# US 7,608,619 B2 · Substituted oxazole compounds with analgesic activity

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- Number: US 7,608,619 B2
- Document ID: US7608619B2
- Status: Granted
- Kind: B2
- Application number: 12/143,519
- Filed: 2008-06-20
- Published: 2009-03-12
- Granted: 2009-10-27
- Earliest claimed: 2005-12-22
- Assignees: Gruenenthal GmbH
- Inventors: Beatrix Merla; Stefan Oberboersch; Bernd Sundermann; Werner Englberger; Hagen-Heinrich Hennies; Heinz Graubaum
- Web page: https://patentgrep.com/patent/US7608619B2

## CPC

- C07D 263/48: Nitrogen atoms not forming part of a nitro radical
- A61P 1/12: Antidiarrhoeals
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 17/04: Antipruritics
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/32: Alcohol-abuse
- A61P 25/36: Opioid-abuse
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- 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

Substituted oxazole derivatives corresponding to formula I: a method for producing such compounds, pharmaceutical compositions containing such compounds, and the use of such compounds to treat pain, depression, urinary incontinence, diarrhoea, pruritus, alcohol and drug misuse, drug dependency, lethargy and/or anxiety.

## Claims

### Claim 1

A substituted oxazole compound corresponding to Formula I:
wherein
n is 0, 1 or 2;
R1 denotes optionally mono- or polysubstituted aryl or heteroaryl bonded via a C1-3-alkylene chain;
R2 denotes optionally mono- or polysubstituted aryl or heteroaryl, or optionally mono- or polysubstituted aryl bonded via a C1-3-alkylene chain;
R3 and R4 independently denote optionally mono- or polysubstituted, saturated or unsaturated, branched or unbranched C1-6-alkyl; optionally mono- or polysubstituted aryl; or optionally mono- or polysubstituted aryl bonded via a C1-3-alkylene chain; or
R3 and R4 together form a saturated or unsaturated 5-, 6- or 7-membered non-aromatic ring optionally containing a further heteroatom selected from the group consisting of S, O or N, said non-aromatic ring being optionally mono- or polysubstituted and optionally condensed to an aromatic ring;
R5 and R6 independently denote H, or saturated or unsaturated, branched or unbranched C1-6-alkyl, with the proviso that R5 and R6 are not simultaneously H; or
R5 and R6 together denote —CH2CH2OCH2CH2—, or —(CH2)3-6—;
R7 and R8 independently denote optionally mono- or polysubstituted, saturated or unsaturated, branched or unbranched C1-6-alkyl; optionally mono- or polysubstituted aryl or heteroaryl bonded via a C1-3-alkylene chain; or
R7 and R8 together form a saturated or unsaturated 5-, 6- or 7-membered non-aromatic ring optionally containing a further heteroatom selected from the group consisting of S, O and N, said non-aromatic ring being optionally mono- or polysubstituted and optionally condensed to an aromatic ring;
or a salt thereof with a physiologically acceptable acid.

### Claim 2 (depends on 1)

A compound as claimed in claim 1, wherein said compound is in the form of an isolated stereoisomer.

### Claim 3 (depends on 1)

A compound as claimed in claim 1, wherein said compound is in the form of a mixture of stereoisomers.

### Claim 4 (depends on 3)

A compound as claimed in claim 3, wherein said compound is in the form of a racemic mixture.

### Claim 5 (depends on 1)

A compound as claimed in claim 1, wherein R1 denotes a phenyl group bonded via a C1-3-alkylene chain, wherein said phenyl group is optionally mono- or polysubstituted with F, Cl, CN, NO2, SH, S—C1-6-alkyl, OH, O—C1-6-alkyl, CO2H, CO2—C1-6-alkyl, CF3, or C1-6-alkyl.

### Claim 6 (depends on 5)

A compound as claimed in claim 5, wherein R1 denotes a benzyl group.

### Claim 7 (depends on 1)

A compound as claimed in claim 1, wherein R2 denotes phenyl or thienyl optionally mono- or polysubstituted with F, Cl, CN, NO2, SH, S—C1-6-alkyl, OH, O—C1-6-alkyl, CO2H, CO2—C1-6-alkyl, CF3, or C1-6-alkyl; or a phenyl group bonded via a C1-3-alkylene chain, wherein said phenyl group is optionally mono- or polysubstituted with F, Cl, CN, NO2, SH, S—C1-6-alkyl, OH, O—C1-6-alkyl, CO2H, CO2—C1-6-alkyl, CF3, or C1-6-alkyl.

### Claim 8 (depends on 7)

A compound as claimed in claim 7, wherein R2 denotes phenyl optionally monosubstituted with Cl or F, or denotes thienyl.

