Vanilloid receptor ligand compounds, pharmaceutical compositions containing them, a method of producing them and the use thereof to treat pain and various other conditions

• US 20080269289A1
• Filed: 04/11/2008
• Published: 10/30/2008
• Est. Priority Date: 04/13/2007
• Status: Active Grant

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Schiene, Klaus, Bahrenberg, Gregor, De Vry, Jean, Christoph, Thomas, Frank, Robert, Saunders, Derek, Lee, Jeewoo
• Granted Patent: US 8,252,816 B2
• Time in Patent Office: Days
• US Class Current: 514/318
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: 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
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 25/36 : Opioid-abuse
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 311/08 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 323/41 : Y being a hydrogen or an acyclic carbon atom
• CPC Class Codes: C07D 211/08 : with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
• CPC Class Codes: C07D 211/14 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 213/70 : Sulfur atoms
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond

Abstract

Compounds corresponding to formula I:

which act as vanilloid receptor ligands, pharmaceutical composition s containing such compounds, a method for producing the compounds, and the use of such compounds to treat pain and various other conditions.

Claims

1. A compound corresponding to formula I:

2. A compound according to claim 1, wherein said compound is in the form of an isolated stereoisomer.

3. A compound according to claim 1, wherein said compound is in the form of a mixture of stereoisomers in any mixing ratio.

4. A compound according to claim 1, wherein said compound is in the form of a racemic mixture.

5. A compound according to claim 1, wherein:

X represents O;

n is 0, 1 or 2;

R¹, R², R³ and R⁴ each independently represent H;

F;

Cl;

Br;

I;

—

SF₅;

—

NO₂;

—

CN;

—

NH₂;

—

OH;

—

SH;

—

C(═

O)—

NH₂;

—

S(═

O)₂—

NH₂;

—

C(═

O)—

NH—

OH;

—

C(═

O)—

OH;

—

C(═

O)—

H;

—

S(═

O)₂—

OH;

—

NHR¹⁰;

—

NR¹¹R¹²;

—

OR¹³;

—

SR¹⁴;

—

S(═

O)—

R²³;

—

S(═

O)₂—

R²⁴ or a residue selected from the group consisting of methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CCl₂F, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, n-butyl, sec.-butyl, isobutyl and tert.-butyl;

R⁵ represents —

NH₂;

—

NHR²⁵;

—

NR²⁶R²⁷;

or an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl and isobutyl;

R⁶ represents —

C(═

O)—

R²⁸ or a residue selected from the group consisting of methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CCl₂F, —

CH₂—

CN, —

CH₂—

O—

CH₃, —

CH₂—

O—

CF₃, —

CH₂—

SF₃, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, —

CH₂—

CH₂—

CN, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, —

CH₂—

CH₂—

CH₂—

CN, —

CH₂—

O—

CH₂—

CH₃, —

CH₂—

CH₂—

SF₃, —

CH₂—

CH₂—

OCF₃, —

CH(CH₃)(O—

CH₃), —

CH(CH₃)(S—

CH₃), n-butyl, —

CF₂—

CF₂—

CF₂—

CF₃, —

CH₂—

CH₂—

CH₂—

CH₂—

CN, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-heptyl, 4-heptyl, n-octyl, n-nonyl, 5-nonyl, (2,6)-dimethyl-hept-4-yl, 3-methylbutyl, n-hexyl, (3,3)-dimethylbutyl, —

CH₂—

CH₂—

O—

CH₃, —

CH₂—

CH₂—

O—

C₂H₅, —

CH₂—

CH₂—

CH₂—

O—

CH₃, ethenyl, propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 3-pentenyl;

R⁷ and R⁸ each independently represent hydrogen or an alkyl residue selected from the group consisting of —

CH₂—

OH, —

CH₂—

CH₂—

OH, —

CH₂—

CH₂—

CH₂—

OH, —

CH₂—

CH₂—

CH₂—

CH₂—

OH, isopropyl, n-butyl, sec.-butyl, isobutyl, methyl, ethyl and n-propyl;

or

a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl, pyrimidinyl, indazolyl, quinoxalinyl, quinolinyl and isoquinolinyl, which optionally may be attached via a —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃ group, and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

NH₂, —

NO₂, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl and n-pentyl;

or

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

with the proviso that R⁷ and R⁸ are not both hydrogen;

or

R⁷ and R⁸ together with the carbon atom to which they are attached form a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

T denotes C—

R²⁹;

U denotes C—

R³⁰;

