3-aza spiro[5,5]undec-8-ene derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
This invention relates to novel 3-aza-spiro[5.5]undec-8-ene 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 an aryl or a heteroaryl group; which aryl or heteroaryl 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.
2. The compound of claim 1 , any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein
R a represents hydrogen or alkyl.
3. The compound of claim 1 , any of its stereoisomers or any mixture of its stereoisomers, 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 and alkoxy.
4. The compound of claim 1 , any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein
R b represents a 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 , any of its stereoisomers or any mixture of its stereoisomers, 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 , any of its stereoisomers or any mixture of its stereoisomers, 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 and alkoxy.
7. The compound of claim 1 , any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein
R b represents a benzofuranyl group, which benzofuranyl group is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.
8. The compound of claim 1 , any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein
R b represents a benzo[b]thienyl group, which benzo[b]thienyl group is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.
9. The compound of claim 1 , which is
9-(3,4-Dichloro-phenyl)-3-aza-spiro[5.5]undec-8-ene;
9-Benzo[b]thiophen-2-yl-3-aza-spiro[5.5]undec-8-ene;
9-Benzofuran-2-yl-3-aza-spiro[5.5]undec-8-ene;
9-(6-Methoxy-naphthalen-2-yl)-3-aza-spiro[5.5]undec-8-ene;
9-(2,3-Dichloro-phenyl)-3-aza-spiro[5.5]undec-8-ene;
9-(2-Chloro-phenyl)-3-aza-spiro[5.5]undec-8-ene;
9-(3-Chloro-phenyl)-3-aza-spiro[5.5]undec-8-ene;
9-(4-Chloro-phenyl)-3-aza-spiro[5.5]undec-8-ene;
9-(4-Chloro-3-methoxy-phenyl)-3-aza-spiro[5.5]undec-8-ene;
9-(6-Bromo-pyridin-2-yl)-3-aza-spiro[5.5]undec-8-ene;
9-Naphthalen-2-yl-3-aza-spiro[5.5]undec-8-ene;
9-(3,4-Dichloro-phenyl)-3-methyl-3-aza-spiro[5.5]undec-8-ene;
9-Benzofuran-2-yl-3-methyl-3-aza-spiro[5.5]undec-8-ene;
9-Benzo[b]thiophen-2-yl-3-methyl-3-aza-spiro[5.5]undec-8-ene;
9-(6-Methoxy-naphthalen-2-yl)-3-methyl-3-aza-spiro[5.5]undec-8-ene;
any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition, comprising a therapeutically effective amount of 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.
11. The compound of claim 9 , which is 9-(3,4-dichlorophenyl)-3-aza-spiro[5.5]undec-8-ene;
any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof.