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

1. A compound of formula I

wherein

each n is one or two independently

R 1 is C═O; C═S; C 1 –C 2 alkyl optionally substituted with one or more R 4 independently; C 2 alkenylene substituted with one or more R 4 independently; C 2 alkynylene; C 3 –C 7 cycloalkylene optionally substituted with one or more R 4 independently; C 3 –C 7 cycloheteroalkylene optionally substituted with one or more R 4 independently; arylene optionally substituted with one or more R 4 independently; arylene C 1 –C 3 alkylene optionally substituted with one or more R 4 independently; heteroarylene optionally substituted with one or more R 4 independently; heteroarylene C 1 –C 3 alkylene optionally substituted with one or more R 4 independently; perhalo C 1 –C 10 alkylene; and, perhalo C 1 –C 10 alkyloxyene;

R 2 is H; C 1 alkyl optionally substituted with one or more R 4 independently; C 2 –C 7 alkenyl optionally substituted with one or more R 4 independently; C 2 –C 7 alkynyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloalkyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloheteroalkyl optionally substituted with one or more R 4 independently; aryl optionally substituted with one or more R 4 independently; aryl C 1 –C 3 alkyl optionally substituted with one or more R 4 independently, heteroaryl C 1 –C 3 alkyl optionally substituted with one or more R 4 independently; heteroaryl optionally substituted with one or more R 4 independently, —SH; —SR 5 ; SOR 5 ; SO 2 R 5 ; —CHO; —CH(OR 5 ) 2 ; carboxy; —CO 2 R 4 ; NHCONNH 2 ; —NHCSNH 2 ; —NHCONH 2 ; —NHCOR 4 ; —NHSO 2 R 5 ; —O—CO—(C 1 –C 5 ) alkyl optionally substituted with one or more R 4 independently; cyano; nitro; halogen; hydroxy; perhalo C 1 –C 7 alkyl; perhalo C 1 –C 7 alkyloxy; —SO 2 NH 2 ; —SO 2 NH(R 5 ); —SO 2 (R 5 ) 2 ; —CONH 2 ; —CSNH 2 ; —CON 2 H 3 ; —CONH(R 5 ); —CON(R 5 ) 2 ; C 1 –C 10 alkyloxy optionally substituted with R 4 independently; C 2 –C 10 alkenyloxy optionally substituted with R 4 ; C 2 –C 10 alkynyloxy optionally substituted with R 4 independently, aryloxy optionally substituted with R 4 independently; heteroaryloxy optionally substituted with R 4 independently;

R 3 is H; C 1 –C 10 alkyl optionally substituted with one or more R 4 independently; C 2 –C 10 alkenyl optionally substituted with one or more R 4 independently; C 2 –C 10 alkynyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloalkyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloheteroalkyl optionally substituted with one or more R 4 independently; aryl optionally substituted with one or more R 4 independently; aryl C 1 –C 3 alkyl optionally substituted with one or more R 4 independently; heteroaryl C 1 –C 3 alkyl optionally substituted with one or more R 4 independently; heteroaryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-NH(CH 2 ) 1-4 NH-aryl optionally substituted with one or more R 4 independently; C 1 –C 19 alkyl-NH(CH 2 ) 1-4 NH-heteroaryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-O(CH 2 ) 1-4 NH-aryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-O(CH 2 ) 1-4 NH-heteroaryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-O(CH 2 ) 1-4 O-aryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-O(CH 2 ) 1-4 -heteroaryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-S(CH 2 ) 1-4 NH-aryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-S(CH 2 ) 1-4 NH-heteroaryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-S(CH 2 ) 1-4 S-aryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-S(CH 2 ) 1-4 S-heteroaryl optionally substituted with one or more R 4 independently; C 1 –C 10 alkyl-O—C 1 –C 5 alkyl optionally substituted with one or more R 4 ; —NHCOR 4 ; —NHSO 2 R 5 ; —O—SO—(C 1 –C 5 ) alkyl optionally substituted with one or more R 4 independently; —SH; —SR 5 ; —SOR 5 ; —SO 2 R 5 ; —CHO; —CH(OR 5 ) 2 ; carboxy; cyano; nitro; halogen; hydroxy; —SO 2 NH 2 ; —SO 2 NH(R 5 ); —SO 2 N(R 5 ) 2 ; —CONH 2 ; —CONH(R 5 ); —CON(R 5 ) 2 ; —CSNH 2 ; —CONHNH 2 ; —CO 2 R 4 ; —NHCNHNH 2 ; —NHCSNH 2 ; —NHCONH 2 ;

