US2002161001A1PendingUtilityA1

Heterocyclic compounds, which are inhibitors of the enzyme DPP-IV

Priority: Jul 4, 2000Filed: Aug 22, 2001Published: Oct 31, 2002
Est. expiryJul 4, 2020(expired)· nominal 20-yr term from priority
C07D 473/08C07D 473/04A61P 43/00A61P 3/10A61P 3/04
44
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Claims

Abstract

The present invention relates to therapeutically active and selective inhibitors of the enzyme DPP-IV, pharmaceutical compositions comprising the compounds and the use of such compounds for and the manufacture of medicaments for treating diseases that are associated with proteins which are subject to inactivation by DPP-IV, such as type 2 diabetes and obesity, as well as methods for treating diseases that are associated with proteins which are subject to inactivation by DPP-IV, such as type 2 diabetes and obesity

Claims

exact text as granted — not AI-modified
1 . A compound of formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 n and m is one or two independently;  
 R 1  is C═O; C═S; C 1 -C 2  alkyl; C 2  alkenyl; C 2  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl; heteroaryl-C 1 -C 3  alkyl, wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl, or heteroaryl-C 1 -C 3  alkyl is optionally substituted with one or more R 4  independently;  
 R 2  is H; C 1 -C 7  alkyl; C 2 -C 7  alkenyl; C 2 -C 7  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl-C 1 -C 3  alkyl; heteroaryl; cyano; halogen; hydroxy, nitro; —SH; —SR 5 ; —SOR 5 ; —SO 2 R 5 ; carboxy; —CO 2 R 4 ; —CON(R 5 ) 2 ; C 1 -C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy, aryloxy; heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl, heteroaryl-C 1 -C 3  alkyl, alkyloxy; alkenyloxy; alkynyloxy, aryloxy, or heteroaryloxy is optionally substituted with one or more R 11  independently;  
 R 3  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl-C 1 -C 3  alkyl; heteroaryl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; carboxy; cyano; nitro; halogen; hydroxy; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl-C 1 -C 3  alkyl, heteroaryl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system;  
 R 4 , R 11 , R 12 , and R 17  are independently C 1 -C 10  alkyl; C 2 -C 10 alkenyl; C 2 -C 10 alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl; cyano; halogen; hydroxy, nitro; trifluormethyl; N(R 13 ) 2 ; ═O; ═S; C 1 C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy; aryloxy; heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, alkyloxy; alkenyloxy; alkynyloxy, aryloxy, or heteroaryloxy is optionally substituted with one or more R 8  independently; two R 4  attached to the same carbon atom may form a spiroheterocyclic system, preferably hydantoine; thiohydantoine; oxazolidine-2,5-dione;  
 R 5  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 5  alkyl; heteroaryl; heteroaryl-C 1 -C 5  alkyl , wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl alkyl, heteroaryl, or heteroaryl alkyl is optionally substituted with one or more R 14  independently;  
 R 6  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl, wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 15  independently;  
 R 7 is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl, wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 16  independently;  
 R 8 , R 14 , R 15 , and R 16  are independently H; nitro; —OCH 3 ; cyano; halogen; —OH; —SH; —SCH 3 ;  
 R 9  is H; halogen; C 1 -C 10  alkyl or aryl, wherein alkyl or aryl is optionally substituted with one or more R 17  independently  
 R 10  is H; halogen;  
 or, R 9  and R 10  may be connected to form a cyclopropyl ring;  
 R 13  is H; C 1 -C 10  alkyl or aryl;  
 or a salt thereof with a pharmaceutically acceptable acid or base;  
 with the exception of the following compounds:  
 1,3-dimethyl-7-(2-oxo-propyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 1,3,1′,3′,7′-pentamethyl-8-piperazin-1-yl-3,7,3′,7′-tetrahydro-7,8′-methanediyl-bis-purine-2,6-dione,  
 3,4,5-trimethoxy-benzoic acid 2-(1,3-dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydro-purin-7-yl)-ethyl ester,  
 7-[2-Hydroxy-3-(4-methoxy-phenoxy)-propyl]-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-[2-hydroxy-2-(4-nitro-phenyl)-ethyl]-3-methyl-8-piperazin-1-yl-3,7,8,9-tetrahydro-purine-2,6-dione,  
 7-Benzyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-(4-Chloro-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-(2-Chloro-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-Ethyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 3-Methyl-8-piperazin-1-yl-1,7-dipropyl-3,7-dihydro-purine-2,6-dione,  
 3-Methyl-7-(3-methyl-butyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-Butyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 3-Methyl-7-(3-phenyl-propyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-But-2-enyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 7-(3-Chloro-but-2-enyl)-3-methyl-8-piperazin- -yl-3,7-dihydro-purine-2,6-dione,  
 7-Heptyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 3-Methyl-7-(3-phenyl-ethyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 3-Methyl-7-(3-methyl-benzyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione,  
 3-Methyl-7-propyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione, and  
 3-Methyl-7-pentyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione.  
 