V denotes N, and W denotes C—

R³²;

or

T denotes C—

R²⁹;

U denotes N;

V denotes C—

R³¹, and W denotes C—

R³²;

or

T denotes N;

U denotes C—

R³⁰;

V denotes C—

R³¹, and W denotes C—

R³²;

or

T denotes N;

U denotes N;

V denotes C—

R³¹, and W denotes C—

R³²;

or

T denotes N;

U denotes C—

R³⁰;

V denotes N, and W denotes C—

R³²;

or

T denotes C—

R²⁹;

U denotes N;

V denotes N, and W denotes C—

R³²;

or

T denotes C—

R²⁹;

U denotes C—

R³⁰;

V denotes C—

R³¹, and W denotes C—

R³²;

R⁹ represents F;

Cl;

Br;

I;

—

SF₅;

—

OR¹³;

—

SR¹⁴;

—

S(═

O)—

R²³;

—

S(═

O)₂—

R²⁴;

or

a residue selected from the group consisting of methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CCl₂F, —

CH₂—

CN, —

CH₂—

O—

CH₃, —

CH₂—

O—

CF₃, —

CH₂—

SF₃, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, —

CH₂—

CH₂—

CN, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, —

CH₂—

CH₂—

CH₂—

CN, —

CH₂—

O—

CH₂—

CH₃, —

CH₂—

CH₂—

SF₃, —

CH₂—

CH₂—

OCF₃, —

CH(CH₃)(O—

CH₃), —

CH(CH₃)(S—

CH₃), n-butyl, —

CF₂—

CF₂—

CF₂—

CF₃, —

CH₂—

CH₂—

CH₂—

CH₂—

CN, n-butyl, sec.-butyl, isobutyl, —

C(CH₃)₂(CH₂OH) and tert.-butyl;

or

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl and cyclohexenyl, which optionally may be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of oxo (═

O), thioxo (═

S), —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl and n-pentyl;

R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R²¹ and R²³ and R²⁴ each independently represent a residue selected from the group consisting of methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CCl₂F, —

CH₂—

CN, —

CH₂—

O—

CH₃, —

CH₂—

O—

CF₃, —

CH₂—

SF₃, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, —

CH₂—

CH₂—

CN, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, —

CH₂—

CH₂—

CH₂—

CN, —

CH₂—

O—

CH₂—

CH₃, —

CH₂—

CH₂—

SF₃, —

CH₂—

CH₂—

OCF₃, —

CH(CH₃)(O—

CH₃), —

CH(CH₃)(S—

CH₃), n-butyl, —

CF₂—

CF₂—

CF₂—

CF₃, —

CH₂—

CH₂—

CH₂—

CH₂—

CN, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-heptyl, 4-heptyl, n-octyl, n-nonyl, 5-nonyl, (2,6)-dimethyl-hept-4-yl, 3-methylbutyl, n-hexyl, (3,3)-dimethylbutyl, —

CH₂—

CH₂—

O—

CH₃, —

CH₂—

CH₂—

O—

C₂H₅, —

CH₂—

CH₂—

CH₂—

O—

CH₃, ethenyl, propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 3-pentenyl;

or

a residue selected from the group consisting of 2,3-dihydro-1H-indenyl, cyclopropyl, oxetanyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, diazepanyl, azocanyl and thiomorpholinyl, which optionally may be attached via a —

CH₂—

O—

, —

CH₂—

CH₂—

O—

, —

CH₂—

CH₂—

O—

CH₂—

, —

CH₂—

CH(CH₃)—

O—

CH₂—

, —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group, and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of oxo (═

O), thioxo (═

S), —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂ and —

C(═

O)—

O—

C(CH₃)₃;

or

a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl and isoxazolyl, which optionally may be attached via a —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

NH₂, —

NO₂, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂, —

C(═

O)—

O—

C(CH₃)₃, —

NH—

CH₃, —

NH—

C₂H₅, —

NH—

C(CH₃)₃, —

N(CH₃)₂, —

N(C₂H₅)₂, —

N(CH₃)(C₂H₅), —

NH—

C(═

O)—

O—

CH₃, —

NH—

C(═

O)—

O—

C₂H₅, —

NH—

C(═

O)—

O—

C(CH₃)₃, —

C(═

O)—

H, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

CH₃, —

C(═

O)—

NH—

C₂H₅, —

C(═

O)—

N(CH₃)₂, —

C(═

O)—

N(C₂H₅)₂, —

O-phenyl, —

O-benzyl, phenyl and benzyl;