### Claim 9 (depends on 1)

A compound as claimed in claim 1, wherein:
R3 and R4 independently denote C1-6-alkyl optionally mono- or polysubstituted with F, Cl, —CN, SH, S—C1-6-alkyl, benzyl, OH, O-benzyl, O—C1-6-alkyl, CO2H, or CO2—C1-6-alkyl; or phenyl optionally mono- or polysubstituted with F, Cl, CN, NO2, SH, S—C1-6-alkyl, OH, O—C1-6-alkyl, CO2H, CO2—C1-6-alkyl, CF3, or C1-6-alkyl; or
R3 and R4 together denote —CH2CH2OCH2CH2—, —CH2CH2NR9CH2CH2—, —(CH2)4-5—, or
wherein
R9 denotes a C1-6-alkyl group or a phenyl group bonded via a C1-3-alkylene chain, wherein said phenyl group is optionally mono- or polysubstituted with F, Cl, Br, I, CN, NH2, NH—C1-6-alkyl, NH—C1-6-alkyl-OH, N(C1-6-alkyl)2, N(C1-6-alkyl-OH)2, NO2, SH, S—C1-6-alkyl, OH, O—C1-6-alkyl, O—C1-6alkyl-OH, C(═O)C1-6-alkyl, CO2H, CO2—C1-6-alkyl, CF3, or C1-6-alkyl.

### Claim 10 (depends on 1)

A compound as claimed in claim 1, wherein R3 and R4 independently denote phenyl, ethyl or methyl; or R3 and R4 together denote —CH2CH2OCH2CH2—, —CH2CH2NR9CH2CH2—, —(CH2)4-5— or
wherein R9 denotes benzyl, 4-F-phenyl or 4-methoxyphenyl.

### Claim 11 (depends on 1)

A compound as claimed in claim 1, wherein R5 and R6 each denote CH3.

### Claim 12 (depends on 1)

A compound as claimed in claim 1, wherein R7 and R8 independently denote benzyl or phenethyl optionally mono- or polysubstituted with F, Cl, CN, NO2, SH, S—C1-6-alkyl, OH, O—C1-6-alkyl, CO2H, CO2—C1-6-alkyl, CF3, or C1-6-alkyl; or
R7 and R8 together denote —CH2CH2SCH2CH2—, —CH2CH2OCH2CH2—, —(CH2)5— or —CH2CH2NR10CH2CH2—, wherein individual H atoms can be replaced by branched or unbranched C1-4-alkyl optionally mono- or polysubstituted with OH, OCH3, CN, F, Cl, SH, SCH3, CF3 or benzyl;
wherein R10 denotes phenyl, benzyl or phenethyl optionally mono- or polysubstituted with CH3, OCH3, OH, F, Cl, CN, SH, SCH3 or CF3.

### Claim 13 (depends on 12)

A compound as claimed in claim 12, wherein
R7 and R8 independently denote methyl, ethyl, benzyl or phenethyl; or
R7 and R8 denote —CH2CH2SCH2CH2—, —CH2CH2OCH2CH2—, —(CH2)4— or —(CH2)5—, —CH2CH2NR10CH2CH2—, wherein individual H atoms can be replaced by methyl or benzyl, and
R10 denotes phenyl, 4-methoxyphenyl or benzyl.

