Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto

Abstract

The present invention relates to certain fused aryl and heteroaryl derivatives of Formula (I) 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 (I):  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, hydrate or solvate thereof; 
 wherein:  
 A and B are each independently C 1-3  alkylene 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;  
 D is O, S, S(O), S(O) 2 , CR 1 R 2  or N—R 2 , wherein R 1  is selected from the group consisting of H, C 1-8  alkyl, C 1-4  alkoxy, halogen and hydroxyl;  
 E is N, C or CR 3 , wherein R 3  is H or C 1-8  alkyl;  
 - - - is a single bond when E is N or CR 3 , or a double bond when E is C;  
 K is a C 3-6  cycloalkylene or C 1-3  alkylene 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 K is a bond;  
 Q is NR 4 , O, S, S(O) or S(O) 2 , wherein R 4  is H or C 1-8  alkyl and the C 1-8  alkyl is optionally substituted with C 2-8  dialkylamine;  
 T is N or CR 5 ;  
 M is N or CR 6 ;  
 J is N or CR 7 ;  
 U is C or N;  
 V is N, CR 8  or V is a bond;  
 W is N or C;  
 X is O, S, N, CR 9  or NR 11 ;  
 Y is O, S, N, CR 10  or NR 12 ;  
 Z is C or N;  
 R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are each independently selected from the group consisting of H, 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, 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, hydroxyl, hydroxylamino and nitro; wherein said C 2-6  alkenyl, C 1-8  alkyl, C 2-6  alkynyl and C 3-6  cycloalkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, 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 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, hydroxyl, hydroxylamino and nitro;  
 R 11  and R 12  are each independently selected from C 2-6  alkenyl, C 1-8  alkyl, C 2-6  alkynyl or C 3-6  cycloalkyl each optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 1-4  alkoxy, 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 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, hydroxyl, hydroxylamino and nitro;  
 Ar 1  is aryl or heteroaryl each optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; wherein R 13  is selected from the group consisting of C 1-5  acyl, C 1-6  acylsulfonamide, C 1-5  acyloxy, C 2-6  alkenyl, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylthiocarboxamide, C 2-6  alkynyl, 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, arylsulfonyl, carbamimidoyl, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-7  cycloalkyl, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, C 2-6  dialkylthiocarboxamide, guanidinyl, halogen, C 1-4  haloalkoxy, C 1-4  haloalkyl, C 1-4  haloalkylsulfinyl, C 1-4  haloalkylsulfonyl, C 1-4  haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C 4-7  oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid, and thiol, and wherein said C 1-5  acyl, C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, arylsulfonyl, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, heteroaryl, phenoxy and phenyl are 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 1-7  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, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-7  cycloalkyl, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, 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, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; or  
 R 13  is a group of Formula (A):  
                     
  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 3-7  cycloalkyl, C 2-6  dialkylcarboxamide, halogen, heteroaryl or phenyl, and wherein said heteroaryl or 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;  
 
 R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of H, 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 3-7  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 14 , R 15 , R 16  and R 17  together with the atoms to which they are attached form a 5, 6 or 7 member cycloalkyl, cycloalkenyl or heterocyclic group fused with Ar 1  wherein the 5, 6 or 7 member group is optionally substituted with halogen; and  
 R 2  is selected from the group consisting of C 1-8  alkyl, C 2-6  alkynyl, amino, aryl, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl and hydroxyl; and wherein said C 1-8  alkyl, aryl and heteroaryl 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 -heteroalkylene, C 2-8  dialkylamino, C 2-6  dialkylcarboxamide, C 2-6  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 each 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, C 1-4  alkylamino, carbo-C 1-6 -alkoxy, carboxamide, carboxy, cyano, C 3-6 -cycloalkyl, C 2-8  dialkylamino, 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 19  is H, C 1-8  alkyl, C 3-7  cycloalkyl, aryl, heteroaryl or OR 21 ; and  
 
 R 20  is F, Cl, Br, CN or NR 22 R 23 ; where R 21  is H, C 1-8  alkyl or C 3-7  cycloalkyl, and R 22  and R 23  are independently H, C 1-8  alkyl, C 3-7  cycloalkyl, aryl or heteroaryl; or  
 R 2  is a group of Formula (C):  
                     
  wherein:  
 G is:  
 i) —C(O)—, —C(O)NR 25 —, —NR 25 C(O)—, —NR 25 —, —NR 25 C(O)O—, —OC(O)NR 25 —, —CR 25 R 26 NR 27 C(O)—, —CR 25 R 26 C(O)NR 27 —, —C(O)O—, —OC(O)—, —C(S)—, —C(S)NR 25 —, —C(S)O—, —OC(S)—, —CR 25 R 26 —, —O—, —S—, —S(O)—, —S(O) 2 — or a bond when D is CR 2 R 3 ; or  
 ii) —CR 25 R 26 C(O)—, —C(O)—, —CR 25 R 26 C(O)NR 27 —, —C(O)NR 25 —, —C(O)O—, —C(S)—, —C(S)NR 25 —, —C(S)O—, —CR 25 R 26 —, —S(O) 2 —, or a bond when D is NR 2 ;  
 wherein R 25 , R 26  and R 27  are each independently H or C 1-8  alkyl; and R 24  is H, C 1- 8 alkyl, C 3-7  cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-5  acyl, C 1-5  acyloxy, C 2-6  alkenyl, C 1-4  alkoxy, C 1-7  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 3-7  cycloalkyl, C 2-8  dialkylamino, C 2-6  dialkylcarboxamide, C 2-6  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, heterocyclic, hydroxyl, hydroxylamino, nitro, phenyl, phenoxy, and sulfonic acid, wherein said C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylamino, heteroaryl, phenyl and phenoxy 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 3-7  cycloalkyl, C 2-8  dialkylamino, C 2-6  dialkylcarboxamide, C 2-6  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, nitro, and phenyl;  
 provided that Z and U are not both N.  
 
