# US 2014/0194437 A1 · Acylaminocycloalkyl compounds suitable for treating disorders that respond to modulation of dopamine d3 receptor

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- Number: US 2014/0194437 A1
- Document ID: US20140194437A1
- Status: Published application
- Kind: A1
- Application number: 14/051,626
- Filed: 2013-10-11
- Published: 2014-07-10
- Earliest claimed: 2012-10-22
- Assignees: AbbVie Deutschland GmbH & Co. KG; AbbVie Inc.
- Applicants: AbbVie Deutschland GmbH & Co. KG
- Inventors: Andreas Haupt
- Web page: https://patentgrep.com/patent/US20140194437A1

## CPC

- C07D 239/26: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A61P 13/12: of the kidneys
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 29/02: without antiinflammatory effect
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 239/42: One nitrogen atom (nitro radicals C07D239/30)
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to novel acylaminocycloalkyl compounds, in particular to the compounds of the formula I as described herein and to their salts and N-oxides. The compounds possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of the dopamine D3 receptor. In formula I, the variables have the following meanings: m is 1 or 2, n is 1 or 2, A is selected from the group consisting of CH2, CH2CH2, CHFCH2 and CF2CH2, R1 is hydrogen or C1-C3-alkyl, R2 is selected from the group consisting of hydrogen, and fluorine, R3a is selected from the group consisting of hydrogen and methyl, R3b is selected from the group consisting of hydrogen and methyl, R4 is branched C4-C6 alkyl or branched fluorinated C4-C6 alkyl, and R5 is an oxygen containing radical such as C1-C2-alkoxy-C1-C4-alkyl, fluorinated C1-C2-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, fluorinated hydroxy-C1-C4-alkyl, oxetanyl, fluorinated oxetanyl, oxolanyl, fluorinated oxolanyl, C3-C5 cycloalkyl, fluorinated C3-C5 cycloalkyl, C3-C5 cycloalkoxy-C1-C4-alkyl and fluorinated C3-C5 cycloalkoxy-C1-C4-alkyl.

## Claims

### Claim 1

A compound of the formula I
where
m is 1 or 2,
n is 1 or 2,
A is selected from the group consisting of CH2, CH2CH2, CHFCH2 and CF2CH2,
R1 is hydrogen or C1-C3-alkyl,
R2 is selected from the group consisting of hydrogen and fluorine,
R3a is selected from the group consisting of hydrogen and methyl,
R3b is selected from the group consisting of hydrogen and methyl,
R4 is branched C4-C6 alkyl or branched fluorinated C4-C6 alkyl, and
R5 is an oxygen containing radical selected from the group consisting of C1-C2-alkoxy-C1-C4-alkyl, fluorinated C1-C2-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, fluorinated hydroxy-C1-C4-alkyl, oxetanyl, fluorinated oxetanyl, oxolanyl, fluorinated oxolanyl,
C3-C5 cycloalkyl, fluorinated C3-C5 cycloalkyl, where the cycloalkyl moiety in the last two mentioned radicals carries 1 or 2 radicals selected from hydroxyl, C1-C2-alkoxy and fluorinated C1-C2-alkoxy and may additionally carry 1 or 2 radicals selected from C1-C2-alkyl and fluorinated C1-C2-alkyl, C3-C5 cycloalkoxy-C1-C4-alkyl and fluorinated C3-C5 cycloalkoxy-C1-C4-alkyl, where the cycloalkoxy moiety in the last two mentioned radicals may carry 1 or 2 radicals selected from hydroxyl, C1-C2-alkoxy, fluorinated C1-C2-alkoxy, C1-C2-alkyl and fluorinated C1-C2-alkyl,
the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is hydrogen or methyl.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is methyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R1 is hydrogen.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R2 is hydrogen.

### Claim 6 (depends on 1)

The compound of claim 1, wherein m is 2.

### Claim 7 (depends on 1)

The compound of claim 1, wherein n is 2.

### Claim 8 (depends on 1)

The compound of claim 1, wherein both m and n are 1.