### Claim 14 (depends on 1)

A compound as claimed in claim 1, selected from the group consisting of:
17. [{4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-piperidin-1-yl-methyl]-cyclohexyl}-(4-fluorophenyl)-methyl]-dimethylamine;
18. ((4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-methyl)-methylphenylamine;
19. ([4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-methyl)-methylphenylamine;
20. ([4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-methyl)-diethylamine;
21. benzyl-[4-benzyl-2-({4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-diethylaminomethyl)-oxazol-5-yl]-methylamine;
22. benzyl-{4-benzyl-2-[{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-(methylphenylamine)-methyl]-oxazol-5-yl}-methylamine;
23. [(4-{[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-piperidin-1-yl-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
24. [(4-{[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-piperidin-1-yl-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
25. benzyl-(4-benzyl-2-{[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-piperidin-1-yl-methyl}-oxazol-5-yl)-methylamine;
26. [(4-{[4-benzyl-5-(4-phenylpiperazin-1-yl)-oxazol-2-yl]-piperidin-1-yl-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
27. {[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-diethylamine;
28. {[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-diethylamine;
29. {[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-diethylamine;
30. benzyl-(4-benzyl-2-{diethylamino-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-oxazol-5-yl)-methylamine;
31. {[4-benzyl-5-(4-phenylpiperazin-1-yl)-oxazol-2-yl]-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-diethylamine;
32. ({4-[[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-(4-benzylpiperazin-1-yl)-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
33. [(4-{[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-piperidin-1-yl-methyl}-cyclohexyl)-(4-fluorophenyl)-methyl]-dimethylamine;
34. [4-benzyl-2-(diethylamino-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-methyl)-oxazol-5-yl]-methylphenethylamine;
35. [4-benzyl-2-(diethylamino-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-methyl)-oxazol-5-yl]-diethylamine;
36. ([4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-methyl)-diethylamine;
37. ([4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-methyl)-methylphenylamine;
38. {4-benzyl-2-[{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-(methylphenylamine)-methyl]-oxazol-5-yl}-methylphenethylamine;
39. [4-benzyl-2-({4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-piperidin-1-yl-methyl)-oxazol-5-yl]-diethylamine;
40. [(4-{[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-piperidin-1-yl-methyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
41. ([4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-methyl)-diethylamine;
42. ([4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-methyl)-methylphenylamine;
43. {4-benzyl-2-[{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-(methylphenylamine)-methyl]-oxazol-5-yl}-methylphenethylamine;
44. [4-benzyl-2-((4-benzylpiperazin-1-yl)-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-methyl)-oxazol-5-yl]-diethylamine;
45. [(4-{[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-piperidin-1-yl-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
46. (4-benzyl-2-{[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-piperidin-1-yl-methyl}-oxazol-5-yl)-methylphenethylamine;
47. (4-benzyl-2-{[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-piperidin-1-yl-methyl}-oxazol-5-yl)-diethylamine;
48. ({4-[(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-piperidin-1-yl-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
49. (4-benzyl-2-{diethylamino-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-oxazol-5-yl)-methylphenethylamine;
50. (4-benzyl-2-{diethylamino-[4-(dimethylamino-thiophen-2-yl-methyl)-cyclohexyl]-methyl}-oxazol-5-yl)-diethylamine;
51. {[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-diethylamine;
52. {(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-methylphenylamine;
53. ({4-[[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-(4-benzylpiperazin-1-yl)-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
54. (4-benzyl-2-{(4-benzylpiperazin-1-yl)-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-methyl}-oxazol-5-yl)-methylphenethylamine;
55. ({4-[(4-benzylpiperazin-1-yl)-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
56. [(4-{2-[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
57. [(4-{2-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
58. benzyl-[4-benzyl-2-(2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-1-piperidin-1-yl-ethyl)-oxazol-5-yl]-methylamine;
59. (1-[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-diethylamine;
60. (1-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-diethylamine;
61. benzyl-[4-benzyl-2-(2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-1-diethylaminoethyl)-oxazol-5-yl]-methylamine;
62. [{4-[2-[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-(4-chlorophenyl)-methyl]-dimethylamine;
63. [{4-[2-[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-(4-chlorophenyl)-methyl]-dimethylamine;
64. [{4-[2-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-(4-benzyl-piperazin-1-yl)-ethyl]-cyclohexyl}-(4-chlorophenyl)-methyl]-dimethylamine;
65. [(4-{2-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-(4-fluorophenyl)-methyl]-dimethylamine;
66. benzyl-[4-benzyl-2-(2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-1-piperidin-1-yl-ethyl)-oxazol-5-yl]-methylamine;
67. (1-[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-diethylamine;
68. (1-[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-diethylamine;
69. (1-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-diethylamine;
70. benzyl-[4-benzyl-2-(1-diethylamino-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-oxazol-5-yl]-methylamine;
71. [{4-[2-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-(4-fluorophenyl)-methyl]-dimethylamine;
72. [(4-{2-[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
73. [(4-{2-[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
74. [(4-{2-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
