1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia

Abstract

The present invention relates to certain 1,2,3-trisubstituted aryl and heteroaryl derivatives of Formula (Ia) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

1 . A compound of Formula (Ia): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, hydrate or solvate thereof, 
         wherein:
 A and B are independently C 1-3  alkylene optionally substituted with 1 to 4 methyl groups; 
 D is O, S, S(O), S(O) 2 , CR 2 R 3  or N—R 2 ; 
 V is selected from the group consisting of C 1-3  alkylene, ethynylene and C 1-2  heteroalkylene wherein each are optionally substituted with 1 to 4 substituents selected from the group consisting of C 1-3  alkyl, C 1-4  alkoxy, carboxy, cyano, C 1-3  haloalkyl and halogen; or 
 V is absent; 
 W is NR 4 , O, S, S(O) or S(O) 2 ; or 
 W is absent; 
 X is N or CR 5 ; 
 Y is N or CR 6 ; 
 Z is selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylthioureyl, C 1-4  alkylureyl, amino, C 1-2  alkylamino, C 2-4  dialkylamino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 4-8  diacylamino, C 2-6  dialkylcarboxamide, C 1-4  dialkylthiocarboxamide, C 2-6  dialkylsulfonamide, C 1-4  dialkylsulfonylamino, formyl, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylcarboxamide, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio, halogen, aryl, heterocyclic, heteroaryl, hydroxyl, hydroxylamino, nitro and tetrazolyl, wherein C 1-8  alkyl and C 1-5  acyl are each optionally substituted with 1, 2, 3 or 4 groups selected from the group consisting of C 1-5  acyl, C 1-6  acyloxy, C 1-4  alkoxy, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylureyl, amino, C 1-2  alkylamino, C 2-4  dialkylamino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, formyl, C 1-4  haloalkoxy, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio, halogen, hydroxyl, hydroxylamino and nitro; or 
 Z is a group of Formula (A): 
 
       
       
         
           
           
               
               
           
         
         
           
             wherein:
 R 7  is H, C 1-8  alkyl or C 3-6  cycloalkyl; and 
 R 3  is H, nitro or nitrile; 
 
           
           Ar 1  is aryl or heteroaryl wherein each are optionally substituted with R 9 -R 13 ; 
           R 1  is selected from the group consisting of H, C 1-3  acyloxy, C 2-6  alkenyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 2-6  alkynyl, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylureyl, amino, C 1-4  alkylamino, C 2-8  dialkylamino, carboxamide, cyano, C 3-6  cycloalkyl, C 2-6  dialkylcarboxamide, C 2-6  dialkylsulfonamide, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio and hydroxyl; 
           R 2  is selected from the group consisting of H, C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 2-6  dialkylcarboxamide, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, hydroxyl and phenyl; and wherein C 1-8  alkyl, heteroaryl and phenyl are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylthioureyl, C 1-4  alkylureyl, amino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-3 -alkylene, C 3-6 -cycloalkyl-C 1-3 -heteroalkylene, C 2-8  dialkylamino, C 2-6  dialkylcarboxamide, C 1-4  dialkylthiocarboxamide, C 2-6  dialkylsulfonamide, C 1-4  alkylthioureyl, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkyl, C 1-4  haloalkylthio, halogen, heterocyclic, hydroxyl, hydroxylamino and nitro; or 
           R 2  is —Ar 2 -Ar 3  wherein Ar 2  and Ar 3  are independently aryl or heteroaryl each optionally substituted with 1 to 5 substituents selected from the group consisting of H, C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 2-6  dialkylcarboxamide, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, hydroxyl and nitro; or 
           R 2  is a group of Formula (B): 
         
       
       
         
           
           
               
               
           
         
         
           
             wherein:
 R 14  is C 1-8  alkyl or C 3-6  cycloalkyl; and R 15  is F, Cl, Br or CN; or 
 
           
           R 2  is a group of Formula (C): 
         
       
       
         
           
           
               
               
           
         
         
           
             wherein:
 G is C═O, CR 16 R 17 , O, S, S(O), S(O) 2 ; where R 16  and R 17  are independently H or C 1-8  alkyl; and 
 Ar 4  is phenyl or heteroaryl optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylthioureyl, C 1-4  alkylureyl, amino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 2-6  dialkylcarboxamide, C 1-4  dialkylthiocarboxamide, C 2-6  dialkylsulfonamide, C 1-4  alkylthioureyl, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkyl, C 1-4  haloalkylthio, halogen, heteroaryl, hydroxyl, hydroxylamino and nitro; 
 
           
           R 3  is H, C 1-8  alkyl, C 1-4  alkoxy, halogen or hydroxyl; 
           R 4  is H or C 1-8  alkyl; 
           R 5  and R 6  are independently H, C 1-8  alkyl or halogen; 
           R 9  is selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 2-6  alkenyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 2-6  alkynyl, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylureyl, amino, arylsulfonyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6  cycloalkyl, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, C 2-6  dialkylsulfonamide, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio, heterocyclic, heterocyclicsulfonyl, heteroaryl, hydroxyl, nitro, C 4-7  oxo-cycloalkyl, phenoxy, phenyl, sulfonamide and sulfonic acid, and wherein C 1-5  acyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylsulfonamide, alkylsulfonyl, arylsulfonyl, heteroaryl, phenoxy and phenyl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 2-6  alkenyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 2-6  alkynyl, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylureyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6  cycloalkyl, C 2-6  dialkylcarboxamide, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio, heteroaryl, heterocyclic, hydroxyl, nitro and phenyl; or 
           R 9  is a group of Formula (D): 
         
       
       
         
           
           
               
               
           
         
         
           
             wherein:
 “p” and “r” are independently 0, 1, 2 or 3; and 
 R 18  is H, C 1-5  acyl, C 2-6  alkenyl, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 2-6  alkynyl, C 1-4  alkylsulfonamide, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6  cycloalkyl, C 2-6  dialkylcarboxamide, halogen, heteroaryl or phenyl, and wherein the heteroaryl and phenyl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-4  alkoxy, amino, C 1-4  alkylamino, C 2-6  alkynyl, C 2-8  dialkylamino, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl and hydroxyl; and 
 
           
           R 10 -R 13  are independently selected form the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 2-6  alkenyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, 
         
         C 2-4  alkynyl, C 1-4  alkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, C 1-4  alkylureyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6  cycloalkyl, C 2-6  dialkylcarboxamide, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio, hydroxyl and nitro; or
 two adjacent R 10 -R 11  groups together with Ar 1  form a 5, 6 or 7 membered cycloalkyl, cycloalkenyl or heterocyclic group wherein the 5, 6 or 7 membered group is optionally substituted with halogen. 
 
