Azabicyclic carbamates and their use as alpha-7 nicotinic acetylcholine receptor agonists

1. A pharmaceutical composition, comprising a compound represented by formula (I):

wherein:

R 1 represents 1-azabicyclo[2.2.2]oct-3-yl;

R 2 represents hydrogen or C 1 -C 6 -alkyl;

R 3 represents hydrogen, halogen, amino, hydroxy or C 1 -C 6 -alkyl;

R 4 represents hydrogen or C 1 -C 6 -alkyl which is optionally substituted by a radical selected from the group of hydroxy, halogen, cyano, C 1 -C 6 -alkoxy, trifluoromethyl, or trifluoromethoxy,

R 5 represents hydrogen or C 1 -C 6 -alkyl; or R 4 and R 5 represent together with the nitrogen atom to which they are bonded are a 5- to 6-membered heterocycle which is optionally substituted by up to 2 substituents independently of one another selected from the group of C 1 -C 6 -alkyl, C 1 -C 4 -acyl, oxo, thioxo;

R 6 represents (i) hydrogen, (ii) C 1 -C 6 -alkyl, (iii) C 3 -C 8 -cycloalkyl, (iv) C 6 -C 10 -aryl, (v) 5- to 10-membered heteroaryl, or (vi) C 6 -C 10 -arylcarbonyl, where (ii) is optionally substituted by phenyl, C 1 -C 6 -alkoxycarbonyl or C 1 -C 6 -alkoxy, and (iv), (v) and (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, halogen, cyano, C 1 -C 6 -alkoxy, C 1 -C 6 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkylamino, or C 1 -C 6 -acylamino; or R 5 and R 6 represent together with the nitrogen atom to which they are bonded are a 3- to 10-membered heterocycle which is optionally substituted by C 1 -C 6 -alkyl or C 1 -C 6 -hydroxyalkyl;

A represents oxygen or sulfur;

X represents oxygen or sulfur;

ring B represents benzo which is optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy;

or a salt thereof; and

a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 , wherein:

R 6 represents (i) hydrogen, (ii) C 1 -C 6 -alkyl, (iii) C 1 -C 8 -cycloalkyl, (iv) C 6 -C 10 -aryl, or (v) 5- to 10-membered heteroaryl, where (ii) is optionally substituted by phenyl, or C 1 -C 6 -alkoxy, and (iv) and (v) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, halogen, cyano, C 1 -C 6 -alkoxy, C 1 -C 6 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkylamino, or C 1 -C 6 -acylamino; or R 5 and R 6 together with the nitrogen atom to which they are bonded are a 3- to 8-membered heterocycle which is optionally substituted by C 1 -C 6 -alkyl or C 1 -C 6 -hydroxyalkyl; and

A represents oxygen.

3. The pharmaceutical composition of claim 1 , wherein:

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

R 3 represents hydrogen, halogen, amino, hydroxy or C 1 -C 4 -alkyl;

represents hydrogen or C 1 -C 4 -alkyl which is optionally substituted by a radical selected from the group of hydroxy, halogen, cyano, C 1 -C 3 -alkoxy, trifluoromethyl or trifluoromethoxy;

R 5 represents hydrogen or C 1 -C 4 -alkyl, or R 4 and R 5 represents together with the nitrogen atom to which they are bonded are a 5- to 6-membered heterocycle which is optionally substituted by up to 2 substituents independently of one another selected from the group of C 1 -C 6 -alkyl, C 1 -C 4 -acyl, oxo, thioxo;

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) C 5 -C 6 -cycloalkyl, (iv) phenyl, (v) 5- to 6-membered heteroaryl, or (vi) C 6 -C 10 -arylcarbonyl, where (ii) is optionally substituted by phenyl, C 1 -C 4 -alkoxycarbonyl or C 1 -C 3 -alkoxy, and (iv), (v) and (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, fluorine, chlorine, cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 3 -alkylamino, or C 1 -C 3 -acylamino, or R 5 and R 6 together with the nitrogen atom to which they are bonded are a 3- to 10-membered heterocycle which is optionally substituted by C 1 -C 3 -alkyl or C 1 -C 3 -hydroxyalkyl;

A represents oxygen;

X represents oxygen; and

ring B represents benzo which is optionally substituted by radicals from the series chlorine, fluorine, cyano, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy.

4. The pharmaceutical composition of claim 3 , wherein:

R 4 represents hydrogen or C 1 -C 4 -alkyl which is optionally substituted by a radical selected from the group of hydroxy, C 1 -C 3 -alkoxy, trifluoromethyl, trifluoromethoxy; and

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) C 5 -C 6 -cycloalkyl, (iv) phenyl, or (v) 5- to 6-membered heteroaryl, where (ii) is optionally substituted by phenyl, and (iv) and (v) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, hydroxy, chlorine, fluorine, cyano, C 1 -C 3 -alkoxy, C 1 -C 6 -acyl, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 3 -alkylamino, or C 1 -C 3 -acylamino, or R 5 and R 6 together with the nitrogen atom to which they are bonded are a 5- to 6-membered heterocycle which is optionally substituted by C 1 -C 3 -alkyl or C 1 -C 3 -hydroxyalkyl.

5. The pharmaceutical composition of claim 1 , wherein:

R 2 -R 4 each represents hydrogen;

R 5 represents hydrogen or C 1 -C 4 -alkyl, or R 4 and R 5 together with the nitrogen atom to which they are bonded are a 5- to 6-membered heterocycle which is optionally substituted by up to 2 substituents independently of one another selected from the group of C 1 -C 4 -alkyl, C 1 -C 4 -acyl, oxo, thioxo;

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) C 5 -C 6 -cycloalkyl, (iv) phenyl, (v) pyridyl, (vi) C 6 -C 10 -arylcarbonyl, where (ii) is optionally substituted by phenyl, C 1 -C 4 -alkoxycarbonyl or C 1 -C 3 -alkoxy, and (iv), (v) and (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, fluorine, chlorine, cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 3 -alkylamino, or C 1 -C 3 -acylamino, or R 5 and R 6 together with the nitrogen atom to which they are bonded are a 3- to 10-membered heterocycle which is optionally substituted by C 1 -C 3 -alkyl or C 1 -C 3 -hydroxyalkyl;

A represents oxygen;

X represents oxygen; and

ring B represents benzo.

6. The pharmaceutical composition of claim 1 , wherein:

R 2 represents hydrogen;

R 3 represents hydrogen, chlorine, fluorine, amino or C 1 -C 3 -alkyl;

R 4 represents hydrogen, methyl or ethyl, where methyl and ethyl are optionally substituted by a radical selected from the group of hydroxy, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy, or R 4 and R 5 together with the nitrogen atom to which they are bonded are a 5- to 6-membered heterocycle which is optionally substituted by up to 2 substituents independently of one another selected from the group of C 1 -C 3 -alkyl, C 1 -C 4 -acyl, oxo, thioxo;

R 5 represents hydrogen or C 1 -C 3 -alkyl;

R 6 represents (i) hydrogen, C 1 -C 4 -alkyl, (iii) cyclohexyl, (iv) phenyl, benzyl, or (vi) phenethyl, where (iv) to (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of hydroxy, chlorine, fluorine, cyano, methoxy, ethoxy, C 1 -C 4 -acyl, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 3 -alkylamino;

A represents oxygen;

X represents oxygen; and

ring B represents benzo which is optionally substituted by radicals from the series chlorine, fluorine, cyano, trifluoromethyl, trifluoromethoxy, C 1 -C 4 -alkyl, methoxy and ethoxy.

7. The pharmaceutical composition of claim 1 , wherein the compound is represented by formula:

wherein to R 1 to R 6 , A, and X have the meanings indicated in claim 1 , or a salt thereof.

8. The pharmaceutical composition of claim 1 , wherein the compound is represented by formula:

wherein R 1 to R 6 , A, and X have the meanings indicated in claim 1 , or a salt thereof.

9. The pharmaceutical composition of claim 1 , wherein the compound is represented by formula:

wherein R 1 to R 6 have the meanings indicated in claim 1 , or a salt thereof.

10. The pharmaceutical composition of claim 1 , wherein the compound is represented by formula:

wherein R 1 to R 6 have the meanings indicated in claim 1 , or a salt thereof.

11. The pharmaceutical composition of claim 1 , wherein:

R 2 -R 5 each represents hydrogen;

R 6 represents (i) hydrogen, (ii) C 1 -C 6 -alkyl, (iii) C 3 -C 8 -cycloalkyl, (iv) C 6 -C 10 -aryl, (v) 5- to 10-membered heteroaryl, (vi) C 6 -C 10 -arylcarbonyl, where (ii) is optionally substituted by phenyl, C 1 -C 6 -alkoxycarbonyl or C 1 -C 6 -alkoxy, and (iv), (v) and (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, halogen, cyano, C 1 -C 6 -alkoxy, C 1 -C 6 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkylamino, or C 1 -C 6 -acylamino;

A represents sulfur;

X represents oxygen; and

ring B represents benzo.

12. The pharmaceutical composition of claim 11 , wherein:

R 6 (i) hydrogen, (ii) C 1 -C 6 -alkyl, (iii) C 3 -C 8 -cycloalkyl, (iv) C 6 -C 10 -aryl, (v) 5- to 10-membered heteroaryl, where (ii) is optionally substituted by phenyl, or C 1 -C 6 -alkoxy, and (iv) and (v) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, halogen, cyano, C 1 -C 6 -alkoxy, C 1 -C 6 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkylamino, or C 1 -C 6 -acylamino.

13. The pharmaceutical composition of claim 11 , wherein:

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) C 5 -C 6 -cycloalkyl, (iv) phenyl, (v) 5- to 6-membered heteroaryl, (vi) C 6 -C 10 -arylcarbonyl, where (ii) is optionally substituted by phenyl, C 1 -C 4 -alkoxycarbonyl or C 1 -C 3 -alkoxy, and (iv), (v) and (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, fluorine, chlorine, cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 3 -alkylamino, or C 1 -C 3 -acylamino.

14. The pharmaceutical composition of claim 11 , wherein:

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) C 5 -C 6 -cycloalkyl, (iv) phenyl, (v) 5- to 6-membered heteroaryl, where (ii) is optionally substituted by phenyl, and (iv) and (v) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 4 -alkyl, C 1 -C 4 -hydroalkyl, hydroxy, chlorine, fluorine, cyano, C 1 -C 3 -alkoxy, C 1 -C 6 -acyl, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 3 -alkylamino, or C 1 -C 3 -acylamino.

15. The pharmaceutical composition of claim 11 , wherein:

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) C 5 -C 6 -cycloalkyl, (iv) phenyl, (v) pyridyl, (vi) C 6 -C 10 -arylcarbonyl, where (ii) is optionally substituted by phenyl, C 1 -C 4 -alkoxycarbonyl or C 1 -C 3 -alkoxy, and (iv), (v) and (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, 3- to 8-membered heterocyclyl, C 6 -C 10 -aryl, 5- to 10-membered heteroaryl, hydroxy, fluorine, chlorine, cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -acyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 3 -alkylamino, or C 1 -C 3 -acylamino.

16. The pharmaceutical composition of claim 11 , wherein:

R 6 represents (i) hydrogen, (ii) C 1 -C 4 -alkyl, (iii) cyclopentyl, cyclohexyl, (iv) phenyl, (v) benzyl, (vi) phenethyl, where (iv) to (vi) are optionally substituted by up to 3 radicals selected independently of one another from the group of hydroxy, chlorine, fluorine, cyano, methoxy, ethoxy, C 1 -C 4 -acyl, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 3 -alkylamino.

17. The pharmaceutical composition of claim 11 , wherein the compound is represented by formula:

wherein R 1 to R 6 , A, and X have the meanings indicated in claim 11 , or a salt thereof.

18. The pharmaceutical composition of claim 11 , wherein the compound is represented by formula:

wherein R 1 to R 6 , A, and X have the meanings indicated in claim 11 , or a salt thereof.

19. The pharmaceutical composition of claim 11 , wherein the compound is represented by formula:

wherein R 1 to R 6 have the meanings indicated in claim 11 , or a salt thereof.

20. The pharmaceutical composition of claim 11 , wherein the compound is represented by formula:

wherein R 1 to R 6 have the meanings indicated in claim 11 , or a salt thereof.