# US 7,612,113 B2 · Hydroxy tetrahydro-naphthalenylurea derivatives

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- Number: US 7,612,113 B2
- Document ID: US7612113B2
- Status: Granted
- Kind: B2
- Application number: 10/513,848
- Filed: 2003-04-28
- Published: 2006-11-16
- Granted: 2009-11-03
- Earliest claimed: 2002-05-08
- Assignees: Xention Limited
- Inventors: Takeshi Yura; Muneto Mogi; Klaus Urbahns; Hiroshi Fujishima; Tsutomu Masuda; Toshiya Moriwaki; Nagahiro Yoshida; Toshio Kokubo; Masahiro Shiroo; Masaomi Tajimi; Yasuhiro Tsukimi; Noriyuki Yamamoto
- Web page: https://patentgrep.com/patent/US7612113B2

## CPC

- C07C 275/42: being further substituted by carboxyl groups
- 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 11/06: Antiasthmatics
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/10: of the bladder
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07C 275/32: being further substituted by singly-bound oxygen atoms
- C07C 275/40: being further substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to tetrahydro-naphthalene derivatives and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The tetrahydro-naphthalene derivatives of the present invention have an excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, incontinence, inflammatory disorders such as asthma and COPD.

## Claims

### Claim 1

A hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof:
wherein
X represents C1-6 alkyl,
in which
Y represents a direct bond,
R1, R2 and R3 independently represent hydrogen, halogen, hydroxy, nitro, carboxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, C3-8 cycloalkylamino, C1-6 alkoxycarbonyl phenyl, benzyl, sulfonamide, C1-6 alkanoyl, C1-6 alkanoylamino, carbamoyl, C1-6 alkylcarbamoyl, cyano, C1-6 alkyl optionally substituted by cyano, C1-6 alkoxycarbonyl or-mono-, di-, or tri-halogen, C1-6 alkoxy optionally substituted by mono-, di-, or tri-halogen, phenoxy optionally substituted by halogen or C1-6 alkyl, or C1-6 alkylthio optionally substituted by mono-, di-, or tri-halogen;
R4, R5, R6 and R7 independently represent hydrogen, C1-6 alkyl or phenyl;
Z1 represents hydrogen or C1-6 alkyl; and
Z2 represents hydrogen, halogen or C1-6 alkyl.

### Claim 2 (depends on 1)

The hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof as claimed in claim 1, wherein X represents
in which
Y represents a direct bond, or
R1, R2 and R3 independently represent hydrogen, halogen, hydroxy, nitro, carboxyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, C3-8 cycloalkylamino, C1-6 alkoxycarbonyl, phenyl, benzyl, sulfonamide, C1-6 alkanoyl, C1-6 alkanoylamino, carbamoyl, C1-6 alkylcarbamoyl, cyano, C1-6 alkyl optionally substituted by cyano, C1-6 alkoxycarbonyl or mono-, di-, or tri-halogen, C1-6 alkoxy optionally substituted by mono-, di-, or tri-halogen, phenoxy optionally substituted by halogen or C1-6 alkyl, or C1-6 alkylthio optionally substituted by mono-, di-, or tri-halogen;
R4 and R5 independently represent hydrogen or C1-6 alkyl; and
Z1 and Z2 each represent hydrogen.

### Claim 3 (depends on 1)

The hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof as claimed in claim 1, wherein X represents
in which
Y represents a direct bond or
R1, R2 and R3 independently represent hydrogen, halogen, di(C1-6 alkyl)amino, C3-8 cycloalkylamino, C1-6 alkoxycarbonyl, C1-6 alkyl optionally substituted by cyano, C1-6 alkoxycarbonyl or mono-, di-, or tri-halogen, C1-6 alkoxy optionally substituted by mono-, di-, or tri-halogen, phenoxy optionally substituted by halogen or C1-6 alkyl, or C1-6 alkylthio optionally substituted by mono-, di-, or tri-halogen;
R4 and R5 each represent hydrogen; and
Z1 and Z2 each represent hydrogen.

### Claim 4 (depends on 1)

The hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof as claimed in claim 1, wherein X represents
in which
Y represents a direct bond or
in which
R1 and R2 independently represent hydrogen, chloro, bromo, fluoro, cyclopentylamino, trifluoromethyl, or trifluoromethoxy;
R3, R4 and R5 each represent hydrogen; and
Z1 and z2 each represent hydrogen.

### Claim 5 (depends on 1)

The hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof as claimed in claims 1, wherein
X represents
in which
Y represents a direct bond or
in which
R1 and R2 independently represent hydrogen, chloro, bromo, fluoro, cyclopentylamino, trifluoromethyl, or trifluoromethoxy;
R3, R4 and R5 each represent hydrogen; and
Z1 and Z2 each represent hydrogen.

### Claim 6 (depends on 1)

A hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof as claimed in claim 1, wherein said hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I) is selected from the group consisting of:
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(3-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[3-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4(trifluoromethyl)-phenyl]urea;
Ethyl 3-({[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)amino]carbonyl}-amino)benzoate;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(1-naphthyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2-naphthyl)urea;
N-(3,4dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(4isopropylphenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(4-phenoxyphenyl)urea;
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-phenylurea;
N-(4-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[2-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2,4,6-trimethoxybenzyl)urea;
N-(2,6-difluorobenzyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-[2-(4-chlorophenyl)ethyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-[3-fluoro-4-(trifluoromethyl)benzyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
a tautomeric or steroisomeric form of any of the foregoing compounds; and
a pharmaceutically acceptable salt of any of the foregoing compounds.

### Claim 7

A hydroxy-tetrahydro-naphthalenylurea derivative selected from the group consisting of:
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(7S)-7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]urea;
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(7R)-7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]urea;
N-[(7R)-7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]-N′-[4-(trifluoromethyl)benzyl]urea;
N-[(7S)-7-hydroxy-5,6,1,8-tetrahydro-1-naphthalenyl]-N′-[4-(trifluoromethyl)benzyl]urea;
N-[(7R)-7-hydroxy 5,6,7,8-tetrahydro-1-naphthalenyl]-N′-[4-(trifluoro-methoxy)benzyl]urea;
N-[(7S)-7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]-N′-[4-(trifluoro-methoxy)benzyl]urea; and
a tautomeric or steroisomeric form of any of the foregoing compounds; and
a pharmaceutically acceptable salt of any of the foregoing compounds.

### Claim 8 (depends on 1)

A medicament comprising hydroxy-tetrahydro-naphthalenylurea derivative of the formula (I), its tautomeric or stereoisomeric form, or a pharmaceutically acceptable salt thereof as claimed in claim 1 as an active ingredient.

### Claim 9 (depends on 8)

The medicament as claimed, in claim 8, further comprising one or more pharmaceutically acceptable excipients.

### Claim 10 (depends on 1)

A method of treating a urological disorder or disease mediated in a human or animal by VR1 comprising administering to the human or animal a VR1 antagonistically effective amount of at least one compound according to claim 1.

### Claim 11 (depends on 1)

A method of treating pain mediated in a human or animal by VR1comprising administering to the human or animal a VR1 antagonistically effective amount of at least one compound according to claim 1.

### Claim 12 (depends on 1)

A method of treating a urological disorder or disease in a human or animal comprising administering to the human or animal an effective amount of at least one compound according to claim 1, wherein the urological disorder or disease is selected from the group consisting of urge urinary incontinence and overactive bladder.