       
     
     
         2 . The compound according to  claim 1  wherein W is NR 4 . 
     
     
         3 . The compound according to  claim 2  wherein R 4  is H. 
     
     
         4 . The compound according to  claim 2  wherein R 4  is CH 3  or CH 2 CH 3 . 
     
     
         5 . The compound according to  claim 1  wherein W is O. 
     
     
         6 . The compound according to  claim 1  wherein W is S. 
     
     
         7 . The compound according to  claim 1  wherein W is absent. 
     
     
         8 . The compound according to  claim 1  wherein W is absent and V is ethynylene. 
     
     
         9 . The compound according to  claim 1  wherein V is —CH 2 — or —CH 2 CH 2 —. 
     
     
         10 . The compound according to  claim 1  wherein V is —OCH 2 CH 2 —. 
     
     
         11 . The compound according to  claim 1  wherein V is absent. 
     
     
         12 . The compound according to  claim 1  wherein A is ethylene and B is methylene. 
     
     
         13 . The compound according to  claim 1  wherein A is propylene and B is methylene. 
     
     
         14 . The compound according to any  claim 1  wherein A and B are both ethylene wherein A and B are optionally substituted with 1 to 4 methyl groups. 
     
     
         15 . The compound according to  claim 1  wherein D is O, S, S(O) or S(O) 2 . 
     
     
         16 . The compound according to  claim 1  wherein D is CR 2 R 3 . 
     
     
         17 . The compound according to  claim 16  wherein R 2  is selected from the group consisting of H, C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbo-C 1-6 -alkoxy, carboxamide, carboxyl, C 3-6  cycloalkyl, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen and hydroxyl. 
     
     
         18 . The compound according to  claim 17  wherein R 2  is selected from the group consisting of C(O)CH 3 , C(O)CH 2 CH 3 , C(O)CH 2 CH 2 CH 3 , C(O)CH(CH 3 ) 2 , C(O)CH 2 CH 2 CH 2 CH 3 , OC(O)CH 3 , OC(O)CH 2 CH 3 , OC(O)CH 2 CH 2 CH 3 , OCH 3 , OCH 2 CH 3 , OCH 2 CH 2 CH 3 , OCH(CH 3 ) 2 , OCH 2 (CH 2 ) 2 CH 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH(CH 3 )(CH 2 CH 3 ), CH 2 (CH 2 ) 2 CH 3 , CH 2 (CH 2 ) 3 CH 3 , C(O)NH 2 , CO 2 CH 3 , CO 2 CH 2 CH 3 , CO 2 CH 2 CH 2 CH 3 , CO 2 CH(CH 3 ) 2 , CO 2 CH 2 (CH 2 ) 2 CH 3 , and CO 2 H. 
     
     
         19 . The compound according to  claim 17  wherein R 2  is selected from the group consisting of S(O) 2 CH 3 , S(O) 2 CH 2 CH 3 , S(O) 2 CH 2 CH 2 CH 3 , S(O) 2 CH(CH 3 ) 2 , S(O) 2 CH 2 (CH 2 ) 2 CH 3 , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, hydroxyl, and F. 
     
     
         20 . The compound according to  claim 16  wherein R 2  is C 1-8  alkyl, or heteroaryl each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylsulfonyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-3 -alkylene, C 3-6 -cycloalkyl-C 1-3 -heteroalkylene, and hydroxyl. 
     
     
         21 . The compound according to  claim 20  wherein R 2  is selected from the group consisting of CH 2 OCH 3 , CH 2 CH 2 OCH 3 , CH 2 OCH 2 CH 3 , CH 2 OCH 2 CH 2 CH 3 , CH 2 CH 2 OCH 2 CH 3 , CH 2 CH 2 OCH 2 CH 2 CH 3 , CH 2 OCH(CH 3 ) 2 , CH 2 OCH 2 CH(CH 3 ) 2 , CH 2 CO 2 H, CH 2 CH 2 CO 2 H, CH 2 OH, CH 2 CH 2 OH and CH 2 CH 2 CH 2 OH. 
     
     
         22 . The compound according to  claim 20  wherein R 2  is selected from the group consisting of CH 2 S(O) 2 CH 3 , CH 2 S(O) 2 CH 2 CH 3 , CH 2 S(O) 2 CH 2 CH 2 CH 3 , CH 2 S(O) 2 CH(CH 3 ) 2 , CH 2 S(O) 2 CH 2 (CH 2 ) 2 CH 3 , CH 2 CH 2 S(O) 2 CH 3 , CH 2 CH 2 S(O) 2 CH 2 CH 3 , CH 2 CH 2 S(O) 2 CH 2 CH 2 CH 3 , CH 2 CH 2 S(O) 2 CH(CH 3 ) 2 , CH 2 CH 2 S(O) 2 CH 2 (CH 2 ) 2 CH 3 , CH 2 OCH 2 -cyclopropyl, CH 2 OCH 2 -cyclobutyl, CH 2 OCH 2 -cyclopentyl, and CH 2 OCH 2 -cyclohexyl. 
     
     
         23 . The compound according to  claim 20  wherein R 2  is selected from the group consisting of 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 3-isopropyl-1,2,4-oxadiazol-5-yl, 3-propyl-1,2,4-oxadiazol-5-yl, 3-t-butyl-1,2,4-oxadiazol-5-yl, and 3-cyclopropyl-1,2,4-oxadiazol-5-yl. 
     
     
         24 . The compound according to  claim 16  wherein R 2  is —Ar 2 -Ar 3  wherein Ar 2  and Ar 3  are independently aryl or heteroaryl each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 2-6  dialkylcarboxamide, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, hydroxyl and nitro. 
     
     
         25 . The compound according to  claim 24  wherein Ar 2  is a heteroaryl and Ar 3  is phenyl. 
     
     
         26 . The compound according to  claim 16  wherein R 2  is Formula (C): 
       
         
           
           
               
               
           
         
         wherein:
 G is C═O, CR 16 R 17 , O, S, S(O), S(O) 2 ; wherein R 16  and R 17  are independently H or C 1-2  alkyl; 
 and 
 Ar 4  is phenyl or heteroaryl optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, C 1-8  alkyl, C 1-4  haloalkoxy, C 1-4  haloalkyl, and halogen. 
 
