# US 5,703,235 A · N-Aminoalkyl-2-anthracenecarboxamides; new dopamine receptor subtype specific ligands

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- Number: US 5,703,235 A
- Document ID: US5703235A
- Status: Granted
- Kind: A
- Application number: 08/619,351
- Filed: 1996-03-21
- Granted: 1997-12-30
- Earliest claimed: 1996-03-21
- Assignees: Neurogen Corporation
- Inventors: Jun Yuan; Xi Chen
- Web page: https://patentgrep.com/patent/US5703235A

## CPC

- C07D 295/13: to an acyclic saturated chain
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- 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
- C07D 211/14: with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- C07D 211/70: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07C 2603/24: Anthracenes; Hydrogenated anthracenes
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Disclosed are compounds of the formula: ##STR1## or the pharmaceutically acceptable acid addition salts thereof, wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are the same or different and represent hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, hydroxy, amino, cyano, nitro, trifluoromethyl, trifluoromethoxy, C.sub.1 -C.sub.6 alkoxy, --O.sub.2 CR', --NHCOR', --COR', --SO.sub.m R', where R' is C.sub.1 -C.sub.6 alkyl and wherein m is 0, 1 or 2; or R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 independently represent --CONR'R", or --NR'R" where R' and R" independently represent hydrogen or C.sub.1 -C.sub.6 alkyl; R.sub.10 is hydrogen or C.sub.1 -C.sub.6 alkyl; and R represents an aminoalkyl group; which compounds are useful in the treatment of affective disorders such as schizophrenia, depression, Alzheimer's disease, movement disorders such as Parkinsonism and dystonia, and other disorders which respond to dopaminergic blockade such as substance abuse and obsessive compulsive disorders. Further, compounds of this invention may be useful in treating the extrapyramidal side effects associated with the use of conventional neuroleptic agents.

## Claims

### Claim 1

A compound of the formula: ##STR24## or the pharmaceutically acceptable acid addition salts thereof, wherein:
R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are the same or different and represent hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, hydroxy, amino, cyano, nitro, trifluoromethyl, trifluoromethoxy, C.sub.1 -C.sub.6 alkoxy, --O.sub.2 CR', --NHCOR', --COR', --SO.sub.m R', where R' is C.sub.1 -C.sub.6 alkyl and wherein m is 0, 1 or 2; or
R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 independently represent --CONR'R", or --NR'R" where R' and R" independently represent hydrogen or C.sub.1 -C.sub.6 alkyl;
R.sub.10 is hydrogen or C.sub.1 -C.sub.6 alkyl; and
A represents an alkylene group of 2 to 6 carbon atoms optionally substituted with one or more alkyl groups having from 1 to 4 carbon atoms;
R.sub.11 and R.sub.12 are the same or different and represent hydrogen or C.sub.1 -C.sub.6 alkyl; and
W is phenyl, naphthyl, 1-(5,6,7,8-tetrahydro)naphthyl or 4-(1,2-dihydro)indenyl, pyridinyl, pyrimidyl, quinolinyl, isoquinolinyl, benzofuranyl, benzothienyl; each of which is optionally substituted with up to three groups independently selected from halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.4 alkoxy, thioalkoxy, hydroxy, amino, monoalkylamino, dialkylamino, cyano, nitro, trifluoromethyl or trifluoromethoxy.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein R.sub.1 -R.sub.9 are hydrogen; R.sub.11 and R.sub.12 are hydrogen; A is C.sub.3 -C.sub.5 alkylene; and W is naphthyl or phenyl optionally substituted with up to three groups independently selected from halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.4 alkoxy, thioalkoxy, hydroxy, amino, monoalkylamino, dialkylamino, cyano, nitro, trifluoromethyl or trifluoromethoxy.

### Claim 3 (depends on 1)

A compound according to claim 1, wherein R.sub.1 -R.sub.10 are hydrogen; R.sub.11 and R.sub.12 are hydrogen; A is C.sub.3 -C.sub.5 alkylene; and W is naphthyl or phenyl optionally substituted with up to two groups in the 2 and/or 3 and/or 6 positions, the groups being independently selected from halogen, C.sub.1 -C.sub.4 alkyl, and C.sub.1 -C.sub.4 alkoxy.

### Claim 4 (depends on 1)

A compound according to claim 1, wherein R.sub.1 -R.sub.10 are hydrogen; R.sub.11 and R.sub.12 are hydrogen; A is C.sub.4 alkylene; and W is naphthyl or phenyl optionally substituted with up to two groups in the 2 and/or 3 and/or 6 positions, the groups being independently selected from chloro, methyl, and methoxy.

### Claim 5 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2,3-Dichlorophenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 6 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(1-Naphthyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 7 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2,3-Dimethylphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 8 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2-Methylphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 9 (depends on 1)

A compound according to claim 1 which is N-{4-›4-(2-Chlorophenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 10 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2-Methoxyphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 11 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(8-Isoquinolinyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide hydrochloride.

### Claim 12 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(3-Chloro-2-methylphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxa mide hydrochloride.

### Claim 13 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2,3-Dichlorophenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 14 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(1-Naphthyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 15 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2,3-Dimethylphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 16 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2-Methylphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 17 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2-Chlorophenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 18 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(2-Methoxyphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 19 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(8-Isoquinolinyl)-1-piperazinyl!butyl}-2-anthracenecarboxamide.

### Claim 20 (depends on 1)

A compound according to claim 1, which is N-{4-›4-(3-Chloro-2-methylphenyl)-1-piperazinyl!butyl}-2-anthracenecarboxa mide.