### Claim 13 (depends on 10)

The method of claim 10, wherein the compound is selected from the group consisting of:
N-[4-chloro-3-trifluromethyl)phenyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(3-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-7-hydroxy-5,6,7,8-tetrahydro-1-naphtalenyl)-N′-[3-(trifluoromethyl)-phenyl]urea;
N-7-hydroxy-5,6,7,8-tetrahydro-1-naphtalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
Ethyl 3-({[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)amino]carbonyl}-amino)benzoate;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(1-napthyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2-napthyl)urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1naphtaleny)-urea;
N-(7-hydroxy-5,6,7,8tetrahydro-1-naphthalenyl)-N′-(4-isopropylphenyl)urea;
N-(7-hydroxy-5,6,7,8tetrahydro-1-naphthalenyl)-N′-(4-phenoxyphenyl)urea;
N-[4-chloro-3-trifluoromethyl)phenyl]-N′-[(7-hydroxy-5,6,7,8tetrahydro-1-naphthalenyl]urea;
N-(7-hydroxy-5,6,7,8tetrahydro-1-naphthalenyl)-N′-phenylurea;
N-(4-chlorophenyl)-N′-(7-hydroxy-5,6,7,8tetrahydro-1-naphthalenyl)urea;
N-(7-hydroxy-5,6,7,8tetrahydro-1-naphthalenyl)-N′-[2-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8,-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2,4,6-trimethoxy-benzyl)urea;
N-(2,6-difluorobenzyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-[2-(4-chlorophenyl)ethyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-[3-fluoro-4-(trifluoromethyl)benzyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea; and
a tautomeric or stereoisomeric form of any of the foregoing compounds; and
a pharmaceutically acceptable salt of any of the foregoing compounds.

### Claim 14 (depends on 1)

A method of treating pain comprising administering to the human or animal an effective amount of at least one compound according to claim 1, wherein the pain is selected from the group consisting of chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, musculoskeletal pain, back pain, orofascial pain, headache, visceral pain, pelvic pain, vulvodynia, orchialgia and prostatodynia.

### Claim 15 (depends on 11)

The method of claim 11, wherein the pain is pain related to a disease or disorder.

### Claim 16 (depends on 1)

A method of treating pain related to a disease or disorder comprising administering to the human or animal an effective amount of at least one compound according to claim 1, wherein the disease or disorder is selected from the group consisting of neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, arthritis, cancer, irritable bowel syndrome and inflammatory lesions of joints, skin, muscles and nerves.

### Claim 17 (depends on 11)

The method of claim 11, wherein the compound is selected from the group consisting of
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(3-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[3-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
Ethyl 3-({[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)amino]carbonyl}-amino)benzoate;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(1-naphthyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2-naphthyl)urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(4-isopropylphenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl-N′-(4-phenoxyphenyl)urea;
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-phenylurea;
N-(4-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[2-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8,-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2,4,6-trimethoxy-benzyl)urea;
N-(2,6-difluorobenzyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-[2-(4-chlorophenyl)ethyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-[3-fluoro-4-(trifluoromethyl)benzyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea; and
a tautomeric or stereoisomeric form of any of the foregoing compounds; and
a pharmaceutically acceptable salt of any of the foregoing compounds.

### Claim 18 (depends on 1)

A method of treating an inflammatory disorder or disease in a human or animal comprising administering to the human or animal an effective amount of at least one compound according to claim 1, wherein the inflammatory disorder or disease is selected from asthma and COPD.

### Claim 19 (depends on 18)

The method of claim 18, wherein the compound is selected from the group consisting of:
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(3-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[3-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
Ethyl 3-({[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)amino]carbonyl }-amino)benzoate;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(1-naphthyl)urea;
N-(7-hydroxy-5 ,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2-naphthyl)urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(4-isopropylphenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl-N′-(4-phenoxyphenyl)urea;
N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-phenylurea;
N-(4-chlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[2-(trifluoromethyl)-phenyl]urea;
N-(7-hydroxy-5,6,7,8,-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-phenyl]urea;
N-(3,4-dichlorophenyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-phenyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-(2,4,6-trimethoxy-benzyl)-urea;
N-(2,6-difluorobenzyl)-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)-N′-[4-(trifluoromethyl)-benzyl]urea;
N-(7-hydroxy-5,6,7,8-tetrahydro-1naphthalenyl)-N′-[4-(trifluoromethoxy)-benzyl]urea;
N-[2-(4-chlorophenyl)ethyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
N-[3-fluoro-4-(trifluoromethyl)benzyl]-N′-(7-hydroxy-5,6,7,8-tetrahydro-1-naphthalenyl)urea;
a tautomeric of stereoisomeric form of any of the foregoing compounds; and
a pharmaceutically acceptable salt of any of the foregoing compounds.