### Claim 9 (depends on 1)

The compound of claim 1, wherein R3a and R3b are hydrogen.

### Claim 10 (depends on 1)

The compound of claim 1, wherein either R3a is methyl and R3b is hydrogen or R3a is hydrogen and R3b is methyl.

### Claim 11 (depends on 1)

The compound of claim 1, wherein A is CH2.

### Claim 12 (depends on 1)

The compound of claim 1, wherein A is CH2CH2, CHFCH2 or CF2CH2.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R4 is branched C4-C6 alkyl and in particular tert-butyl.

### Claim 14 (depends on 1)

The compound of claim 1, wherein R5 is selected from the group consisting of C1-C2-alkoxy-C1-C2-alkyl, fluorinated C1-C2-alkoxy-C1-C2-alkyl and hydroxy-C1-C4-alkyl.

### Claim 15 (depends on 14)

The compound of claim 14, wherein R5 is selected from the group consisting of methoxymethyl, ethoxymethyl, 2-methoxyethyl, difluoromethoxymethyl, 2-(difluoromethoxy)ethyl, trifluoromethoxymethyl, 2-(trifluoromethoxy)ethyl, methoxydifluoromethyl, ethoxydifluoromethyl, 2-methoxy-1,1-difluoroethyl, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl and 2-hydroxy-2-methylpropyl.

### Claim 16 (depends on 14)

The compound of claim 14, wherein R5 is C1-C2-alkoxy-C1-C2-alkyl.

### Claim 17 (depends on 1)

The compound of claim 1, wherein R5 is selected from the group consisting of oxetanyl, fluorinated oxetanyl, oxolanyl, fluorinated oxolanyl, and C3-C5 cycloalkyl, which carries 1 or 2 radicals selected from hydroxy and C1-C2-alkoxy.

### Claim 18 (depends on 17)

The compound of claim 17, wherein R5 is selected from the group consisting of 2-oxetanyl, 3-oxetanyl, 2-oxolanyl, 3-oxolanyl, 3-methoxycyclobutyl and 3-hydroxycyclobutyl.

### Claim 19 (depends on 1)

The compound of claim 1, wherein
A is CH2, CH2CH2, CHFCH2 or CF2CH2;
R1 is hydrogen or methyl;
R2 is hydrogen;
R3a and R3b are hydrogen or either R3a is methyl and R3b is hydrogen or R3a is hydrogen and R3b is methyl; and
R4 is tert-butyl.

### Claim 20 (depends on 1)

The compound of claim 1, which is a compound of the formula Ia,
where R1, R3a, R3b, R5 and A are as defined in claim 1, the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 21 (depends on 1)

The compound of claim 1, which is a compound of the formula Ib,
where R1, R3a, R3b, R5 and A are as defined in claim 1, the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 22 (depends on 1)

The compound of claim 1, which is a compound of the formula Ic,
where R1, R3a, R3b, R5 and A are as defined in claim 1, the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 23 (depends on 1)

The compound of claim 1, where in formulae I or Ia or Ic the radical R1—C(═O)—NH and the radical R2 predominately adopt cis-configuration.

### Claim 24 (depends on 1)

The compound of claim 1, where formulae in I or Ia or Ic the radical R1—C(═O)—NH and the radical R2 predominately adopt trans-configuration.