R 4 is C 1 alkyl optionally substituted with one or more R 8 independently; C 2 –C 10 alkenyl optionally substituted with one or more R 8 independently; C 2 –C 10 alkynyl optionally substituted with one or more R 8 independently; C 3 –C 7 cycloalkyl optionally substituted with one or more R 8 independently; C 3 –C 7 cycloheteroalkyl optionally substituted with one or more R 8 independently; aryl optionally substituted with one or more R 8 independently; heteroaryl optionally substituted with one or more R 8 independently; amino; amino substituted with one or more C 1 –C 10 alkyl optionally substituted with one or more R 8 ; amino substituted with one or two aryl optionally substituted with one or more R 8 independently; heteroaryl optionally substituted with one or more R 8 independently; ═O; ═S; —CO—R 5 ; —COOR 5 ; —O—CO—(C 1 –C 5 ) alkyl optionally substituted with one or more R 8 independently; NH(CH 2 ) 1-4 NH-aryl; NH(CH 2 ) 1-4 NH-heteroaryl; —NHCOR 5 ; —SOR 5 ; SO 2 R 5 ; carboxy; cyano; N-hydroxyimino; nitro; halogen; hydroxy; perhalo C 1 –C 10 alkyl; perhalo C 1 –C 10 alkyloxy; —SH; —SR 5 ; —SO 3 H; —SO 3 R 5 ; —SO 2 R 5 ; —SO 2 NH 2 ; —SO 2 NH(R 5 ); —SO 2 N(R 5 ) 2 ; CONH 2 ; —CONH(R 5 ); —CON(R 5 ) 2 ; C 1 –C 10 alkyloxy optionally substituted with one or more R 8 independently; C 2 –C 10 alkenyloxy optionally substituted with one or more R 8 independently; C 2 –C 10 alkynyloxy optionally substituted with one or more R 8 independently; aryloxy optionally substituted with one or more R 8 independently; heteroaryloxy optionally substituted with one or more R 8 independently;

and when two R 4 are attached to the same carbon atom , they together with the carbon atom, may form a spiroheterocyclic system selected from hydantoin; thiohydantoin; oxazolidine-2,5-dione;

R 5 is C 1 –C 10 alkyl optionally substituted with one or more R 8 independently; C 2 –C 10 alkenyl optionally substituted with one or more R 8 independently; C 2 –C 10 alkynyl optionally substituted with one or more R 8 independently; C 3 –C 7 cycloalkyl optionally substituted with one or more R 8 independently; C 3 –C 7 cycloheteroalkyl optionally substituted with one or more R 8 independently; aryl optionally substituted with one or more R 8 independently; aryl C 1 –C 5 alkyl optionally substituted with one or more R 8 independently; heteroaryl optionally substituted with one or more R 8 independently; heteroaryl C 1 –C 5 alkyl optionally substituted with one or more R 8 independently;

R 6 is H; C 1 –C 10 alkyl optionally substituted with one or more R 4 independently; C 2 –C 10 alkenyl optionally substituted with one or more R 4 independently; C 2 –C 10 alkynyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloalkyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloheteroalkyl optionally substituted with one or more R 4 independently; aryl optionally substituted with one or more R 4 independently; heteroaryl optionally substituted with one or more R 4 independently;

R 7 is H; C 1 –C 10 alkyl optionally substituted with one or more R 4 independently; C 2 –C 10 alkenyl optionally substituted with one or more R 4 independently; C 2 –C 10 alkynyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloalkyl optionally substituted with one or more R 4 independently; C 3 –C 7 cycloheteroalkyl optionally substituted with one or more R 4 independently; aryl optionally substituted with one or more R 4 independently; heteroaryl optionally substituted with one or more R 4 independently;