     
     
         2 . The compound according to  claim 1  wherein: 
 M, J, X, and W are all N;    T is CR 5 ;    Y is CR 10 ;    V is a bond; and    Z and U are both C.    
     
     
         3 . The compound according to  claim 1  wherein: 
 M, J, X, and W are all N;    T is CR 5 , wherein R 5  is —H, —CH 3 , or —N(CH 3 ) 2 ;    Y is CR 10 , wherein R 10  is —H or —CH 3 ;    V is a bond; and    Z and U are both C.    
     
     
         4 . The compound according to  claim 1  wherein: 
 M, J, X, and W are all N;    T is C—H;    Y is C—H;    V is a bond; and    Z and U are both C.    
     
     
         5 . The compound according to  claim 1  wherein  is a single bond.  
     
     
         6 . The compound according to  claim 1  wherein Q is O.  
     
     
         7 . The compound according to  claim 1  wherein Q is S, S(O) or S(O) 2 .  
     
     
         8 . The compound according to  claim 1  wherein Q is NR 4 .  
     
     
         9 . The compound according to  claim 1  wherein R 4  is C 1-8  alkyl optionally substituted with C 2-8  dialkylamino.  
     
     
         10 . The compound according to  claim 1  wherein R 4  is selected from the group consisting of methyl, ethyl, isopropyl, and 2-dimethylamino-ethyl.  
     
     
         11 . The compound according to  claim 1  wherein R 4  is H.  
     
     
         12 . The compound according to  claim 1  wherein K is selected from the group consisting of —CH 2 —, —CH 2 CH 2 —, and —CH(CH 3 )CH 2 —.  
     
     
         13 . The compound according to  claim 1  wherein K is a bond.  
     
     
         14 . The compound according to  claim 1  wherein both A and B are —CH 2 —.  
     
     
         15 . The compound according to  claim 1  wherein A is —CH 2 CH 2 — and B is —CH 2 —.  
     
     
         16 . The compound according to  claim 1  wherein both A and B are —CH 2 CH 2 —.  
     
     
         17 . The compound according to  claim 1  wherein A is —CH 2 — and B is —CH 2 CH 2 CH 2 —.  
     
     
         18 . The compound according to  claim 1  wherein E is CH and D is N—R 2 .  
     
     
         19 . The compound according to  claim 1  wherein E is CH and D is CHR 2 .  
     
     
         20 . The compound according to  claim 1  wherein R 2  is a group of Formula (C):  
       
         
           
           
               
               
           
         
       
       wherein G is: 
 —NHC(O)—, —NH—, —NHC(O)O—, —CH 2 NHC(O)—, or a bond; and R 24  is H, C 1-8  alkyl, or heteroaryl, each optionally substituted with 1 to 2 substituents selected from the group consisting of C 1-4  alkoxy, and C 1-7  alkyl.  
 
     
     
         21 . The compound according to  claim 1  wherein R 2  is of Formula (C):  
       
         
           
           
               
               
           
         
       
       wherein: 
 G is —CR 25 R 26 C(O)—, —C(O)—, —C(O)NR 25 —, —C(O)O—, —C(S)NR 25 —, —CR 25 R 26 —, or a bond, wherein R 25 , and R 26  are each independently H or C 1-8  alkyl; and R 24  is H, C 1-8  alkyl, C 3-7  cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylamino, amino, carbo-C 1-6 -alkoxy, carboxy, C 3-7  cycloalkyl, C 2-8  dialkylamino, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, heterocyclic, hydroxyl, and nitro, wherein said C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylamino, heteroaryl, and phenyl are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, carbo-C 1-6 -alkoxy, carboxamide, carboxy, C 3-7  cycloalkyl, halogen, heterocyclic, and phenyl.  
 
     
     
         22 . The compound according to  claim 1  wherein R 2  is —C(O)OR 24  and R 24  is C 1-8  alkyl, C 3-7  cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylsulfonyl, amino, carbo-C 1-6 -alkoxy, carboxy, cyano, C 3-7  cycloalkyl, C 2-8  dialkylamino, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, heterocyclic, hydroxyl, phenyl, phenoxy, and sulfonic acid, wherein said C 1-7  alkyl, phenyl and phenoxy are each optionally substituted with 1 to 5 substituents selected from the group consisting of amino, C 1-4  haloalkoxy, and heterocyclic.  
     
     
         23 . The compound according to  claim 1  wherein R 2  is —C(O)OR 24  and R 24  is C 1-8  alkyl, or C 3-7  cycloalkyl each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylsulfonyl, carboxy, cyano, C 3-7  cycloalkyl, C 2-8  dialkylamino, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, heterocyclic, hydroxyl, phenyl, phenoxy, and sulfonic acid.  
     
     
         24 . The compound according to  claim 1  wherein R 2  is —C(O)OR 24  and R 24  is C 1-8  alkyl, or C 3-7  cycloalkyl wherein said C 3-7  cycloalkyl is optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, C 1-7  alkyl, carboxy, C 2-8  dialkylamino, and halogen.  
     
     
         25 . The compound according to  claim 1  wherein R 2  is —C(O)OR 24  and R 24  is C 1-8  alkyl, or C 3-7  cycloalkyl  
     
     
         26 . The compound according to  claim 1  wherein R 2  is —C(O)R 24  and R 24  is C 1-8  alkyl, C 3-7  cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of C 2-6  alkenyl, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylsulfonyl, amino, carbo-C 1-6 -alkoxy, carboxy, cyano, C 3-7  cycloalkyl, C 2-8  dialkylamino, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, heterocyclic, hydroxyl, phenyl, phenoxy, and sulfonic acid, wherein said C 1-7  alkyl, phenyl and phenoxy are each optionally substituted with 1 to 5 substituents selected from the group consisting of amino, C 1-4  haloalkoxy, and heterocyclic.  
     