       
     
     
         27 . The compound according to  claim 26  wherein G is C═O, CH 2  or O. 
     
     
         28 . The compound according to  claim 26  wherein G is S, S(O) or S(O) 2 . 
     
     
         29 . The compound according  claim 26  wherein Ar 4  is selected from the group consisting of pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl. 
     
     
         30 . The compound according  claim 26  wherein Ar 4  is 2-pyridyl. 
     
     
         31 . The compound according to  claim 26  wherein R 16  and R 17  are both H. 
     
     
         32 . The compound according to  claim 16  wherein R 3  is H. 
     
     
         33 . The compound according to  claim 1  wherein D is N—R 2 . 
     
     
         34 . The compound according to  claim 33  wherein R 2  is H, or carbo-C 1-6 -alkoxy. 
     
     
         35 . The compound according to  claim 34  wherein R 2  is selected from the group consisting of CO 2 CH 3 , CO 2 CH 2 CH 3 , CO 2 CH 2 CH 2 CH 3 , CO 2 CH(CH 3 ) 2  and CO 2 CH 2 (CH 2 ) 2 CH 3 . 
     
     
         36 . The compound according to  claim 33  wherein R 2  is C 1-8  alkyl optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkylsulfonyl, carbo-C 1-6 -alkoxy, and carboxy. 
     
     
         37 . The compound according to  claim 36  wherein R 2  is CH 2 CO 2 Et, or CH 2 CH 2 CO 2 H. 
     
     
         38 . The compound according to  claim 36  wherein R 2  is selected from the group consisting of CH 2 CH 2 S(O) 2 CH 3 , CH 2 CH 2 S(O) 2 CH 2 CH 3 , CH 2 CH 2 S(O) 2 CH 2 CH 2 CH 3 , CH 2 CH 2 S(O) 2 CH(CH 3 ) 2  and CH 2 CH 2 S(O) 2 CH 2 (CH 2 ) 2 CH 3 . 
     
     
         39 . The compound according to  claim 1  wherein Z is selected from the group consisting of C 1-5  acyl, C 1-8  alkyl, C 1-4  alkylcarboxamide, amino, cyano, C 4-8  diacylamino, C 2-6  dialkylsulfonamide, formyl, halogen, heterocyclic, and nitro wherein C 1-8  alkyl and C 1-5  acyl are each optionally substituted with 1, or 2 groups selected from the group consisting of C 2-4  dialkylamino, hydroxy, and halogen. 
     
     
         40 . The compound according to  claim 39  wherein Z is selected from the group consisting of nitro, amino, formyl, NHC(O)CF 3 , Br, NHC(O)CH 3 , N(C(O)CH 3 ) 2 , N(S(O) 2 CH 3 ) 2 , CH 3 , [1,3]dioxolan-2-yl, CH 2 OH, CH 2 N(CH 3 ) 2 , and C(O)CH 3 . 
     
     
         41 . The compound according to  claim 1  wherein R 1  is selected from the group consisting of H, C 1-8  alkyl, and amino. 
     
     
         42 . The compound according to  claim 1  wherein Ar 1  is phenyl optionally substituted with R 9 -R 13 . 
     
     
         43 . The compound according to  claim 42  wherein R 9  is selected from the group consisting of C 1-5  acyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 2-6  alkynyl, C 1-4  alkylsulfonamide, C 2-6  dialkylsulfonamide, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, arylsulfonyl, C 2-6  dialkylamino, C 2-6  dialkylsulfonamide, and carboxamide. 
     
     
         44 . The compound according to  claim 43  wherein R 9  is selected from the group consisting of C(O)CH 3 , C(O)CH 2 CH 3 , C(O)CH 2 CH 2 CH 3 , C(O)CH(CH 3 ) 2 , C(O)CH 2 CH 2 CH 2 CH 3 , OCH 3 , OCH 2 CH 3 , OCH 2 CH 2 CH 3 , OCH(CH 3 ) 2 , OCH 2 CH 2 CH 2 CH 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH(CH 3 )(CH 2 CH 3 ), CH 2 (CH 2 ) 2 CH 3 , CH 2 (CH 2 ) 3 CH 3 , CH 2 (CH 2 ) 4 CH 3 , CH 2 (CH 2 ) 5 CH 3 , C(O)NHCH 3 , C(O)NHCH 2 CH 3 , C(O)NHCH 2 CH 2 CH 3 , C(O)NHCH(CH 3 ) 2 , C≡CH, S(O) 2 NHCH 3 , S(O) 2 NHCH 2 CH 3 , S(O) 2 NHCH 2 CH 2 CH 3 , S(O) 2 NHCH(CH 3 ) 2 , S(O) 2 NHCH 2 (CH 2 ) 2 CH 3 , S(O) 2 NHCH(CH 3 )CH 2 CH 3 , S(O) 2 N(CH 3 ) 2 , S(O) 2 N(Et)(CH 3 ), S(O) 2 CH 3 , S(O) 2 CH 2 CH 3 , S(O) 2 CH 2 CH 2 CH 3 , S(O) 2 CH(CH 3 ) 2 , S(O) 2 CH 2 (CH 2 ) 2 CH 3 , S(O) 2 CH(CH 3 )CH 2 CH 3 , SCH 3 , SCH 2 CH 3 , SCH 2 CH 2 CH 3 , SCH(CH 3 ) 2 , SCH 2 (CH 2 ) 2 CH 3 , amino, S(O) 2 Ph, N(CH 3 ) 2 , N(CH 3 )(Et), N(Et) 2  and C(O)NH 2 . 
     
     
         45 . The compound according to  claim 42  wherein R 9  is selected from the group consisting of cyano, C 3-6  cycloalkyl, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfonyl, and C 1-4  haloalkylthio. 
     
     
         46 . The compound according to  claim 45  wherein R 9  is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Cl, F, Br, OCF 3 , OCHF 2 , OCH 2 CF 3 , CF 3 , CHF 2 , CH 2 CF 3 , SCF 3 , SCHF 2  and SCH 2 CF 3 . 
     
     
         47 . The compound according to  claim 42  wherein R 9  is selected from the group consisting of heterocyclic, heterocyclicsulfonyl, heteroaryl, hydroxy, C 4-7  oxo-cycloalkyl, phenoxy and phenyl. 
     
