# US 7,612,068 B2 · Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives

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- Number: US 7,612,068 B2
- Document ID: US7612068B2
- Status: Granted
- Kind: B2
- Application number: 10/551,737
- Filed: 2004-04-27
- Published: 2006-10-19
- Granted: 2009-11-03
- Earliest claimed: 2003-04-30
- Assignees: H. Lundbeck A/S
- Inventors: Garrick P. Smith; Gitte K. Mikkelsen; Kim Andersen; Daniel R. Greve; Jorgen Eskildsen
- Web page: https://patentgrep.com/patent/US7612068B2

## CPC

- C07D 207/16: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 323/20: with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07D 207/12: Oxygen or sulfur atoms
- C07D 211/46: having a hydrogen atom as the second substituent in position 4
- C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07C 2601/14: The ring being saturated
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to compounds of formula I wherein the substituents are as defined below. The compounds of formula I are useful for the treatment of diseases such as schizophrenia, including both the positive and the negative symptoms of schizophrenia and other psychoses.

## Claims

### Claim 1

A compound of the formula I
wherein
X is O, S or CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl;
Y is O or S;
R1, R2, R3 and R4 are each independently hydrogen; halogen; cyano; nitro; C1-6-alk(en/yn)yl; C1-6-alk(en/yn)yloxy; C1-6-alk(en/yn)ylsulfanyl; hydroxy; hydroxy-C1-6-alk(en/yn)yl; halo-C1-6-alk(en/yn)yl; halo-C1-6-alk(en/yn)yloxy; C3-8-cycloalk(en)yl; C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl; acyl; C1-6-alk(en/yn)yloxycarbonyl; C1-6-alk(en/yn)ylsulfonyl; aryl optionally substituted with a halogen, cyano, nitro, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, acyl, C1-6-alk(en/yn)yloxycarbonyl or C1-6-alk(en/yn)ylsulfonyl; monocyclic heteroaryl optionally substituted with a halogen, cyano, nitro, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, acyl, C1-6-alk(en/yn)yloxycarbonyl or C1-6-alk(en/yn)ylsulfonyl; or —NR13R14 wherein R13 and R14 are each independently hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6 alk(en/yn)yl or aryl, or R13 and R14 together with the nitrogen atom to which they are attached form a 3-7-membered heterocyclic ring which optionally contains one further heteroatom selected from O, S and N;
R5 is aryl or monocyclic heteroaryl, optionally substituted with a halogen, cyano, nitro, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, acyl, C1-6-alk(en/yn)yloxycarbonyl, C1-6-alk(en/yn)ylsulfonyl or —NR15R16 wherein R15 and R16 are each independently hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6 alk(en/yn)yl or aryl, or R15 and R16 together with the nitrogen atom to which they are attached form a 3-7-membered heterocyclic ring which optionally contains one further heteroatom selected from O, S and N;
R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl;
R7 and R8 are each independently H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl; or
R6 and R8 together with the atoms to which they are attached and the intervening carbon atom form a saturated 3-7 membered heterocyclic ring, and R7 is H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl, and R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl; or
R7 and R8 together with the atoms to which they are attached form a saturated 3-7 membered heterocyclic ring, and R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl, and R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl; or
R8 and R9 together with the atoms to which they are attached and the intervening carbon atom form a saturated 3-7 membered heterocyclic ring, and R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl, and R7 is H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl, and R9′ is H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
R10 is H, C1-6-alk(en/yn)yl, aryl, aryl-C1-6-alk(en/yn)yl, wherein aryl is optionally substituted with a halogen, CF3, OCF3, CN, NO2 or C1-6-alk(en/yn)yl, or an alkali metal;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1 wherein X is O or CH2.

### Claim 3 (depends on 1)

The compound of claim 1 wherein Y is O.

### Claim 4 (depends on 1)

The compound of claim 1 wherein Y is S.

### Claim 5 (depends on 1)

The compound of claim 1 wherein R1 is hydrogen, C1-6-alkyl, halogen, phenyl, or phenyl substituted with one or two subtituents selected from C1-6-alkyl and C1-6-alkoxy.