R²⁵, R²⁶ and R²⁷ each independently represent an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl and isobutyl;

R²⁸ represents a residue selected from the group consisting of methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CH₂—

CN, —

CH₂—

O—

CH₃, —

CH₂—

O—

CF₃, —

CH₂—

SF₃, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, —

CH₂—

CH₂—

CN, n-propyl, isopropyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-heptyl, 4-heptyl, n-octyl, n-nonyl, 5-nonyl, (2,6)-dimethyl-hept-4-yl, 3-methylbutyl, n-hexyl, (3,3)-dimethylbutyl, ethenyl, propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 3-pentenyl;

R²⁹, R³⁰ and R³¹ each independently represent H;

F;

Cl;

Br;

I;

—

SF₅;

—

NO₂;

—

CN;

—

NH₂;

—

OH;

—

SH;

—

C(═

O)—

NH₂;

—

S(═

O)₂—

NH₂;

—

C(═

O)—

NH—

OH;

—

C(═

O)—

OH;

—

C(═

O)—

H;

—

S(═

O)₂—

OH;

—

NHR¹⁰;

—

NR¹¹R¹²;

—

OR¹³;

—

SR¹⁴;

—

C(═

O)—

OR²¹;

—

S(═

O)—

R²³;

—

S(═

O)₂—

R²⁴;

or a residue selected from the group consisting of —

CH₂—

OH, methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CCl₂F, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, n-butyl, sec.-butyl, isobutyl and tert.-butyl, or a phenyl residue, which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

NH₂, —

NO₂, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl and n-pentyl;

R³² represents H;

—

SF₅;

—

NO₂;

—

CN;

—

NH₂;

—

OH;

—

SH;

—

C(═

O)—

NH₂;

—

S(═

O)₂—

NH₂;

—

C(═

O)—

NH—

OH;

—

C(═

O)—

OH;

—

C(═

O)—

H;

—

S(═

O)₂—

OH;

—

NHR³³;

—

NR³⁴R³⁵;

—

OR³⁶;

—

SR³⁷;

—

C(═

O)—

OR⁴⁴;

—

S(═

O)—

R⁴⁶;

—

S(═

O)₂—

R⁴⁷;

—

C(═

NH)—

NH₂;

—

C(═

NH)—

NH—

R⁴⁸;

—

N═

C(NH₂)₂;

—

N═

C(NHR⁴⁹)(NHR⁵⁰);

or

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, diazepanyl, azocanyl and thiomorpholinyl, which is attached via a carbon atom of the respective ring of the said residues or via a —

(CH═

CH)—

, —

C≡

C—

or —

C≡

C—

CH₂—

group to the parent structure and may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of —

CN, —

CH₂—

N(CH₃)₂, —

CH₂—

N(C₂H₅)₂, —

CH₂—

NH—

CH₃, —

CH₂—

NH—

C₂H₅, —

N—

[C(═

O)—

C₂H₅]-phenyl, —

N—

[C(═

O)—

CH₃]-phenyl, oxo (═

O), thioxo (═

S), —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂ and —

C(═

O)—

O—

C(CH₃)₃;

or

a residue selected from the group consisting of (1,3)-benzodioxolyl, (1,4)-benzodioxanyl, tetrazolyl, (2,3)-dihydrothieno[3,4-b)][1,4]dioxinyl, benzo[b]furanyl, phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl, pyrimidinyl, indazolyl, quinoxalinyl, quinolinyl and isoquinolinyl, which optionally may be attached via a —

(CH═

CH)—

, —

C≡

C—

, —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group, and may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

NH₂, —

NO₂, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂, —

C(═

O)—

O—

C(CH₃)₃, —

NH—

CH₃, —

NH—

C₂H₅, —

NH—

C(CH₃)₃, —

N(CH₃)₂, —

N(C₂H₅)₂, —

N(CH₃)(C₂H₅), —

NH—

C(═

O)—

O—

CH₃, —

NH—

S(═

O)₂—

CH₃, —

NH—

S(═

O₂)—

C₂H₅, —

NH—

S(═

O)₂—

CH(CH₃)₂, —

NH—

C(═

O)—

O—

C₂H₅, —

NH—

C(═

O)—

O—

C(CH₃)₃, —

C(═

O)—

H, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

CH₃, —

C(═

O)—

NH—

C₂H₅, —

C(═

O)—

N(CH₃)₂, —

C(═

O)—

N(C₂H₅)₂, —

O-phenyl, —

O-benzyl, phenyl and benzyl;

