# US 7,407,968 B2 · Compounds

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- Number: US 7,407,968 B2
- Document ID: US7407968B2
- Status: Granted
- Kind: B2
- Application number: 10/530,499
- Filed: 2003-10-15
- Published: 2007-05-10
- Granted: 2008-08-05
- Earliest claimed: 2003-10-15
- Assignees: AstraZeneca AB
- Inventors: Daniel Pagé; Christopher Walpole; Hua Yang
- Web page: https://patentgrep.com/patent/US7407968B2

## CPC

- C07D 235/12: Radicals substituted by oxygen atoms
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- 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 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/14: containing three or more hetero rings
- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/14: containing three or more hetero rings
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 413/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of formula (I) wherein RF1, RF2, Z, R1, R2, Ar, X and Y are as defined in the specification as well as salts and pharmaceutical compositions including the compounds were prepared. These compounds are useful in therapy, in particular in the management of pain.

## Claims

### Claim 1

A compound of formula (I) or pharmaceutically acceptable salts thereof:
wherein
RF1 and RF2 are independently selected from —CF3, —CH2CF3, —CH2CHF2, —CHFCF3, —CHFCHF2, —CHFCH2F, —CF2CF3, —CF2CH3, —CF2CH2F, —CF2CHF2, —CF3, —CH2CCl3, —CH2CHCl2, —CH2CBr3, —CH2CHBr3, —CH2NO2, —CH2CH2NO2, —CH2CN, —CH2CH2CN, and —CH2CH2OCH3;
Z is selected from O═ and S═;
R1 is selected from C1-10alkyl; C1-10alkyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; C2-10alkenyl; C2-10alkenyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; C2-10alkynyl; C2-10alkynyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; R3R4N—C1-6alkyl; R3R4NO(═O)—C1-6alkyl; R3O—C1-6alkyl; R3OC(═O)—C1-6alkyl; R3O(═O)—C1-6alkyl; R3O(═O)NR3—C1-6alkyl; R3R4NSO2—C1-6alkyl; R3OSO2N(R4)—C1-6alkyl; R3R4NO(═O)N(R5)—C1-6alkyl; R3R4NSO2N(R5)—C1-6alkyl; aryl-C1-6alkyl; aryl-O(═O)—C1-6alkyl; heterocyclyl-C1-6alkyl; heterocyclyl-O(═O)—C1-6alkyl; substituted aryl-C1-6alkyl; substituted aryl-O(═O)—C1-6alkyl; substituted heterocyclyl-C1-6alkyl; substituted heterocyclyl-O(═O)—C1-6alkyl; and C1-10hydrocarbylamino;
R2 is selected from C1-6alkyl, substituted C1-6alkyl, C2-6alkenyl, substituted C2-6alkenyl, C2-6alkynyl, substituted C2-6alkynyl, C3-6cycloalkyl, substituted C3-6cycloalkyl, aryl, substituted aryl, and C5-6heteroaryl, and substituted C5-6heteroaryl;
R3, R4 and R5 are independently selected from —H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and a divalent C1-6 group that together with another divalent C1-6 group forms a portion of a ring;
X is selected from —NR6—, —C(═O)—, —CH2—CH2—, —CH═CH—, —O—, —C(R6)(R7)—, and —S(O)n—, wherein n is 0, 1 or 2, wherein R6 and R7 are independently C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —OH, or —H;
Ar is selected from an arylene; an heteroarylene; an arylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and an heteroarylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and
Y is selected from —CH═ and —N═.

### Claim 2 (depends on 1)

The compound as claimed in claim 1, wherein Z is O═.