     
     
         2 . A compound of formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 n and m is one or two independently;  
 with the proviso that if n is 2 then m is also 2;  
 R 1  is C═O; C═S; C 1 -C 2  alkyl; C 2  alkenyl; C 2  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl; heteroaryl-C 1 -C 3  alkyl, wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl, or heteroaryl-C 1 -C 3  alkyl is optionally substituted with one or more R 4  independently;  
 R 2  is H; C 1 -C 7  alkyl; C 2 -C 7  alkenyl; C 2 -C 7  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl-C 1 -C 3  alkyl; heteroaryl; cyano; halogen; hydroxy, nitro; —SH; —SR 5 ; —SOR 5 ; —SO 2 R 5 ; carboxy; —CO 2 R 4 ; —CON(R 5 ) 2 ; C 1 -C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy, aryloxy; heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl, heteroaryl-C 1 -C 3  alkyl, alkyloxy; alkenyloxy; alkynyloxy, aryloxy, or heteroaryloxy is optionally substituted with one or more R 11  independently;  
 R 3  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl-C 1 -C 3  alkyl; heteroaryl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; carboxy; cyano; nitro; halogen; hydroxy; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl-C 1 -C 3  alkyl, heteroaryl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system;  
 R 4 , R 11 , R 12 , and R 17  are independently C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl; cyano; halogen; hydroxy, nitro; trifluormethyl; N(R 13 ) 2 ; ═O; ═S; C 1 -C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy; aryloxy; heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, alkyloxy; alkenyloxy; alkynyloxy, aryloxy, or heteroaryloxy is optionally substituted with one or more R 8  independently; two R 4  attached to the same carbon atom may form a spiroheterocyclic system, preferably hydantoine; thiohydantoine; oxazolidine-2,5-dione;  
 R 5  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 5  alkyl; heteroaryl; heteroaryl-C,-C 5  alkyl , wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl alkyl, heteroaryl, or heteroaryl alkyl is optionally substituted with one or more R 14  independently;  
 R 6  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl, wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 15  independently;  
 R 7  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl, wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 16  independently;  
 R 8 , R 14 , R 15 , and R 16  are independently H; nitro; —OCH 3 ; cyano; halogen; —OH; —SH; —SCH 3 ;  
 R 9  is H; halogen; C 1 -C 10  alkyl optionally substituted with one or more R 17  independently  
 R 10  is H; halogen;  
 or, R 9  and R 10  may be connected to form a cyclopropyl ring;  
 R 13  is H; C 1 -C 10  alkyl or aryl;  
 or a salt thereof with a pharmaceutically acceptable acid or base;  
 
     
     