75. benzyl-(4-benzyl-2-{2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-1-piperidin-1-yl-ethyl}-oxazol-5-yl)-methylamine;
76. [(4-{2-[4-benzyl-5-(4-phenylpiperazin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
77. {1-[4-benzyl-5-(4-benzylpiperidin-1-yl)-oxazol-2-yl]-2-[4-(dimethylamino-thiophen-2-yl-methyl)-cyclohexyl]-ethyl}-diethylamine;
78. {1-[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-2-[4-(dimethylamino-thiophen-2-yl-methyl)-cyclohexyl]-ethyl}-diethylamine;
79. {1-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-[4-(dimethylamino-thiophen-2-yl-methyl)-cyclohexyl]-ethyl}-diethylamine;
80. benzyl-(4-benzyl-2-{1-diethylamino-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-oxazol-5-yl)-methylamine;
81. ({4-[2-[4-benzyl-5-(4-benzyl-piperidin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
82. ({4-[2-[4-benzyl-5-(4-benzylpiperazin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
83. ({4-[2-[4-benzyl-5-(4-methylpiperidin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
84. benzyl-(4-benzyl-2-{1-(4-benzylpiperazin-1-yl)-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-oxazol-5-yl)-methylamine;
85. ({4-[2-[4-benzyl-5-(4-phenylpiperazin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
86. [4-benzyl-2-(2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-1-piperidin-1-yl-ethyl)-oxazol-5-yl]-methylphenethylamine;
87. [4-benzyl-2-(2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-1-piperidin-1-yl-ethyl)-oxazol-5-yl]-diethylamine;
88. (1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-diethylamine;
89. [4-benzyl-2-(2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-1-diethylaminoethyl)-oxazol-5-yl]-methylphenethylamine;
90. [4-benzyl-2-(2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-1-diethylaminoethyl)-oxazol-5-yl]-diethylamine;
91. (1-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-diethylamine;
92. (1-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-methylphenylamine;
93. [4-benzyl-2-(1-(4-benzylpiperazin-1-yl)-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-oxazol-5-yl]-methylphenethylamine;
94. [4-benzyl-2-(1-(4-benzylpiperazin-1-yl)-2-{4-[(4-chlorophenyl)-dimethylaminomethyl]-cyclohexyl}-ethyl)-oxazol-5-yl]-diethylamine;
95. [4-benzyl-2-(2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-1-piperidin-1-yl-ethyl)-oxazol-5-yl]-methylphenethylamine;
96. (1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-diethylamine;
97. [4-benzyl-2-(1-diethylamino-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-oxazol-5-yl]-methylphenethylamine;
98. [4-benzyl-2-(1-diethylamino-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-oxazol-5-yl]-diethylamine;
99. (1-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-diethylamine;
100. (1-[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-diethylamine;
101. (1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-methylphenylamine;
102. {4-benzyl-2-[2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-1-(methylphenylamine)-ethyl]-oxazol-5-yl}-methylphenethylamine;
103. {4-benzyl-2-[2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-1-(methylphenylamine)-ethyl]-oxazol-5-yl}-diethylamine;
104. (1-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-methylphenylamine;
105. (1-[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-2-{4-[dimethylamino-(4-fluorophenyl)-methyl]-cyclohexyl}-ethyl)-methylphenylamine;
106. [{4-[2-[4-benzyl-5-(3-methyl piperidin-1-yl)-oxazol-2-yl]-2-(4-benzyl piperazin-1-yl)-ethyl]-cyclohexyl}-(4-fluorophenyl)-methyl]-dimethylamine;
107. [(4-{2-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
108. (4-benzyl-2-{2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-1-piperidin-1-yl-ethyl}-oxazol-5-yl)-methylphenethylamine;
109. (4-benzyl-2-{2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-1-piperidin-1-yl-ethyl}-oxazol-5-yl)-dimethylamine;
110. ({4-[2-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-2-piperidin-1-yl-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
111. [(4-{2-[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-2-piperidin-1-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
112. {1-[4-benzyl-5-(3,5-dimethylpiperidin-1-yl)-oxazol-2-yl]-2-[4-(dimethylamino-thiophen-2-yl-methyl)-cyclohexyl]-ethyl}-diethylamine;
113. (4-benzyl-2-{1-diethylamino-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-oxazol-5-yl)-methylphenethylamine;
114. (4-benzyl-2-{1-diethylamino-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-oxazol-5-yl)-diethylamine;
115. {1-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-diethylamine;
116. {1-[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-diethylamine;
117. {1-[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-2-[4-(dimethylaminothiophen-2-yl-methyl)-cyclohexyl]-ethyl}-methylphenylamine;
118. ({4-[2-(4-benzylpiperazin-1-yl)-2-(4-benzyl-5-thiomorpholin-4-yl-oxazol-2-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
119. ({4-[2-[4-benzyl-5-(3-methylpiperidin-1-yl)-oxazol-2-yl]-2-(4-benzylpiperazin-1-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
120. [{4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-morpholin-4-yl-methyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
121. [{4-[(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-morpholin-4-yl-methyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
122. [(4-{(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-[4-(4-fluorophenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
123. [(4-{(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-[4-(4-methoxyphenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
124. [(4-{(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-[4-(4-methoxyphenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
125. [{4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
126. [{4-[(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
127. [{4-[{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
128. [{4-[[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
129. [{4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-morpholin-4-yl-methyl]-cyclohexyl}-(4-chlorophenyl)-methyl]-dimethylamine;
130. [{4-[(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-morpholin-4-yl-methyl]-cyclohexyl}-(4-chlorophenyl)-methyl]-dimethylamine;