R³³, R³⁴, R³⁵, R³⁶, R³⁷, R⁴⁴, R⁴⁶, R⁴⁷, R⁴⁸, R⁴⁹ and R⁵⁰ each independently represent a residue selected from the group consisting of methyl, —

CF₃, —

CCl₃, —

CBr₃, —

CHF₂, —

CH₂F, —

CF₂Cl, —

CCl₂F, —

CH₂—

CN, —

CH₂—

O—

CH₃, —

CH₂—

O—

CF₃, —

CH₂—

SF₃, ethyl, —

CF₂—

CH₃, —

CH₂—

CF₃, —

C₂F₅, —

CH₂—

CCl₃, —

CH₂—

CBr₃, —

CHF—

CF₂Cl, —

CF₂—

CF₂Cl, —

CFCl—

CF₂Cl, —

CH₂—

CH₂—

CN, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, —

CH₂—

CH₂—

CH₂—

CN, —

CH₂—

O—

CH₂—

CH₃, —

CH₂—

CH₂—

SF₃, —

CH₂—

CH₂—

OCF₃, —

CH(CH₃)(O—

CH₃), —

CH(CH₃)(S—

CH₃), n-butyl, —

CF₂—

CF₂—

CF₂—

CF₃, —

CH₂—

CH₂—

CH₂—

CH₂—

CN, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-heptyl, 4-heptyl, n-octyl, n-nonyl, 5-nonyl, (2,6)-dimethyl-hept-4-yl, 3-methylbutyl, n-hexyl, (3,3)-dimethylbutyl, —

CH₂—

CH₂—

O—

CH₃, —

CH₂—

CH₂—

O—

C₂H₅, —

CH₂—

CH₂—

CH₂—

O—

CH₃, ethenyl, propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 3-pentenyl;

or

a residue selected from the group consisting of 2,3-dihydro-1H-indenyl, cyclopropyl, oxetanyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, diazepanyl, azocanyl and thiomorpholinyl, which optionally may be attached via a —

CH₂—

O—

, —

CH₂—

CH₂—

O—

, —

CH₂—

CH₂—

O—

CH₂—

, —

CH₂—

CH(CH₃)—

O—

CH₂—

, —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group, and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of oxo (═

O), thioxo (═

S), —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂ and —

C(═

O)—

O—

C(CH₃)₃;

or

a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl and isoxazolyl, wherein the residue optionally may be attached via a —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group and may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

NH₂, —

NO₂, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂, —

C(═

O)—

O—

C(CH₃)₃, —

NH—

CH₃, —

NH—

C₂H₅, —

NH—

C(CH₃)₃, —

N(CH₃)₂, —

N(C₂H₅)₂, —

N(CH₃)(C₂H₅), —

NH—

C(═

O)—

O—

CH₃, —

NH—

C(═

O)—

O—

C₂H₅, —

NH—

C(═

O)—

O—

C(CH₃)₃, —

C(═

O)—

H, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

CH₃, —

C(═

O)—

NH—

C₂H₅, —

C(═

O)—

N(CH₃)₂, —

C(═

O)—

N(C₂H₅)₂, —

O-phenyl, —

O-benzyl, phenyl and benzyl;

or

R³⁴ and R³⁵ together with the nitrogen atom to which they are attached form a residue selected from the group consisting of 3-aza-bicyclo[3.1.1]heptyl, 6-aza-spiro[2.5]octyl, 3-aza-bicyclo[3.2.1]octyl, 6-aza-bicyclo[3.3.1]heptyl, 8-aza-bicyclo[3.2.1]octyl, 1-oxa-2,8-diaza-spiro[4.5]dec-2-enyl, azocanyl, isoindolyl, indolyl, (1,2,3,6)-tetrahydropyridinyl, (4,5,6,7)-tetrahydroisoxazolo[5,4-c]pyridinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, diazepanyl and thiomorpholinyl, wherein the heterocycloaliphatic moiety may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 residues R⁵¹;

R⁵¹ represents —

NHR⁵², —

NR⁵³R⁵⁴ or an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl and isobutyl;

R⁵², R⁵³ and R⁵⁴ each independently represent —

C(═

O)—

R⁵⁵;

or an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl, and isobutyl;

or

a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl and isoxazolyl, wherein the residue optionally may be attached via a —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group and may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

