# US 8,772,510 B2 · PDE10 modulators

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- Number: US 8,772,510 B2
- Document ID: US8772510B2
- Status: Granted
- Kind: B2
- Application number: 13/598,848
- Filed: 2012-08-30
- Published: 2013-03-07
- Granted: 2014-07-08
- Earliest claimed: 2011-09-06
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Stephan Bachmann; Alexander Flohr; Katrin Groebke Zbinden; Matthias Koerner; Bernd Kuhn; Jens-Uwe Peters; Markus Rudolph
- Inventors: Stephan Bachmann; Alexander Flohr; Katrin Groebke Zbinden; Matthias Koerner; Bernd Kuhn; Jens-Uwe Peters; Markus Rudolph
- Web page: https://patentgrep.com/patent/US8772510B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/00: Drugs for disorders of the nervous system
- 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 25/22: 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 35/00: Antineoplastic agents
- C07D 231/14: 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 ring carbon atoms
- C07D 233/90: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 413/14: containing three or more hetero rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: 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 compounds of formula (I) wherein R1, R2, R3, R5, W, X, X1, Y, Y1, Z and Z1 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used in the treatment of CNS disorders such as schizophrenia, Alzheimer's disease, and Parkinson's disease.

## Claims

### Claim 1

A compound of formula (I)
wherein:
X and X1 are each independently CR4 or N;
Y and Y1 are each independently C or N;
Z and Z1 are each independently CR6, NR7, N, O or S;
R1 and R2 are each independently selected from hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl, C1-C7-alkoxy-C1-C7-alkyl, heterocycloalkyl and C1-C7-alkyl optionally substituted by aryl or heteroaryl or
R1 and R2, together with the nitrogen atom to which they are attached, form a bicyclic ring system or a heterocycloalkyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of hydroxyl, halogen, C1-C7-alkyl, C1-C7-alkoxy, C1-C7-haloalkyl and oxo;
R3 is hydrogen or C1-C7-alkyl;
R4 is hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl or halogen;
R5 is aryl or heteroaryl each of which is optionally substituted by C1-C7-alkyl, C3-C8-cycloalkyl, halogen, C1-C7-haloalkyl, C1-C7-alkoxy, hydroxyl, C1-C7-hydroxyalkyl, C1-C7-alkoxyalkyl, acetyl, cyano, or amino optionally substituted by one or two C1-C7-alkyl groups;
R6 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; or
R5 and R6, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl;
R7 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7 alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; or
R5 and R7, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7 haloalkyl; and
W is ethylene which is optionally substituted by C1-C7 alkyl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein
X and X1 are each independently CR4 or N;
Y and Y1 are each independently C or N;
Z and Z1 are each independently CR6, NR7, O or S;
R1 and R2 are each independently selected from hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl, C1-C7-alkoxy-C1-C7-alkyl, heterocycloalkyl and C1-C7-alkyl optionally substituted by aryl or heteroaryl; or
R1 and R2, together with the nitrogen atom to which they are attached, form a heterocycloalkyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of hydroxyl, halogen, C1-C7-alkyl, C1-C7-alkoxy, C1-C7-haloalkyl and oxo;
R3 is hydrogen or C1-C7-alkyl;
R4 is hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl or halogen;
R5 is aryl or heteroaryl each of which is optionally substituted by C1-C7-alkyl, C3-C8-cycloalkyl, halogen, C1-C7-haloalkyl, C1-C7-alkoxy, hydroxyl, C1-C7-hydroxyalkyl, C1-C7-alkoxyalkyl, acetyl, cyano, or amino optionally substituted by one or two C1-C7-alkyl groups;
R6 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; or
R5 and R6, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl;
R7 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; or
R5 and R7, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl; and
W is ethylene which is optionally substituted by C1-C7 alkyl.

### Claim 3 (depends on 1)

The compound of claim 1, wherein W optionally substituted by C1-C7 alkyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R1 and R2, together with the nitrogen atom to which they are attached, form a 4, 5 or 6 membered heterocycloalkyl containing two heteroatoms selected from N and O;
R3 is hydrogen or methyl;
X is nitrogen; and
X1 is CR4, wherein R4 is hydrogen.