         3 . A compound of formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 n and m is one or two independently;  
 R 1  is C═O; C═S; C 1 -C 2  alkyl; C 2  alkenyl; C 2  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl; heteroaryl-C 1 -C 3  alkyl, wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl, or heteroaryl-C 1 -C 3  alkyl is optionally substituted with one or more R 4  independently;  
 R 2  is H; C 1 -C 7  alkyl; C 2 -C 7  alkenyl; C 2 -C 7  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl-C 1 -C 3  alkyl; heteroaryl; cyano; halogen; hydroxy, nitro; —SH; —SR 5 ; —SOR 5 ; —SO 2 R 5 ; carboxy; —CO 2 R 4 ; —CON(R 5 ) 2 ; C 1 -C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy, aryloxy; heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl, heteroaryl-C 1 -C 3  alkyl, alkyloxy; alkenyloxy; alkynyloxy, aryloxy, or heteroaryloxy is optionally substituted with one or more R 11  independently;  
 R 3  is C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 3  alkyl; heteroaryl-C 1 -C 3  alkyl; heteroaryl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; carboxy; cyano; nitro; halogen; hydroxy; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl-C 1 -C 3  alkyl, heteroaryl-C 1 -C 3  alkyl, heteroaryl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system;  
 R 4 , R 11 , R 12 , and R 17  are independently C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl; cyano; halogen; hydroxy, nitro; trifluormethyl; N(R 13 ) 2 ; ═O; ═S; C 1 -C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy; aryloxy; heteroaryloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, alkyloxy; alkenyloxy; alkynyloxy, aryloxy, or heteroaryloxy is optionally substituted with one or more R 8  independently; two R 4  attached to the same carbon atom may form a spiroheterocyclic system, preferably hydantoine; thiohydantoine; oxazolidine-2,5-dione;  
 R 5  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; aryl-C 1 -C 5  alkyl; heteroaryl; heteroaryl-C 1 -C 5  alkyl , wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, aryl alkyl, heteroaryl, or heteroaryl alkyl is optionally substituted with one or more R 14  independently;  
 R 6  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl, wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 15  independently;  
 R 7  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl, wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 16  independently;  
 R 8 , R 14 , R 15 , and R 16  are independently H; nitro; —OCH 3 ; cyano; halogen; —OH; —SH; —SCH 3 ;  
 R 9  is H; halogen; C 1 -C 10  alkyl optionally substituted with one or more R 17  independently  
 R 10  is H; halogen;  
 or, R 9  and R 10  may be connected to form a cyclopropyl ring;  
 R 13  is H; C 1 -C 10  alkyl or aryl;  
 or a salt thereof with a pharmaceutically acceptable acid or base;  
 
     
     
         4 . A compound according to any one of the  claims 1  to  3  wherein R 1  is C═O; C 1 -C 2  alkyl; C 2  alkenyl; C 2  alkynyl ; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; or heteroaryl, wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl is optionally substituted with one or more R 4  independently.  
     
     
         5 . A compound according to  claim 4  wherein R 1  is C═O; C 1 -C 2  alkyl; C 3 -C 7  cycloalkyl; aryl; or heteroaryl, wherein each alkyl, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more R 4  independently.  
     
     
         6 . A compound according to  claim 5  wherein R 1  is C═O or aryl optionally substituted with one or more R 4  independently.  
     
     
         7 . A compound according to  claim 6  wherein R 1  is aryl optionally substituted with one or more R 4  independently.  
     
     
         8 . A compound according to  claim 7  wherein R 1  is aryl.  
     
     
         9 . A compound according to  claim 8  wherein R 1  is phenyl.  
     
     
         10 . A compound according to any one of the  claims 1  to  9  wherein R 2  is H; C 1 -C 7  alkyl; C 2 -C 7  alkenyl; C 2 -C 7  alkynyl; C 3 -C 7  cycloalkyl; C 3 -C 7  cycloheteroalkyl; aryl; heteroaryl; cyano; halogen; hydroxy, nitro; —SH; —SR 5 ; —SOR 5 ; —SO 2 R 5 ; —CO 2 R 4 ; C 1 -C 10  alkyloxy; C 2 -C 10  alkenyloxy; C 2 -C 10  alkynyloxy, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, alkyloxy, alkenyloxy, or alkynyloxy is optionally substituted with one or more R 11  independently.  
     