     
         27 . The compound according to  claim 1  wherein R 2  is —C(O)R 24  and R 24  is C 1-8  alkyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of H, C 1-4  alkoxy, C 1-8  alkyl, amino, carboxy, halogen, heteroaryl, hydroxyl, phenoxy, and sulfonic acid, wherein said alkyl and phenoxy are optionally substituted with 1 to 5 substituents selected from the group consisting of amino, C 1-4  haloalkoxy, and heterocyclic.  
     
     
         28 . The compound according to  claim 1  wherein Ar 1  is aryl or heteroaryl optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, and sulfonamide, and wherein said C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonamide, alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, cyano, C 2-6  dialkylamino, and halogen.    
     
     
         29 . The compound according to  claim 28  wherein Ar 1  is aryl.  
     
     
         30 . The compound according to  claim 28  wherein Ar 1  is heteroaryl.  
     
     
         31 . The compound according to  claim 1  wherein Ar 1  is phenyl optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, C 1-4  haloalkyl, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, and sulfonamide, and wherein said C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, cyano, C 2-6  dialkylamino, C 1-4  haloalkyl, and halogen.    
     
     
         32 . The compound according to  claim 1  wherein Ar 1  is phenyl optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, and sulfonamide, and wherein said C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, cyano, C 2-6  dialkylamino, and halogen.    
     
     
         33 . The compound according to  claim 1  wherein Ar 1  is phenyl optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, and sulfonamide, and wherein said C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of C 1-8  alkyl, and halogen.    
     
     
         34 . The compound according to  claim 1  wherein Ar 1  is pyridyl optionally substituted with R 13 , R 14 , R 15 , and R 16 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, and sulfonamide, and wherein said C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonamide, alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , and R 16  are each independently selected form the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, cyano, C 2-6  dialkylamino, and halogen.    
     
     
         35 . The compound according to  claim 1  wherein Ar 1  is pyridyl optionally substituted with R 13 , R 14 , R 15 , and R 16 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, C 2-6  dialkylamino, halogen, heterocyclic, and sulfonamide, and wherein said C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, alkylsulfonyl, C 1-4  alkylthio, C 2-6  dialkylamino, and heterocyclic are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-4  alkylsulfonyl, C 3-7  cycloalkyloxy, heteroaryl, hydroxyl, phenyl, and phosphonooxy; and    R 14 , R 15 , and R 16  are each independently selected form the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, cyano, C 2-6  dialkylamino, and halogen.    
     
     
         36 . The compound according to  claim 1  wherein Ar 1  is pyridyl optionally substituted with R 13 , R 14 , R 15 , and R 16 ; 
 wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, C 2-6  dialkylamino, halogen, heterocyclic, and sulfonamide, and wherein said C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, alkylsulfonyl, C 1-4  alkylthio, C 2-6  dialkylamino, and heterocyclic are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-4  alkylsulfonyl, C 3-7  cycloalkyloxy, heteroaryl, hydroxyl, phenyl, and phosphonooxy; and    R 14 , R 15 , and R 16  are each independently selected form the group consisting of C 1-8  alkyl, and halogen.    
     
     
         37 . The compound according to  claim 1  is of Formula (H7):  
       
         
           
           
               
               
           
         
       
       wherein: 
 A is —CH 2 —, or —CH 2 CH 2 —;  
 B is —CH 2 —, —CH 2 CH 2 —, or —CH 2 CH 2 CH 2 —;  
 E is CH;  
   is a single bond;  
 D is N—R 2 ;  
 K is —CH 2 —, —CH 2 CH 2 —, —CH(CH 3 )CH 2 —, or a bond;  
 Q is O, S, S(O), S(O) 2 , NH;  
 R 5  is H, CH 3  or N(CH 3 ) 2 ;  
 R 10  is H or CH 3 ;  
 R 2  is —CR 25 R 26 C(O)R 24 , —C(O)R 24 , —C(O)NR 25 R 24 , —R 24 , —C(O)OR 24 , —C(S)NR 25 R 24 , or —CR 25 R 26 R 24 , wherein R 24  is C 1-8  alkyl, C 3-7  cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of C 2-6  alkenyl, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylsulfonyl, amino, carbo-C 1-6 -alkoxy, carboxy, cyano, C 3-7  cycloalkyl, C 2-8  dialkylamino, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, heterocyclic, hydroxyl, phenyl, phenoxy, and sulfonic acid, wherein said C 1-7  alkyl, phenyl and phenoxy are each optionally substituted with 1 to 5 substituents selected from the group consisting of amino, C 1-4  haloalkoxy, and heterocyclic; and R 25  and R 26  are each independently H or C 1-8  alkyl; and  
 Ar 1  is aryl or heteroaryl optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, and sulfonamide, and wherein said C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonamide, alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy; and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and  
 R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, cyano, C 2-6  dialkylamino, and halogen.  
 
     
     
         38 . The compound according to  claim 1  is of Formula (H7) wherein: 
 A and B are both —CH 2 CH 2 —;    E is CH;      is a single bond;    D is N—R 2 ;    K is a bond;    Q is O, or NH;    R 5  and R 10  are both H;    R 2  is —C(O)OR 24  wherein R 24  is C 1-8  alkyl, or C 3-7  cycloalkyl each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylsulfonyl, amino, carbo-C 1-6 -alkoxy, carboxy, cyano, C 3-7  cycloalkyl, C 2-8  dialkylamino, C 1-4  haloalkoxy, C 1-4  haloalkyl, halogen, heteroaryl, heterocyclic, hydroxyl, phenyl, and phenoxy; and    Ar 1  is aryl or heteroaryl optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ; wherein R 13  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, amino, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, and sulfonamide, and wherein said C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-4  alkylsulfonamide, alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 3-7  cycloalkyloxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , R 16 , and R 17  are each independently selected form the group consisting of C 1-4  alkoxy, C 1-8  alkyl, and halogen.    
     