### Claim 6 (depends on 1)

The compound of claim 1 wherein R2 is hydrogen; cyano; C1-6-alkyl; halogen; phenyl; phenyl substituted with one or two subtituents selected from cyano, C1-6-alkyl, C1-6-alkoxy, and C1-6-alkylsulfonyl; —NR13R14 wherein R13 and R14 together with the nitrogen atom to which they are attached form a 3-7-membered heterocyclic ring which optionally contains one further heteroatom selected from O, S and N; or monocyclic heteroaryl.

### Claim 7 (depends on 1)

The compound of claim 1 wherein R3 is hydrogen; C1-6-alkyl; halogen; phenyl; phenyl substituted with one or two subtituents selected from cyano, C1-6-alkyl, and C1-6-alkoxy; or monocyclic heteroaryl.

### Claim 8 (depends on 1)

The compound of claim 1 wherein R4 is hydrogen, C1-6-alkyl, halogen, phenyl or phenyl substituted with one or two substituents selected from C1-6-alkyl and C1-6-alkoxy.

### Claim 9 (depends on 1)

The compound of claim 1 wherein R5 is phenyl, optionally substituted with a halogen, C1-6-alkyl, C1-6-alkyloxy, C1-6-alkylsulfanyl, or halo-C1-6-alkyl.

### Claim 10 (depends on 1)

The compound of claim 1 wherein R6 from H or C1-6-alkyl.

### Claim 11 (depends on 1)

The compound of claim 1 wherein R7 is H or C1-6-alkyl.

### Claim 12 (depends on 1)

The compound of claim 1 wherein R8 is H, C1-6-alkyl or C3-8-cycloalkyl.

### Claim 13 (depends on 1)

The compound of claim 1 wherein R9 and R9′ are each independently H or C1-6-alkyl.

### Claim 14 (depends on 1)

The compound of claim 1 wherein R10 is H.

### Claim 15 (depends on 1)

The compound of claim 1 wherein R6 and R8 together with the atoms to which they are attached and the intervening carbon atom form a 1-pyrrolidinyl, 1-piperidinyl or 1-azepinyl, optionally substituted with a C1-6-alkyl, and R7 is H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl, and R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl.

### Claim 16 (depends on 1)

The compound of claim 1 wherein R7 and R8 together with the atoms to which they are attached form a 1-pyrrolidinyl, 1-piperidinyl or 1-azepinyl, optionally substituted with a C1-6-alkyl, and R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently from H or C1-6 alkyl and R9 and R9′ are independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl.

### Claim 17 (depends on 1)

The compound of claim 1 wherein R8 and R9 together with the atoms to which they are attached and the intervening carbon atom form a 1-pyrrolidinyl, 1-piperidinyl or 1-azepinyl, optionally substituted with a C1-6-alkyl, and R6 is selected from H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl, and R7 is selected from H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl, and R9′ is H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl.

