# US 8,541,409 B2 · Carbamoyloxy arylalkanoyl arylpiperazine analgesics

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- Number: US 8,541,409 B2
- Document ID: US8541409B2
- Status: Granted
- Kind: B2
- Application number: 12/600,291
- Filed: 2008-04-30
- Published: 2011-08-11
- Granted: 2013-09-24
- Earliest claimed: 2007-05-14
- Assignees: SK Biopharmaceuticals Co., Ltd.
- Applicants: Byong Sung Kwak; Hong Sik Moon; Han Ju Yi; Young Soon Kang; Dae Joong Im; Eun Hee Chae; Sang Mi Chae; Ki Ho Lee
- Inventors: Byong Sung Kwak; Hong Sik Moon; Han Ju Yi; Young Soon Kang; Dae Joong Im; Eun Hee Chae; Sang Mi Chae; Ki Ho Lee
- Web page: https://patentgrep.com/patent/US8541409B2

## CPC

- C07D 239/42: One nitrogen atom (nitro radicals C07D239/30)
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 241/04: having no double bonds between ring members or between ring members and non-ring members
- C07D 241/44: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D 265/18: with hetero atoms directly attached in position 2
- C07D 265/36: condensed with one six-membered ring
- C07D 295/033: with the ring nitrogen atoms directly attached to carbocyclic rings
- C07D 307/54: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 317/58: Radicals substituted by nitrogen atoms (nitro radicals C07D317/52)
- C07D 317/66: Nitrogen atoms not forming part of a nitro radical
- C07D 319/18: Ethylenedioxybenzenes, not substituted on the hetero ring
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

There is provided a novel carbamoyloxy arylalkanoyl arylpiperazine derivative compound having abundant racemic or enantiomeric characteristics, represented by the Formula 1, and pharmaceutically available salts or hydrates thereof. Also, there are provided a pharmaceutical composition for treating pain, anxiety or depression including an effective amount of the compound, and a method for treating pain, anxiety or depression in mammals by administering an effective amount of the compound to the mammals in need of treatment thereof.

## Claims

### Claim 1

A compound of Formula 1:
or a pharmaceutically acceptable salt or hydrate thereof, wherein - - - denotes an optional bond forming a cyclic moiety;
each of R1 and R2 is independently selected from the group consisting of H- and straight- or branched-chain C1-C6 alkyl, or
R1 and R2 are taken together to form piperidinyl or piperazinyl, or R1 and R2 are taken together with Ar1 to form benzo[d][1,3]oxazin-2-one moiety;
Ar1 is selected from the group consisting of furanyl, methylenedioxyphenyl and phenyl which is optionally substituted by one or more substituents independently selected from the group consisting of H-, straight- or branched-chain C1-C6 alkyl, fluoro, chloro, bromo, straight- or branched-chain C1-C6 alkoxy, nitro and trifluoromethyl;
z is H- or fluoro;
Ar2 is selected from the group consisting of phenyl, methylenedioxyphenyl, pyridinyl, pyrimidinyl, naphthyl, and quinoxalinyl, wherein Ar2 is optionally substituted by one or more substituents independently selected from the group consisting of H-, straight- or branched-chain C1-C6 alkyl, hydroxy, halo, straight- or branched- chain C1-C6 alkoxy, nitro, acetyl, t-butylacetyl, trifluoromethyl, amino and acetyloxy;
n is 1 or 2; and
m is 0, 1 or 2.

### Claim 2 (depends on 1)

The compound of claim 1, which is a compound of Formula 2:
wherein
each of R1, R2, z, n, m and Ar2 is as defined in claim 1; and
X1 is one or more substituents independently selected from the group consisting of H-, straight- or branched-chain C1-C6 alkyl, fluoro, chloro, bromo, straight- or branched-chain C1-C6 alkoxy, nitro and trifluoromethyl.

