Vasopressin v1a antagonists

Abstract

The present invention concerns compounds inter alia according to general formula 1a. Compounds according to the invention are vasopressin V 1a receptor antagonists. Pharmaceutical compositions of the compounds are useful as treatment of dysmenorrhoea.

1 - 73 . (canceled) 
     
     
         74 . A method of treatment of a disorder selected among dysmenorrhoea, pre-term labour, hypertension, Raynaud's disease, brain oedema, motion sickness, hyperlipemia, small cell lung cancer, depression, anxiety, hyponatremia, liver cirrhosis and congestive heart failure, comprising the administration to a person in need of such treatment of an effective amount of a compound according to general formula 1a, or a compound which is a tautomer or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein G is a group selected among general formula 2a, 3a, 4a, 5a, and 6a, 
       
         
           
           
               
               
           
         
       
       wherein:
 A 1  is selected among CH 2 , CH(OH), NH, N-alkyl, O and S; 
 A 2  is selected among CH 2 , CH(OH), C(═O) and NH; 
 A 3  and A 12  are independently selected among S, NH, N-alkyl, —C(R 8 )═CH—, —C(R 8 )═N—, —N═C(R 8 )— and —CH═C(R 8 )—; 
 A 4  and A 13  are independently selected among C(R 9 ) and N; 
 A 5  and A 14  are independently selected among C(R 10 ) and N; 
 A 6  is selected among CH 2 , NH, N-alkyl and O; 
 A 7  and A 11  are independently selected among C and N; 
 A 8  and A 9  are independently selected among CH, N, NH, N(CH 2 ) b R 11  and S; 
 A 10  is selected among —CH═CH—, CH, N, NH, N—(CH 2 ) b —R 11  and S; 
 wherein the ring constituted by A 7 , A 8 , A 9 , A 10  and A 11  is aromatic; 
 R 1 , R 2  and R 3  are independently selected among H, alkyl, O-alkyl, NO 2 , F, Cl and Br; 
 R 4  is selected among H, alkyl, aryl, heteroaryl, —(CH 2 ) c —R 12  and 
 
       
         
           
           
               
               
           
         
         R 5  and R 6  are independently selected among alkyl, aryl, —(CH 2 ) f -aryl and —CH 2 ) f -heteroaryl; 
         R 7  is selected among H, alkyl, heteroaryl and —(CH 2 ) g —R 14 ; 
         R 8 , R 9  and R 10  are independently selected among H, alkyl, alkoxy, F, Cl, Br, CN, NH 2 , NO 2 , NH(alkyl), N(alkyl) 2 : 
         with the provisos that when G is 3a, and R 4  is H, alkyl, aryl, heteroaryl or —(CH 2 ) c —R 2 , then the ring containing A 3 , A 4  and A 5  is substituted in at least one position by alkyl, alkoxy, F, Cl, Br, CN, NH S , NO 2 , NH(alkyl) or N(alkyl) 2 ; and 
         when G is 4a, R 4  is H, alkyl, aryl, heteroaryl or —(CH 2 ) c —R 12 , and A 8  is NH, NCH 3  or S, then the ring containing A 3 , A 4  and A 5  is substituted in at least one position by alkyl, alkoxy, F, Cl, Br, CN, or NH 2 , NO 2 , NH(alkyl) or N(alkyl) 2 ; 
         R 11  and R 12  are independently selected among H, alkyl, aryl; heteroaryl, F, OH, O-alkyl, S-alkyl, O-acyl NH 2 , NH-alkyl, N(alkyl) 2 , NH-acyl, N(alkyl)-acyl, CO 2 H, CO 2 -alkyl, CONH 2 , CONH-alkyl, CON(alkyl) 2 , CN and CF 3 ; 
         R 13  is selected among H, alkyl, aryl, heteroaryl, —(CH 2 ) h —R 15  and Z—R 16 ; 
         R 14  and R 15  are independently selected among H, alkyl, alkenyl, aryl, heteroaryl, F, OH, O-alkyl, S-alkyl, O-acyl, NH 2 , NH-alkyl, N(alkyl) 2 , NH-acyl, N(alkyl)-acyl, CO 2 H, CO 2 -alkyl, CO-alkyl, CO-aryl, CONH 2 , CONH-alkyl, CON(alkyl) 2 , alkenyl-CO 2 -alkyl, alkenyl-aryl, CN and CF 3 ; 
         R 16  is selected among H, alkyl, alkenyl, aryl, heteroaryl, O-aryl, —(CH 2 ) i —R 17 , cyclopropyl-aryl and O—(CH 2 ) i —R 17 ; 
         R 17  is selected among H, alkyl, aryl, heteroaryl, F, OH, O-alkyl, S-alkyl, O-acyl, NH 2 , NH-alkyl, N(alkyl) 2 , NH-acyl, N(alkyl)-acyl, CO 2 H, CO 2 -alkyl, CONH 2 , CONH-alkyl, CON(alkyl) 2 , CN and CF 3 ; 
         W is selected among O and NH; 
         X is selected among (CH 2 ) m , C(═O) and S(═O) j ; 
         Y is selected among O, S, NH and N-alkyl; 
         Z is selected among —C(═O), —C(═O)—O and —S(═O) k ; 
         a is selected among 1 and 2; 
         b and c are independently selected among 0, 1, 2 and 3; 
         d, e and f are independently selected among 1 and 2; 
         g, h and i are independently selected among 1, 2 and 3; 
         j and k are independently selected among 1 and 2; and 
         m and n are independently selected among 0, 1 and 2. 
       
     
     
         75 . The method of  claim 74 , wherein G is selected among: 
       
         
           
           
               
               
           
         
       
     
     
         76 . The method of  claim 74 , wherein G is selected among: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         77 . The method of  claim 74 , wherein at least one of R 1 , R 2  and R 3  is other than hydrogen. 
     