     
         39 . The compound according to  claim 1  wherein: 
 A and B are both —CH 2 CH 2 —;    E is CH;      is a single bond;    D is N—R 2      K is a bond;    Q is O, or NH;    R 5  and R 10  are both H;    R 2  is —C(O)OR 24  wherein R 24  is C 1-8  alkyl or C 3-7  cycloalkyl;    Ar 1  is phenyl, 3-pyridyl, or 2-pyridyl each optionally substituted with R 13 , R 14 , R 15 , R 16 , and R 17 ,    wherein R 11  is selected from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, carboxamide, carboxy, cyano, C 2-6  dialkylamino, halogen, heterocyclic, heterocyclic-oxy, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, and sulfonamide, and wherein said C 1-4  alkoxy, C 1-8  alkyl, C 1-4  alkylamino, C 1-6  alkylcarboxamide, C 1-4  alkylsulfonamide, C 1-4  alkylsulfonyl, C 1-4  alkylthio, carbamimidoyl, C 2-6  dialkylamino, heterocyclic, heterocyclic-carbonyl, and heteroaryl are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C 1-6  acylsulfonamide, C 1-4  alkoxy, C 1-7  alkyl, C 1-4  alkylcarboxamide, C 1-4  alkylsulfonyl, carboxy, C 2-6  dialkylamino, C 2-6  dialkylcarboxamide, heteroaryl, heterocyclic, hydroxyl, phenyl, and phosphonooxy, and wherein said C 1-7  alkyl and C 1-4  alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C 1-4  alkoxy and hydroxy; and    R 14 , R 15 , R 16 , and R 17  are each independently CH 3 , or F.    
     
     
         40 . The compound according to  claim 39  wherein R 2  is selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, iso-propoxycarbonyl, n-propoxycarbonyl, n-butoxycarbonyl, tert-butoxycarbonyl, iso-butoxycarbonyl, and n-pentyloxycarbonyl.  
     
     
         41 . The compound according to  claim 40  wherein R 13  is selected from the group consisting of sulfamoyl, acetylsulfamoyl, propionylsulfamoyl, butyrylsulfamoyl, pentanoylsulfamoyl, methanesulfonyl, ethanesulfonyl, propane-1-sulfonyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxy-butyl, phosphonooxymethyl, 2-phosphonooxy-ethyl, 3-phosphonooxy-propyl, and 4-phosphonooxy-butyl.  
     
