Benzodiazepine and pyridodiazepine derivatives

Abstract

The present application relates to benzodiazepine and pyridodiazepine derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 , X 1 , Y 1 , Y 2 , and Y 3 are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

What is claimed is: 
     
         1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or prodrug thereof, wherein
 R 1  is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, haloalkyl, G 1 , —(CR 4a R 5a ) m -G 1 , —C(O)-G 1 , —S(O) 2 G 1 , —C(O)OR 6  and —C(O)NR 7 R 8 ; wherein R 1  is other than hydrogen, alkyl, alkylcarbonyl, or haloalkyl when one of Y 1  or Y 2  is CH 2  and the other is NR 9 ; 
 R 2 , R 3 , R 4 , and R 5  are each independently hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —NO 2 , —OR 1a , —S(O) 2 R 2a , —C(O)OR 1a , or haloalkyl; 
 R 6  is alkyl or —(CR 4a R 5a ) m -G 1 ; 
 R 7  and R 8  are independently hydrogen, alkyl, G 1 , or —(CR 4a R 5a ) m -G 1 ; 
 R 9  is hydrogen or alkyl; 
 R 1a , at each occurrence, is independently hydrogen, alkyl, haloalkyl, or —(CR 4a R 5a ) m -G 1 ; 
 R 2a , at each occurrence, is independently alkyl, haloalkyl, or G 1 ; 
 R 4a  and R 5a , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl, or R 4a  and R 5a  together with the carbon to which they are attached form a cycloalkyl; 
 R 1b , at each occurrence, is independently hydrogen, alkyl, or haloalkyl; 
 R 2b , at each occurrence, is independently alkyl, cyanoalkyl or haloalkyl; 
 G 1 , at each occurrence, is independently aryl or heteroaryl, wherein each G 1  is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, halogen, cyano, —NO 2 , —OR 1b ), —S(O) 2 R 2b , —C(O)OR 1b , —(CR 4a R 5a ) m —N(R 1b ) 2 , and haloalkyl; 
 G 2 , at each occurrence, is independently cycloalkyl or heterocycle, wherein each G 2  is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, halogen, cyano, —NO 2 , —OR 1b , —S(O) 2 R 2b , —C(O)OR 1b , —C(O)R 2b , —C(O)N(R 1b ) 2 , haloalkyl, and oxo; 
 m, at each occurrence, is independently 1, 2, 3, 4, or 5; 
 X 1  is N or CR 5 ; 
 one of Y 1  or Y 2  is CH 2  and the other is selected from the group consisting of NR 9 , N-G 1 , N—(CR 4a R 5a ) m -G 1 , N + -[(CR 4a R 5a ) m -G 1 ] 2 , NC(O)—R 2b , NC(O)—(CR 4a R 5a ) m -G 1 , NC(O)—(CR 4a R 5a ) m —W 1 , NC(O)—CH═CH-G 1 , NC(O)-G 1 , NC(O)-G 2 -G 1 ; N-G 2 ; N-G 2 -C(O)-G 1 ; N—(CR 4a R 5a ) m -G 2 , NC(O)—(CR 4a R 5a ) m -G 2 , NC(O)-G 2 , NC(O)NH—W 3 , NC(O)N(R 2b )—W 3 , and NC(O)N(R 1b )—(CR 4A R 5a ) m —W 2 ; wherein
 W 1  is NHC(O)G 1  or —O—(CR 4a R 5a ) m R 1b ; 
 W 2  is G 1 , G 2 , N(R 1b ) 2 , —O—(CR 4a R 5a ) m —R 1b ; 
 W 3  is R 1b , G 1  or G 2 ; and 
 
 Y 3  is CH 2  or C(O). 
 
     
     
         2 . The compound of  claim 1 , wherein X 1  is CR 5 ;
 R 5  is hydrogen;   Y 1  is CH 2 ;   Y 2  is NR 9 , N-G 1 , N—(CR 4a R 5a ) m -G 1 , N + —[(CR 4a R 5a ) m -G 1 ] 2 , NC(O)—(CR 4a R 5a ) m -G 1 , NC(O)—CH═CH-G 1 , NC(O)-G 1 , NC(O)-G 2 -G 1 , N-G 2 , N—(CR 4a R 5a ) m -G 2 , NC(O)—(CR 4a R 5a ) m -G 2 , or NC(O)-G 2 ; and   Y 3  is C(O).   
     