131. [[4-({4-benzyl-5-[4-(4-methoxy-phenyl)-piperazin-1-yl]-oxazol-2-yl}-morpholin-4-yl-methyl)-cyclohexyl]-(4-chlorophenyl)-methyl]-dimethylamine;
132. [(4-{[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-morpholin-4-yl-methyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
133. [(4-{(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-[4-(4-fluorophenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
134. [(4-{(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-[4-(4-methoxyphenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
135. [(4-{(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-[4-(4-methoxyphenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
136. [(4-{[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-[4-(4-methoxy-phenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-(4-chlorophenyl)-methyl]-dimethylamine;
137. [{4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-(4-chlorophenyl)-methyl]-dimethylamine;
138. ({4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-morpholin-4-yl-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
139. ({4-[(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-morpholin-4-yl-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
140. {[4-({4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-morpholin-4-yl-methyl)-cyclohexyl]-thiophen-2-yl-methyl}-dimethylamine;
141. [(4-{[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-morpholin-4-yl-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
142. [(4-{(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-[4-(4-fluorophenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine
143. [(4-{(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-[4-(4-methoxyphenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
144. [(4-{(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-[4-(4-methoxyphenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
145. [(4-{[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-[4-(4-methoxy-phenyl)-piperazin-1-yl]-methyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
146. ({4-[(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
147. ({4-[{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
148. ({4-[[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-(3,4-dihydro-1H-isoquinolin-2-yl)-methyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
149. [{4-[2-(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-2-morpholin-4-yl-ethyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
150. [{4-[2-(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-2-morpholin-4-yl-ethyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
151. [[4-(2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-morpholin-4-yl-ethyl)-cyclohexyl]-(3-fluorophenyl)-methyl]-dimethylamine;
152. [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-2-morpholin-4-yl-ethyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
153. [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-2-[4-(4-fluorophenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
154. [(4-{2-(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-2-[4-(4-methoxyphenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
155. [(4-{2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-[4-(4-methoxyphenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
156. [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-(3-fluorophenyl)-methyl]-dimethylamine;
157. [{4-[2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-(3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-cyclohexyl}-(3-fluorophenyl)-methyl]-dimethylamine;
158. ({4-[2-(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-2-morpholin-4-yl-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
159. {[4-(2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-morpholin-4-yl-ethyl)-cyclohexyl]-thiophen-2-yl-methyl}-dimethylamine;
160. [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-2-morpholin-4-yl-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
161. [(4-{2-(4-benzyl-5-morpholin-4-yl-oxazol-2-yl)-2-[4-(4-fluorophenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
162. [(4-{2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-[4-(4-fluorophenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
163. [(4-{2-(4-benzyl-5-pyrrolidin-1-yl-oxazol-2-yl)-2-[4-(4-methoxyphenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
164. [(4-{2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-[4-(4-methoxyphenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine;
165. [(4-{2-[4-benzyl-5-(2,6-dimethylmorpholin-4-yl)-oxazol-2-yl]-2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-cyclohexyl)-thiophen-2-yl-methyl]-dimethylamine; and
166. ({4-[2-{4-benzyl-5-[4-(4-methoxyphenyl)-piperazin-1-yl]-oxazol-2-yl}-2-(3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-cyclohexyl}-thiophen-2-yl-methyl)-dimethylamine;
or a salt thereof with a physiologically compatible acid.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising a compound as claimed in claim 1 and at least one pharmaceutically acceptable carrier or auxiliary substance.

### Claim 16 (depends on 1)

A process for preparing a substituted oxazole compound as claimed in claim 1, said process comprising heating an aldehyde of Formula A with an amine of Formula B and an isonitrile amide of Formula C
wherein n and R1 through R8 have the meanings given in claim 1, in an organic solvent for 1-10 hours at a temperature between 30° and 100° C.

### Claim 17 (depends on 16)

A process as claimed in claim 16, wherein the solvent is methanol or ethanol, and the heating is effected at a temperature of 40° to 80° C.

### Claim 18 (depends on 1)

A method of treating a condition selected from the group consisting of pain, depression, urinary incontinence, diarrhea, pruritus, alcohol and drug misuse, drug dependency, lethargy and anxiety in a subject in need thereof, said method comprising administering to said subject a pharmacologically effective amount of a compound as claimed in claim 1.

### Claim 19 (depends on 18)

A method as claimed in claim 18, wherein said condition is pain.

### Claim 20 (depends on 19)

A method as claimed in claim 19, wherein said pain comprises acute pain, neuropathic pain or chronic pain.