Heterocyclic condensed compounds useful as antidiuretic agents

1. A compound according to formula 1, or a compound which is a tautomer or a pharmaceutically acceptable salt thereof,

wherein:

W is selected from N and CR 4 ;

X is selected from CH(R 8 ), O, S, N(R 8 ), C(═O), C(═O)O, C(═O)N(R 8 ), OC(═O), N(R 8 )C(═O), C(R 8 )═CH, and C(═R 8 );

G 1 is a bicyclic or tricyclic fused azepine derivative selected from general formulae 2 to 9 or an aniline derivative according to general formula 10

A 1 , A 4 , A 7 and A 10 are each independently selected from CH 2 , C═O, O, and NR 10 ;

A 2 , A 3 , A 9 , A 11 , A 13 , A 14 , A 15 , A 19 , and A 20 are each independently selected from CH and N;

either A 5 is a covalent bond, and A 6 is S; or A 5 is N═CH, and A 6 is a covalent bond;

A 8 , A 12 , A 18 , and A 21 are each independently selected from CH═CH, NH, NCH 3 , and S;

A 16 and A 17 are both CH 2 , or one of A 16 and A 17 is CH 2 , and the other is selected from C═O, CH(OH), CF 2 , O, SO c , and NR 10 ;

Y is selected from CH═CH or S;

R 1 and R 2 are independently selected from H, F, Cl, Br, alkyl, CF 3 , and O-alkyl;

R 3 is selected from H and alkyl;

R 4 -R 7 are independently selected from H, F, Cl, Br, alkyl, CF 3 , OH, and O-alkyl;

R 8 is selected from H, (CH 2 ) b R 9 , and (C═O)(CH 2 ) b R 9 ;

R 9 is selected from H, alkyl, optionally substituted aryl, optionally substituted heteroaryl, OH, O-alkyl, OC(═O)alkyl, NH 2 , NHalkyl, N(alkyl) 2 , CHO, CO 2 H, CO 2 alkyl, CONH 2 , CONHalkyl, CON(alkyl) 2 , and CN;

R 10 is selected from H, alkyl, COalkyl, and (CH 2 ) d OH;

R 11 is selected from alkyl, (CH 2 ) d Ar, (CH 2 ) d OH, (CH 2 ) d NH 2 , (CH 2 ) d COOalkyl, (CH 2 ) d COOH, and (CH 2 ) d OAr;

R 12 and R 13 are each independently selected from H, alkyl, F, Cl, Br, CH(OCH 3 ) 2 , CHF 2 , CF 3 , COOalkyl, CONHalkyl, (CH 2 ) d NHCH 2 Ar, CON(alkyl) 2 , CHO, COOH, (CH 2 ) d OH, (CH 2 ) d NH 2 , N(alkyl) 2 , CONH(CH 2 ) d Ar, and Ar;

Ar is selected from optionally substituted heterocycles or optionally substituted phenyl;

a is selected among 1, 2 and 3;

b is selected among 1, 2, 3 and 4;

c is selected among 0, 1 and 2; and

d is selected among 0, 1, 2 and 3.

2. The compound according to claim 1 , wherein G 1 is selected from

wherein R 11 , R 12 and R 13 are as previously defined.

3. The compound according to claim 2 , wherein G 1 is selected from

and wherein R 11 and R 12 are as previously defined.

4. The compound according to claim 3 , wherein G 1 is selected from

5. The compound according to claim 1 , wherein at least one of R 1 , R 2 , and R 3 is not H.

6. The compound according to claim 5 , wherein one of R 1 , R 2 , and R 3 is methyl, Cl or F, and the rest are H.

7. The compound according to claim 6 , wherein R 2 is methyl or Cl, and R 1 and R 3 are both H.

8. The compound according to claim 1 , wherein W is C—F, C—Cl or C—Br.

9. The compound according to claim 8 , wherein W is C—F.

10. The compound according to claim 1 , wherein X is N(R 8 )C(═O), and a is 1.

11. The compound according to claim 10 , wherein X is N(R 8 )C(═O), R 8 is (CH 2 ) b R 9 , and a is 1.

12. The compound according to claim 1 , wherein R.sup.5 is either H or F, and both R 6 and R 7 7 are H.

13. The compound according to claim 1 , wherein W is CR 4 , X is N(R 8 )C(═O), R 1 is H, R 2 is methyl or Cl, R 3 is H, R 4 is F, and R 5 , R 6 6, and R 7 are H, and a is 1.

14. The compound according to claim 1 , wherein G 1 is a group according to general formula 7 wherein Y is CH═CH, A 16 is CH 2 , A 17 is CH 2 , R 1 is H, R 2 is methyl or Cl, and R 3 is H.

15. The compound according to claim 1 , wherein G. 1 is a group according to general formula 2, and wherein Y is CH═CH, A 1 is CH 2 , both A 2 and A 3 are CH, R 1 is H, R 2 is methyl or Cl, and R 3 is H.

16. The compound according to claim 1 selected from

{1-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylcarbamoyl]-8-fluoro-1,2,3,4-tetrahydroquinolin-4-yl}acetic acid ethyl ester;

{4-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylcarbamoyl]-5-fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid methyl ester;

{5,6-Difluoro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid;

{5-Chloro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid;

{5-Fluoro-4-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid;

{6-Fluoro-5-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl}acetic acid;

4-(3-Aminopropyl)-8-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

4-Cyanomethyl-8-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

4-Cyanomethyl-8-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide;

7,8-Difluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

7,8-Difluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide;

8-Chloro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-3,4-dihydro-2H-quinoline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide;

8-Fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-chloro-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(6,7-dihydrodibenzo[b,d]azepine-5-carbonyl)-2-methylbenzylamide;

8-Fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-[5-(2-hydroxyethyl)-2,3,4,5-tetrahydrobenzo[b][1,4]diazepine-1-carbonyl]-2-methylbenzylamide;

8-Fluoro-3-oxo-4-(1H-tetrazol-5-ylmethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-3-oxo-4-(2-oxoethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide;

8-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(7,8-dihydro-6H-5-oxa-9-azabenzocycloheptene-9-carbonyl)-2-methylbenzylamide;

8-Fluoro-4-(2-methoxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide;

8-Fluoro-4-(2-methylaminoethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-4-methyl-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(4H,10H-3,3a,9-triaza-benzo[f]azulene-9-carbonyl)benzylamide;

8-Fluoro-4-methyl-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide;

9-Fluoro-5-(2-hydroxyethyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepine-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

9-Fluoro-5-oxo-2,3-dihydro-5H-benzo[e][1,4]oxazepine-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

9-Fluoro-5-oxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepine-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide;

8-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-[(2-furan-2-ylphenyl)methylcarbamoyl]-2-methylbenzylamide; and

8-Fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-[methyl-(2-thiophen-2-ylphenyl)carbamoyl]benzylamide.

17. A pharmaceutical composition comprising a compound according to claim 1 as an active agent and at least one excipient.

18. A pharmaceutical composition according to claim 17 , formulated for oral administration.