2-aza-bicyclo[3.3.0]octane derivatives

1. A compound of formula (I) with the stereogenic centers in (1S,3S,5S)-configuration

wherein

A represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono- or disubstituted, wherein the substituents are independently selected from the group consisting of (C 1-4 )alkyl, (C 3-6 )cycloalkyl, (C 2-6 )alkinyl,

(C 1-4 )alkoxy, NR 2 R 3 , halogen and unsubstituted or independently mono- or disubstituted phenyl, wherein the substituents are independently selected from the group consisting of (C 1-4 ) alkyl, (C 1-4 )alkoxy, fluorine and chlorine;

B represents an aryl- or heterocyclyl-group, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or trisubstituted, wherein the substituents are independently selected from the group consisting of (C 1-4 )alkyl, (C 1-4 )alkoxy, trifluoromethyl, NR 2 R 3 , NHC(O)CH 3 and halogen;

R 1 represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or trisubstituted wherein the substituents are independently selected from the group consisting of (C 1-4 )alkyl, (C 1-4 )alkoxy, halogen, trifluoromethyl and NR 2 R 3 ; or R 1 represents a 2,3-dihydro-benzofuranyl- or a 2,3-dihydro-benzo[1,4]dioxinyl-group which groups are unsubstituted or independently mono- or disubstituted with (C 1-4 )alkyl, (C 1-4 )alkoxy and halogen;

R 2 represents hydrogen or (C 1-4 )alkyl;

R 3 represents hydrogen or (C 1-4 )alkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein

A represents heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-sub-stituted, wherein the substituent is selected from the group consisting of (C 1-4 )alkyl, (C 3-6 )cycloalkyl or NR 2 R 3 ; or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 , wherein

B represents aryl, wherein the aryl is unsubstituted or independently mono- or disubstituted, wherein the substituents are independently selected from the group consisting of (C 1-4 )alkyl, (C 1-4 )alkoxy, trifluoromethyl, NHC(O)CH 3 and halogen;

or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 1 , wherein

R 1 represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono- or disubstituted wherein the substituents are independently selected from the group consisting of (C 1-4 )alkyl, (C 1-4 )alkoxy and halogen; or R 1 represents a 2,3-dihydro-benzofuranyl- or a 2,3-dihydro-benzo[1,4]dioxinyl-group;

or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 1 , wherein

A represents an oxazolyl, a thiazolyl or a pyrimidyl group, which groups are unsubstituted or monosubstituted, wherein the substituent is selected from the group consisting of (C 1-4 )alkyl, (C 3-6 )cycloalkyl or NH 2 ;

or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 1 , wherein

B represents phenyl, wherein the phenyl is unsubstituted or independently mono- or disubstituted, wherein the substituents are independently selected from the group consisting of (C 1-4 )alkyl, trifluoromethyl and halogen;

or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 1 , wherein

R 1 represents an imidazo[2,1-b]thiazolyl or a benzoisoxazolyl group which groups are unsubstituted or monosubstituted wherein the substituent is selected from the group consisting of (C 1-4 )alkyl, trifluoromethyl and halogen; or R 1 represents a 2,3-dihydro-benzofuranyl-group;

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 1 , wherein

A represents a thiazolyl group, which group is unsubstituted or monosubstituted, wherein the substituent is selected from the group consisting of (C 1-4 )alkyl, (C 3-6 )cycloalkyl or NH 2 ;

or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 1 , wherein

R 2 and R 3 both represent hydrogen;

or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 1 selected from the group consisting of:

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,3S,5S)-2-(2-methyl-5-p-tolyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethyl]-amide;

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,3S,5S)-2-(2-amino-5-p-tolyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethyl]-amide;

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid {(1S,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid {(1S,3S,5S)-2-[5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid {(1S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid {(1S,3S,5S)-2-[2-cyclopropyl-5-(4-fluoro -phenyl)-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3 -ylmethyl}-amide;

6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid {(1S,3S,5S)-2-[2-cyclopropyl-5-(3-trifluoromethyl-phenyl)-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

Benzo[d]isoxazole-3-carboxylic acid [(1S,3S,5S)-2-(2-methyl-5-p-tolyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethyl]-amide;

Benzo[d]isoxazole-3-carboxylic acid {(1S,3S,5S)-2[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

Benzo[d]isoxazole-3-carboxylic acid {(1S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

Benzo[d]isoxazole-3-carboxylic acid [(1S,3S,5S)-2-(2-cyclopropyl-5-phenyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethyl]-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(4-fluoro-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid [(1S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethyl]-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[2-methyl-5-(3-trifluoromethyl -phenyl)-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3 -ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(4-bromo-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3,5-dimethyl-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3-bromo-4-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3,4-difluoro-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(2,4-dimethyl-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3,4-dichloro-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo [3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3,4-dimethyl-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid {(1S,3S,5S)-2-[5-(3-acetylamino-phenyl)-2-methyl -thiazole-4-carbonyl]-2-azabicyclo[3.3.0]octane-3-ylmethyl}-amide;

2,3-Dihydro-benzofuran-4-carboxylic acid [(1S,3S,5S)-2-(2-methyl-5-phenyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethy]-amide; and

2,3-Dihydro-benzofuran-4-carboxylic acid [(1S,3S,5S)-2-(2-cyclopropyl-5-phenyl-thiazole-4-carbonyl)-2-azabicyclo[3.3.0]octane-3-ylmethyl]-amide;

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound of claim 1 , in free or a pharmaceutically acceptable salt form, and at least one therapeutically inert excipient.

12. A compound according to claim 1 in the form of a pharmaceutically acceptable salt.

13. A method for the treatment of sleep disorders selected from the group consisting insomnias, restless leg syndrome, jet-lag syndrome, shift-work syndrome, delayed or advanced sleep phase syndrome, and insomnias related to psychiatric disorders, comprising administering the compound of claim 1 , in free or pharmaceutically acceptable salt form to a subject in need of such prophylaxis or treatment.