### Claim 18 (depends on 1)

The compound of claim 1 selected from the group consisting of:
(S)-1-{2-[2-(4-Fluoro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(4-Trifluoromethyl-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3-Fluoro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-{2-[2-(4-Chloro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3-Chloro-phenoxy)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(4-Chloro-phenoxy)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(4-Methoxy-phenoxy)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3,4-Difluoro-phenoxy)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
1-{2(R/S)-[2-(4-Chloro-phenoxy)-phenoxy]-propyl}-pyrrolidine-2(S)-carboxylic acid,
1-{2(R/S)-[2-(3,4-Difluoro-phenoxy)-phenoxy]-propyl}-pyrrolidine-2(S)-carboxylic acid,
(S)-1-{2-[2-(3-Fluoro-phenoxy)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
1-{2(R/S)-[2-(3-Fluoro-phenoxy)-phenoxy]-propyl}-pyrrolidine-2(S)-carboxylic acid,
1-{2(R/S)-[2-(3-Fluoro-phenylsulfanyl)-phenoxy]-propyl}-pyrrolidine-2(S)-carboxylic acid,
1-{2(R/S)-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-propyl}-pyrrolidine-2(S)-carboxylic acid,
({2-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-ethyl}-N-ethyl-amino)-acetic acid,
2-{3-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
({2-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-ethyl}-N-methyl-amino)-acetic acid,
({2-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-ethyl}-N-methyl-amino)-acetic acid,
{2-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxymethyl]-piperidin-1-yl}-acetic acid,
({2-[2-(3-Fluoro-phenylsulfanyl)-phenoxy]-ethyl}-N-methyl-amino)-acetic acid,
{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-piperidin-1-yl}-acetic acid,
(N-2-propyl-{2-[2-(4-trifluoromethyl-phenylsulfanyl)-phenoxy]-ethyl}-amino)-acetic acid,
({2-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-ethyl}-N-ethyl-amino)-acetic acid,
(N-Ethyl-{2-[2-(4-methylsulfanyl-phenylsulfanyl)-phenoxy]-ethyl}-amino)-acetic acid,
2-{3-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
(S)-{3-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-acetic acid,
({2-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-ethyl}-N-ethyl-amino)-acetic acid,
(N-2-propyl-{2-[2-(4-methylsulfanyl-phenylsulfanyl)-phenoxy]-ethyl}-amino)-acetic acid,
{3-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-acetic acid,
({2-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-ethyl}-N-ethyl-amino)-acetic acid,
({2-[2-(4-Chloro-phenylsulfanyl)-phenoxy]-ethyl-}N-methyl-amino)-acetic acid,
{4-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-piperidin-1-yl}-acetic acid,
2-{3-[2-(4-Trifluoromethyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
({2-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-ethyl}-N-2-propyl-amino)-acetic acid
({2-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-ethyl}-N-methyl-amino)-acetic acid,
{2-[2-(4-Methylsulfanyl-phenylsulfanyl)-phenoxymethyl]-piperidin-1-yl}-acetic acid,
({2-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-ethyl}-N-methyl-amino)-acetic acid,
(N-Methyl-{2-[2-(4-trifluoromethyl-phenylsulfanyl)-phenoxy]-ethyl}-amino)-acetic acid,
2-{3(R)-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
2-{3(R)-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
2-[3(R)-(2-(4-methylphenyl)-sulfanyl-phenoxy)-pyrrolidin-1-yl]-propionic acid,
{3(R)-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-acetic acid,
2-{3(R)-[2-(4-Trifluoromethyl-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
2-{3(R)-[2-(4-Chloro-phenylsulfanyl)-phenoxy]-pyrrolidin-1-yl}-propionic acid,
({1-[2-(3-Chloro-phenylsulfanyl)-phenoxymethyl]-propan-2yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-butan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-butan-3-methyl-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-butan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[1-(3-Chloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-butan-4-methyl-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]propan-2-yl}-N-ethyl-amino)-acetic acid,
(S)-({1-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-methyl-amino)-acetic acid,