     
         11 . A compound according to  claim 10  wherein R 2  is H; C 1 -C 7  alkyl; C 3 -C 7  cycloheteroalkyl; aryl; cyano; halogen; nitro; —SR 5 ; —SO 2 R 5 ; —CO 2 R 4 ; or C 1 -C 10  alkyloxy; wherein each alkyl, cycloheteroalkyl, aryl, or alkyloxy is optionally substituted with one or more R 11  independently.  
     
     
         12 . A compound according to  claim 11  wherein R 2  is H; C 1 -C 7  alkyl; C 3 -C 7  cycloheteroalkyl; aryl; cyano; halogen; —CO 2 R 4 ; or C 1 -C 10  alkyloxy; wherein each alkyl, cycloheteroalkyl, aryl, or alkyloxy is optionally substituted with one or more R 11  independently.  
     
     
         13 . A compound according to  claim 12  wherein R 2  is H; C 1 -C 7  alkyl; cyano; halogen; or C 1 -C 10  alkyloxy; wherein each alkyl or alkyloxy is optionally substituted with one or more R 11  independently.  
     
     
         14 . A compound according to  claim 13  wherein R 2  is H; cyano or halogen.  
     
     
         15 . A compound according to  claim 14  wherein R 2  is H.  
     
     
         16 . a compound according to any one of the claims  1 ,  2  and  4  to  15  wherein R 3  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; aryl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; cyano; nitro; halogen; hydroxy; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system.  
     
     
         17 . A compound according to  claim 16  wherein R 3  is H; C 1 -C 10  alkyl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; hydroxy; wherein alkyl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system.  
     
     
         18 . A compound according to  claim 17  wherein R 3  is H or C 1 -C 10  alkyl optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system.  
     
     
         19 . A compound according to  claim 18  wherein R 3  is H or C 1 -C 10  alkyl.  
     
     
         20 . A compound according to  claim 19  wherein R 3  is methyl, ethyl, or isopropyl.  
     
     
         21 . A compound according to  claim 19  wherein R 3  is H.  
     
     
         22 . A compound according to  claim 3  wherein R 3  is C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; aryl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; cyano; nitro; halogen; hydroxy; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system.  
     
     
         23 . A compound according to  claim 22  wherein R 3  is C 1 -C 10  alkyl; C 1 -C 10 alkyl-O-C 1 -C 5 alkyl; hydroxy; wherein alkyl, or alkyl-O-alkyl is optionally substituted with one or more R 12  independently; two R 3 attached to the same carbon atom may form a spiro system.  
     
     
         24 . A compound according to  claim 23  wherein R 3  is C 1 -C 10  alkyl optionally substituted with one or more R 12  independently; two R 3  attached to the same carbon atom may form a spiro system.  
     
     
         25 . A compound according to  claim 24  wherein R 3  is C 1 -C 10  alkyl.  
     
     
         26 . A compound according to  claim 30  wherein R 3  is methyl, ethyl, or isopropyl  
     
     
         27 . A compound according to any one of the  claims 1  to  26  wherein R 4  is C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; aryl; heteroaryl; cyano; halogen; hydroxy, nitro; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more R 8  independently.  
     
     
         28 . A compound according to  claim 27  wherein R 4  is C 1 -C 10  alkyl; C 2 -C 10  alkenyl; or C 2 -C 10  alkynyl; wherein each alkyl, alkenyl, or alkynyl is optionally substituted with one or more R 8  independently.  
     
     
         29 . A compound according to  claim 28  wherein R 4  is C 1 -C 10  alkyl optionally substituted with one or more R 8  independently.  
     
     
         30 . A compound according to  claim 29  wherein R 4  is C 1 -C 10  alkyl.  
     
     
         31 . A compound according to  claim 30  wherein R 4  is methyl.  
     
     
         32 . A compound according to any one of the  claims 1  to  31  wherein R 5  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; aryl; heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more R 14  independently.  
     
     
         33 . A compound according to  claim 32  wherein R 5  is C 1 -C 10  alkyl or aryl; wherein each alkyl or aryl is optionally substituted with one or more R 14  independently.  
     