     
         42 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-3,6-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isobutyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    1-(4-Methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-pyridin-3-yl-methanone.    (3-Fluoro-phenyl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (1-tert-Butyl-5-methyl-1H-pyrazol-4-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidine-1-carboxylic acid isobutyl ester;    Furan-2-yl-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(1-methyl-1H-pyrrol-2-yl)-methanone;    2-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-pyridin-3-yl-ethanone;    2-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-pyridin-2-yl-ethanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-methyl-pyridin-3-yl)-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(2-methyl-pyridin-3-yl)-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(6-methyl-pyridin-3-yl)-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-methyl-isoxazol-3-yl)-methanone;    2-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-thiophen-2-yl-ethanone;    4-(1-Benzyl-azetidin-3-yloxy)-1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine;    3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester;    1-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-3,3-dimethyl-butan-2-one;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-pyrazin-2-yl-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-methyl-pyrazin-2-yl)-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-pyrimidin-5-yl-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-pyridazin-4-yl-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-thiophen-2-yl-methanone;    (3,4-Dimethyl-isoxazol-5-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    3-tert-Butoxy-1-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-propan-1-one;    (3-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-3-oxo-propyl)-methyl-carbamic acid tert-butyl ester;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(6-trifluoromethyl-pyridin-3-y l)-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester;    N-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-cyclohexane-1,4-diamine;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(4-methyl-[1,2,3]thiadiazol-5-yl)-methanone;    (3,5-Dimethyl-isoxazol-4-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (2,5-Dimethyl-2H-pyrazol-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(3-methyl-isoxazol-5-yl)-methanone;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carbothioic acid pyridin-4-ylamide;    N-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexyl}-nicotinamide;    3-tert-Butoxy-N-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexyl}-propionamide;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester;    (3,5-Dimethyl-isoxazol-4-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    4-[1-(3,5-Bis-trifluoromethyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-azetidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid propyl ester;    4-[1-(3-Fluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(2,4-Difluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    {4-[1-(2,4-Difluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester;    {4-[1-(3-Fluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester;    N-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-cyclohexane-1,4-diamine;    {3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidin-1-yl}-(6-methyl-pyridin-3-yl)-methanone;    {3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidin-1-yl}-(2-methyl-pyridin-3-yl)-methanone;    {3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidin-1-yl}-(5-methyl-pyridin-3-yl)-methanone;    {3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidin-1-yl}-pyridin-3-yl-methanone;    {3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidin-1-yl}-(1-methyl-1H-pyrrol-3-yl)-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-cyclohexyl}-carbamic acid tert-butyl ester;    N-[1-(2,4-Difluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-cyclohexane-1,4-diamine;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(4-trifluoromethyl-pyridin-3-yl)-methanone;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid cyclohexyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tetrahydro-pyran-4-yl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid cyclopentyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tetrahydro-furan-3-yl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tetrahydro-furan-3-yl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tetrahydro-thiopyran-4-yl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid cyclobutyl ester;    (6-tert-Butyl-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (4-{[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-methyl}-cyclohexyl)-carbamic acid tert-butyl ester;    N-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexylmethyl}-nicotinamide;    N-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-cyclohexylmethyl}-6-methyl-nicotinamide;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-({[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-methyl-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-{[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester;    3-{[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester;    4-({Ethyl-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-{1-[2-(2-Dimethylamino-ethoxy)-4-methanesulfonyl-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy}-piperidine-1-carboxylic acid tert-butyl ester;    3-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid pyridin-3-ylmethyl esteracid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 2-pyridin-3-yl-ethyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 3-pyridin-3-yl-propyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 2-dimethylamino-ethyl ester;    4-{[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-methyl-amino}-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(2,4-Difluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-({Ethyl-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-methyl)-piperidine-1-carboxylic acid isopropyl ester;    4-({Ethyl-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-[6-Dimethylamino-1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    1-(4-{[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-methyl-amino}-piperidin-1-yl)-3,3-dimethyl-butan-2-one;    4-{[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-methyl-amino}-piperidine-1-carboxylic acid cyclobutyl ester; and    4-[({1-[4-(2-Methanesulfonyl-ethyl)-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yl}-methyl-amino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         43 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-({[1-(2,5-Difluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-methyl-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    2-{4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-(4-trifluoromethoxy-phenyl)-ethanone;    2-{4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-(3-fluoro-phenyl)-ethanone;    2-{4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-pyridin-2-yl-ethanone;    (2,5-Dimethyl-furan-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    4-({(2-Dimethylamino-ethyl)-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-({(2-Dimethylamino-ethyl)-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(2-Dimethylamino-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-(2-{Ethyl-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-ethyl)-piperazine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid tert-butyl ester;    4-{2-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-ethyl}-piperazine-1-carboxylic acid ethyl ester;    4-{2-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-propyl}-piperazine-1-carboxylic acid ethyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-sulfinyl]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-sulfonyl]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid butyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid 2-methoxy-ethyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid 3,3-dimethyl-butyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid 4-methyl-pentyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid cyclopropylmethyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid cyclobutylmethyl ester;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid 2-cyclopropyl-ethyl ester;    (5-Bromo-furan-2-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-morpholin-4-ylmethyl-furan-2-yl)-methanone;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid pentyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 1-ethyl-propyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 2-ethyl-butyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid cyclopentylmethyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 2-pyrrolidin-1-yl-ethyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 2-morpholin-4-yl-ethyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid ethyl ester;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 2,2-dimethyl-propyl ester;    (5-Butyl-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    Ethyl-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ylmethyl)-amine;    Ethyl-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-(5 ′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ylmethyl)-amine;    [1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-(5 ′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-amine;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    5′-Fluoro-4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-5 ′-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-6′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl;    [1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-[-1-(3-isopropyl-[1,2,4]oxadiazol-5-ylmethyl)-pyrrolidin-3-yl]-amine;    [1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-[1-(3-isopropyl-[1,2,4]oxadiazol-5-ylmethyl)-pyrrolidin-3-yl]-amine;    (4-Ethyl-pyridin-2-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-ylmethyl)-pyrrolidin-3-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-ylmethyl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    (5′-Fluoro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl;-4-yl)-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;    (5-Bromo-pyridin-3-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    3-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester;    3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester;    3-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-pyrrolidine-1-carboxylic acid isopropyl ester;    (6-Chloro-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5-Chloro-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanone;    (2-Chloro-pyridin-4-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (4-Hydroxy-3-methoxy-phenyl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (4-Chloro-3-nitro-phenyl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    1-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-3-methyl-butan-1-one;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(6-pyrazol-1-yl-pyridin-3-yl)-methanone;    (2-Hydroxy-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5,6-Dichloro-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5-Bromo-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    5-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carbonyl}-nicotinic acid;    (1H-Imidazol-4-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    3-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(6-pyrrolidin-1-yl-pyridin-3-yl)-methanone;    (6-Isobutylamino-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (6-Ethylamino-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (6-Cyclobutylamino-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (6-Isopropylamino-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    [6-(1-Ethyl-propylamino)-pyridin-3-yl]-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-[6-(1-propyl-butylamino)-pyridin-3-yl]-methanone;    5-Benzyloxy-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carbonyl}-pyran-4-one;    Benzo[c]isoxazol-3-yl-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (4-Chloro-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (4-Iodo-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    1-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-butan-2-one;    2-(5-Bromo-pyridin-3-yl)-1-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    (6-Fluoro-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5-Fluoro-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (6-Chloro-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (2-Chloro-5-fluoro-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-[5-(2-methyl-pyrrolidin-1-ylmethyl)-pyridin-3-yl]-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(6-methyl-pyridin-2-yl)-methanone;    5-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carbonyl}-nicotinonitrile;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(4-methoxy-pyridin-2-yl)-methanone;    (2-Fluoro-pyridin-4-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (2-Fluoro-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (6-Fluoro-pyridin-3-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(4-methoxy-thiophen-3-yl)-methanone;    2-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carbonyl}-pyran-4-one;    (5-Ethyl-pyridin-2-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (4-Ethoxy-phenyl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-pyridin-2-yl-thiophen-2-yl)-methanone;    (5-Amino-pyridin-2-yl)-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5-Amino-pyridin-2-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-[5-(3-methyl-butylamino)-pyridin-2-yl]-methanone;    {4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(4-trifluoromethoxy-phenyl)-methanone;    (5-Butyl-pyridin-2-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    (5-Ethylamino-pyridin-2-yl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-isopropoxymethyl-pyridin-2-yl)-methanone;    (4-Difluoromethoxy-phenyl)-{4-[1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-methanone;    {4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(5-isopropoxy-pyridin-2-yl)-methanone;    5-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carbonyl}-pyridine-2-carboxylic acid methyl ester;    {4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-acetic acid ethyl ester;    {4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-(3-trifluoromethoxy-phenyl)-methanone;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(4-Chloro-phenyl)-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    2-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-1-(3-trifluoromethyl-phenyl)-ethanone;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-5′-isopropoxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl;    1-(4-Methanesulfonyl-phenyl)-4-[1-(4-trifluoromethoxy-phenyl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(4-trifluoromethoxy-phenyl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(4-Chloro-3-methyl-phenyl)-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    1-(3,4-Dichloro-phenyl)-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    5′-Bromo-4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(3-trifluoromethoxy-phenyl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-5′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[12′]bipyridinyl;    1-(2,4-Dimethoxy-phenyl)-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    1-(4-Difluoromethoxy-phenyl)-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    1-(4-Diethylamino-phenyl)-2-{4-[1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-ethanone;    (2-{4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-5-methyl-pyrimidin-4-yl)-dimethyl-amine;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(5-methyl-4-pyrrolidin-1-yl-pyrimidin-2-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2-Methyl-4-propylamino-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Isopropylamino-2-methyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2-Methyl-4-morpholin-4-yl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-{1-[4-(2-Methoxy-ethylamino)-2-methyl-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester;    4-(1-{4-[(2-Methanesulfonyl-ethyl)-methyl-amino]-2-methyl-phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Bromo-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Propylamino-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Isopropylamino-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-(1-{4-[4-(2-Methanesulfonyl-ethyl)-piperazin-1-yl]-2-methyl-phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester;    4-(1-{2-Methyl-4-[(tetrahydro-furan-2-ylmethyl)-amino]-phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Cyclopropylamino-2-methyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-{1-[4-(2-Dimethylamino-ethylamino)-2-methyl-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Morpholin-4-yl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-({[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-y]-isopropyl-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-[1-(2-Fluoro-4-morpholin-4-yl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2-Fluoro-4-isopropylamino-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-(1-{4-[(2-Methanesulfonyl-ethyl)-methyl-amino]-phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester;    4-{1-[4-(2-Methoxy-ethylamino)-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester;    4-(1-{4-[(Tetrahydro-furan-2-ylmethyl)-amino]-phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester;    4-(1-{4-[4-(2-Methanesulfonyl-ethyl)-piperazin-1-yl]-phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Amino-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-({[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-isopropyl-amino}-methyl)-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(5-Ethyl-pyrimidin-2-yl)-piperidin-4-ylsulfanyl]-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine;    4-[1-(2-Fluoro-4-sulfamoyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2-Fluoro-4-propionylsulfamoyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Cyano-2-fluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    1-(2,5-Difluoro-4-methoxy-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine;    4-[1-(2,5-Difluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Fluoro-6-methoxy-pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(6-Methoxy-2-methyl-pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2,5-Difluoro-4-sulfamoyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2-Fluoro-4-hydroxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-benzonitrile;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-benzenesulfonamide;    1-(2,5-Difluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(4-Fluoro-6-methoxy-pyridin-3-yl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    4-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1-(6-methoxy-2-methyl-pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine;    2,5-Difluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-benzenesulfonamide;    1-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-benzonitrile;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-benzenesulfonamide;    1-(2,5-Difluoro-4-methanesulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(4-Fluoro-6-methoxy-pyridin-3-yl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine;    4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-(6-methoxy-2-methyl-pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine;    2,5-Difluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-benzenesulfonamide;    4-[1-(2-Fluoro-4-methoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(4-Difluoromethoxy-2-fluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2-Fluoro-4-trifluoromethoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[1-(2,5-Difluoro-4-methoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-phenol;    1-(2-Fluoro-4-methoxy-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(4-Difluoromethoxy-2-fluoro-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(2-Fluoro-4-trifluoromethoxy-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(2,5-Difluoro-4-methoxy-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1H-pyrazolo[3,4-d]pyrimidine;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-phenol;    1-(2-Fluoro-4-methoxy-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine;    1-(4-Difluoromethoxy-2-fluoro-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine; and    1-(2-Fluoro-4-trifluoromethoxy-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1H-pyrazolo[3,4-d]pyrimidine; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         44 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[9-(6-Methanesulfonyl-pyridin-3-yl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isobutyl ester;    {4-[9-(6-Methanesulfonyl-pyridin-3-yl)-9H-purin-6-yloxy]-piperidin-1-yl}-pyridin-3-yl-methanone;    4-[9-(4-Methanesulfonyl-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester;    4-[9-(6-Methanesulfonyl-pyridin-3-y)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester and    4-[9-(2-Fluoro-4-methanesulfonyl-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         45 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[9-(2-Fluoro-4-propionylsulfamoyl-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[9-(4-Cyano-2-fluoro-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[9-(2-Fluoro-4-sulfamoyl-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    9-(2-Fluoro-4-methanesulfonyl-phenyl)-6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-9H-purine;    3-Fluoro-4-{6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-purin-9-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-purin-9-yl}-benzonitrile;    3-Fluoro-4-{6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-purin-9-yl}-benzenesulfonamide;    4-[9-(2,5-Difluoro-4-methanesulfonyl1-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[9-(4-Fluoro-6-methoxy-pyridin-3-yl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[9-(6-Methoxy-2-methyl-pyridin-3-yl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[9-(2,5-Difluoro-4-sulfamoyl-phenyl)-9H-purin-6-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    9-(2,5-Difluoro-4-methanesulfonyl-phenyl)-6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-9H-purine;    9-(4-Fluoro-6-methoxy-pyridin-3-yl)-6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-9H-purine;    6-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-9-(6-methoxy-2-methyl-pyridin-3-yl)-9H-purine;    2,5-Difluoro-4-{6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-purin-9-yl}-benzenesulfonamide;    9-(2-Fluoro-4-methanesulfonyl-phenyl)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-9H-purine;    3-Fluoro-4-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-purin-9-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-purin-9-yl}-benzonitrile;    3-Fluoro-4-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-purin-9-yl}-benzenesulfonamide;    9-(2,5-Difluoro-4-methanesulfonyl-phenyl)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-9H-purine;    9-(4-Fluoro-6-methoxy-pyridin-3-yl)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-9H-purine;    6-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-9-(6-methoxy-2-methyl-pyridin-3-yl)-9H-purine; and    2,5-Difluoro-4-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-purin-9-yl}-benzenesulfonamide; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         46 . The compound according to  claim 1  wherein said compound is 4-[3-(4-Methanesulfonyl-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid tert-butyl ester; or 