     
         3 . The compound of  claim 2 , wherein R 1  is selected from the group consisting of hydrogen, —(CR 4a R 5a ) m -G 1 , —C(O)OR 6 ; and
 Y 2  is NR 9 , N—(CR 4a R 5a ) m -G 1  or N—(CR 4a R 5a ) m -G 2 . 
 
     
     
         4 . The compound of  claim 1 , wherein X 1  is CR 5 ;
 R 5  is hydrogen; and   Y 1  and Y 3  are each CH 2 .   
     
     
         5 . The compound of  claim 4 , wherein R 1  is hydrogen, or —(CR 4a R 5a ) m -G 1 ; and
 Y 2  is NR 9 . 
 
     
     
         6 . The compound of  claim 4 , wherein R 1  is hydrogen, —(CR 4a R 5a ) m -G 1 , or —C(O)OR 6 ;
 Y 2  is N—(CR 4a R 5a ) m -G 1 , N—(CR 4d R 5a ) m -G 2 , or N 1 —[(CR 4a R 5a ) m -G 1 ] 2 ; and 
 m, at each occurrence, is independently 1, 2, or 3. 
 
     
     
         7 . The compound of  claim 4 , wherein R 1  is —(CR 4a R 5a ) m -G 1 ;
 Y 2  is N-G 1  or N-G 2 -C(O)-G 1 ; and 
 m is independently 1, 2, or 3. 
 
     
     
         8 . The compound of  claim 4 , wherein R 1  is hydrogen, alkyl, alkylcarbonyl, G 1 , —(CR 4a R 5a ) m -G 1 , —C(O)-G 1 , or —S(O) 2 G 1 ; and
 Y 2  is NC(O)—(CR 4a R 5a ) m -G 1 , NC(O)—CH═CH-G 1 , NC(O)-G 1 , NC(O)-G 2 -G 1 , NC(O)—(CR 4a R 5a ) m -G 2 , NC(O)—(CR 4a R 5a ) m —W 1 , NC(O)—R 2b  or NC(O)-G 2 . 
 
     
     
         9 . The compound of  claim 4 , wherein R 1  is hydrogen, alkyl, G 1 , —(CR 4a R 5a ) m -G 1 , —C(O)-G 1 , or —S(O) 2 G 1 ; and
 Y 2  is NC(O)NH—W 3 , NC(O)N(R 2b )—W 3 , and NC(O)N(R 1b )—(CR 4a R 5a ) m —W 2 . 
 
     
     
         10 . The compound of  claim 1 , wherein Y 2  and Y 3  are each CH 2 . 
     
     
         11 . The compound of  claim 10 , wherein R 1  is —(CR 4a R 5a ) m -G 1 ; and
 Y 1  is NR 9 . 
 
     
     
         12 . The compound of  claim 10 , wherein R 1  is alkyl, —(CR 4a R 5a ) m -G 1 , or —C(O)-G 1 ; and
 Y 1  is N—(CR 4a R 5a ) m -G 1 , or N—(CR 4a R 5a ) m -G 2 . 
 
     
     
         13 . The compound of  claim 10 , wherein X 1  is CR 5  or N;
 R 5  is hydrogen;   R 1  is hydrogen, alkyl, or —(CR 4a R 5a ) m -G 1 ; and   Y 1  is NC(O)—(CR 4a R 5a ) m -G 1 , NC(O)-G 1 , NC(O)—(CR 4a R 5a ) m -G 2 , or NC(O)-G 2 .   
     
     
         14 . The compound of  claim 1 , wherein X 1  is CR 5 ; and
 R 2 , R 3 , R 4 , and R 5  are each hydrogen.   
     