     
         34 . A compound according to any one of the  claims 1  to  33  wherein R 6  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; C 3 -C 7  cycloalkyl; or aryl; wherein each each alkyl, alkenyl, alkynyl, cycloalkyl, or aryl is optionally substituted with one or more R 15  independently.  
     
     
         35 . A compound according to  claim 34  wherein R 6  is H; C 1 -C 10  alkyl; or C 2 -C 10  alkenyl; wherein each each alkyl or alkenyl is optionally substituted with one or more R 15  independently.  
     
     
         36 . A compound according to  claim 35  wherein R 6  is H or C 1 -C 10  alkyl optionally substituted with one or more R 15  independently.  
     
     
         37 . A compound according to  claim 36  wherein R 6  is H.  
     
     
         38 . A compound according to  claim 36  wherein R 6  is C 1 -C 10  alkyl optionally substituted with one or more R 15  independently.  
     
     
         39 . A compound according to  claim 38  wherein R 6  is C 1 -C 10  alkyl.  
     
     
         40 . A compound according to  claim 39  wherein R 6  is methyl.  
     
     
         41 . A compound according to any one of the  claims 1  to  40  wherein R 7  is H; C 1 -C 10  alkyl; C 2 -C 10  alkenyl; or C 2 -C 10  alkynyl, wherein each each alkyl, alkenyl, or alkynyl is optionally substituted with one or more R 16  independently.  
     
     
         42 . A compound according to  claim 41  wherein R 7  is C 1 -C 10  alkyl optionally substituted with one or more R 16  independently.  
     
     
         43 . A compound according to  claim 42  wherein R 7  is C 1 -C 10  alkyl.  
     
     
         44 . A compound according to any one of the  claims 1  to  43  wherein R 8  is —OCH 3 .  
     
     
         45 . A compound according to any one of the  claims 1  to  44  wherein R 9  is aryl.  
     
     
         46 . A compound according to any one of the  claims 1  to  45  wherein R 11  is C 1 -C 10  alkyl; aryl; cyano; halogen; wherein each alkyl or aryl is optionally substituted with one or more R 8  independently.  
     
     
         47 . A compound according to  claim 46  wherein R 11  is halogen.  
     
     
         48 . A compound according to any one of the  claims 1  to  47  wherein R 12  is C 1 -C 10  alkyl; C 2 -C 10  alkenyl; C 2 -C 10  alkynyl; aryl; heteroaryl; cyano; halogen; hydroxy, nitro; wherein each alkyl, alkenyl, alkynyl, aryl, heteroaryl is optionally substituted with one or more R 8  independently.  
     
     
         49 . A compound according to  claim 48  wherein R 12  is aryl; heteroaryl; or hydroxy; wherein each aryl and heteroaryl is optionally substituted with one or more R 8  independently.  
     
     
         50 . A compound according to  claim 49  wherein R 12  is phenyl, pyridyl, or pyrrolidinyl.  
     
     
         51 . A compound according to  claim 49  wherein R 12  is hydroxy.  
     
     
         52 . A compound according to any one of the  claims 1  to  51  wherein R 14  is halogen.  
     
     
         53 . A compound that fulfils all of the following three criteria: 
 1. Contains the structural element of Formula III                           wherein 
 n and m is one or two independently;  
   2. has a molecular weight of 500 daltons or less;    3. has a DPP-IV inhibition constant Ki of 500 nM or less    
     