### Claim 5 (depends on 4)

The compound of claim 4, wherein R1 and R2, together with the nitrogen atom to which they are attached, form an azetidinyl or morpholinyl group.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R1 and R2, together with the nitrogen atom to which they are attached, form a 4, 5 or 6 membered heterocycloalkyl containing two heteroatoms selected from N and O;
R3 is hydrogen or methyl;
X is CR4, wherein R4 is methyl or halogen; and
X1 is nitrogen.

### Claim 7 (depends on 6)

The compound of claim 6, wherein R1 and R2, together with the nitrogen atom to which they are attached, form an azetidinyl or morpholinyl group.

### Claim 8 (depends on 1)

The compound of claim 1, wherein Y is C and Y1 is C or N.

### Claim 9 (depends on 1)

The compound of claim 1, wherein Y is N and Y1 is C.

### Claim 10 (depends on 1)

The compound of claim 1, wherein Z is C and Z1 is N or Z is N and Z1 is C or O.

### Claim 11 (depends on 1)

The compound of claim 1, wherein Y1 is C, Z is CR6 or NR7, wherein R5 and R6 or R5 and R7, together with Y1 and Z to which they are attached, form heteroaryl selected from imidazopyridinyl and benzoimidazolyl, each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl.

### Claim 12 (depends on 1)

The compound of claim 1 having formula (Ib)
wherein R8 is selected from the group consisting of:

### Claim 13 (depends on 10)

The compound of claim 10, wherein R8 is selected from the group consisting of:

### Claim 14 (depends on 1)

The compound of claim 1, wherein R6 is selected from hydrogen, C1-C7-alkyl and heteroaryl.

### Claim 15 (depends on 1)

The compound of claim 1, wherein R7 is selected from hydrogen, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, and C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or C3-C8-cycloalkyl.

### Claim 16 (depends on 1)

The compound of claim 1, wherein R5 is selected from phenyl and pyridinyl, each of which is optionally substituted with halogen or C1-C7 alkoxy.

### Claim 17 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-imidazo[1,2-a]pyridin-2-yl-ethyl)-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-pyridin-3-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(8-methyl-imidazo[1,2-a]pyridin-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[3-(4-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-ethyl}-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(1-methyl-4-phenyl-1-imidazol-2-yl)-ethyl]-amide;
2,3-Dimethyl-5-(morpholine-4-carbonyl)-3H-imidazole-4-carboxylic acid [2-(1-methyl-1-benzoimidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-benzothiazol-2-yl-ethyl)-amide;
5-(Azetidine-1-carbonyl)-3-methyl-3H-imidazole-4-carboxylic acid [2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide; and
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(1,5-dimethyl-1H-benzoimidazol-2-yl)-ethyl]-amide.

### Claim 18 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(3-phenyl-pyrazol-1-yl)-ethyl]-amide;
5-(Azetidine-1-carbonyl)-2-chloro-3-methyl-3H-imidazole-4-carboxylic acid [2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-pyridin-4-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-methyl-5-pyridin-3-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-chloro-1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-methyl-5-pyridin-4-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(3-phenyl-[1,2,4]triazol-1-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-phenyl-2H-[1,2,3]triazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-phenyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; and
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-methyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide.

### Claim 19 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [1,1-dimethyl-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
2-Methyl-4-(morpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(1-methyl-4-phenyl-1-imidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [1,1-dimethyl-2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-pyrimidin-2-yl-thiazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(1-methyl-4-pyridin-3-yl-1H-imidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(1-phenyl-1H-pyrazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-phenyl-thiazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[4-(3-methoxy-phenyl)-1-methyl-1H-imidazol-2-yl]-ethyl}-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[4-(2-methoxy-phenyl)-1-methyl-1H-imidazol-2-yl]-ethyl}-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[1-(2-methoxy-ethyl)-4-phenyl-1H-imidazol-2-yl]-ethyl}-amide; and
5-(Azetidine-1-carbonyl)-2,3-dimethyl-3H-imidazole-4-carboxylic acid [2-(1-methyl-4-phenyl-1-imidazol-2-yl)-ethyl]-amide.