### Claim 25 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(ethoxydifluoromethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(1,1-difluoro-2-methoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-difluoromethoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-trifluoromethoxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-3-yl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxetan-2-yl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(oxolan-3-yl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-methoxycyclobutyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxypropyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxy-2-methylpropyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(3-hydroxycyclobutyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]formamide
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]formamide,
the cis-isomers thereof, the trans-isomers thereof,
and the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 26 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]formamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]acetamide,
N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]-1,4-diazepan-1-yl]ethyl]cyclohexyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-2-methylpiperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclobutyl]formamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclobutyl]acetamide,
N-[3-[2-[4-[2-tert-butyl-6-(ethoxymethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclobutyl]formamide,
the cis-isomers thereof, the trans-isomers thereof,
and the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 27 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
trans-N-[4-(2-{4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[4-(2-{4-[2-tert-butyl-6-(methoxymethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
cis-N-[4-(2-{4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
cis-N-[3-(2-{4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclobutyl]-acetamide
trans-N-[3-(2-{4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclobutyl]-acetamide
trans-N-[4-(2-{(2R)-4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-2-methyl-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[4-(2-{(3R)-4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-3-methyl-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
cis-N-[4-(2-{(2S)-4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-2-methyl-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[4-(2-{(3S)-4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-3-methyl-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[4-(2-{(2S)-4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-2-methyl-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
cis-N-[4-(2-{4-[2-tert-butyl-6-(2-trifluoromethoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[4-(2-{4-[2-tert-butyl-6-(2-trifluoromethoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[4-(2-{4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-formamide
N-[3-(2-{4-[2-tert-butyl-6-(2-methoxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclobutyl]-formamide
trans-N-[4-(2-{4-[2-tert-butyl-6-(2-hydroxy-ethyl)-pyrimidin-4-yl]-piperazin-1-yl}-ethyl)-cyclohexyl]-acetamide
trans-N-[(1R,3S)-3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide
trans-N-[(1S,3R)-3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide
cis-N-[(1S,3S)-3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclopentyl]acetamide
N-[cis-3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]formamide
N-[trans-3-[2-[4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclobutyl]formamide
trans-N-[4-[2-[(3R)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclohexyl]formamide
trans-N-[4-[2-[(3S)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclohexyl]formamide
trans-N-[4-[2-[4-[2-tert-butyl-6-(methoxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide
trans-N-[4-[2-[4-[2-tert-butyl-6-(hydroxymethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]acetamide
trans-N-[4-[2-[4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]piperazin-1-yl]ethyl]cyclohexyl]formamide
trans-N-[4-[2-[(2R)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-2-methyl-piperazin-1-yl]ethyl]cyclohexyl]formamide
trans-N-[4-[2-[(3S)-4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclohexyl]acetamide
trans-N-[4-[2-[(2R)-4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-2-methyl-piperazin-1-yl]ethyl]cyclohexyl]acetamide
trans-N-[4-[2-[4-(2-tert-butyl-6-tetrahydrofuran-3-yl-pyrimidin-4-yl)piperazin-1-yl]ethyl]cyclohexyl]formamide
N-[3-[2-[(3S)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclobutyl]formamide
trans-N-[4-[2-[(3R)-4-[2-tert-butyl-6-(2-hydroxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclohexyl]acetamide
trans-N-[3-[2-[(3S)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclobutyl]acetamide
cis-N-[3-[2-[(3S)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclobutyl]acetamide
trans-N-[4-[2-[(3S)-4-[2-tert-butyl-6-[2-(difluoromethoxy)ethyl]pyrimidin-4-yl]-3-methyl-piperazin-1-yl]ethyl]cyclohexyl]acetamide
and the N-oxides, the prodrugs and the pharmaceutically acceptable salts of these compounds.

### Claim 28 (depends on 1)

A pharmaceutical composition comprising at least one compound as claimed in claim 1, optionally together with at least one physiologically acceptable carrier or auxiliary substance.

### Claim 29 (depends on 1)

A method for treating a medical disorder or condition susceptible to treatment with a dopamine D3 receptor ligand, said method comprising administering an effective amount of at least one compound as claimed in claim 1 to a subject in need thereof.

### Claim 30 (depends on 29)

The method of claim 29, wherein the medical disorder is a disorder or condition of the central nervous system.

### Claim 31 (depends on 29)

The method of claim 29, wherein the medical disorder is a disorder or condition selected from the group of Parkinson's disease, schizophrenia, bipolar disorder, depression, motivation disturbances, anxiety, cognitive dysfunction, pain, disorder associated with drug abuse, and eating disorders.

### Claim 32 (depends on 29)

The method of claim 29, wherein the medical disorder is renal function disorders, such as diabetic nephropathy.