     
         54 . A compound according to any one of the preceding claims selected from the following: 
 7-Benzyl-8-(6-hydroxymethyl-[1,4]diazepan-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione.    7-Benzyl-8-(6-hydroxy-[1,4]diazepan-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    7-Benzyl-8-(3-hydroxymethyl-[1,4]diazepan-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    7-Benzyl-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-7-(4-methylbenzyl)-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    3-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-ylmethyl) benzonitrile    2-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-ylmethyl) benzonitrile    1,3-Dimethyl-7-(1-phenylethyl)-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-(2-Iodobenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-8-piperazin-1-yl-7-(2-trifluoromethylbenzyl)-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-7-naphthalen-1-ylmethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-7-naphthalen-2-ylmethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-(3-Bromobenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-Benzyl-8-(3-isopropylpiperazin-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    1,3-Dimethyl-7-(2-oxo-2-pyrrolidin-1-yl-ethyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    2-(8-[1,4]Diazepan-1-yl-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    7-(2-Difluoromethoxy-benzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    7-(2,3-Dimethoxy-benzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    1,3-Dimethyl-8-piperazin-1-yl-7-(2-trifluoromethoxy-benzyl)-3,7-dihydro-purine-2,6-dione    1,3-Dimethyl-8-piperazin-1-yl-7-(2-trifluoromethylsulfanyl-benzyl)-3,7-dihydro-purine-2,6-dione    4-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydro-purin-7-yl)-butyronitrile    R)-7-Benzyl-8-(3-isopropylpiperazin-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    S)-7-Benzyl-8-(3-isopropylpiperazin-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    7-Benzyl-8-(6,9-diazaspiro[4.5]dec-9-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    7-Benzyl-8-(piperazin-3-spiro-3′-bicyclo[2,2,1]heptane-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-methoxy-benzyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1,3-dimethyl-7-naphthalen-1-ylmethyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-fluoro-benzyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1,3-dimethyl-7-(2-methyl-benzyl)-3,7-dihydro-purine-2,6-dione    7-(2-Chloro-benzyl)-8-[1,4]diazepan-1-yl-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    7-(2-Bromo-benzyl)-8-[1,4]diazepan-1-yl-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1,3-dimethyl-7-(2-trifluoromethyl-benzyl)-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1,3-dimethyl-7-(2-nitro-benzyl)-3,7-dihydro-purine-2,6-dione    3-Benzyl-8-piperazin-1-yl-7-(2-trifluoromethyl-benzyl)-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-1-(2-hydroxy-ethyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    3-Benzyl-7-phenethyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-8-[1,4]diazepan-1-yl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-8-[1,4]diazepan-1-yl-1-propyl-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-8-[1,4]diazepan-1-yl-1-(2-hydroxy-ethyl)-3,7-dihydro-purine-2,6-dione    2-(3,7-Dibenzyl-8-[1,4]diazepan-1-yl-2,6-dioxo-2,3,6,7-tetrahydro-purin-1-yl)-N,N-diethyl-acetamide    1,3,7-Tribenzyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    1,3,7-Tribenzyl-8-[1,4]diazepan-1-yl-3,7-dihydro-purine-2,6-dione    (S)-7-Benzyl-8-(3-benzyloxymethylpiperazin-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    3,7-Dibenzyl-8-piperazin-1-yl-1-propyl-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-8-[1,4]diazepan-1-yl-1-propyl-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    3,7-Dibenzyl-8-[1,4]diazepan-1-yl-3,7-dihydro-purine-2,6-dione    2-(3-Benzyl-2,6-dioxo-8-piperazin-1-yl-1-propyl-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    2-(3-Benzyl-8-[1,4]diazepan-1-yl-2,6-dioxo-1-propyl-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    2-(3-Benzyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    2-(3-Benzyl-8-[1,4]diazepan-1-yl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    3-Benzyl-7-(2-iodo-benzyl)-8-piperazin-1-yl-1-propyl-3,7-dihydro-purine-2,6-dione    3-Benzyl-8-[1,4]diazepan-1-yl-7-(2-iodo-benzyl)-1-propyl-3,7-dihydro-purine-2,6-dione    