### Claim 3 (depends on 1)

The compound of claim 1, which is a compound of Formula 3:
wherein
X2 is one or more substituents independently selected from the group consisting of H-, straight- or branched-chain C1-C6 alkyl, hydroxy, halo, straight- or branched-chain C1-C6 alkoxy, nitro, acetyl, t-butylacetyl, trifluoromethyl and amino.

### Claim 4 (depends on 3)

The compound of claim 3, wherein X2 is straight- or branched-chain C1-C6 alkoxy.

### Claim 5 (depends on 3)

The compound of claim 3, wherein X2 is two methoxy substituents.

### Claim 6 (depends on 1)

The compound of claim 1, which is selected from the group consisting of:
carbamic acid 3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-oxo-1-phenyl-3-(4-p-tolyl-piperazin-1-yl)-propyl ester,
carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 1-(4-chloro-phenyl)-3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-propyl ester,
carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-1-(4-flouro-phenyl)-3-oxo-propyl ester,
carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-p-tolyl-propyl ester,
carbamic acid 3-[4-(2,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3,5-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3,5-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-(4-benzo[1,3]dioxol-5-yl-piperazin-1-yl)-3-oxo-1-phenyl-propyl ester,
carbamic acid 1-(4-methoxy-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(4-chloro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 3-[4-(4-tert-butyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
dimethyl-carbamic acid 3-[4-(4-methoxy-phenyl)-piperazin-1 -yl]-3-oxo-1 -phenyl- propyl ester,
carbamic acid 3-[4-(3,4-dimethyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-oxo-1-phenyl-3-(4-quinoxalin-2-yl-piperazin-1-yl)-propyl ester,
acetic acid 4-[4-(3-carbamoyloxy-3-phenyl-propionyl)-piperazin-1-yl]-phenyl ester,
carbamic acid 3-oxo-1-phenyl-3-(4-pyridin-2-yl-piperazin-1-yl)-propyl ester,
carbamic acid 3-oxo-1-phenyl-3-(4-pyrimidin-2-yl-piperazin-1-yl)-propyl ester,
carbamic acid 3-[4-(3,5-dichloro-pyridin-2-yl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(4-chloro-3-trifluoromethyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-oxo-1-phenyl-3[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propyl ester,
carbamic acid 3-[4-(2-flouro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3-flouro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-oxo-3-(4-phenyl-piperazin-1 -yl)-1 -(4-trifluoromethyl-phenyl)-propyl ester,
carbamic acid 3-oxo-3-(4-phenyl-piperazin-1-yl)-1-p-tolyl-propyl ester,
carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 1 -(4-nitro-phenyl)-3-oxo-3-(4-phenylpiperazin-1 -yl)-propyl ester,
carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-(4-trifluoromethyl-phenyl)-propyl ester,
carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-1-(4-nitro-phenyl)-3-oxo-propyl ester,
carbamic acid 3-[4-(3,4-dichloro-benzyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(4-chloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-{4-[2-(3,4-dichloro-phenyl)-ethyl]-1-piperazin-1 -yl}-3-oxo-1 -phenyl-propyl ester,
carbamic acid 4-[4-(3,4-dichloro-phenyl)-piperazin-1 -yl]-4-oxo-1 -phenyl-butyl ester,
carbamic acid 4-[4-(3,4-dimethoxy-phenyl)-piperazin-1 -yl]-4-oxo-1 -phenyl-butyl ester,
carbamic acid 1-(2-nitro-phenyl)-3-oxo-3-(4-phenylpiperazin-1-yl)-propyl ester,
carbamic acid 1-(2-chloro-phenyl)-3-oxo-3-(4-phenylpiperazin-1-yl)-propyl ester,
carbamic acid 1-(2-methoxy-phenyl)-3-oxo-3-(4-phenylpiperazin-1-yl)-propyl ester
carbamic acid 1-(3-trifluoromethyl-phenyl)-3-oxo-3-(4-phenylpiperazin-1-yl)-propyl ester,
carbamic acid 1-(3-bromo-phenyl)-3-oxo-3-(4-phenylpiperazin-1-yl)-propyl ester,
carbamic acid 1-(3,4-dimethoxy-phenyl)-3-oxo-3-(4-phenylpiperazin-1-yl)-propyl ester,
carbamic acid 1-furan-3-yl-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(3-methyl-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(3-chloro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(3,4-dichloro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(2,3,4,5,6-pentafluoro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(3,5-di-trifluoromethyl-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(2,4-dichloro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(2,5-difluoro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(2,4-dimethyl-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester,
carbamic acid 1-(3,4-methylenedioxy-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)- propyl ester,
carbamic acid 1-(3,4-difluoro-phenyl)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl ester, and
4-[2-oxo-2-(4-phenyl-piperazin-1-yl)-ethyl]-1,4-dihydro-benzo[d][1,3]oxazin-2-one.