### Claim 3 (depends on 1)

The compound as claimed in claim 1, wherein R1 is selected from C1-10alkyl; C1-10alkyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; C2-10alkenyl; C2-10alkenyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; C2-10alkynyl; C2-10alkynyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; R3R4N—C1-6alkyl; R3R4NC(═O)—C1-6alkyl; R3O—C1-6 alkyl; R3OC(═O)—C1-6alkyl; R3C(═O)—C1-6alkyl; R3C(═O)NR3—C1-6alkyl; R3R4NSO2—C1-6alkyl; R3CSO2N(R4)—C1-6alkyl; R3R4NC(═O)N(R5)—C1-6alkyl; R3R4NSO2N(R5)—C1-6alkyl; aryl-C1-6alkyl; aryl-C(═O)—C1-6alkyl; heterocyclyl-C1-6alkyl; heterocyclyl-C(═O)—C1-6alkyl; substituted aryl-C1-6alkyl; substituted aryl-C(═O)—C1-6alkyl; substituted heterocyclyl-C1-6alkyl; substituted heterocyclyl-C(═O)—C1-6alkyl; and C1-10hydrocarbylamino;
R2 is selected from C1-6alkyl, C1-6alkyl substituted by at least one fluorine, C2-6alkenyl, C2-6alkenyl substituted by at least one fluorine, C2-6alkynyl, C2-6alkynyl substituted by at least one fluorine, C3-6cycloalkyl, substituted C3-6cycloalkyl, aryl, substituted aryl, and C5-6heteroaryl, and substituted C5-6heteroaryl;
R3, R4 and R5 are independently selected from —H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and a divalent C1-6 group that together with another divalent C1-6 group forms a portion of a ring; and
X is selected from —NR6—, —C(═O)—, —CH2—CH2—, —OH ═CH—, —O—, —C(R6)(R7)—, and —S(O)n—, wherein n is 0, 1 or 2, wherein R6 and R7 are independently C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —OH, or —H.

### Claim 4 (depends on 1)

A compound according to claim 1,
wherein:
R1 is selected from C1-8alkyl; C2-8alkenyl; C2-8alkynyl; aryl-C1-6alkyl; aryl-C1-6alkyl with the aryl substituted by at least one group selected from C1-6alkyl, acetoxymethyl, nitro and halogen; R8R9NC1-6alkyl; R8OC1-6alkyl; cycloalkyl-C1-6alkyl; heterocycloalkyl-C1-6alkyl; heterocycloalkyl-C1-6alkyl with the heterocycloalkyl thereof substituted by at least one group selected from C1-8alkyl, acetoxymethyl, nitro and halogen; C1-6alkylaryl; C1-6alkyl—C(═O)—; C6-8aryl—C(═O)—; C4-8heteroaryl-C(═O)—; heteroaryl-C1-6alkyl; heteroaryl-C1-6alkyl with the heteroaryl thereof substituted by at least one group selected from C1-6alkyl, acetoxymethyl, nitro and halogen; and RNC1-6alkyl;
R2 is selected from —OH3, —CH2CH3, —CH(CH3)2, C3-6cycloalkyl, —CH2CF3, —CHF2, —CF3 and aryl;
RN is an oxidized pyridyl wherein the nitrogen atom on the pyridyl ring is in an oxidized state (N+—O−);
Ar is selected from an arylene; an heteroarylene; an arylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and an heteroarylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and
R8 and R9 are independently selected from —H and C1-6alkyl.

### Claim 5 (depends on 4)

The compound according to claim 4,
wherein the arylene is para-arylene; and the heteroarylene is selected from six-membered ring para-heteroarylene and five-membered ring meta-heteroarylene.

### Claim 6 (depends on 1)

A compound according to claim 1,
wherein:
R1 is selected from ethyl, propyl, allyl, isopentyl, benzyl, dimethylaminoethyl, 4-pyridylmethyl, 2-pyridyl methyl, 1-pyrrolylethyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-pyrrolidylmethyl, 3-pyrrolidylmethyl, N-methyl-2-pyrrolidylmethyl, N-methyl-3-pyrrolidylmethyl, 2-piperidylmethyl, 3-piperidylmethyl, 4-piperidylmethyl, N-methyl-2-piperidylmethyl, N-methyl-3-piperidylmethyl, N-methyl-4-piperidylmethyl, 3-thienylmethyl, 2-tetrahydrofuranylmethyl, 3-tetrahydrofuranylmethyl, 2-tetrahydropyranyl methyl, 3-tetrahydropyranylmethyl, 4-tetrahydropyranylmethyl, (2-nitrothiophene-5-yl)methyl, (1-methyl-1H-imidazole-2-yl)methyl, (5-(acetoxymethyl)-2-furanyl)methyl, (2,3-dihydro-1H-isoindole-1-yl)methyl, and 5-(2-methylthiazolyl);
R2 is selected from —OH3, —CH2CH3, —CH(CH3)2, —CH2CF3, OF3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl;
RF1 and RF2 are —CH2CF3 and Z is O═;
Ar is selected from a para-arylene; a para-arylene substituted with C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; a six-membered ring para-heteroarylene; and a six-membered ring para-heteroarylene substituted with a group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy.

### Claim 7 (depends on 1)

A compound according to claim 1,
wherein:
RF1 and RF2 are —CH2CF3, and Z is O═;
R2 is —CH2CH3;
Ar is selected from para-phenylene and para-pyridylene; and
X is selected from —OH2— and CH(CH3)—.

### Claim 8 (depends on 1)

A compound according to claim 1, wherein said compound is selected from:
2-[(4-Ethoxyphenyl)methyl]-1-(3-methylbutyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclohexylmethyl)-2-[(4-ethoxyphenyl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-(2-furanylmethyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[(2S)-2-pyrrolidinylmethyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[(2R)-2-pyrrolidinylmethyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-ethoxyphenyl)methyl]-1-(4-pyridinylmethyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[1-(4-Ethoxyphenyl)ethyl]-1-(4-pyridinylmethyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[(tetrahydro-2H-pyran-4-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[[(2R)-tetrahydro-2-furanyl]methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[[(2S)-tetrahydro-2-furanyl]methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[(tetrahydro-2H-pyran-2-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[(2R)-2-piperidinylmethyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxy-2-pyridyl)methyl]-1-[(tetrahydro-2H-pyran-4-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxy-2-pyridinyl)methyl]-1-(3-methylbutyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[[(2R)-1-methyl-2-pyrrolidinyl]methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(4-Ethoxyphenyl)methyl]-1-[[(2R)-1-methyl-2-piperidinyl]methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxy-2-pyridinyl)methyl]-1-[(2R)-2-pyrrolidinylmethyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[1-(4-Ethoxyphenyl)ethyl]-1-[(2R)-2-pyrrolidinylmethyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxy-2-pyridinyl)methyl]-1-[[(2R)-1-methyl-2-piperidinyl]methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxy-2-pyridinyl)methyl]-1-[[(2R)-1-methyl-2-pyrrolidinyl]methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclobutylmethyl)-2-(4-ethoxybenzyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclobutylmethyl)-2-[(5-ethoxypyridin-2-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclopentylmethyl)-2-[(5-ethoxypyridin-2-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-(4-Ethoxybenzyl)-1-[(2S)-piperidin-2-ylmethyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxypyridin-2-yl)methyl]-1-(3-furylmethyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxypyridin-2-yl)methyl]-1-(3-thienylmethyl)-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclohexylmethyl)-2-[(5-ethoxypyridin-2-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
1-(Cyclohexylmethyl)-2-[(5-isopropoxypyridin-2-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-(4-Ethoxybenzyl)-1-[(4-methylmorpholin-3-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-[(5-Ethoxypyridin-2-yl)methyl]-1-[(4-methylmorpholin-3-yl)methyl]-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-(4-Ethoxybenzyl)-1-{[(2S)-1-methylpiperidin-2-yl]methyl}-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
2-(4-Isopropoxybenzyl)-1-{[(2R)-1-methylpiperidin-2-yl]methyl}-N,N-bis(2,2,2-trifluoroethyl)-1H-benzimidazole-5-carboxamide;
and pharmaceutically acceptable salts thereof.

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 1.

