# US 7,407,970 B2 · 8-aza-bicyclo[3.2.1]octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

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- Number: US 7,407,970 B2
- Document ID: US7407970B2
- Status: Granted
- Kind: B2
- Application number: 10/561,417
- Filed: 2004-06-18
- Published: 2006-06-29
- Granted: 2008-08-05
- Earliest claimed: 2003-06-24
- Assignees: NeuroSearch A/S
- Inventors: Dan Peters; Birgitte L. Eriksen; Elsebet Østergaard Nielsen; Jørgen Scheel-Krüger; Gunnar M. Olsen
- Web page: https://patentgrep.com/patent/US7407970B2

## CPC

- C07D 451/04: with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 13/10: of the bladder
- A61P 15/10: for impotence
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61P 25/32: Alcohol-abuse
- A61P 25/34: Tobacco-abuse
- A61P 25/36: Opioid-abuse
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 451/06: Oxygen atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to novel 8-aza-bicyclo[3.2.1]octane 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.

## Claims

### Claim 1

An 8-aza-bicyclo[3.2.1]octane derivative of the Formula I:
or any of its isomers or any mixture of its isomers,
or a pharmaceutically acceptable salt thereof,
wherein
Ra represents hydrogen;
X represents —O—;
Rb represents an aryl group selected from monosubstituted phenyl,
which group is substituted with a substituent selected from the group consisting of
trifluoromethoxy, cyano, hydroxy, and alkoxy; or
Rb represents an aryl group selected from disubstituted phenyl which group is substituted with substituents independently selected from the group consisting of halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, and alkoxy; or
Rb represents a heteroaryl group selected from naphthyl, pyridyl, quinolinyl, isoquinolinyl or quinazolinyl, which heteroaryl group is substituted with one or two substituents independently selected from the group consisting of halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, and alkoxy.

### Claim 2 (depends on 1)

The chemical compound of claim 1, wherein
Rb represents a pyridyl group,
which pyridyl group is substituted with one or two substituents independently selected from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy and alkoxy.

### Claim 3 (depends on 1)

The chemical compound of claim 1, which is
exo-3-(2,3-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(3-Chloro-4-fluorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Chloro-3-fluorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Chloro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(3-Chloro-4-cyanophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Chloro-3-methylphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Chloronaphthalen-1-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(5-Chloro-pyridin-2-yl)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Methoxyphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(6-Bromo-naphthalen-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Bromo-3-chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Cyanophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Methylphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(6-Chloropyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(5-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(6-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(3-Trifluoromethoxyphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Trifluoromethoxyphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(6-Methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(5-Trifluoromethylpyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(6-Ethoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Fluoro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3.2.1]octane;
or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 1, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent.

### Claim 5 (depends on 1)

The chemical compound of claim 1, comprising:
exo-3-(3-Chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane;
or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof.