Fused azepine derivatives and their use as antidiuretic agents

1. A compound according to formula 1 or 2, or a tautomer or a pharmaceutically acceptable salt thereof:

wherein:

W is either N or C—R 4 ;

R 1 –R 4 are independently selected from H, F, Cl, Br, alkyl, CF 3 , phenyl, OH, O-alkyl, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 and CN, or R 2 and R 3 together can be —CH═CH—CH═CH—;

G 1 is a bicyclic fused azepine derivative according to formula 8:

 in which

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 CH(OH), CF 2 , O, SO a and NR 5 ;

R 5 is selected from H, alkyl, CO-alkyl and (CH 2 ) b R 6 ;

R 6 is selected from phenyl, pyridyl, OH, O-alkyl, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , CO 2 H and CN;

a is 0, 1 or 2;

b is 1, 2, 3 or 4;

Y is CH or N;

Z is CH═CH or S; and

G 2 is a group according to formula 9:

 in which

Ar is selected from phenyl, pyridyl, naphthyl and mono- or polysubstituted phenyl or pyridyl wherein the substituents are selected from F, Cl, Br, alkyl, OH, O-alkyl, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 and CN;

V is O, N—CN or S;

c is 0 or 1;

d is 0 or 1; and

e is 0 or 1,

provided that d and e are not both 0.

2. A compound according to claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, wherein the compound is a compound according to general formula 1.

3. A compound according to claim 2 , or a tautomer or pharmaceutically acceptable salt thereof, wherein W is C—R 4 .

4. A compound according to claim 3 , or a tautomer or pharmaceutically acceptable salt thereof, wherein at least one of R 1 –R 4 is not H.

5. A compound according to claim 4 , or a tautomer or pharmaceutically acceptable salt thereof, wherein one of R 1 –R 4 is methyl, F or Cl and the others are all H.

6. A compound according to claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, wherein A 17 is CH 2 .

7. A compound according to either claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, wherein A 16 is CH 2 .

8. A compound according to claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, wherein Ar is mono- or polysubstituted phenyl.

9. A compound according to either claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, wherein Ar is phenyl substituted with at least two halogen atoms selected from F and Cl.

10. A compound according to any of claims 1 , or a tautomer or pharmaceutically acceptable salt thereof, wherein Ar is 2,6-difluorophenyl.

11. A compound according to claim 6 , or a tautomer or pharmaceutically acceptable salt thereof, wherein A 16 is CH 2 .

12. A compound according to claim 8 , or a tautomer or pharmaceutically acceptable salt thereof, wherein Ar is phenyl substituted with at least two halogen atoms selected from F and Cl.

13. A compound according to claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, selected from

1-(4-[3-(2-Chloro-6-fluorophenyl)ureidomethyl]-3-methylbenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine,

1-(4-[3-(2,6-Difluorophenyl)ureidamethyl]-3-methylbenzoyl)-5-(3-pyridyl)methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine,

1-(3-Chloro-4-[3-(2-chloro-6-fluorophenyl)ureidomethyl]benzoyl)-5-ethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine,

4-(3-Chloro-4-[3-(2,6-difluorophenyl)ureidomethyl]benzoyl-5,6,7,8-tetrahydrothieno[3,2-b]azepine, and

1-(2-Methyl-4-(5-(3-pyridylmethyl)-2,3,4,5-tetrahydro-1,5benzodiazepin-1-ylcarbonyl)benzyl)-3-(methyloxycarbonylmethyl)urea.

14. A pharmaceutical composition which comprises, as an active agent, a compound according to claim 1 .

15. A method of treating a condition selected from the group consisting of nocturnal enuresis, nocturia and diabetes insipidus, which method comprises administering to a person in need of such treatment an effective amount of a composition according to claim 14 .

16. A method for the control of urinary incontinence, which method comprises administering to a person in need of such treatment an effective amount of a composition according to claim 14 .

17. A method for the control of urinary incontinence according to claim 16 , wherein the treatment results in voiding postponement.

18. A method for the treatment of bleeding disorders, which method comprises administering to a person in need of such treatment an effective amount of a composition according to claim 14 .