NH₂, —

NO₂, —

O—

CF₃, —

S—

CF₃, —

SH, —

S—

CH₃, —

S—

C₂H₅, —

S—

CH(CH₃)₂, —

S—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, —

C(═

O)—

OH, —

C(═

O)—

O—

CH₃, —

C(═

O)—

O—

C₂H₅, —

C(═

O)—

O—

CH(CH₃)₂, —

C(═

O)—

O—

C(CH₃)₃, —

NH—

CH₃, —

NH—

C₂H₅, —

NH—

C(CH₃)₃, —

N(CH₃)₂, —

N(C₂H₅)₂, —

N(CH₃)(C₂H₅), —

NH—

C(═

O)—

O—

CH₃, —

NH—

C(═

O)—

O—

C₂H₅, —

NH—

C(═

O)—

O—

C(CH₃)₃, —

C(═

O)—

H, —

C(═

O)—

CH₃, —

C(═

O)—

C₂H₅, —

C(═

O)—

CH(CH₃)₂, —

C(═

O)—

C(CH₃)₃, —

C(═

O)—

NH₂, —

C(═

O)—

NH—

CH₃, —

C(═

O)—

NH—

C₂H₅, —

C(═

O)—

N(CH₃)₂, —

C(═

O)—

N(C₂H₅)₂, —

O-phenyl, —

O-benzyl, phenyl and benzyl; and

R⁵⁵ represents an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl, and isobutyl;

or a salt thereof.

6. A compound according to claim 1, wherein:

X represents O;

n is 1;

R¹, R³ and R⁴ each independently represent H;

F;

Cl;

Br;

I;

—

NHR¹⁰;

—

NR¹¹R¹²;

—

OR¹³;

—

SR¹⁴ or a residue selected from the group consisting of methyl, —

CF₃, —

CHF₂, —

CH₂F, ethyl, n-propyl, —

CF₂—

CF₂—

CF₃, —

CF(CF₃)₂, isopropyl, n-butyl, sec.-butyl, isobutyl and tert.-butyl;

R² represents H;

F;

Cl;

Br;

I or methyl;

R⁵ represents an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl, and isobutyl;

R⁶ represents —

C(═

O)—

R²⁸ or a residue selected from the group consisting of methyl, —

CH₂—

CN, ethyl, —

CH₂—

CH₂—

CN, n-propyl, —

CH₂—

CH₂—

CH₂—

CN, n-butyl, —

CH₂—

CH₂—

CH₂—

CH₂—

CN, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-heptyl, ethenyl, propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 3-pentenyl;

R⁷ represents an alkyl residue selected from the group consisting of —

CH₂—

OH, —

CH₂—

CH₂—

OH, —

CH₂—

CH₂—

CH₂—

OH, —

CH₂—

CH₂—

CH₂—

CH₂—

OH, isopropyl, n-butyl, sec.-butyl, isobutyl, methyl, ethyl and n-propyl;

or

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

R⁸ represents hydrogen;

or

R⁷ and R⁸ together with the carbon atom to which they are attached form a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

T denotes C—

R²⁹;

U denotes C—

R³⁰;

V denotes N, and W denotes C—

R³²;

or

T denotes C—

R²⁹;

U denotes C—

R³⁰;

V denotes C—

R³¹, and W denotes C—

R³²;

R⁹ represents F;

Cl;

Br;

I;

—

SF₅;

—

O—

CF₃;

—

O—

CCl₃;

—

O—

CBr₃;

—

O—

CHF₂;

—

O—

CH₂F;

—

O—

CF₂Cl;

—

O—

CCl₂F;

—

O—

CF₂—

CH₃;

—

S—

CF₃;

—

S—

CCl₃;

—

S—

CBr₃;

—

S—

CHF₂;

—

S—

CH₂F;

—

S—

CF₂Cl;

—

S—

CCl₂F;

—

S—

CF₂—

CH₃;

or a residue selected from the group consisting of methyl, —

CF₃, —

CHF₂, —

CH₂F, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, —

C(CH₃)₂(CH₂OH) and tert.-butyl;

R¹⁰, R¹¹, R¹², R¹³ and R¹⁴ each independently represent a residue selected from the group consisting of methyl, —

CF₃, —

CHF₂, —

CH₂F, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl and n-pentyl;

R²⁸ represents a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-heptyl, 4-heptyl, n-octyl, n-nonyl, 5-nonyl, (2,6)-dimethyl-hept-4-yl, 3-methylbutyl, n-hexyl, (3,3)-dimethylbutyl, ethenyl, propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 3-pentenyl;

R²⁹, R³⁰ and R³¹ each independently represent H;

F;

Cl;

Br;

I;

—

SF₅;

—

NO₂;

