3-aza-spiro[5.5]undecane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
This invention relates to novel 3-aza-spiro[5.5]undecane derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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 a phenyl, naphthyl, or coumarinyl group;
wherein said phenyl, naphthyl, or coumarinyl 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
X represents —O— or —NR c —;
wherein R c represents hydrogen or alkyl.
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 the phenyl group,
which phenyl group is optionally substituted with one or more substituents independently selected from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R b represents the phenyl group,
which phenyl group is substituted once or 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 the 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 the optionally substituted coumarinyl group.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X represents —O— or —NH—.
8. The compound of claim 1 , which is
9-(3,4-Dichloro-phenoxy)-3-aza-spiro[5.5]undecane;
9-(6-Methoxy-naphthalen-2-yloxy)-3-aza-spiro[5.5]undecane;
7-(3-Aza-spiro[5.5]undec-9-yloxy)-chromen-2-one;
9-(3-Bromo-4-chloro-phenoxy)-3-aza-spiro[5.5]undecane;
9-(4-Chloro-phenoxy)-3-aza-spiro[5.5]undecane;
9-(4-Chloro-3-fluoro-phenoxy)-3-aza-spiro[5.5]undecane;
9-(3-Chloro-4-fluoro-phenoxy)-3-aza-spiro[5.5]undecane;
9-(4-Chloro-3-trifluoromethyl-phenoxy)-3-aza-spiro[5.5]undecane;
9-(Naphthalen-2-yloxy)-3-aza-spiro[5.5]undecane;
6-(3-Aza-spiro[5.5]undec-9-yloxy)-chromen-2-one;
(3-Aza-spiro[5.5]undec-9-yl)-(3,4-dichloro-phenyl)-amine;
9-(3,4-Dichloro-phenoxy)-3-methyl-3-aza-spiro[5.5]undecane; or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition, comprising a compound of claim 1 , any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent.
10. The compound of claim 8 , which is 9-(3,4-Dichloro -phenoxy)-3-aza-spiro[5.5]undecane.