3-Benzyl-7-(2-iodo-benzyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    3-Benzyl-8-[1,4]diazepan-1-yl-7-(2-iodo-benzyl)-3,7-dihydro-purine-2,6-dione    7-Benzyl-3-methyl-8-piperazin-1-yl-1-propyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-1-propyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione    2-(3-Methyl-2,6-dioxo-8-piperazin-1-yl-1-propyl-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    2-(8-[1,4]Diazepan-1-yl-3-methyl-2,6-dioxo-1-propyl-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    2-(8-[1,4]Diazepan-1-yl-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl)-benzonitrile    7-(2-Iodo-benzyl)-3-methyl-8-piperazin-1-yl-1-propyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-1-propyl-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    3-Benzyl-8-[1,4]diazepan-1-yl-(3-hydroxy-propyl)-7-(2-iodo-benzyl)-3,7-dihydro-purine-2,6-dione    3-Benzyl-8-[1,4]diazepan-1-yl-1-(2-ethoxy-ethyl)-7-(2-iodo-benzyl)-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-1-(3-phenyl-allyl)-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-1-(2-oxo-2-phenyl-ethyl)-3,7-dihydro-purine-2,6-dione    2-(7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-2,6-dioxo-2,3,6,7-tetrahydro-purin-1-ylmethyl)-benzonitrile    (7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-2,6-dioxo-2,3,6,7-tetrahydro-purin-1-yl)-acetonitrile    3-Methyl-7-(2-methyl-thiazol-4-ylmethyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-3-methyl-7-(2-methyl-thiazol-4-ylmethyl)-3,7-dihydro-purine-2,6-dione    3-Methyl-7-(2-oxo-2-phenyl-ethyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-3-methyl-7-(2-oxo-2-phenyl-ethyl)-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-3-methyl-7-phenethyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(3-hydroxy-propyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(3-Hydroxy-propyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2-ethoxy-ethyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(2-Ethoxy-ethyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-1-(2-phenoxy-ethyl)-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-1-[2-(2-methoxy-ethoxy)-ethyl]-3-methyl-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-1-[2-(2-methoxy-ethoxy)-ethyl]-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(3,5-dimethoxy-benzyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-1-(3-methoxy-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    7-Biphenyl-2-ylmethyl-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione    7-(2-Bromo-benzyl)-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione    7-(2-Chloro-benzyl)-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-(3,5-dimethyl-piperazin-1-yl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    7-(4-Methoxybenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    (1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-yl)-phenylacetic acid methyl ester    7-(5-Chloro-2-nitrobenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    4-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-ylmethyl) benzonitrile    7-(4-Methanesulfonylbenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-(2-Fluoro-6-nitrobenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-(4-Benzyloxybenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-(2,4-Dichlorobenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-8-piperazin-1-yl-7-(4-trifluoromethylbenzyl)-3,7-dihydropurine-2,6-dione    7-Biphenyl-4-ylmethyl-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    3-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-ylmethyl) benzoic acid methyl ester    4-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-ylmethyl) benzoic acid methyl ester    7-Biphenyl-2-ylmethyl-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    7-(4-tert-Butylbenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-8-piperazin-1-yl-7-(4-trifluoromethoxybenzyl)-3,7-dihydropurine-2,6-dione    7-(3,4-Dichlorobenzyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione    1,3-Dimethyl-8-piperazin-1-yl-7-(4-[1,2,3]thiadiazol-4-ylbenzyl)-3,7-dihydropurine-2,6-dione    4-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydropurin-7-ylmethyl)-3-methoxybenzoic acid methyl ester    7-Cyclohexylmethyl-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-(2,5-diaza-bicyclo[2.2.1]hept-2-yl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    8-(6-Benzyl-[1,4]diazepan-1-yl)-7-(2-iodo-benzyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    (S)-7-Benzyl-8-(3-hydroxymethylpiperazin-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    