     
         15 . The compound according to  claim 1  or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
 tert-butyl 5-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepine-3(4H)-carboxylate; 
 3-benzyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-phenylethanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(phenyl)methanone; 
 3,6,6-tribenzyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepin-6-ium; 
 3,6-dibenzyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-methyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(pyrimidin-2-yl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(4-fluorophenyl)methanone; 
 3-benzyl-6-(pyrazin-2-yl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(pyrazin-2-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1-phenylcyclopropyl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(morpholin-4-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl) [trans-2-phenylcyclopropyl]methanone; 
 3-benzyl-6-(pyridin-2-yl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-fluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (−)-3-benzyl-6-(4-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (+)-3-benzyl-6-(4-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (2E)-1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)-3-phenylprop-2-en-1-one; 
 3-benzyl-6-[4-(trifluoromethyl)benzyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 7-(4-bromobenzyl)-3-methyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 3-benzyl-6-(4-bromo-3-fluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3,5-difluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3,4-difluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 1-(3-benzyl-2,3,4,4a,5,6-hexahydropyrazino[1,2-a][1,5]benzodiazepin-7(1H)-yl)-2-(4-chlorophenyl)ethanone; 
 3-benzyl-6-(pyridin-3-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(pyridin-2-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(pyridin-4-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(4-bromophenyl)methanone; 
 3-benzyl-6-[(6-methylpyridin-3-yl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(quinolin-3-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-[(6-chloropyridin-3-yl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(quinolin-4-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(isoquinolin-4-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-(4-fluorobenzyl)-2,3,4,4a,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepin-5 (1H)-one; 
 3-benzyl-6-[(6-bromopyridin-3-yl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-(4-fluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (3-benzyl-2,3,4,4a,5,6-hexahydropyrazino[1,2-a][1,5]benzodiazepin-7(1H)-yl)(4-bromophenyl)methanone; 
 3-benzyl-6-[(5-bromopyridin-2-yl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (3-benzyl-2,3,4,4a,5,6-hexahydropyrazino[1,2-a][1,5]benzodiazepin-7(1H)-yl)(pyridin-4-yl)methanone; 
 3-benzyl-7-[2-(4-chlorophenyl)ethyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 3,7-dibenzyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 3-benzyl-6-(4-iodobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-7-(4-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 3-benzyl-7-(pyridin-4-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 3-benzyl-7-methyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine; 
 4-[(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)methyl]phenol; 
 9-benzyl-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 1-(9-benzyl-7,7a,8,9,10,11-hexahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepin-5(6H)-yl)-2-(4-chlorophenyl)ethanone; 
 9-benzyl-5-[2-(4-chlorophenyl)ethyl]-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 9-benzyl-5-methyl-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 6-(4-bromobenzyl)-3-(4-fluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 6-(4-bromobenzyl)-3-methyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (9-benzyl-7,7a,8,9,10,11-hexahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepin-5 (6H)-yl)(2,2,3,3-tetramethylcyclopropyl)methanone; 
 9-benzyl-5-[(2,2,3,3-tetramethylcyclopropyl)methyl]-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-(6-chloropyridin-3-yl)ethanone; 
 (+)-(4 aS)-6-(4-bromobenzyl)-3-(4-fluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 (−)-(4 aR)-6-(4-bromobenzyl)-3-(4-fluorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-[2-(6-chloropyridin-3-yl)ethyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 5-(cyclopropylmethyl)-9-(4-fluorobenzyl)-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 5-(cyclobutylmethyl)-9-(4-fluorobenzyl)-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 tert-butyl 6-(4-bromobenzyl)-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepine-3(4H)-carboxylate; 
 tert-butyl 6-(4-bromobenzyl)-5-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepine-3 (4H)-carboxylate; 
 5-[(2S)-azetidin-2-ylmethyl]-9-(4-fluorobenzyl)-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 5-(azetidin-3-ylmethyl)-9-(4-fluorobenzyl)-5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine; 
 6-(4-bromobenzyl)-2,3,4,4a,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepin-5(1H)-one; 
 6-(4-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 cyclopropyl(7,7a,8,9,10,11-hexahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepin-5(6H)-yl)methanone; 
 6-(4-bromobenzyl)-3-(4-fluorobenzyl)-2,3,4,4a,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepin-5(1H)-one; 
 [5-(cyclopropylmethyl)-6,7,7a,8,10,11-hexahydropyrazino[1,2-d]pyrido[3,2-b]-[1,4]diazepin-9(5H)-yl](pyridin-3-yl)methanone; 
 1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl(morpholin-4-yl)methanone; 
 [3-(4-fluorobenzyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl](morpholin-4-yl)methanone; 
 (3-methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(morpholin-4-yl)methanone; 
 2-[2-(3-benzyl-2,3,4,4a,5,6-hexahydropyrazino[1,2-a][1,5]benzodiazepin-7(1H)-yl)-2-oxoethyl]pyridazin-3(2H)-one; 
 (3-benzoyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(morpholin-4-yl)methanone; 
 morpholin-4-yl[3-(pyrimidin-2-yl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl]methanone; 
 morpholin-4-yl[3-(phenylsulfonyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl]methanone; 
 [3-(4-chlorophenyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl](morpholin-4-yl)methanone; 
 1-[6-(morpholin-4-ylcarbonyl)-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepin-3(4H)-yl]ethanone; 