 a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         47 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    7-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    2,5-Difluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-benzenesulfonamide;    4-[3-(2-Fluoro-4-methanesulfonyl-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-propionylsulfamoyl-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Cyano-2-fluoro-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-sulfamoyl-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Fluoro-6-methoxy-pyridin-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(6-Methoxy-2-methyl-pyridin-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-sulfamoyl-phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3H-[1,2,3]triazolo[4,5-d]pyrimidine;    7-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine; and    2,5-Difluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl}-benzenesulfonamide; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         48 . The compound according to  claim 1  wherein said compound is 4-[3-(4-Methanesulfonyl-phenyl)-isoxazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid tert-butyl ester; or 
 a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         49 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-({Ethyl-[3-(4-methanesulfonyl-phenyl)-isoxazolo[4,5-d]pyrimidin-7-yl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;    4-[3-(4-Methanesulfonyl-phenyl)-isoxazolo[4,5-d]pyrimidin-7-ylsulfanyl]-piperidine-1-carboxylic acid tert-butyl ester; and    4-[3-(4-Methanesulfonyl-phenyl)-isoxazolo[4,5-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         50 . The compound according to  claim 1  wherein said compound is 4-[8-(2-Fluoro-4-methanesulfonyl-phenyl)-[1,7]naphthyridin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester; or 
 a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         51 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[8-(2-Fluoro-4-methanesulfonyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Methylsulfanyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Methanesulfonyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Isopropoxy-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Bromo-2-fluoro-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2-Fluoro-4-propionylsulfamoyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Cyano-2-fluoro-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2-Fluoro-4-sulfamoyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2,5-Difluoro-4-methanesulfonyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Fluoro-6-methoxy-pyridin-3-yl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(6-Methoxy-2-methyl-pyridin-3-yl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2,5-Difluoro-4-sulfamoyl-phenyl)-quinolin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    2,5-Difluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinolin-8-yl}-benzenesulfonamide;    4-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-8-(6-methoxy-2-methyl-pyridin-3-yl)-quinoline;    8-(4-Fluoro-6-methoxy-pyridin-3-yl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinoline;    8-(2,5-Difluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinoline;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinolin-8-yl}-benzenesulfonamide;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinolin-8-yl}-benzonitrile;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinolin-8-yl}-N-propionyl-benzenesulfonamide;    8-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-quinoline;    2,5-Difluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinolin-8-yl}-benzenesulfonamide;    4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-8-(6-methoxy-2-methyl-pyridin-3-yl)-quinoline;    8-(4-Fluoro-6-methoxy-pyridin-3-yl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinoline;    8-(2,5-Difluoro-4-methanesulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinoline;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinolin-8-yl}-benzenesulfonamide;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinolin-8-yl}-benzonitrile;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinolin-8-yl}-N-propionyl-benzenesulfonamide; and    8-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-quinoline; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         52 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[8-(2-Fluoro-4-methanesulfonyl-phenyl)-pyrido[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2-Fluoro-4-propionylsulfamoyl-phenyl)-pyrido [3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Cyano-2-fluoro-phenyl)-pyrido[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2-Fluoro-4-sulfamoyl-phenyl)-pyrido[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2,5-Difluoro-4-methanesulfonyl-phenyl)-pyrido[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(4-Fluoro-6-methoxy-pyridin-3-yl)-pyrido[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(6-Methoxy-2-methyl-pyridin-3-yl)-pyrido [3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[8-(2,5-Difluoro-4-sulfamoyl-phenyl)-pyrido[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    8-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidine;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidin-8-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidin-8-yl}-benzonitrile;    3-Fluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidin-8-yl}-benzenesulfonamide;    8-(2,5-Difluoro-4-methanesulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidine;    8-(4-Fluoro-6-methoxy-pyridin-3-yl)-4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidine;    4-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-8-(6-methoxy-2-methyl-pyridin-3-yl)-pyrido[3,4-d]pyrimidine;    2,5-Difluoro-4-{4-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrido[3,4-d]pyrimidin-8-yl}-benzenesulfonamide;    8-(2-Fluoro-4-methanesulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidine;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidin-8-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidin-8-yl}-benzonitrile;    3-Fluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidin-8-yl}-benzenesulfonamide;    8-(2, 5-Difluoro-4-methanesulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidine;    8-(4-Fluoro-6-methoxy-pyridin-3-yl)-4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidine;    4-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-8-(6-methoxy-2-methyl-pyridin-3-yl)-pyrido[3,4-d]pyrimidine; and    2,5-Difluoro-4-{4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrido[3,4-d]pyrimidin-8-yl}-benzenesulfonamide; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         53 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidine;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidine;    7-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-pyrazolo[1,5-a]pyrimidine;    2,5-Difluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    4-[3-(2-Fluoro-4-methanesulfonyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-propionylsulfamoyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Cyano-2-fluoro-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-sulfamoyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Fluoro-6-methoxy-pyridin-3-yl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(6-Methoxy-2-methyl-pyridin-3-yl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-sulfamoyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidine;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidine;    7-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-pyrazolo[1,5-a]pyrimidine;    2,5-Difluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    4-[3-(2-Fluoro-4-methanesulfonyl-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-propionylsulfamoyl-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Cyano-2-fluoro-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-sulfamoyl-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Fluoro-6-methoxy-pyridin-3-yl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(6-Methoxy-2-methyl-pyridin-3-yl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-sulfamoyl-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    2,5-Difluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    7-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-2-methyl-pyrazolo[1,5-a]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-pyrazolo[1,5-a]pyrimidine;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-pyrazolo[1,5-a]pyrimidine;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-pyrazolo[1,5-a]pyrimidine;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidine;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidine;    7-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-2-methyl-pyrazolo[1,5-a]pyrimidine; and    2,5-Difluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-pyrazolo[1,5-a]pyrimidin-3-yl}-benzenesulfonamide; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         54 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[3-(2-Fluoro-4-methanesulfonyl-phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-propionylsulfamoyl-phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Cyano-2-fluoro-phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-sulfamoyl-phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Fluoro-6-methoxy-pyridin-3-yl)-1-methyl-]1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(6-Methoxy-2-methyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-sulfamoyl-phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    7-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    2,5-Difluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidine;    7-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidine; and    2,5-Difluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide; or    a pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         55 . The compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 4-[3-(2-Fluoro-4-methanesulfonyl-phenyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-propionylsulfamoyl-phenyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Cyano-2-fluoro-phenyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2-Fluoro-4-sulfamoyl-phenyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(4-Fluoro-6-methoxy-pyridin-3-yl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(6-Methoxy-2-methyl-pyridin-3-yl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    4-[3-(2,5-Difluoro-4-sulfamoyl-phenyl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-7-yloxy]-piperidine-1-carboxylic acid isopropyl ester;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    7-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    2,5-Difluoro-4-{7-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2-Fluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-N-propionyl-benzenesulfonamide;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzonitrile;    3-Fluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide;    3-(2,5-Difluoro-4-methanesulfonyl-phenyl)-7-[4-(3-isopropyl-[l,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    3-(4-Fluoro-6-methoxy-pyridin-3-yl)-7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidine;    7-[4-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-3-(6-methoxy-2-methyl-pyridin-3-yl)-2-methyl-2H-pyrazolo[4,3-d]pyrimidine; and    2,5-Difluoro-4-{7-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexyloxy]-2-methyl-2H-pyrazolo[4,3-d]pyrimidin-3-yl}-benzenesulfonamide; or    pharmaceutically acceptable salt, hydrate or solvate thereof.    
     
     
         56 . A pharmaceutical composition comprising at least one compound according to  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         57 . A method for treatment of a metabolic-related disorder in an individual comprising administering to said individual in need of such treatment a therapeutically effective amount of a compound according to any  claim 1 .  
     
     
         58 . The method according to  claim 57  wherein said metabolic-related disorder is selected from the group consisting of type I diabetes, type II diabetes, inadequate glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia and syndrome X.  
     
     
         59 . The method according to  claim 58  wherein said metabolic-related disorder is type II diabetes.  
     
     
         60 . The method according to  claim 58  wherein said metabolic-related disorder is hyperglycemia.  
     
     
         61 . The method according to  claim 58  wherein said metabolic-related disorder is hyperlipidemia.  
     
     
         62 . The method according to  claim 58  wherein said metabolic-related disorder is hypertriglyceridemia.  
     
     
         63 . The method according to  claim 58  wherein said metabolic-related disorder is type I diabetes.  
     
     
         64 . The method according to  claim 58  wherein said metabolic-related disorder is dyslipidemia.  
     
     
         65 . The method according to  claim 58  wherein said metabolic-related disorder is syndrome X.  
     
     
         66 . The method according to  claim 57  wherein said individual is a mammal.  
     
     
         67 . The method according to  claim 66  wherein said mammal is a human.  
     
     
         68 . A method of decreasing food intake of an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound of  claim 1 .  
     
     
         69 . A method of inducing satiety in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 1 .  
     
     
         70 . A method of controlling or decreasing weight gain of an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 1 .  
     
     
         71 . The method according to  claim 70  wherein said individual is a mammal.  
     
     
         72 . The method according to  claim 71  wherein said mammal is a human.  
     
     
         73 . The method according to  claim 72  wherein said human has a body mass index of about 18.5 to about 45.  
     
     
         74 . The method according to  claim 72  wherein said human has a body mass index of about 25 to about 45.  
     
     
         75 . The method according to  claim 72  wherein said human has a body mass index of about 30 to about 45.  
     
     
         76 . The method according to  claim 72  wherein said human has a body mass index of about 35 to about 45.  
     
     
         77 . A method of modulating a RUP3 receptor in an individual comprising contacting the receptor with a compound according to  claim 1 .  
     
     
         78 . The method of modulating the RUP3 receptor according to  claim 77  wherein said compound is an agonist.  
     
     
         79 . The method of modulating the RUP3 receptor according to  claim 77  wherein said modulation of the RUP3 receptor is treatment of a metabolic-related disorder.  
     
     
         80 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is selected from the group consisting of type I diabetes, type II diabetes, inadequate glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia or syndrome X.  
     
     
         81 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is type II diabetes.  
     
     
         82 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is insulin resistance.  
     
     
         83 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is hyperglycemia.  
     
     
         84 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is hyperlipidemia.  
     
     
         85 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is hypertriglyceridemia.  
     
     
         86 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is type I diabetes.  
     
     
         87 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is dyslipidemia.  
     
     
         88 . The method of modulating the RUP3 receptor according to  claim 79  wherein said metabolic-related disorder is syndrome X.  
     
     
         89 . The method of modulating the RUP3 receptor according to  claim 77  wherein said individual is a mammal.  
     
     
         90 . The method of modulating the RUP3 receptor according to  claim 89  wherein said mammal is a human.  
     
     
         91 . The method of modulating the RUP3 receptor according to  claim 77  wherein said modulation of the RUP3 receptor reduces food intake of said individual.  
     
     
         92 . The method of modulating the RUP3 receptor according to  claim 77  wherein said modulation of the RUP3 receptor induces satiety in said individual.  
     
     
         93 . The method of modulating the RUP3 receptor according to  claim 77  wherein said modulation of the RUP3 receptor controls or reduces weight gain of said individual.  
     
     
         94 . The method of modulating the RUP3 receptor according to  claim 93  wherein said individual is a mammal.  
     
     
         95 . The method of modulating the RUP3 receptor according to  claim 94  wherein said mammal is a human.  
     
     
         96 . The method according to  claim 95  wherein said human has a body mass index of about 18.5 to about 45.  
     
     
         97 . The method according to  claim 95  wherein said human has a body mass index of about 25 to about 45.  
     
     
         98 . The method according to  claim 95  wherein said human has a body mass index of about 30 to about 45.  
     
     
         99 . The method according to  claim 95  wherein said human has a body mass index of about 35 to about 45.  
     
     
         100 . The method of producing a pharmaceutical composition comprising admixing at least one compound of  claim 1  and a pharmaceutically acceptable carrier.