     
         48 . The compound according to  claim 47  wherein R 9  is selected from the group consisting of morpholin-4-yl, thiomorpholin-4-yl, 1-oxo-1λ 4 -thiomorpholin-4-yl, 1,1-Dioxo-1λ 6 -thiomorpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, 4-ethyl-piperazin-1-yl, 4-propyl-piperazin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, 2,5-dioxo-imidazolidin-4-yl, 2,4-dioxo-thiazolidin-5-yl, 4-oxo-2-thioxo-thiazolidin-5-yl, 3-methyl-2,5-dioxo-imidazolidin-4-yl, 3-methyl-2,4-dioxo-thiazolidin-5-yl, 3-methyl-4-oxo-2-thioxo-thiazolidin-5-yl, 3-ethyl-2,5-dioxo-imidazolidin-4-yl, 3-ethyl-2,4-dioxo-thiazolidin-5-yl, and 3-ethyl-4-oxo-2-thioxo-thiazolidin-5-yl. 
     
     
         49 . The compound according to  claim 47  wherein R 9  is selected from the group consisting of 1H-imidazol-4-yl, [1,2,4]triazol-1-yl, [1,2,3]triazol-1-yl, [1,2,4]triazol-4-yl, pyrrol-1-yl, pyrazol-1-yl, 1H-pyrazol-3-yl, imidazol-1-yl, oxazol-5-yl, oxazol-2-yl, [1,3,4]oxadiazol-2-yl, [1,3,4]thiadiazol-2-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]thiadiazol-3-yl, tetrazol-1-yl, pyrimidin-5-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl, 1,3-dioxo-1,3-dihydro-isoindol-2-yl and [1,2,3]thiadiazol-4-yl. 
     
     
         50 . The compound according to  claim 42  wherein R 9  is C 1-8  alkyl or C 1-4  alkoxy optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-5  acyl, C 1-4  alkoxy, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, and hydroxyl. 
     
     
         51 . The compound according to  claim 50  wherein R 9  is selected from the group consisting of CH 2 OCH 3 , CH 2 OCH 2 CH 3 , CH 2 OCH 2 CH 2 CH 3 , CH 2 OCH(CH 3 ) 2 , CH 2 OCH 2 (CH 2 ) 2 CH 3 , CH 2 CH 2 OCH 3 , CH 2 CH 2 OCH 2 CH 3 , CH 2 CH 2 OCH 2 CH 2 CH 3 , CH 2 CH 2 OCH(CH 3 ) 2  and CH 2 CH 2 OCH 2 (CH 2 ) 2 CH 3 . 
     
     
         52 . The compound according to  claim 42  wherein R 9  is of Formula (D): 
       
         
           
           
               
               
           
         
         wherein:
 “p” and “r” are independently 0, or 1; and 
 R 18  is H, carbo-C 1-6 -alkoxy, heteroaryl or phenyl, and wherein the heteroaryl and phenyl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-4  alkoxy, amino, C 1-4  alkylamino, C 2-6  alkynyl, C 2-8  dialkylamino, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl and hydroxyl. 
 
       
     
     
         53 . The compound according to  claim 52  wherein p=0 and r=0. 
     
     
         54 . The compound according to  claim 53  wherein R 18  is phenyl optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-4  alkoxy, amino, C 1-4  alkylamino, C 2-6  alkynyl, C 2-8  dialkylamino, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl and hydroxyl. 
     
     
         55 . The compound according to  claim 52  wherein p=0 and r=1. 
     
     
         56 . The compound according to  claim 55  wherein R 18  is carbo-C 1-6 -alkoxy or carboxy. 
     
     
         57 . The compound according to any one of  claims 43  wherein R 9  is substituted at the para position on the phenyl. 
     
     
         58 . The compound according  claim 42  wherein R 10 -R 13  are independently selected from the group consisting of C 1-5  acyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylureyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6  cycloalkyl, halogen, C 1-4  haloalkoxy and C 1-4  haloalkyl. 
     
     
         59 . The compound according to  claim 42  wherein one or two R 10 -R 13  groups are independently halogen. 
     
     
         60 . The compound according to  claim 42  wherein two adjacent R 10 -R 11  groups together with the phenyl form a 5, 6 or 7 membered cycloalkyl, cycloalkenyl or heterocyclic group wherein the 5, 6 or 7 membered group is optionally substituted with halogen. 
     
     
         61 . The compound according to  claim 60  wherein the heterocyclic group together with the phenyl group is a 2,3-dihydro-benzofuran-5-yl, benzo[1,3]dioxol-5-yl group, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydro-benzo[1,4]dioxin-2-yl group, 3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl group. 
     
     
         62 . The compound according to  claim 1  wherein Ar 1  is heteroaryl optionally substituted with R 9 -R 13 . 
     
     
         63 . The compound according to  claim 62  wherein R 9  is selected from the group consisting of C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, C 1-4  haloalkyl, hydroxy, halogen, and phenyl. 
     
     
         64 . The compound according to  claim 63  wherein R 9  is selected from the group consisting OCH 3 , OCH 2 CH 3 , OCH 2 CH 2 CH 3 , OCH(CH 3 ) 2 , OCH 2 CH 2 CH 2 CH 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH(CH 3 )(CH 2 CH 3 ), CH 2 (CH 2 ) 2 CH 3 , CH 2 (CH 2 ) 3 CH 3 , CH 2 (CH 2 ) 4 CH 3 , CH 2 (CH 2 ) 5 CH 3 , C(O)NHCH 3 , C(O)NHCH 2 CH 3 , C(O)NHCH 2 CH 2 CH 3 , C(O)NHCH(CH 3 ) 2 , C(O)NHCH 2 (CH 2 ) 2 CH 3 , S(O) 2 CH 3 , S(O) 2 CH 2 CH 3 , S(O) 2 CH 2 CH 2 CH 3 , S(O) 2 CH(CH 3 ) 2 , Cl, F, Br, CF 3 , CHF 2 , CH 2 CF 3 , and hydroxy. 
     
     
         65 . The compound according to  claim 62  wherein R 10 -R 13  are independently C 1-5  acyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylureyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6  cycloalkyl, halogen, C 1-4  haloalkoxy and C 1-4  haloalkyl. 
     
     
         66 . The compound according to  claim 62  wherein one or two R 10 -R 13  groups are independently halogen. 
     
     
         67 . The compound according to  claim 1  wherein X is N and Y is CH. 
     
     
         68 . The compound according to  claim 1  wherein X is N and Y is CF. 
     
     
         69 . The compound according to  claim 1  wherein X is CH and Y is N. 
     
