Amides of aminoalkyl-substituted azetidines, pyrrolidines, piperidines and azepanes

1. A compound of formula (II):

wherein

m is 1, 2 or 3,

n is 1, or 2,

wherein,

when n is 1, R 1 and R 2 together form a C 5 -alkylene bridge, which may optionally be substituted with one or more substituents selected from halogen and hydroxyl; and when n is 2, R 1 and R 2 together form a C 4 -alkylene bridge, which may optionally be substituted with one or more substituents selected from halogen and hydroxyl;

R 11 and R 12 independently are hydrogen,

C 1-6 -alkyl, which may optionally be substituted with one or more substituents selected from C 3-8 -cycloalkyl, C 5-8 -cycloalkenyl, halogen and hydroxyl, or

C 3-8 -cycloalkyl or C 5-8 -cycloalkenyl, which may optionally be substituted with one or more substituents selected from halogen and hydroxyl,

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 independently are

hydrogen, halogen, cyano, —NR 15 R 16 , hydroxyl, carbamoyl, carboxyl, —CF 3 , —OCF 3 , carboxyl, amidino, guanidino or nitro, or

C 1-6 -alkoxy, C 1-6 -alkyl, C 1-7 -alkanoyl, C 1-6 -alkylcarbamoyl, di-C 1-6 -alkylcarbamoyl, C 1-6 -alkyloxycarbonyl, C 3-8 -cycloalkyl, C 3-8 cycloalkanoyl, C 3-8 -cycloalkylcarbamoyl, C 3-8 -cycloalkyl-oxycarbonyl, C 1-6 -alkylthio, C 1-6 -alkylsulfinyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyl-O—, aryl, aroyl, aryloxy, aryloxycarbonyl, heteroaryl, heteroaroyl, or heteroaryloxy which may optionally be substituted with one or more substituents selected from halogen, hydroxyl, cyano and —NR 15 R 16 ,

R 15 and R 16 independently are

hydrogen or carbamoyl,

C 1-6 -alkyl, which may optionally be substituted with, one or more substituents selected from C 3-8 -cycloalkyl, C 5-8 -cycloalkenyl, halogen, hydroxyl, cyano and amino, or

C 3-8 -cycloalkyl, C 5-8 -cycloalkenyl, C 1-6 -alkylcarbamoyl, di-C 1-6 -alkylcarbamoyl or C 1-6 -alkyloxycarbonyl, which may optionally be substituted with one or more substituents selected from halogen, hydroxyl, cyano, amino, C 1-6 -alkyl, C 2-6 -alkenyl and C 2-6 -alkynyl,

or R 15 and R 16 together form a C 3-6 -alkylene bridge or a C 3-6 -alkenylene bridge, which may optionally be substituted with one or more substituents selected from halogen and hydroxyl,

or two or more of R 3 and R 4 , R 4 and R 5 , R 5 and R 6 , R 6 and R 7 , R 7 and R 8 , R 8 and R 9 , R 9 and R 6 , and R 8 and R 10 together form a bridge selected from —OCH 2 O—, —OCH 2 CH 2 O—, —OCH 2 CH 2 CH 2 O— and C 3-5 -alkylene,

or R 11 and R 3 , R 11 and R 7 , or R 11 and R 10 together form a bridge selected from —O—, —S—, —CH 2 —, —C(═O)—, —CH(OH)—, —NR 13 —, —OCH 2 — and —CH 2 O—,

R 13 is hydrogen,

C 1-6 -alkyl, which may optionally be substituted with one or more substituents selected from C 3-8 -cycloalkyl, C 5-8 -cycloalkenyl, halogen, hydroxyl, cyano and amino,

C 3-8 -cycloalkyl or C 5-8 -cycloalkenyl, which may optionally be substituted with one or more substituents selected from halogen, hydroxyl, cyano, amino, C 1-6 -alkyl, C 2-6 -alkenyl and C 2-6 -alkynyl,

—Y— is —CH 2 —, —C(═O)—, —NR 14 —, —O—, —S—, —CH 2 O—, —OCH 2 — or —CH(OH)—, R 14 is hydrogen,

C 1-6 -alkyl, which may optionally be substituted with one or more substituents selected from C 3-8 -cycloalkyl, C 5-8 -cycloalkenyl, halogen, hydroxyl, cyano and amino,

C 3-8 -cycloalkyl or C 5-8 -cycloalkenyl, which may optionally be substituted with one or more substituents selected from halogen, hydroxyl, cyano and amino,

R 17 is hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl or C 2-6 -alkynyl,

R 18 and R 19 independently are hydrogen, halogen, hydroxyl, amino, C 1-6 -alky, C 2-6 -alkenyl or C 2-6 -alkynyl,

as well as any diasteromer or enantiomer or tautomeric form thereof, mixtures of these or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein m is 1.

