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United States PatentRE39634
Sit , ; et al.May 15, 2007
Title
Bisarylimidazoly fatty acid amide hydrolase inhibitors
Abstract
The present invention relates to bisarylimidazolyl derivatives and pharmaceutical compositions comprising said compounds inhibiting fatty acid amide hydrolase and useful for the treatment of pain, particularly neuropathic pain, psychomotor disorder, hypertension, cardiovascular disease, eating disorder, nausea, AIDS-related complex, glaucoma, inflammation, psoriasis or multiple sclerosis, and other conditions the treatment of which can be effected by inhibiting fatty acid amide hydrolase.
Inventors:Sit; Sing-Yuen (Meriden, CT), Xie; Kai  (Wallingford, CT)
Assignee:Bristol-Myers Squibb Company (Princeton, NJ)
Appl. No.:10/883,195
Filed:July 1, 2004
PCT Pub Date:May 15, 2007
Current U.S. Class:514/341 514/399 546/275.1 548/336.1 548/338.1 548/341.5 
Current International Class:A61K 31/4164 (20060101) A61K 31/4439 (20060101) C07D 233/64 (20060101) C07D 401/12 (20060101)
Field of Search:548/338.1,341.5,336.1 546/275.1 514/341,399
U.S. Patent Documents
5648373July 1997Winkler et al.
Other References
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Jaggar, et al., "The Anti-hyperalgesic Actions of the Cannabiniod Anandamide and the Putative CB2 Receptor Agonist Palmitoylethanolamide in Visceral and Somatic Inflammatory Pain," Pain, vol. 76, pp. 189-199, 1998. cited by other .
Huang, et al., "Identification of New Class of Molecules, the Arachidonyl Amide Acids, and Characterization of One Member That Inhibits Pain," Journal of Biological Chemistry, vol. 276, No. 46, pp. 42639-42644, 2001. cited by other .
Richardson, et al., "Hypoactivity of the Spinal Cannabinoid System Results in NMDA-Dependant Hyperalgesia," Journal of Neuroscience, vol. 18, No. 1, pp. 451-457, 1998. cited by other .
Calignano, et al., "Control of Pain Initiation by Endogenous Cannabinoids," Nature, vol. 394, pp. 277-280, Jul. 16, 1998. cited by other .
Meng, et al., "An Analgesia Circuit Activated by Cannabinoids," Nature, vol. 395, pp. 381-383, Sep. 24, 1998. cited by other .
Meanwell, et al., "Nonprostanoid Prostacyclin Mimetics. 3. Structural Variations of the Diphenyl Heterocycle Molety," Journal of Medicinal Chemistry, 1992, vol. 35, pp. 3498-3512. cited by other.~
Primary Examiner: Stockton; Laura L.
Attorney, Agent or Firm:Makujina; Shah R.
Parent Case Text


.[.CROSS REFERENCE TO RELATED APPLICATION

This non-provisional application claims priority from provisional application U.S. Ser. No. 60/286,827 filed Apr. 27, 2001..].

.Iadd.CROSS REFERENCE TO RELATED APPLICATIONS

This application is a reissue application of U.S. Pat. No. 6,562,846, issued May 13, 2003, on non-provisional application No. 10/128,480, filed Apr. 23, 2002 which claims priority from provisional application USSN 60/286,827 filed Apr. 27, 2001..Iaddend.
Claims

