# US 5,346,896 A · 1-(aryl or heteroaryl)-4[.omega.-(aryl or heteroaryl).omega.-(aryl or heteroaryl)alkylene]piperazines

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- Number: US 5,346,896 A
- Document ID: US5346896A
- Status: Granted
- Kind: A
- Application number: 07/867,221
- Filed: 1992-06-03
- Granted: 1994-09-13
- Earliest claimed: 1990-10-03
- Assignees: John Wyeth & Brother Limited
- Inventors: Terence J. Ward; Graham J. Warrellow
- Web page: https://patentgrep.com/patent/US5346896A

## CPC

- C07D 295/092: with aromatic radicals attached to the chain
- A61P 9/12: Antihypertensives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/24: Antidepressants
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/38: having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are piperazine derivatives of the formula ##STR1## or a pharmaceutically acceptable acid addition salt thereof, wherein W is (CH.sub.2).sub.m, CHOH or O, m is one of the integers 1 or 2, A is an alkylene chain of 1 to 3 carbon atoms optionally substituted by one or more (lower)alkyl groups, R is hydrogen or lower alkyl, R.sup.1 and R.sup.2 are each, independently, aryl or heteroaryl radicals with the proviso that R.sup.1 is not an optionally substituted indolyl radical, R.sup.3 is hydrogen or lower alkyl and R.sup.4 is an aryl or heteroaryl radical. The compounds are 5HT.sub.1A binding agents which may be used, for example, in the treatment of CNS disorders such as anxiety.

## Claims

### Claim 1

A compound of the formula (I) ##STR14## or a pharmaceutically acceptable acid addition salt thereof, wherein W is (CH.sub.2).sub.m, CHOH or O,
m is one of the integers 1 or 2,
A is an alkylene chain of 1 to 3 carbon atoms optionally substituted by one or more (lower)alkyl groups,
R is hydrogen or lower alkyl,
R.sup.1 and R.sup.2 are each, independently, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl or tetrazolyl each of which may be optionally substituted by one or more substituents selected from lower alkyl, lower alkoxy, halogen, halo(lower)alkyl, nitro, amino, (lower)alkylamino, di(lower)alkylamino, phenyl, halophenyl, (lower)alkylphenyl or (lower)alkoxyphenyl,
R.sup.3 is hydrogen or lower alkyl and
R.sup.4 is phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl each of which may be optionally substituted by one or more substituents selected from lower alkyl, lower alkoxy, halogen, halo(lower)alkyl, nitro, amino, (lower)alkylamino, di(lower)alkylamino, phenyl, halophenyl, (lower)alkylphenyl (lower)alkoxyphenyl, hydroxy, hydroxy(lower)alkyl, and --CONR.sup.5 R.sup.6 (where R.sup.5 and R.sup.6 are each hydrogen, lower alkyl or --NHSO.sub.2 (lower)alkyl).

### Claim 2 (depends on 1)

A compound of claim 1 wherein A is --CH.sub.2 --, --CH.sub.2 CH.sub.2 -- or --CH.sub.2 CH.sub.2 CH.sub.2 --.

### Claim 3 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.4 is optionally substituted by one or more substituents selected from lower alkyl, lower alkoxy, halogen, halo(lower)alkyl, nitro, amino, (lower)alkylamino, di(lower)alkylamino, phenyl, halophenyl, (lower)alkylphenyl or (lower)alkoxyphenyl.

### Claim 4 (depends on 1)

A compound as claimed in claim 1 which is
1-(2-methoxyphenyl)-4-(2-phenoxy-2-phenylethyl)-piperazine or
1-(2-methoxyphenyl-4-[2-(3-methylphenoxy)-2-phenylethyl]piperazine or
1-(2- methoxyphenyl )-4-[2-(4-fluorobenzyl)-2-methyl-2-(2-pyridyl)ethyl]piperazine or
1-(2-methoxyphenyl)4-[(3-(1H-imidazol-1-yl)-2-phenylpropyl]piperazine or
1-(2-methoxyphenyl)-4-[2-(4-fluorobenzyl)-2-(4-pyridyl)ethyl]piperazine,
or a pharmaceutically acceptable acid addition salt thereof.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 in association with a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

A method of treating anxiety or depression in a mammal in need thereof, comprising administering to said mammal an amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, effective to alleviate anxiety or depression.