     
         70 . The compound according to  claim 1  wherein X and Y are N. 
     
     
         71 . The compound according to  claim 1  wherein X and Y are CH. 
     
     
         72 . The compound according to  claim 1  wherein X is CH and Y are CF. 
     
     
         73 . The compound according to  claim 1  wherein said compound is selected from the group consisting of:
 1-[6-(4-Imidazol-1-yl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Methanesulfonyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(Benzo[1,2,5]oxadiazol-5-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(2-Methoxycarbonyl-acetyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Amino-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-(2,2,2-trifluoro-acetylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 Propionic acid 1-[2-amino-5-formyl-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidin-4-yl ester; 
 4-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperazine-1-carboxylic acid ethyl ester; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid methyl ester; 
 2,6-Dimethyl-4-[6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-morpholine; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-3-carboxylic acid ethyl ester; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethylamide; 
 1-[6-(2-Methyl-5-phenyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 4-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-6-piperidin-1-yl-pyrimidine; 
 1-[5-Nitro-6-(2-trifluoromethyl-benzyloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3-trifluoromethyl-benzyloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethyl-benzyloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Bromo-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Acetylamino-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Diacetylamino-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid; 
 1-{5-Nitro-6-[2-(2-trifluoromethyl-phenyl)-ethoxy]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{5-Nitro-6-[2-(3-trifluoromethyl-phenyl)-ethoxy]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Di-(methanesulfonyl)amino-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3-trifluoromethyl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Methyl-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(2-trifluoromethyl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethyl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Fluoro-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2,5-Dimethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Bromo-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Chloro-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Carbamoyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(2-Methoxy-ethyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Cyclopentyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-pyrrol-1-yl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Benzoyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(4-Hydroxy-benzenesulfonyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4′-Cyano-biphenyl-4-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Amino-4-ethanesulfonyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(5-Hydroxy-pyrimidin-2-yl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-sulfo-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-[1,2,4]triazol-1-yl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Carbamoylmethyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4′-Methoxy-biphenyl-4-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(2,5-Dioxo-imidazolidin-4-yl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 4-(4,4-Difluoro-piperidin-1-yl)-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 1-{5-Nitro-6-[4-(4-oxo-cyclohexyl)-phenoxy]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{5-Nitro-6-[4-(3-oxo-butyl)-phenoxy]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-propionyl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxy ic acid ethyl ester; 
 1-{6-[4-(2-Hydroxy-ethyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 {4-[6-(4,4-Difluoro-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-phenyl-methanone; 
 3-{4-[6-(4,4-Difluoro-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-3-oxo-propionic acid methyl ester; 
 2-[6-(4,4-Difluoro-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-5-ethanesulfonyl-phenylamine; 
 4-(4-Cyclopentyl-phenoxy)-6-(4,4-difluoro-piperidin-1-yl)-5-nitro-pyrimidine; 
 1-[6-(2,6-Dichloro-4-methanesulfonyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(4-Chloro-benzoyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(4-Hydroxy-benzoyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Cyanomethyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 (4-{6-[4-(2-Methanesulfonyl-ethyl)-piperazin-1-yl]-5-nitro-pyrimidin-4-yloxy}-phenyl)-phenyl-methanone; 
 4-(4-{6-[4-(2-Methanesulfonyl-ethyl)-piperazin-1-yl]-5-nitro-pyrimidin-4-yloxy}-phenyl)-butan-2-one; 
 3-(4-{6-[4-(2-Methanesulfonyl-ethyl)-piperazin-1-yl]-5-nitro-pyrimidin-4-yloxy}-phenyl)-3-oxo-propionic acid methyl ester; 
 4-(4-Methyl-piperidin-1-yl)-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-(4-Bromo-piperidin-1-yl)-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidine; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid amide; 
 1-[5-Nitro-6-(2-oxo-2H-chromen-6-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(2-oxo-benzo[1,3]oxathiol-6-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(9H-Carbazol-2-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(9-oxo-9H-fluoren-2-yloxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{5-Amino-6-[4-(3-oxo-butyl)-phenoxy]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-[4-(3-Oxo-butyl)-phenoxy]-5-(2,2,2-trifluoro-acetylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{5-Amino-6-[4-(hydroxy-phenyl-methyl)-phenoxy]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Benzoyl-5-methoxy-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(6-Chloro-pyridin-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(Benzo[1,3]dioxol-5-yloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Benzyloxy-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3-Morpholin-4-yl-phenoxy)-5-nitro-pyrimidin-4-34]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethylsulfanyl-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethoxy-phenoxy)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Benzoyl-phenoxy)-5-(2,2,2-trifluoro-acetylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 {4-[5-Nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenyl}-phenyl-methanone; 
 {4-Methoxy-2-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenyl}-phenyl-methanone; 
 4-{4-[5-Nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 5-Nitro-4-(4-propyl-piperidin-1-yl)-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidine; 
 3-{4-[5-Nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenyl}-3-oxo-propionic acid methyl ester; 
 5-Ethanesulfonyl-2-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenylamine; 
 1-[6-(4-Difluoromethoxy-benzyloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3-Difluoromethoxy-benzyloxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 2-{1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-ethanol; 
 3-{1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-propionic acid; 
 4-[4-(4-Methyl-benzyl)-piperidin-1-yl]-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-(3-Methanesulfonyl-pyrrolidin-1-yl)-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-6-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-pyrimidine; 
 4-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidine; 
 4′-(4-Benzoyl-phenoxy)-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-carboxylic acid ethyl ester; 
 3′-Nitro-4′-[4-(3-oxo-butyl)-phenoxy]-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-carboxylic acid ethyl ester; 
 4′-[4-(2-Methoxycarbonyl-acetyl)-phenoxy]-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-carboxylic acid ethyl ester; 
 4′-(2-Amino-4-ethanesulfonyl-phenoxy)-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid ethyl ester; 
 4′-(4-Imidazol-1-yl-phenoxy)-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-carboxylic acid ethyl ester; 
 4-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-6-(4-trifluoromethyl-piperidin-1-yl)-pyrimidine; 
 4-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-6-(4-phenylsulfanyl-piperidin-1-yl)-pyrimidine; 
 1-[6-(3-Ethynyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Chloro-2-fluoro-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2,4-Difluoro-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Bromo-2-fluoro-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 4-(3-Ethynyl-phenoxy)-5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidine; 
 4-(4-Chloro-2-fluoro-phenoxy)-5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidine; 
 4-(2,4-Difluoro-phenoxy)-5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidine; 
 4-(4-Bromo-2-fluoro-phenoxy)-5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidine; 
 3′-Nitro-2′-[4-(3-oxo-butyl)-phenoxy]-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-carboxylic acid ethyl ester; 
 4-[4-(3′-Nitro-4-propyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yloxy)-phenyl]-butan-2-one; 
 2′-(4-Benzoyl-phenoxy)-3′-nitro-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-carboxylic acid ethyl ester; 
 4-(4-{5-Nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yloxy}-phenyl)-butan-2-one; 
 [4-(3′-Nitro-4-propyl-3,4,5,6-tetrahydro-2H-[1,4]bipyridinyl-2′-yloxy)-phenyl]-phenyl-methanone; 
 4-(4-{5-Nitro-6-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-pyrimidin-4-yloxy}-phenyl)-butan-2-one; 
 4-(4-{6-[4-(3-Methyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yloxy}-phenyl)-butan-2-one; 
 (4-{6-[4-(3-Methyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yloxy}-phenyl)-phenyl-methanone; 
 1-{6-[4-(4-Fluoro-benzoyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 (4-Fluoro-phenyl)-{4-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenyl}-methanone; 
 4-[4-(3-Methyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-(4-Methoxymethyl-piperidin-1-yl)-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-{4-[6-(4-Methoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 4-[4-(2-Methoxy-ethyl)-piperidin-1-yl]-6-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidine; 
 4-{4-[6-(4-Ethoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 4-(2,4-Difluoro-phenoxy)-5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidine; 
 (4-Methoxy-2-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yloxy}-phenyl)-phenyl-methanone; 
 4-(2,4-Difluoro-phenoxy)-6-(4-ethoxymethyl-piperidin-1-yl)-5-nitro-pyrimidine; 
 4-{4-[6-(4-Cyclopropylmethoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 4-{4-[5-Nitro-6-(4-propoxymethyl-piperidin-1-yl)-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 1-{4-[6-(4-Methoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-ethanone; 
 4-{4-[2-Nitro-3-(4-propyl-piperidin-1-yl)-phenoxy]-phenyl}-butan-2-one; 
 1-{4-[2-Nitro-3-(4-propyl-piperidin-1-yl)-phenoxy]-phenyl}-ethanone; 
 {4-[2-Nitro-3-(4-propyl-piperidin-1-yl)-phenoxy]-phenyl}-phenyl-methanone; 
 3-{4-[2-Nitro-3-(4-propyl-piperidin-1-yl)-phenoxy]-phenyl}-3-oxo-propionic acid methyl ester; 
 4-{4-[6-(4-Butoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 4-{4-[6-(4-Isobutoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-butan-2-one; 
 (4-Fluoro-phenyl)-[4-(3′-nitro-4-propyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4′-yloxy)-phenyl]-methanone; 
 4-[4-(3′-Nitro-4-propyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4′-yloxy)-phenyl]-butan-2-one; 
 3′-Nitro-4-propyl-4′-(4-[1,2,4]triazol-1-yl-phenoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 
 1-{2-Nitro-3-[4-(3-oxo-butyl)-phenoxy]-phenyl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[3-(4-Benzoyl-phenoxy)-2-nitro-phenyl]-piperidine-4-carboxylic acid ethyl ester; 
 {4-[6-(4-Ethoxy-piperidin-1-yl)-5-nitro-pyrimidin-4-yloxy]-phenyl}-(4-fluoro-phenyl)-methanone; 
 1-[6-(2-Methyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-5-nitro-pyrimidin-4-yl]-piperidin-4-ol; 
 1-[6-(4-Acetyl-phenoxy)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 (1-{6-[4-(4-Fluoro-benzoyl)-phenoxy]-5-nitro-pyrimidin-4-yl}-piperidin-4-yl)-(4-fluoro-phenyl)-methanone; 
 4-(4-{6-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yloxy}-phenyl)-butan-2-one; 
 4-(4-Methanesulfonyl-phenoxy)-5-nitro-6-[4-(pyridin-2-ylsulfanyl)-cyclohexyl]-pyrimidine; 
 4-(4-Methanesulfonyl-phenoxy)-5-nitro-6-[4-(pyridin-4-ylsulfanyl)-cyclohexyl]-pyrimidine; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenoxy)-pyrimidine-5-carbonitrile; 
 5-[1,3]Dioxolan-2-yl-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenoxy)-pyrimidine; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenoxy)pyrimidine-5-carbaldehyde; 
 5-[1,3]Dioxolan-2-yl-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidine; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidine-5-carbaldehyde; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidine-5-carboxylic acid; 
 [4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidin-5-yl]-methanol; 
 [4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-[1,2,3]thiadiazol-4-yl-phenoxy)-pyrimidin-5-ylmethyl]-dimethyl-amine; 
 4-(4-Methanesulfonyl-phenoxy)-5-nitro-6-(4-phenylsulfanyl-cyclohexyl)-pyrimidine; 
 4-[4-(3-tert-Butyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(6-methanesulfonyl-pyridin-3-yloxy)-5-nitro-pyrimidine; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenoxy)-2-methyl-pyrimidine-5-carbonitrile; 
 and 
 1-[4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenoxy)-pyrimidin-5-yl]-ethanone; 
 or a pharmaceutically acceptable salt, hydrate or solvate thereof. 
 