8-[1,4]Diazepan-1-yl-1,3-dimethyl-7-(2-oxo-2-pyrrolidin-1-yl-ethyl)-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-1,3-dimethyl-8-(6-pyridin-2-ylmethyl-[1,4]diazepan-1-yl)-3,7-dihydro-purine-2,6-dione    7-(2-Bromo-benzyl)-1,3-dimethyl-8-(6-pyridin-2-ylmethyl-[1,4]diazepan-1-yl)-3,7-dihydro-purine-2,6-dione    (S) 7-Benzyl-8-(3-benzyl-piperazin-1-yl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-1,3-dimethyl-8-(3-phenethyl-piperazin-1-yl)-3,7-dihydro-purine-2,6-dione    (R)-7-Benzyl-8-(3-benzylpiperazin-1-yl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione    7-Benzyl-8-(3-(2-hydroxy-benzyl)-piperazin-1-yl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-(3-(2-methoxy-benzyl)-piperazin-1-yl)1,3-dimethyl-3,7-dihydro-purine-2,6-dione    (R) 7-Benzyl-8-(3-(4-methoxy-benzyl)-piperazin-1-yl)1,3-dimethyl-3,7-dihydro-purine-2,6-dione    (R)-7-Benzyl-8-(3-(4-hydroxy-benzyl)-piperazin-1-yl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    (R)-7-Benzyl-1,3-dimethyl-8-(3-(4-nitro-benzyl)-piperazin-1-yl)-3,7-dihydro-purine-2,6-dione    (R)-7-Benzyl-8-(3-(4-fluoro-benzyl)-piperazin-1-yl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione    (R)-4-(4-(7-Benzyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-piperazin-2-ylmethyl)-benzonitrile    (R)-6-(8-(3-Benzyl-piperazin-1-yl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl)-nicotinonitrile    (R)-7-Benzyl-1,3-dimethyl-8-(3-thiazol-4-ylmethyl-piperazin-1-yl)-3,7-dihydro-purine-2,6-dione    (R)-2-[1,3-Dimethyl-2,6-dioxo-8-(3-thiophen-2-ylmethyl-piperazin-1-yl)-1,2,3,6-tetrahydro-purin-7-ylmethyl]-benzonitrile    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-1-(tetrahydro-furan-2-ylmethyl)-3,7-dihydro-purine-2,6-dione    7-Benzyl-1-(2-cyclohexyl-ethyl)-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-1-(5-methyl-hexyl)-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-1-(3-methyl-butyl)-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-1-(2-ethoxy-ethyl)-3-methyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-1-(tetrahydro-furan-2-ylmethyl)-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-3-methyl-8-piperazin-1-yl-1-(tetrahydro-furan-2-ylmethyl)-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-1-(tetrahydro-pyran-2-ylmethyl)-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-3-methyl-8-piperazin-1-yl-1-(tetrahydro-pyran-2-ylmethyl)-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-3-methyl-1-(2-phenoxy-ethyl)-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-1-(2-methoxy-ethyl)-3-methyl-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-1-(2-methoxy-ethyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    1-(2-Benzyloxy-ethyl)-8-[1,4]diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(2-Benzyloxy-ethyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    1-(3,5-Dimethoxy-benzyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-1-(3-methoxy-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-1-(3-trifluoromethoxy-benzyl)-3,7-dihydro-purine-2,6-dione    7-(2-Iodo-benzyl)-3-methyl-8-piperazin-1-yl-1-(3-trifluoromethoxy-benzyl)-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2-hydroxy-propyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2,2-diethoxy-ethyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2,2-dimethoxy-ethyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2-[1,3]dioxolan-2-yl-ethyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(2-[1,3]Dioxolan-2-yl-ethyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    1-[1,3]Dioxolan-2-ylmethyl-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2-[1,3]dioxan-2-yl-ethyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(2-[1,3]Dioxan-2-yl-ethyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2,3-dihydroxy-propyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(2,3-Dihydroxy-propyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(3-hydroxy-2-methyl-propyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    1-(3-Hydroxy-2-methyl-propyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-3-methyl-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-3,7-dihydro-purine-2,6-dione    8-[1,4]Diazepan-1-yl-1-(2-fluoro-ethyl)-7-(2-iodo-benzyl)-3-methyl-3,7-dihydro-purine-2,6-dione    7-Benzyl-8-[1,4]diazepan-1-yl-1-(3-hydroxy-propyl)-3-methyl-3,7-dihydro-purine-2,6-dione    7-Biphenyl-2-ylmethyl-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione

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