(S)-({1-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(4-Chloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3-Chloro-phenylsulfanyl)-phenoxymethyl]-propyl}-N-methyl-amino)-acetic acid,
({1-[2-(4-Chloro-phenylsulfanyl)-phenoxymethyl]-propyl}-N-ethyl-amino)-acetic acid,
(N-Ethyl-{1-[2-(3-fluoro-phenylsulfanyl)-phenoxymethyl]-propyl}-amino)-acetic acid,
(R)-({2-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-1-methyl-ethyl}-N-ethyl-amino)-acetic acid,
(S)-(2-{1-[2-(4-Chloro-phenoxy)-phenoxy]-propan-2-}-N-methyl-amino)-acetic acid,
(R)-(2-{1-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-methyl-amino)-acetic acid,
({2-[2-(3-Fluoro-phenylsulfanyl)-phenoxy]-propyl}-N-methyl-amino)-acetic acid,
({2-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-propan-1yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-3-methyl-butan-2-yl}-N-methyl-amino)-acetic acid,
({3-methyl-1-[2-(4-trifluoromethyl-phenylsulfanyl)-phenoxy]-butan-2-yl}-N-ethyl-amino)-acetic acid,
({1-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-butan-2-yl}-N-methyl-amino)-acetic acid,
(S)-({1-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-propan-2-yl}N-methyl-amino)-acetic acid,
(S)-({1-[2-(3-Fluoro-phenylsulfanyl)-phenoxy]-propan-2yl}-N-methyl-amino)-acetic acid,
({1-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-3-methyl-butan-2-yl}-N-ethyl-amino)-acetic acid,
(S)-({1-[2-(3,4-Dichloro-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-methyl-amino)-acetic acid,
({1-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-3-methyl-butan-2-yl}-N-methyl-amino)-acetic acid,
({1-[2-(4-tert-Butyl-phenylsulfanyl)-phenoxy]-propan-2-yl}-N-ethyl-amino)-acetic acid,
({2-[2-(3-Chloro-4-fluoro-phenylsulfanyl)-phenoxy]-propan-1-yl}-N-ethyl-amino)-acetic acid,
({2-[2-(4-methoxy-phenylsulfanyl)-phenoxy]-propan-1-yl}-N-Cyclohexyl-amino)-acetic acid,
{[2-(2-(4-methyl-phenylsulfanyl-phenoxy)-propan-1-yl-]-N-cyclohexyl-amino}-acetic acid,
({2-[2-(3-Chloro-phenylsulfanyl)-phenoxy]-propan-1-yl}-N-cyclohexyl-amino)-acetic acid,
(S)-1-{3-[2-(3-Fluoro-phenylsulfanyl)-phenyl]-propyl}-pyrrolidine-2-carboxylic acid,
(S)-2-({2-[3-(3-Fluoro-phenylsulfanyl)-biphenyl-4-yloxy]-ethyl}-methyl-amino)-propionic acid,
({2-[3-(3-Fluoro-phenylsulfanyl)-biphenyl-4-yloxy]-ethyl}-methyl-amino)-acetic acid,
(S)-1-{2-[4-Chloro-2-(3-fluoro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[3-Chloro-2-(3-fluoro-phenylsulanyl)-phenoxy]-ethyl}pyrrolidine-2-carboxylic acid,
(S)-1-{2-[5-Chloro-2-(3-fluoro-phenylsulfanyl)-phenoxy]-ethyl}pyrrolidine-2-carboxylic acid,
(S)-1-{2-[4-Cyano-2-(3-fluoro-phenylsulfanyl)-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid
(S)-1-[2-(5-Chloro-2-phenylsulfanyl-phenoxy)-ethyl]pyrrolidine-2-carboxylic acid,
(S)-1-{2-[3-(3-Fluoro-phenylsulfanyl)-biphenyl-4-yloxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-{2-[4′-Methoxy-3-(3-fluoro-phenylsulfanyl)-biphenyl-4-yloxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-{2-[4′-Cyano-3-(3-fluoro-phenylsulfanyl)-biphenyl-4-yloxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[4′-Cyano-4-(3-fluoro-phenylsulfanyl)-biphenyl-3-yloxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3-Fluoro-phenylsulfanyl)-5-thiophen-3-yl-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[2-(3-Fluoro-phenylsulfanyl)-4-pyrimidin-5-yl-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
(S)-1-{2-[3-(3-Fluoro-phenylsulfanyl)-3-methanesulfonyl-biphenyl-4-yloxy]-ethyl}-pyrrolidine-2(S)-carboxylic acid,
(S)-1-{2-[2-(3-Fluoro-phenylsulfanyl)-4-morpholin-4-yl-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid, and
(S)-1-{2-[2-(3-Fluoro-phenylsulfanyl)-4-piperidin-1-yl-phenoxy]-ethyl}-pyrrolidine-2-carboxylic acid,
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.

### Claim 20 (depends on 1)

A method for the treatment of schizophrenia comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1.

### Claim 21 (depends on 20)

The method of claim 20, wherein said method is for the treatment of the positive symptoms, negative symptoms, or both the positive and negative symptoms of schizophrenia.

### Claim 22 (depends on 20)

The method of claim 20 wherein said subject is a human.

### Claim 23 (depends on 18)

A pharmaceutical composition comprising a compound according to claim 18 and a pharmaceutically acceptable carrier or diluent.