R 8 is H; nitro; tetrazole; pentafluorophenyl; —CH 2 OH; —CHO; —C(OCH 3 ) 2 ; —COCH 3 ; —CF 3 ; —CCl 3 ; —OCF 3 ; —OCH 3 ; —CN; —CO 2 H; —CO 2 CH 3 ; —CONH 2 ; —CSNH 2 ; —CON 2 H 3 ; —SO 3 H; —SO 2 NH 2 ; —SO 2 NHCH 3 ; —SO 2 N(CH 3 ) 2 ; —SO 2 (1-piperazinyl); —SO 2 (4-methylpiperazin-1-yl); —SO 2 (pyrrolidin-1-yl); —SO 2 (piperidin-1-yl); —SO 2 (morpholin-4-yl); N-hydroxyimino; —NH 2 ; —NHCH 3 ; —N(CH 3 ) 2 ; —NHCNHNH 2 ; —NHCNHNHCH 3 ; —NHCSNH 2 ; —NHCSNHCH 3 ; —NHCONH 2 ; —NHCONHCH 3 ; —NHCOCH 3 ; —NHSO 2 CH 3 ; piperazinyl; morhpolin-4-yl; thiomorpholin-4-yl; pyrrolidin-1-yl; piperidin-1-yl; halogen; —OH; —SH; —SCH 3 ; -aminoacetyl; —OPO 3 H; —OPO 2 OCH 3 ; —PO 3 H 2 ; —PO(OCH 3 ) 2 ; PO(OH)(OCH 3 );

R 9 is H; halogen; C 1 –C 10 alkyl optionally substituted with one or more R 4 independently

R 10 is H; halogen;

or, R 9 and R 10 , together with the carbon atom to which they are attached, may be connected to form a cyclopropyl ring;

or a salt thereof with a pharmaceutically acceptable acid or base;

with the exception of the following compounds:

7-(3-Chloro-propyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione;

7-(3-Amino-propyl)-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione;

3-(1,3-Dimethyl-2,6-dioxo-8-piperazin-1-yl-1,2,3,6-tetrahydro-purin-7-yl)-propionaldehyde;

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,

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-3,1-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-1-yl-3,7-dihydro-purine-2,6-dione,

3-Methyl-7-(1-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, and

3-Methyl-7-propyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione.

2. A pharmaceutical composition comprising at least one compound according to claim 1 together with a pharmaceutically acceptable carrier or diluent.

3. A compound according to claim 1 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]diezepan-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-naphthaien-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, and

1,3-Dimethyl-8-piperazin-1-yl-7-(2-trifluoromethoxy-benzyl)-3,7-dihydro-purine-2,6-dione.

4. A compound according to claim 1 selected from the following:

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-nephthalen-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, and

7-Benzyl-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-216-dione.

5. A compound according to claim 1 selected from the following:

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, and

7-Benzyl-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione.

6. A compound according to claim 1 selected from the following:

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-1-(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, and

1-(3-Hydroxy-propyl)-7-(2-iodo-benzyl)-3-methyl-8-piperazin-1-yl-3,7-dihydro-purine-2,6-dione.

7. A compound according to claim 1 selected from the following:

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, and

7-Biphenyl-4-ylmethyl-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione.

8. A compound according to claim 1 selected from the following:

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, and

7-Benzyl-8-(3-(2-methoxy-benzyl)-piperazin-1-yl) 1,3-dimethyl-3,7-dihydro-purine-2,6-dione.

9. A compound according to claim 1 selected from the following:

(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, and

8-[1,4]Diazepan-1-yl-7-(2-iodo-benzyl)-1-(2-methoxy-ethyl)-3-methyl-3,7-dihydro-purine-2,6-dione.

10. A compound according to claim 1 selected from the following:

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-dion,

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, and

7-Biphenyl-2-ylmethyl-8-[1,4]diazepan-1-yl-3-methyl-3,7-dihydro-purine-2,6-dione.