y—W together is at least 3 atoms in length, 
         or a pharmaceutically acceptable salts thereof, or an enantiomeric mixture of 2 enantiomers in all ratios, and/or as a mixture of diastereoisomers in all ratios. 
       
     
     
         133 . The method according to  claim 114  for treating a condition selected from Multiple sclerosis, Rheumatoid arthritis, Psoriasis, Type 1 Diabetes, Type II Diabetes, Systemic lupus nephritis, Oncology, Glomerulonephritis, Sjögrens's syndrome, Transplant rejection, Graft versus host disease, Allergic contact dermatitis, Neointimal hyperplasia/restenosis, Periodontal disease, Leprosy, or Obesity.