3. A compound according to claim 1 wherein X is.

4. A compound according to claim 1 wherein —Y— is —O— or —S—.

5. A compound according to claim 4 wherein —Y— is —O—.

6. A compound according to claim 3 wherein X is.

7. A compound according to any claim 1 wherein R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from

hydrogen, halogen, cyano, —NR 15 R 16 , —CF 3 , —OCE 3 , or nitro,

C 1-6 -alcoxy, C 3-6 -cycloalkyl-carbonyl, aryl, heteroaryl, C 3-8 -cycloalkanoyl, C 1-6 -alkylsulfonyl, or C 1-6 -alkylsulfonyl-O— which may optionally be substituted with one or more halogen

or R 4 and R 5 together form a —OCH 2 O— bridge,

or R11 and R 3 together form a bridge selected from —O— or —S—.

8. A compound according to claim 7 wherein R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from

hydrogen, halogen, cyano, —CF 3 , or —OCF 3

C 1-6 -alkoxy, 1,2,4-triazolyl, cyclopropanoyl or C 1-6 -alkylsulfonyl-O— which may optionally be substituted with one or more halogen

or R 4 and R 5 together form a —OCH 2 O— bridge,

or R 11 and R 3 together form a bridge selected from —O— or —S—.

9. A compound according to claim 8 wherein R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from

hydrogen, halogen, cyano, —CF 3 , or —OCF 3

—O—CH 3 , 1,2,4-triazolyl, —O—CH 2 CH 3 , or CH 3 -sulfonyl-O— which may optionally be substituted with one or more halogen

or R 11 and R 3 together form a bridge selected from —O— or —S—.

10. A compound according to claim 9 wherein R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from

hydrogen, halogen, cyano, —CF 3 , or —OCF 3

—O—CH 3 , —O—CH 2 CH 3 , or CH 3 -sulfonyl-O— or CF 3 -sulfonyl-O—

or R 11 and R 3 together form a bridge selected from —O— or —S—.

11. A compound according to claim 1 wherein R 11 is hydrogen.

12. A compound according to claim 1 wherein R 12 is hydrogen or C 1-6 -alkyl.

13. A compound according to claim 12 wherein R 12 is hydrogen or methyl.

14. A compound according to claim 1 wherein R 15 is hydrogen.

15. A compound according to claim 1 wherein R 16 is hydrogen.

16. A compound according to claim 1 wherein R 17 , R 18 and R 19 are all hydrogen.

17. A compound according to claim 1 , wherein n is 1.

18. A compound according to claim 1 , wherein n is 2.

19. A pharmaceutical composition comprising at least one compound according to claim 1 together with one or more pharmaceutically acceptable carriers or excipients.

20. A pharmaceutical composition according to claim 19 in unit dosage form, said compositon comprising from about 0.05 mg to about 1000 mg of said compound.

21. A pharmaceutical composition according to claim 19 in unit dosage form, said composition comprising from about 0.1 mg to about 500 mg of said compound.

22. A pharmaceutical composition according to claim 19 in unit dosage form, said composition comprising from about 0.5 mg to about 200 mg of said compound.

23. A method for the treatment of disorders or diseases selected from the following: obesity, overweight, impaired glucose tolerance (IGT), type 1 diabetes, type 2 diabetes, dyslipidemia, progression from IGT to type II diabetes, and progression of non-insulin-requiring type II diabetes to insulin-requiring type II diabetes comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 .

24. The method according to claim 23 wherein the effective amount of the compound is in the range of from about 0.05 mg to about 2000 mg per day.

25. The method according to claim 23 wherein the effective amount of the compound is in the range of from about 0.1 mg to about 1000 mg per day.

26. The method according to claim 23 wherein the effective amount of the compound is in the range of from about 0.5 mg to about 500 mg per day.

27. A method according to claim 23 , wherein the disorder or disease is selected from impaired glucose tolerance and type II diabetes.

28. A method according to claim 23 , wherein the disorder or disease is selected from: progression from IGT to type II diabetes, and progression of non-insulin-requiring type II diabetes to insulin-requiring type II diabetes.

29. A method according to claim 23 , wherein the disorder or disease is selected from: obesity and overweight.

30. A method according to claim 23 , wherein the disorder or disease is dyslipidemia.