 1-{4[(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)carbonyl]piperidin-1-yl}ethanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1H-pyrazol-4-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1-pyrazol-5-yl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-(morpholin-4-yl)ethanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1,3-thiazol-4-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1,3-thiazol-5-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1,2-oxazol-5-yl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-3-(pyrrolidin-1-yl)propan-1-one; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-cyclopropylethanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1H-pyrrol-2-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(3-furyl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1,2,5-trimethyl-1H-pyrrol-3-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(2,5-dimethyl-1H-pyrrol-3-yl)methanone; 
 1-[(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)carbonyl]cyclopropanecarboxamide; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-(pyridin-3-yl)ethanone; 
 N-[2-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-oxoethyl]-2-furamide; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-methylpropan-1-one; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(3,5-dimethyl-1,2-oxazol-4-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(5-methylpyrazin-2-yl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-(4-methylpiperazin-1-yl)ethanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(2-furyl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1-methyl-1H-pyrrol-2-yl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)propan-1-one; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(pyridin-4-yl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)butan-1-one; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(tetrahydrofuran-3-yl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(pyridin-3-yl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-3-(piperidin-1-yl)propan-1-one; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(cyclopropyl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-2-ethoxyethanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(1-methylcyclopropyl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(cyclobutyl)methanone; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(2-methylcyclopropyl)methanone; 
 1-(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)-3,3,3-trifluoropropan-1-one; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(tetrahydrofuran-2-yl)methanone; 
 3-benzyl-6-(4-methoxy-3-methylbenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-[(4,5-dimethyl-2-furyl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-ethoxybenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-[(5-methyl-2-thienyl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(2-naphthylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(cyclopentylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(quinolin-2-ylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-[(5-ethyl-2-furyl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 4-[(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)methyl]benzonitrile; 
 3-benzyl-6-butyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-chlorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(2-methylbenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(2-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(2-methoxybenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-methoxybenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3-methoxybenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3-bromobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(4-methylbenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(1-naphthylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(2-chlorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3-chlorobenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(2,2-dim ethylpropyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-[(3-methyl-2-thienyl)methyl]-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3-methylbutyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(cyclohexylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-(3-methylbenzyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-[(3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)methyl]benzonitrile; 
 3-benzyl-6-(2-thienylmethyl)-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-6-isobutyl-1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine; 
 3-benzyl-N-(2-methoxyethyl)-N-methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-[2-(pyridin-3-yl)ethyl]-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-[2-(pyridin-2-yl)ethyl]-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-[2-(pyridin-4-yl)ethyl]-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(2-cyanoethyl)-N-cyclopropyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 [4-(2-aminoethyl)-1H-imidazol-1-yl](3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)methanone; 
 3-benzyl din-4-ylmethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-[(5-methyl-2-furyl)methyl]-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-ethyl-N-(2-methoxyethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N,N-di ethyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(1,3-thiazol-2-yl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(cyclopropylmethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)(4-isopropylpiperazin-1-yl)methanone; 
 3-benzyl-N-isobutyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(pyridin-3-ylmethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-[3-(dimethylamino)propyl]-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-butyl-N-(cyanomethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(3-methoxypropyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(2-methoxyethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-(pyridin-2-ylmethyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-cyclobutyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 3-benzyl-N-methyl-N-propyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepine-6(7H)-carboxamide; 
 (3-benzyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6 (7H)-yl)(piperidin-1-yl)methanone; 
 6-(cyclopropylmethyl)-2,3,4,4a,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepin-5(1H)-one; 
 [4-(3-methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)piperidin-1-yl](phenyl)methanone; 
 (2-chlorophenyl)(3-methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)methanone; 
 (3-chlorophenyl)(3-methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)methanone; and 
 (4-chlorophenyl)(3-methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,4]benzodiazepin-6(7H)-yl)methanone. 
 
     
     
         16 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to  claim 1  or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.