### Claim 11

A method of producing a compound of Formula (I) comprising the step of reacting a compound represented by formula (II) with R2OArXCOA:
wherein
RF1 and RF2 are independently selected from —CF3, —CH2CF3, —CH2CHF2, —CHFCF3, —CHFCHF2, —CHFCH2F, —CF2CF3, —CF2CH3, —CF2CH2F, —CF2CHF2, —CF3, —CH2CCl3, —CH2CHCl2, —CH2CBr3, —CH2CHBr3, —CH2NO2, —CH2CH2NO2, —CH2CN, —CH2CH2CN, and —CH2CH2OCH3;
Z is selected from O═ and S═;
R1 is selected from C1-10alkyl; C1-10alkyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; C2-10alkenyl; C2-10alkenyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; C2-10alkynyl; C2-10alkynyl substituted by at least one of halogen, cyano, acetoxymethyl and nitro; R3R4N—C1-6alkyl; R3R4NC(═O)—C1-6alkyl; R3O—C1-6alkyl; R3OC(═O)—C1-6alkyl; R3C(═O)—C1-6alkyl; R3C(═O)NR3—C1-6alkyl; R3R4NSO2—C1-6alkyl; R3OSO2N(R4)—C1-6alkyl; R3R4NO(═O)N(R5)—C1-6alkyl; R3R4NSO2N(R5)—C1-6alkyl; aryl-C1-6alkyl; aryl-O(═O)—C1-6alkyl; heterocyclyl-C1-6alkyl; heterocyclyl-O(═O)—C1-6alkyl; substituted aryl-C1-6alkyl; substituted aryl-O(═O)—C1-6alkyl; substituted heterocyclyl-C1-6alkyl; substituted heterocyclyl-O(═O)—C1-6alkyl; and C1-10hydrocarbylamino;
R2 is selected from C1-6alkyl, substituted C1-6alkyl, C2-6alkenyl, substituted C2-6alkenyl, C2-6alkynyl, substituted C2-6alkynyl, C3-6cycloalkyl, substituted C3-6cycloalkyl, aryl, substituted aryl, and C5-6heteroaryl, and substituted C5-6heteroaryl;
R3, R4 and R5 are independently selected from —H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and a divalent C1-6 group that together with another divalent C1-6 group forms a portion of a ring;
X is selected from —NR6—, —C(═O)—, —CH2—CH2—, —CH═CH—, —O—, —C(R6)(R7)—, and —S(O)n—, wherein n is 0, 1 or 2, wherein R6 and R7 are independently C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —OH, or —H;
A is selected from —OH, —Cl, —Br, and —I;
Ar is selected from an arylene: an heteroarylene: an arylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and an heteroarylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and
Y is selected from CH═ and N═.

### Claim 12

A method of producing a compound of Formula (I) comprising the step of reacting a compound represented by formula (III) with formaldehyde:
wherein
r and s are selected from 0, 1 and 2;
R10 is selected from C1-6alkylene, —O—, and —NR11—, wherein R11 is a C1-6alkyl;
RF1 and RF2 are independently selected from —CF3, —CH2CF3, —CH2CHF2, —CHFCF3, —CHFCHF2, —CHFCH2F, —CF2CF3, —CF2CH3, —CF2CH2F, —CF2CHF2, —CF3, —CH2CCl3, —CH2CHCl2, —CH2CBr3, —CH2CHBr3, —CH2NO2, —CH2CH2NO2, —CH2CN, —CH2CH2CN, and —CH2CH2OCH3;
X is selected from —NR6—, —C(═O)—, —CH2—CH2—, —CH═CH—, —O—, —C(R6)(R7)—, and —S(O)n—, wherein n is 0, 1 or 2, wherein R6 and R7 are independently C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —OH, or —H;
Ar is selected from an arylene; an heteroarylene; an arylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy; and an heteroarylene substituted by at least one group selected from C1-6alkyl, halogen, trifluoromethyl, cyano, nitro, hydroxy and C1-6alkoxy;
R2 is selected from C1-6alkyl, substituted C1-6alkyl, C2-6alkenyl, substituted C2-6alkenyl, C2-6alkynyl, substituted C2-6alkynyl, C3-6cycloalkyl, substituted C3-6cycloalkyl, aryl, substituted aryl, and C5-6heteroaryl, and substituted C5-6heteroaryl; and
Y is selected from CH═ and N═.

### Claim 13 (depends on 6)

A pharmaceutical composition comprising a compound according to claim 6 and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 7)

A pharmaceutical composition comprising a compound according to claim 7 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 8)

A pharmaceutical composition comprising a compound according to claim 8 and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 6)

A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 6.

### Claim 17 (depends on 7)

A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 7.

### Claim 18 (depends on 8)

A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 8.