     
     
         74 . The compound according to  claim 1  wherein said compound is selected from the group consisting of:
 1-{6-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3,4,5-trimethoxy-benzylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 (5-Nitro-6-piperidin-1-yl-pyrimidin-4-yl)-(3-trifluoromethyl-benzyl)-amine; 
 1-[5-Nitro-6-(2-trifluoromethyl-benzylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethyl-benzylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3-trifluoromethyl-benzylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 (5-Nitro-6-piperidin-1-yl-pyrimidin-4-yl)-(2-trifluoromethyl-benzyl)-amine; 
 (5-Nitro-6-piperidin-1-yl-pyrimidin-4-yl)-(4-trifluoromethyl-benzyl)-amine; 
 1-[5-Amino-6-(3-trifluoromethyl-benzylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Amino-6-(4-trifluoromethyl-benzylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Bromo-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethyl-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(Methyl-phenyl-amino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Fluoro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Difluoro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Dichloro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(Benzo[1,3]dioxol-5-ylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Bromo-4-trifluoromethoxy-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Fluoro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3-Fluoro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(2-Fluoro-phenyl)-methyl-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(Ethyl-phenyl-amino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(4-Chloro-phenyl)-methyl-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Difluoromethyl-benzylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(2,3-Dihydro-benzofuran-5-ylmethyl)-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(6-Fluoro-4H-benzo[1,3]dioxin-8-ylmethyl)-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-ylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(Morpholine-4-sulfonyl)-phenylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2,2-Difluoro-benzo[1,3]dioxol-4-ylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2,2-Difluoro-benzo[1,3]dioxol-5-ylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(1,1-Dioxo-1H-1λ 6 -benzo[b]thiophen-6-ylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[(Furan-3-ylmethyl)-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[2-(4-Methoxy-phenoxy)-ethylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[2-(5-Methoxy-1H-indol-3-yl)-ethylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 (3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 (3-Fluoro-phenyl)-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 (3-Methoxy-phenyl)-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 1-{6-[(3-Fluoro-phenyl)-methyl-amino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Benzoyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(1,1-Dioxo-1λ 6 -thiomorpholin-4-ylmethyl)-phenylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Methanesulfonyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Dimethylsulfamoyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3-Methoxy-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Methoxy-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Bis-trifluoromethyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2,5-Dimethoxy-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Dimethoxy-benzylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 [5-Nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-(3,4,5-trimethoxy-benzyl)-amine; 
 (3,5-Dim ethoxy-benzyl)-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 (4-{5-Nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-ylamino}-phenyl)-phenyl-methanone; 
 (4-{5-Nitro-6-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-pyrimidin-4-ylamino}-phenyl)-phenyl-methanone; 
 1-[6-(4-Cyano-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Dimethoxy-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-sec-Butyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Heptyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 2′-(4-Benzoyl-phenylamino)-3′-nitro-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-pentyl-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(3-Carboxy-propyl)-phenylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(Cyano-phenyl-methyl)-phenylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Cyclohexyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-[1,2,4]triazol-1-yl-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethanesulfonyl-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-[1,2,3]thiadiazol-4-yl-phenylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 [6-(4-Ethoxymethyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yl]-(4-methanesulfonyl-phenyl)-amine; 
 [5-Nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-(4-[1,2,4]triazol-1-yl-phenyl)-amine; 
 {5-Nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-(4-[1,2,4]triazol-1-yl-phenyl)-amine; 
 (2-Fluoro-phenyl)-{6-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine; 
 (4-Methanesulfonyl-phenyl)-{6-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine; 
 {6-[4-(3-Methyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-[1,2,4]triazol-1-yl-phenyl)-amine; 
 1-{5-Nitro-6-[4-(4-trifluoromethyl-phenoxy)-phenylamino]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 {6-[4-(3-Ethyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(2-fluoro-phenyl)-amine; 
 {6-[4-(2-Methoxy-phenylsulfanyl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-[1,2,4]triazol-1-yl-phenyl)-amine; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (3-Methoxy-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 Benzo[1,3]dioxol-5-yl-[5-nitro-6-(4-propyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 (4-Fluoro-phenyl)-{1-[5-nitro-6-(4-[1,2,4]triazol-1-yl-phenylamino)-pyrimidin-4-yl]-piperidin-4-yl}-methanone; 
 [5-Nitro-6-(4-phenylsulfanyl-piperidin-1-yl)-pyrimidin-4-yl]-(4-[1,2,4]triazol-1-yl-phenyl)-amine; 
 (4-Fluoro-phenyl)-{1-[6-(2-fluoro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-methanone; 
 1-[6-(2-Methyl-5-phenyl-2H-pyrazol-3-ylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 (4-Methanesulfonyl-phenyl)-[5-nitro-6-(4-phenylsulfanyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(pyridin-2-yloxy)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 {6-[4-(4-Fluoro-phenoxy)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(pyridin-4-yloxy)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(pyrimidin-2-yloxy)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(pyridin-4-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (4-Methanesulfonyl-phenyl)-{6-[4-(4-methoxy-phenylsulfanyl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine; 
 [6-(4-Benzenesulfonyl-piperidin-1-yl)-5-nitro-pyrimidin-4-yl]-(4-methanesulfonyl-phenyl)-amine; 
 {4-[6-(4-Methanesulfonyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperazin-1-yl}-acetic acid ethyl ester; 
 (2-Fluoro-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 2-Methoxy-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (4-Methanesulfonyl-phenyl)-(5-nitro-6-{4-[3-(3-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-pyrimidin-4-yl)-amine; 
 {6-[4-(3-Ethyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 (6-{4-[5-(4-Fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-piperidin-1-yl}-5-nitro-pyrimidin-4-yl)-(4-methanesulfonyl-phenyl)-amine; 
 (4-Methanesulfonyl-phenyl)-[5-nitro-6-(4-pyridin-2-ylmethyl-piperidin-1-yl)-pyrimidin-4-yl]-amine; 
 1-{6-[4-(4,5-Dichloro-imidazol-1-yl)-phenylamino]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 Benzo[1,3]dioxol-5-yl-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (4-Fluoro-phenyl)-{1-[6-(2-fluoro-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-methanone; 
 {1-[6-(Benzo[1,3]dioxol-5-ylamino)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-(4-fluoro-phenyl)-methanone; 
 (2,3-Difluoro-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (2,4-Difluoro-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 (2,5-Difluoro-phenyl)-{5-nitro-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 1-[6-(4-Benzenesulfonyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(2-trifluoromethyl-3H-benzoimidazol-5-ylamino)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{5-Nitro-6-[3-(1,1,2,2-tetrafluoro-ethoxy)-phenylamino]-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 {6-[4-(4-Iodo-phenoxy)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 (2-Fluoro-4-methanesulfonyl-phenyl)-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine; 
 {6-[4-(3-Ethyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(2-fluoro-4-methanesulfonyl-phenyl)-amine; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(3-propyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 {6-[4-(3-Cyclopropylmethyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 {6-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 {6-[4-(3-Cyclopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methylsulfanyl-phenylamino)-pyrimidine-5-carbonitrile; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfinyl-phenylamino)-pyrimidine-5-carbonitrile; 
 (4-Methanesulfonyl-phenyl)-{5-nitro-6-[4-(4-trifluoromethoxy-phenoxy)-piperidin-1-yl]-pyrimidin-4-yl}-amine; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenylamino)-pyrimidine-5-carbonitrile; 
 1-{1-[6-(2-Fluoro-4-methanesulfonyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-hexan-1-one; 
 1-{1-[6-(4-Methanesulfonyl-phenylamino)-5-nitro-pyrimidin-4-yl]-piperidin-4-yl}-hexan-1-one; 
 {6-[4-(3-tert-Butyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(2-fluoro-4-methanesulfonyl-phenyl)-amine; 
 {6-[4-(3-tert-Butyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(4-methanesulfonyl-phenyl)-amine; 
 [6-(4-Benzofuran-2-yl-piperidin-1-yl)-5-nitro-pyrimidin-4-yl]-(4-methanesulfonyl-phenyl)-amine; 
 4-(3-Fluoro-4-methanesulfonyl-phenylamino)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidine-5-carbonitrile; 
 {6-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(5-methanesulfonyl-pyridin-2-yl)-amine; 
 (3-Fluoro-4-methanesulfonyl-phenyl)-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine; 
 {6-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-(6-methanesulfonyl-pyridin-3-yl)-amine; 
 4-(2,3-Difluoro-phenylamino)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidine-5-carbonitrile; 
 4-(2,5-Difluoro-phenylamino)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidine-5-carbonitrile; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methylsulfanyl-phenylamino)-pyrimidine-5-carbonitrile; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenylamino)-pyrimidine-5-carbonitrile; 
 4-(4-Hexanoyl-piperidin-1-yl)-6-(6-methylsulfanyl-pyridin-3-ylamino)-pyrimidine-5-carbonitrile; 
 4-(4-Hexanoyl-piperidin-1-yl)-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidine-5-carbonitrile; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(6-methylsulfanyl-pyridin-3-ylamino)-pyrimidine-5-carbonitrile; 
 4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidine-5-carbonitrile; 
 1-[4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(4-methanesulfonyl-phenylamino)-pyrimidin-5-yl]-ethanone; 
 and 
 1-[4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-5-yl]-ethanone; 
 or a pharmaceutically acceptable salt, hydrate or solvate thereof. 
 