### Claim 7 (depends on 1)

The compound of claim 1, which is selected from the group consisting of:
carbamic acid 3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3,4-dichloro-benzyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 4-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-4-oxo-1-phenyl-butyl ester,
carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(4-methyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3-chloro-4-trifluoromethyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester, and
carbamic acid 3-oxo-1-phenyl-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propyl ester.

### Claim 8 (depends on 1)

The compound of claim 1, wherein the compound is carbamic acid 3-[4-(3,4- dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 9 (depends on 1)

The compound of claim 1, which is selected from the group consisting of:
(R)-carbamic acid 3-[4-(4-chloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-flouro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-ethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
piperidine -1-carboxylic acid-(R)-3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl propyl ester,
butyl-carbamic acid-(R)-3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-amino-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3-hydroxy-4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-methyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(4-methyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(4-chloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid (R)-3-[4-(3-hydroxy-4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester, and
carbamic acid (R)-3-[4-(3-methoxy-4-hydroxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 10 (depends on 1)

The compound of claim 1, which is selected from the group consisting of:
(R)-carbamic acid 3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester, and
(S)-carbamic acid 3-[4-(4-chloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 11 (depends on 1)

The compound of claim 1, wherein the compound is (R)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 12 (depends on 1)

The compound of claim 1, wherein the pharmaceutically acceptable salt is selected from the group consisting of methanesulfonate and hydrochloride.

### Claim 13

A compound which is selected from the group consisting of:
carbamic acid 3-{4-[bis-(4-flouro-phenyl)-methyl]-piperazin-1-yl}-3-oxo-1-phenyl-propyl ester,
carbamic acid 2,2-difluoro-3-oxo-1-phenyl-3-(4-phenylpiperazin-1-yl)-propyl ester,
carbamic acid 2-(4-phenyl-piperazine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl ester,
phenethyl-carbamic acid-(R)-3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester, and
4-methyl-piperazine-1-carboxylic acid-(R)-3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, wherein the compound is selected from the group consisting of:
carbamic acid 3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3,4-dichloro-benzyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 4-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-4-oxo-1-phenyl-butyl ester,
carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(4-methyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
carbamic acid 3-[4-(3-chloro-4-trifluoromethyl-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester, and
carbamic acid 3-oxo-1-phenyl-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propyl ester.

### Claim 16 (depends on 14)

The pharmaceutical composition of claim 14, wherein the compound is
carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 17 (depends on 14)

The pharmaceutical composition of claim 14, wherein the compound is selected from the group consisting of:
(R)-carbamic acid 3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-methoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(S)-carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(3,4-difluoro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester,
(R)-carbamic acid 3-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester, and
(S)-carbamic acid 3-[4-(4-chloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 18 (depends on 14)

The pharmaceutical composition of claim 14, wherein the compound is (R)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester.

### Claim 19 (depends on 14)

The pharmaceutical composition of claim 14, wherein the therapeutically effect amount is in the range of 20 to 500 mg.