—

CN;

—

NH₂;

—

OH;

—

SH;

—

NHR¹⁰;

—

NR¹¹R¹²;

—

OR¹³;

—

SR¹⁴;

or a residue selected from the group consisting of —

CH₂—

OH, methyl, —

CF₃, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl and tert.-butyl;

R³² represents H;

—

SF₅;

—

NO₂;

—

CN;

—

NH₂;

—

OH;

—

;

—

NHR³³;

—

NR³⁴R³⁵;

—

OR³⁶;

—

SR³⁷;

or

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, diazepanyl, azocanyl and thiomorpholinyl, which is attached via a carbon atom of the ring of the residue to the parent structure, and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of —

CH₂—

N(CH₃)₂, —

CH₂—

N(C₂H₅)₂, —

CH₂—

NH—

CH₃, —

CH₂—

NH—

C₂H₅, —

N—

[C(═

O)—

C₂H₅]-phenyl, —

N—

[C(═

O)—

CH₃]-phenyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl and tert.-butyl;

or

a residue selected from the group consisting of phenyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl and pyrimidinyl, which optionally may be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

SF₅, —

OH, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, —

O—

CF₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl and n-pentyl;

R³³, R³⁴, R³⁵, R³⁶ and R³⁷ each independently represent a residue selected from the group consisting of methyl, —

CH₂—

O—

CH₃, ethyl, n-propyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, 3-pentyl, n-hexyl, (3,3)-dimethylbutyl, —

CH₂—

CH₂—

O—

CH₃, —

CH₂—

CH₂—

O—

C₂H₅ and —

CH₂—

CH₂—

CH₂—

O—

CH₃;

or

a residue selected from the group consisting of 2,3-dihydro-1H-indenyl, cyclopropyl, oxetanyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, diazepanyl, azocanyl and thiomorpholinyl, which may in each case optionally be substituted with 1, 2, 3, 4 or 5 substituents mutually independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl;

or

R³⁴ and R³⁵ together with the nitrogen atom to which they are attached form a residue selected from the group consisting of 3-aza-bicyclo[3.1.1]heptyl, 6-aza-spiro[2.5]octyl, 3-aza-bicyclo[3.2.1]octyl, 6-aza-bicyclo[3.3.1]heptyl, 8-aza-bicyclo[3.2.1]octyl, 1-oxa-2,8-diaza-spiro[4.5]dec-2-enyl, azocanyl, isoindolyl, indolyl, (1,2,3,6)-tetrahydropyridinyl, (4,5,6,7)-tetrahydroisoxazolo[5,4-c]pyridinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, diazepanyl and thiomorpholinyl, wherein the heterocycloaliphatic moiety may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 residues R⁵¹;

R⁵¹ represents —

NHR⁵², —

NR⁵³R⁵⁴ or an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl and isobutyl;

R⁵², R⁵³ and R⁵⁴ each independently represent —

C(═

O)—

R⁵⁵;

or an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl and isobutyl;

or

a residue selected from the group consisting of phenyl and naphthyl, wherein said phenyl or naphthyl residue optionally may be attached via a —

(CH₂)—

, —

(CH₂)₂—

or —

(CH₂)₃—

group, and may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —

CN, —

CF₃, —

O—

CH₃, —

O—

C₂H₅, —

O—

CH(CH₃)₂, —

O—

C(CH₃)₃, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl and n-pentyl; and

R⁵⁵ represents an alkyl residue selected from the group consisting of —

CF₃, —

CH₂—

CF₃, methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl, and isobutyl;

or a salt thereof.

7. A compound according to claim 1, wherein:

X represents O;

n is 1;

R¹, R³ and R⁴ each represent H;

R² represents F;

Cl or Br;

R⁵ represents an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl and isopropyl;

R⁶ represents —

C(═

O)—

R²⁸ or a residue selected from the group consisting of methyl, —

CH₂—

CN, ethyl, —

CH₂—

CH₂—

CN, n-propyl, —

CH₂—

CH₂—

CH₂—

CN, n-butyl, —

CH₂—

CH₂—

CH₂—

CH₂—

CN, sec.-butyl, isobutyl, tert.-butyl and n-pentyl;

R⁷ represents an alkyl residue selected from the group consisting of —

CH₂—

OH, —

CH₂—

CH₂—

OH, —

CH₂—

CH₂—

CH₂—

OH, —

CH₂—

CH₂—

CH₂—

CH₂—

OH, isopropyl, n-butyl, sec.-butyl, isobutyl, methyl, ethyl and n-propyl;