     
     
         75 . The compound according to  claim 1  wherein said compound is selected from the group consisting of:
 1-(5-Nitro-6-phenyl-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-(6-Naphthalen-2-yl-5-nitro-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Methanesulfonyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(6-Benzofuran-5-yl-5-nitro-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3-trifluoromethyl-phenyl)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Methoxy-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 4-(4-Butyl-piperidin-1-yl)-6-furan-3-yl-5-nitro-pyrimidine; 
 1-[6-(3-Chloro-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2,6-Dimethoxy-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(6-Naphthalen-1-yl-5-nitro-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Methylsulfanyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(2′,4′-Dihydroxy-5-nitro-[4,5′]bipyrimidinyl-6-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Methanesulfonyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Bis-trifluoromethyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(6-Dibenzothiophen-4-yl-5-nitro-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Dimethyl-isoxazol-4-yl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(5-Nitro-6-thiophen-2-yl-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Dichloro-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(6-Dibenzofuran-4-yl-5-nitro-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3,5-Dimethyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Acetyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(4-Ethanesulfonyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Fluoro-biphenyl-4-yl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(3-Methanesulfonyl-phenyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(2-Carboxy-ethyl)-phenyl]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 1-{6-[4-(2-Methoxycarbonyl-ethyl)-phenyl]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester; 
 and 
 1-{6-[4-(2-Methoxycarbonyl-ethyl)-phenyl]-5-nitro-pyrimidin-4-yl}-piperidine-4-carboxylic acid ethyl ester; 
 or a pharmaceutically acceptable salt, hydrate or solvate thereof. 
 
     
     
         76 . The compound according to  claim 1  wherein said compound is selected from the group consisting of:
 1-[5-Nitro-6-(2-trifluoromethyl-phenylethynyl)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(5-Nitro-6-phenylethynyl-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(4-trifluoromethyl-phenylethynyl)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-(5-Nitro-6-m-tolylethynyl-pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester; 
 1-[6-(2-Fluoro-phenylethynyl)-5-nitro-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 1-[5-Nitro-6-(3-trifluoromethyl-phenylethynyl)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 and 
 1-[5-Amino-6-(3-trifluoromethyl-phenylethynyl)-pyrimidin-4-yl]-piperidine-4-carboxylic acid ethyl ester; 
 or a pharmaceutically acceptable salt, hydrate or solvate thereof. 
 
     
     
         77 . The compound according to  claim 1  wherein said compound is 5-Nitro-4-(5-phenyl-[1,3,4]oxadiazol-2-ylsulfanyl)-6-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-pyrimidine or a pharmaceutically acceptable salt, hydrate or solvate thereof. 
     
     
         78 . A pharmaceutical composition comprising at least one compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         79 . A method for prophylaxis or treatment of a metabolic disorder in an individual comprising administering to the individual a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         80 . The method according to  claim 79  wherein the metabolic disorder is type I, type II diabetes, inadequate glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, syndrome X or metabolic syndrome. 
     
     
         81 . The method according to  claim 79  wherein the metabolic disorder is type II diabetes. 
     
     
         82 . A method for controlling or decreasing weight gain of an individual comprising administering to the individual a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         83 . A method of modulating a RUP3 receptor comprising contacting the receptor with a compound according to  claim 1 . 
     
     
         84 . A method of modulating a RUP3 receptor in an individual comprising contacting the receptor with a compound according to  claim 1 . 
     
     
         85 . The method of modulating the RUP3 receptor according to  claim 83  wherein the compound is an agonist. 
     
     
         86 . The method of modulating the RUP3 receptor according to  claim 83  wherein the compound is an inverse agonist. 
     
     
         87 . The method of modulating the RUP3 receptor according to  claim 84  wherein the modulation of the RUP3 receptor is prophylaxis or treatment of a metabolic disorder. 
     
     
         88 . The method of modulating the RUP3 receptor according to  claim 87  wherein the metabolic disorder is type I, type II diabetes, inadequate glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, syndrome X or metabolic syndrome. 
     
     
         89 . The method of modulating the RUP3 receptor according to  claim 87  wherein the metabolic disorder is type II diabetes. 
     
     
         90 . The method of modulating the RUP3 receptor according to  claim 84  wherein the modulation of the RUP3 receptor controls or reduces weight gain of the individual. 
     
     
         91 . The method according to  claim 84  wherein the individual is a mammal. 
     
     
         92 . The method according to  claim 91  wherein the mammal is a human. 
     
     
         93 - 99 . (canceled) 
     
     
         100 . The method of producing a pharmaceutical composition comprising admixing at least one compound according to  claim 1  and a pharmaceutically acceptable carrier.