# US 7,612,074 B2 · Diazabicyclic aryl derivatives as cholinergy ligands

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- Number: US 7,612,074 B2
- Document ID: US7612074B2
- Status: Granted
- Kind: B2
- Application number: 11/663,967
- Filed: 2005-11-29
- Published: 2007-11-15
- Granted: 2009-11-03
- Earliest claimed: 2004-11-30
- Assignees: NeuroSearch A/S
- Inventors: Dan Peters; Daniel B. Timmermann; Gunnar M. Olsen; Elsebet Østergaard Nielsen; Tino Dyhring Jørgensen
- Web page: https://patentgrep.com/patent/US7612074B2

## CPC

- C07D 487/08: Bridged systems
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/12: Antidiarrhoeals
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 9/06: Antiarrhythmics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/06: Antiasthmatics
- A61P 15/06: Antiabortive agents; Labour repressants
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 15/10: for impotence
- A61P 17/00: Drugs for dermatological disorders
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- 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 25/36: Opioid-abuse
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to novel diazabicyclic aryl compounds of the formula wherein: R′ represents hydrogen or alkyl; A represents an aromatic monocyclic or bicyclic carbocyclic or heterocyclic; and is hydrogen or a subsituent as defined in the specification. The compounds are cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. The compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

## Claims

### Claim 1

A diazabicyclic aryl compound represented by Formula (I)
any of its enantiomers or diastereomers, or a pharmaceutically acceptable salt thereof, wherein
R′ represents hydrogen or alkyl;
A represents a furanyl group; and
B represents phenyl, which phenyl is optionally substituted one or two times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cyanoalkyl, halo, trihaloalkyl, trihaloalkoxy, cyano, amino, nitro, alkyl-carbonyl-amino, ureido, and N-alkyl-ureido.

### Claim 2 (depends on 1)

The diazabicyclic aryl compound of claim 1, any of its enantiomers or diastereomers, or a pharmaceutically acceptable salt thereof, wherein R′ represents alkyl.

### Claim 3 (depends on 1)

The diazabicyclic aryl compound of claim 1, any of its enantiomers or diastereomers, or a pharmaceutically acceptable salt thereof, wherein B represents phenyl optionally substituted with amino, nitro, alkyl-carbonyl-amino, ureido, or N-alkyl-ureido.

### Claim 4 (depends on 1)

The diazabicyclic aryl compound of claim 1, which is
(8-Methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-[5-(4-nitro-phenyl)-furan-2-yl]-methanone;
(8-Methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]-methanone;
[5-(4-Amino-phenyl)-furan-2-yl]-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-methanone;
[5-(3-Amino-phenyl)-furan-2-yl]-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-methanone;
N-{4-[5-(8-Methyl-3,8-diaza-bicyclo[3.2.1]octane-3-carbonyl)-furan-2-yl]-phenyl}-acetamide;
N-{3-[5-(8-Methyl-3,8-diaza-bicyclo[3.2.1]octane-3-carbonyl)-furan-2-yl]-phenyl}-acetamide; or
1-Ethyl-3-{4-[5-(8-methyl-3,8-diaza-bicyclo[3.2.1]octane-3-carbonyl)-furan-2-yl]-phenyl}-urea;
or an enantiomer or a diastereomer, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a diazabicyclic aryl compound of claim 1, or an enantiomer or a diastereomers, or a pharmaceutically-acceptable salt thereof, together with at least one pharmaceutically-acceptable carrier or diluent.