3,9-diaza-spiro[5.5]undecane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

1. A compound of Formula I:

any of its stereoisomers or any mixture of its stereoisomers,

or a pharmaceutically acceptable salt thereof;

wherein

R a represents hydrogen or alkyl;

which alkyl is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; and

R b represents an aryl or a heteroaryl group;

which aryl or heteroaryl group group is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, alkoxy, cycloalkoxy, alkoxyalkyl, cycloalkoxyalkyl, methylenedioxy, ethylenedioxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, —NR′R″, —(C═O)NR′R″ or —NR′(C═O)R″;

wherein R′ and R″ independent of each other are hydrogen or alkyl;

with the proviso that the compound is not

4-(3,9-diaza-spiro[5.5]undec-3-yl)-benzonitrile or

3-pyridin-4-yl-3,9-diaza-spiro[5.5]undecane.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R a represents hydrogen or alkyl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R b represents a phenyl group,

which phenyl group is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano arid alkoxy.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R b represents a phenyl group,

which phenyl group is substituted twice with substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R b represents a naphthyl group,

which naphthyl group is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R b represents a pyridyl group,

which pyridyl group is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano arid alkoxy.

7. The compound of claim 1 , which is

3-(3,4-Dichloro-phenyl)-9-methyl-3,9-diaza-spiro[5.5]undecane;

3-(6-Chloro-pyridin-2-yl)-9-methyl-3,9-diaza-spiro[5.5]undecane;

3-(6-Chloro-pyridin-2-yl)-3,9-diaza-spiro[5.5]undecane;

3-(5-Chloro-pyridin-2-yl)-3,9-diaza-spiro[5.5]undecane;

3-(6-Methoxy-naphthalen-2-yl)-3,9-diaza-spiro[5.5]undecane;

3-(3,4-Dichloro-phenyl)-3,9-diaza-spiro[5.5]undecane;

3-(6-Bromo-pyridin-2-yl)-3,9-diaza-spiro[5.5]undecane;

3-(2,3-Dichloro-phenyl)-3,9-diaza-spiro[5.5]undecane;

3-(4-Chloro-phenyl)-3,9-diaza-spiro[5.5]undecane;

3-(3-Chloro-4-fluoro-phenyl)-3,9-diaza-spiro[5.5]undecane;

3-(5-Bromo-pyridin-2-yl)-3,9-diaza-spiro[5.5]undecane;

3-Naphthalen-2-yl-3,9-diaza-spiro[5.5]undecane;

3-(6-Methoxy-naphthalen-2-yl)-9-methyl-3,9-diaza-spiro[5.5]undecane;

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition, comprising:

a therapeutically effective amount of a compound of Formula I:

wherein

R a represents hydrogen or alkyl;

which alkyl is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; and

R b represents an aryl or a heteroaryl group;

which aryl or heteroaryl group group is optionally substituted with one or more substituents independently selected from the group consisting of:

halo, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, alkoxy, cycloalkoxy, alkoxyalkyl, cycloalkoxyalkyl, methylenedioxy, ethylenedioxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, —NR′R″, —(C═O)NR′R″ or —NR′(C═O)R″;

wherein R′ and R″independent of each other are hydrogen or alkyl;

with the proviso that the compound is not 4-(3,9-diaza-spiro[5.5]undec-3-yl)-benzonitrile or

3-pyridin-4-yl-3,9-diaza-spiro[5.5]undecane,

any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and

at least one pharmaceutically acceptable carrier, excipient or diluent.

9. The compound 3-(3,4-Dichlorophenyl)-3,9-diaza-spiro [5.5]undecane or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition, comprising:

a therapeutically effective amount of said compound of claim 9 or a pharmaceutically acceptable salt thereof; and

a pharmaceutically acceptable carrier.

11. A method for treating depression, which comprises:

administering to a subject in need thereof an effective amount to treat depression of the composition of claim 8 , wherein R b represents an aryl group or a substituted aryl group.

12. A method for treatment of depression in a human which comprises the step of:

administering to a human in need thereof a therapeutically effective amount of the compound 3-(3,4-Dichlorophenyl)-3,9-diaza-spiro[5.5]undecane or a pharmaceutically acceptable salt thereof.