### Claim 20 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[2-(2-methoxy-ethyl)-5-phenyl-2H-[1,2,4]triazol-3-yl]-ethyl}-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-cyclopropylmethyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
2-Methyl-4-(morpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
2-Methyl-4-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
4-(3-Fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
2-Methyl-2H-pyrazole-3,4-dicarboxylic acid 4-(cyclopropyl-methyl-amide) 3-{[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide};
2-Methyl-4-(2-oxa-6-aza-spiro[3.3]heptane-6-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
2-Methyl-4-(thiomorpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-phenyl-thiazol-4-yl)-ethyl]-amide; and
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-methyl-3-phenyl-[1,2,4]triazol-1-yl)-ethyl]-amide.

### Claim 21 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-benzyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-methyl-2-p-tolyl-thiazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-1-phenyl-1H-pyrazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[2-(2-ethyl-pyridin-4-yl)-5-methyl-thiazol-4-yl]-ethyl}-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-(5-phenyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-A-ethyl}-amide;
2-Methyl-4-(morpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide;
2-Methyl-4-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide;
5-(Azetidine-1-carbonyl)-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid [2-(1-methyl-4-phenyl-1-imidazol-2-yl)-ethyl]-amide;
2-Methyl-2H-pyrazole-3,4-dicarboxylic acid 4-(cyclopropyl-methyl-amide) 3-{[2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide};
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-methyl-4-phenyl-thiazol-2-yl)-ethyl]-amide; and
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2,5-diphenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide.

### Claim 22 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-cyclopropyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-phenyl-2-pyridin-2-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-phenyl-2-pyridin-3-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[5-(3-fluoro-phenyl)-2-phenyl-2H-[1,2,4]triazol-3-yl]-ethyl}-amide;
2-Methyl-2H-pyrazole-3,4-dicarboxylic acid 4-(cyclopentyl-methyl-amide) 3-{[2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-ethyl]-amide};
2-Methyl-2H-pyrazole-3,4-dicarboxylic acid 4-(cyclobutyl-methyl-amide) 3-{[2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-ethyl]-amide};
5-(Azetidine-1-carbonyl)-3-methyl-2-trifluoromethyl-3H-imidazole-4-carboxylic acid [2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-[1,2,4]triazolo[1,5-a]pyridin-2-yl-ethyl)-amide; and
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-phenyl-5-pyridin-3-yl-oxazol-4-yl)-ethyl]-amide.

### Claim 23 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid {2-[1-(2-methoxy-ethyl)-4-phenyl-1H-imidazol-2-yl]-ethyl}-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(1-methyl-4-pyridin-3-yl-1H-imidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-methyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-methyl-5-pyridin-3-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-chloro-1-methyl-1H-benzoimidazol-2-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-phenyl-2H-[1,2,3]triazol-4-yl)-ethyl]-amide; and
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-phenyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide.

### Claim 24 (depends on 1)

The compound of claim 1, selected from the group consisting of
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [1,1-dimethyl-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [1,1-dimethyl-2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-cyclopropylmethyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2,5-diphenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(2-cyclopropyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
4-(Azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid [2-(5-phenyl-2-pyridin-2-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-amide;
2-Methyl-2H-pyrazole-3,4-dicarboxylic acid 4-(cyclobutyl-methyl-amide) 3-{[2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-ethyl]-amide}.

### Claim 25

A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I)
wherein:
X and X1 are each independently CR4 or N;
Y and Y1 are each independently C or N;
Z and Z1 are each independently CR6, NR7, N, O or S;
R1 and R2 are each independently selected from hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl, C1-C7-alkoxy-C1-C7-alkyl, heterocycloalkyl and C1-C7-alkyl optionally substituted by aryl or heteroaryl; or
R1 and R2, together with the nitrogen atom to which they are attached, form a bicyclic ring system or a heterocycloalkyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of hydroxyl, halogen, C1-C7-alkyl, C1-C7-alkoxy, C1-C7-haloalkyl and oxo;
R3 is hydrogen or C1-C7-alkyl;
R4 is hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl or halogen;
R5 is aryl or heteroaryl each of which is optionally substituted by C1-C7-alkyl, C3-C8-cycloalkyl, halogen, C1-C7-haloalkyl, C1-C7-alkoxy, hydroxyl, C1-C7-hydroxyalkyl, C1-C7-alkoxyalkyl, acetyl, cyano, or amino optionally substituted by one or two C1-C7-alkyl groups;
R6 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; or
R5 and R6, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl;
R7 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; or
R5 and R7, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl; and
W is selected from ethylene which is optionally substituted by C1-C7 alkyl
and a pharmaceutically acceptable carrier.