R⁸ represents hydrogen;

T denotes C—

R²⁹;

U denotes C—

R³⁰;

V denotes N, and W denotes C—

R³²;

or

T denotes C—

R²⁹;

U denotes C—

R³⁰;

V denotes C—

R³¹, and W denotes C—

R³²;

R⁹ represents —

SF₅;

—

O—

CF₃;

—

CF₃;

—

CHF₂;

—

CH₂F;

—

C(CH₃)₂(CH₂OH) or tert.-butyl;

R²⁸ represents a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, sec.-butyl, isobutyl, tert.-butyl, ethenyl and propenyl;

R²⁹, R³⁰ and R³¹ each represent H;

R³² represents H;

—

NHR³³;

—

NR³⁴R³⁵;

—

OR³⁶ or —

SR³⁷;

R³³, R³⁶ and R³⁷ each independently represent a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, which optionally may be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl;

R³⁴ and R³⁵ together with the nitrogen atom to which they are attached form a residue selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and azepanyl, wherein the heterocycloaliphatic moiety may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 residues R⁵¹;

R⁵¹ represents —

NHR⁵², —

NR⁵³R⁵⁴ or an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl and isobutyl;

R⁵², R⁵³ and R⁵⁴ each independently represent —

C(═

O)—

R⁵⁵;

or an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl, and isobutyl;

or

a phenyl residue, wherein the phenyl residue may be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, methyl, ethyl, n-propyl and isopropyl; and

R⁵⁵ represents an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert.-butyl, n-butyl, sec.-butyl, and isobutyl;

or a salt thereof.

8. A compound according to claim 3, wherein said compound corresponds to formula Ia:

9. A compound according to claim 4, wherein said compound corresponds to formula Ia:

10. A compound according to claim 3, wherein said compound corresponds to formula Ib:

11. A compound according to claim 4, wherein said compound corresponds to formula Ib:

12. A compound according to claim 1, wherein said compound is selected from the group consisting of:

[1] N-(2-fluoro-4-(1-oxo-1-((2-(4-(N-phenylpropionamido)piperidin-1-yl)-6-(trifluoro-methyl)pyridin-3-yl)methylamino)propan-2-yl)phenyl)-N-(methylsulfonyl)propionamide,

[2] 2-(3-fluoro-4-(N-(methylsulfonyl)acetamido)phenyl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,

[3] 2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,

[4] N-(4-tert.-butylbenzyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

[5] (S)—

N-(4-tert.-butylbenzyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

[6] (S)—

N-(4-tert.-butylbenzyl)-2-(4-(N-ethylmethylsulfonamido)-3-fluorophenyl)propanamide,

[7] N-((2-(cyclohexylthio)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

[8] N-((2-(cyclohexylthio)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(4-(N-ethylmethylsulfonamido)-3-fluorophenyl)propanamide,

[9] 2-(4-(N-ethylmethylsulfonamido)-3-fluorophenyl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,

[10] N-((6-tert.-butyl-2-(4-methylpiperidin-1-yl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

[11] N-((6-tert.-butyl-2-(cyclohexylthio)pyridin-3-yl)methyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

[12] 2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)-N-(2-(4-methylpiperidin-1-yl)-4-(trifluoromethyl)benzyl)propanamide,

[13] N-(2-(cyclohexylthio)-4-(trifluoromethyl)benzyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

[14] N-(4-tert.-butyl-2-(4-methylpiperidin-1-yl)benzyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide, and

[15] N-(4-tert.-butyl-2-(cyclohexylthio)benzyl)-2-(3-fluoro-4-(N-methylmethylsulfonamido)phenyl)propanamide,

or a salt thereof.

13. A compound according to claim 1, wherein, in a FLIPR assay with CHO K1 cells transfected with the human gene VR1, said compound at a concentration of less than 2000 nM, brings about a 50% displacement of capsaicin which is present in a concentration of 100 nM.

14. A compound according to claim 13, wherein said compound at a concentration of less than 300 nM, brings about a 50% displacement of capsaicin which is present in a concentration of 100 nM.

15. A compound according to claim 13, wherein said compound at a concentration of less than 75 nM, brings about a 50% displacement of capsaicin which is present in a concentration of 100 nM.

16. A compound according to claim 13, wherein said compound at a concentration of less than 10 nM, brings about a 50% displacement of capsaicin which is present in a concentration of 100 nM.