     
         78 . The method of  claim 77 , wherein one of R 1 , R 2  and R 3  is selected among methyl, chlorine and fluorine, and the others are hydrogen 
     
     
         79 . The method of  claim 74 , wherein W is NH. 
     
     
         80 . The method of  claim 74 , wherein R 4  is alkyl. 
     
     
         81 . The method of  claim 74 , wherein d is 2 and e is 2. 
     
     
         82 . The method of  claim 74 , wherein R 13  is alkyl. 
     
     
         83 . The method of  claim 74 , wherein n is 0. 
     
     
         84 . The method of  claim 74 , wherein R 2  is H, R 4  is a piperidine where d is 2 and e is 2, W is NH, X is C(═O) and n is 0, as shown in formula 18a: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected among methyl, chlorine and fluorine, and R 3  is H; or R 1  is H, and R 3  is selected among methyl, chlorine and fluorine, and R 13  is alkyl. 
     
     
         85 . The method of  claim 74 , wherein X is C(═O), n is 0 and R 4  is a piperidine where d is 2 and e is 2, as shown in formula 19a: 
       
         
           
           
               
               
           
         
       
       wherein G is selected among general formulae 7a to 17a, and R 13  is alkyl: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         86 . The method of  claim 74 , wherein R 2  is H and W is NH as shown in formula 20a: 
       
         
           
           
               
               
           
         
       
       wherein either R 1  is selected among methyl, chlorine and fluorine, and R 3  is H; or R 1  is H, and R 3  is selected among methyl, chlorine and fluorine; and G is selected from general formulae 7a to 17a: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         87 . The method of  claim 74 , wherein R 2  is H, W is NH and X is C(═O) as shown in formula 21a: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected among methyl, chlorine and fluorine, and R 3  is H; or R 1  is H, and R 3  is selected among methyl, chlorine and fluorine; and R 4  is alkyl. 
     
     
         88 . The method of  claim 74 , wherein X is C(═O) as shown in formula 22a: 
       
         
           
           
               
               
           
         
       
       wherein G is selected among general formulae 7a to 17a, and R 4  is alkyl: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         89 . The method of  claim 74 , wherein R 2  and R 3  are both H, W is NH and X is C(═O) as shown in formula 23a: 
       
         
           
           
               
               
           
         
       
       wherein G is selected among general formulae 9a, 10a, 15a, 16a and 17a, R 1  is selected among methyl, chlorine and fluorine, and R 4  is alkyl: 
       
         
           
           
               
               
           
         
       
     
     
         90 . The method of  claim 74 , wherein R 2  and R 3  are both H, R 4  is a piperidine where d is 2 and e is 2, W is NH, X is C(═O) and n is 0 as shown in formula 24a: 
       
         
           
           
               
               
           
         
       
       wherein G is selected among general formulae 9a, 10a, 15a, 16a and 17a, R 1  is selected among methyl, chlorine and fluorine, and R 13  is alkyl: 
       
         
           
           
               
               
           
         
       
     
     
         91 . The method of  claim 74 , wherein the compound is selected among the group consisting of:
 1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-chloro-4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo-[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-methyl-4-(2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-methyl-4-(2-methyl-4,5-dihydro-1-oxa-3,6-diaza-benzo[e]azulene-6-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 3-chloro-4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 3-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo-[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-methyl-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-fluoro-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-methyl-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-fluoro-benzylamide;   1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic acid 4-[(4-chloro-phenyl)-methyl-carbamoyl]-2-methyl-benzylamide;   1-Cyclopropyl-methyl-piperidine-4-carboxylic acid 2-chloro-4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 2-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-chloro-4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-methyl-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-fluoro-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-methyl-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-fluoro-benzylamide;   1-Cyclopropylmethyl-piperidine-4-carboxylic acid 4-[(4-chloro-phenyl)-methyl-carbamoyl]-2-methyl-benzylamide;   Cyclobutanecarboxylic acid 2-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   Cyclobutanecarboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   Cyclobutanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   Cyclopentanecarboxylic acid 2-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   Cyclopentanecarboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   Cyclopentanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   Cyclopropanecarboxylic acid 2-chloro-4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   Cyclopropanecarboxylic acid 2-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   Cyclopropanecarboxylic acid 3-chloro-4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   Cyclopropanecarboxylic acid 3-chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide;   Cyclopropanecarboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzylamide;   Cyclopropanecarboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   Cyclopropanecarboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-fluoro-benzylamide;   Cyclopropanecarboxylic acid 4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-methyl-benzylamide;   Cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-benzylamide;   Cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-fluoro-benzylamide;   Cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   Cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-3-methyl-benzylamide;   N-[2-Chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-propionamide;   N-[-2-Chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-2,2-dimethyl-propionamide;   N-[2-Chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-isobutyramide;   N-[2-Chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-butyramide;   N-[4-(3,6-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-propionamide;   N-[4-(3,6-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-2,2-dimethyl-propionamide;   N-[4-(3,6-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-isobutyramide;   N-[4-(3,6-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-butyramide;   N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-propionamide;   N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-2,2-dimethyl-propionamide;   N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-isobutyramide;   N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-acetamide;   N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-butyramide;   N-[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-formamide;   N-[4-(6-Chloro-3-ethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzyl]-propionamide;   Cyclopropane-carboxylic acid 4-(6-chloro-3-ethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide;   N-[2-Fluoro-4-(6-fluoro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-propionamide;   N-[2-Fluoro-4-(6-fluoro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-isobutyramide;   Cyclopropanecarboxylic acid 2-fluoro-4-(6-fluoro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; and   N-[4-(9-Chloro-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzyl]-isobutyramide.