17. A method of producing a compound according to claim 1, said method comprising:

reacting a compound corresponding to formula II;

18. A method according to claim 17, wherein the compound of formula II is reacted in the presence of at least one reducing agent selected from the group consisting of sodium hydride, sodium, potassium hydride, lithium aluminium hydride, sodium borohydride and di(isobutyl)aluminium hydride;

or wherein the compound of formula IV is reacted in the presence of at least one reducing agent selected from the group consisting of sodium hydride, potassium hydride, lithium aluminium hydride, sodium borohydride and di(isobutyl)aluminium hydride;

or wherein the compound of formula IV is reacted in the presence of a platinum or palladium catalyst;

or wherein a compound corresponding to formula VI is reacted in the presence of a palladium or platinum catalyst and of hydrochloric acid;

or wherein LG denotes a chlorine or bromine atom;

or wherein each of the phenyl groups in the compound of formula IX is substituted by 1 or 2 phenoxy or methoxy residues.

19. A method of producing a compound according to claim 1, said method comprising:

reacting a compound corresponding to formula X;

20. A method according to claim 19, wherein LG denotes a chlorine or bromine atom;

or wherein each of the phenyl groups in the compound of formula IX is substituted with 1 or 2 phenoxy or methoxy residues;

or wherein each of the phenyl groups in the compound of formula IX is substituted with a methoxy residue in the para position.

21. A pharmaceutical composition comprising a compound according to claim 1, and at least one pharmaceutically acceptable carrier or pharmaceutical auxiliary substance.

22. A method of treating or inhibiting pain in a subject, said method comprising administering to said subject a pharmacologically effective amount of a compound according to claim 1.

23. A method according to claim 22, wherein said pain is selected from the group consisting of acute pain, chronic pain, neuropathic pain, visceral pain, joint pain, hyperalgesia, allodynia, causalgia and migraine.

24. A method of treating or inhibiting a disorder or condition selected from the group consisting of depression, neuropathy, nerve injury, neurodegenerative diseases, cognitive dysfunction, and epilepsy in a subject, said method comprising administering to said subject a pharmacologically effective amount of a compound according to claim 1.

25. A method according to claim 24, wherein said disorder or condition is a neurodegenerative disease selected from the group consisting of multiple sclerosis, Alzheimer'"'"'s disease, Parkinson'"'"'s disease and Huntington'"'"'s chorea;

or a cognitive dysfunction selected from the group consisting of cognitive deficiency states and memory disorders.

26. A method of treating or inhibiting a disorder or condition selected from the group consisting of airway diseases, coughing;

urinary incontinence;

overactive bladder, diseases of or injuries to the gastrointestinal tract, duodenal ulcers, gastric ulcers, irritable bowel syndrome, strokes, eye irritation;

skin irritation;

neurotic skin conditions, allergic skin diseases, psoriasis, vitiligo, herpes simplex, inflammation, diarrhea, pruritus, osteoporosis, arthritis, osteoarthritis, rheumatic diseases, food intake disorders, dependency on a pharmaceutical substance, abuse of a pharmaceutical substance, withdrawal symptoms associated with dependency on a pharmaceutical substance, development of tolerance towards a pharmaceutical substance, dependency on drugs, drug abuse, withdrawal symptoms associated with dependency on drugs, dependency on alcohol, alcohol abuse, withdrawal symptoms associated with dependency on alcohol;

or for effecting dieresis, antinatriuresis, influencing the cardiovascular system, increasing vigilance, treating wounds or burns, treating severed nerves, increasing libido, modulating locomotor activity, anxiolysis, local anaesthesia or inhibiting undesired side-effects triggered by the administration of vanilloid receptor 1 agonists in a subject, said method comprising administering to said subject a pharmacologically effective amount of a compound according to claim 1.

27. A method according to claim 26, wherein said disorder or condition is an airway disease selected from the group consisting of asthma, bronchitis and pulmonary inflammation;

or said disorder or condition is an inflammation selected from the group consisting of inflammation of the intestines, the eyes, the bladder, the skin and the nasal mucosa;

or said disorder or condition is a food intake disorder selected from the group consisting of bulimia, cachexia, anorexia and obesity;

or said disorder or condition is development of a tolerance towards natural or synthetic opioids;

or said disorder or condition is an undesired side effect selected from the group consisting of hyperthermia, high blood pressure and constriction of bronchial tubes, triggered by administration of a vanilloid receptor 1 agonist selected from the group consisting of capsaicin, resiniferatoxin, olvanil, arvanil, SDZ-249665, SDZ-249482, nuvanil and capsavanil.