What is claimed is:
.[.1. Compounds of Formula (I) ##STR00111## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3 alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.2. Compounds of Formula (I) ##STR00112## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is HYC(O)O; X is C and is attached to A; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.3. Compounds of Formula (I) ##STR00113## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H; C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.4. Compounds of Formula (I) ##STR00114## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is C.sub.3-7cycloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.5. Compounds of Formula (I) ##STR00115## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is --C.sub.1-2alkylene-phenyl said --C.sub.1-2alkylene-phenyl is optionally substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.6. Compounds of Formula (I) ##STR00116## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are optionally substituted with the same or different substitutents selected from the group consisting of halo, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.7. Compounds of Formula (I) ##STR00117## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with halo, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl or C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.8. Compound of Formula (I) ##STR00118## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with fluoro; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.9. Compounds of Formula (I) ##STR00119## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3 alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with cyano; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.10. Compounds of Formula (I) ##STR00120## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.7-10alkylene; D is HYC(O)O; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; and G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl..].
.[.11. Compounds of Formula (I) ##STR00121## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.1-5alkylene; D is HYC(O)O; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
.[.12. Compounds of Formula (I) ##STR00122## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.7-10alkylene; D is HYC(O)ON.dbd.C(G'); Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; and G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl..].
.[.13. Compounds of Formula (I) ##STR00123## and pharmaceutically acceptable salts and solvates thereof wherein R.sup.1 are R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.1-5alkylene; D is HYC(O)ON.dbd.C(G'); Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substitutents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12 alkylene..].
14. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid tert-butyl ester; .[.6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid sec-butyl ester;.]. .Iadd.[6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid sec-butyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid benzyl ester; .[.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime; O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid methyl ester; .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-cyano-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid methyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid ethyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,4-difluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
4-chloro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid o-tolyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
4-cyano-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid ethyl ester; .[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbami- c acid 3,4-difluoro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 4-chloro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 3,4-difluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-chloro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 3-chloro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 2-fluoro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 4-fluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 4-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2-fluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2,6-difluoro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid ethyl ester; [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Ethyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
2-fluoro-phenyl ester; [1-Isopropyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; or [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-1-phenyl-hexyl]-carbamic acid 2-fluoro-phenyl ester .Iadd.or a pharmaceutically acceptable salt or solvate thereof.Iaddend..
15. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; .[.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid cyclohexyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid methyl ester; .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
4-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-cyano-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
2,6-dimethoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid methyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid ethyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
2,4-difluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-chloro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid o-tolyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-cyano-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid isopropyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carb- amic acid 2-fluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid ethyl ester; .[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbam- ic acid 3,4-difluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-chloro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 3-chloro-phenyl ester; [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Ethyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Isopropyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; or [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-1-phenyl-hexyl]-carbamic acid 2-fluoro-phenyl ester .Iadd.or a pharmaceutically acceptable salt or solvate thereof.Iaddend..
16. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; .[.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
4-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,4-difluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-chloro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-cyano-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester; .[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; or [1-Ethyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester .Iadd.or a pharmaceutically acceptable salt or solvate thereof.Iaddend..
17. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-cyano-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester; or [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester .Iadd.or a pharmaceutically acceptable salt or solvate thereof.Iaddend..
.[.18. A method of treating chronic pain, acute pain or neuropathic pain in a mammal in need thereof by the administration of an effective amount of a pharmaceutical composition comprising a compound according to claims 1, 2, 3 or 4..].
19. A method of treating chronic pain, acute pain and neuropathic pain by the administration of a pharmaceutical composition comprising ##STR00124## or .Iadd.a pharmaceutically acceptable .Iaddend.salt or solvate thereof.
20. A method of treating neuropathic pain by the administration of a pharmaceutical composition comprising ##STR00125## or .Iadd.a pharmaceutically acceptable .Iaddend.salt or solvate thereof.
.Iadd.21. A compound of Formula (I) ##STR00126## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with fluoro; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12alkylene..Iaddend.
.Iadd.22. A compound of Formula (I) ##STR00127## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with cyano; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12alkylene..Iaddend.
.Iadd.23. A compound of Formula (I) ##STR00128## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; D is X(O)O; X is C and is attached to A; and G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy..Iaddend.
.Iadd.24. A compound of Formula (I) ##STR00129## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene; D is HYC(O)ON.dbd.C(G'); Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; and G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl..Iaddend.
.Iadd.25. A compound of Formula (I) ##STR00130## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is --C.sub.1-2alkylene-phenyl, said --C.sub.1-2alkylene-phenyl is optionally substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12alkylene..Iaddend.
.Iadd.26. A compound of Formula (I) ##STR00131## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H, C.sub.1-3alkyl or halo; R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl; A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are optionally substituted with one or more of the same or different substituents selected from the group consisting of halo, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; provided that if A--D is interrupted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrupted with --Z-phenyl-, then A is C.sub.5-12alkylene..Iaddend.
.Iadd.27. A compound of Formula (I) ##STR00132## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.7-10alkylene; D is HYC(O)O; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy..Iaddend.
.Iadd.28. A compound of Formula (I) ##STR00133## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.1-5alkylene; D is HYC(O)O; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxyl and C.sub.1-3alkoxy; and wherein A--D is interrupted with --Z-phenyl-; wherein Z is O or S and is attached to A..Iaddend.
.Iadd.29. A compound of Formula (I) ##STR00134## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each independently H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.7-10alkylene; D is HYC(O)ON.dbd.C(G'); Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxyl and C.sub.1-3alkoxy; and G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl..Iaddend.
.Iadd.30. A compound of Formula (I) ##STR00135## or a pharmaceutically acceptable salt or solvate thereof wherein R.sup.1 and R.sup.2 are each H; R.sup.3 is C.sub.1-C.sub.3alkyl; A is C.sub.1-5alkylene; D is HYC(O)ON.dbd.C(G'); Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy; G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; and wherein A--D is interrupted with --Z-phenyl-; wherein Z is O or S and is attached to A..Iaddend.
.Iadd.31. A method of treating chronic pain, acute pain or neuropathic pain in a mammal in need thereof by the administration of an effective amount of a pharmaceutical composition comprising a compound according to claims 21, 22 or
23-30..Iaddend.
Description
FIELD OF THE INVENTION

The present invention relates to bisarylimidazolyl derivatives and pharmaceutical compositions comprising said derivatives which inhibit fatty acid amide hydrolase and are useful for the treatment of conditions affected by inhibiting fatty acid amide hydrolase.

BACKGROUND

Neuropathic pain is caused by injury to nerves as the result of many factors including physical damage (e.g., trauma, surgery), drugs such as Zidovudine (AZT), Carmustine (BCNU) and disease (e.g., diabetes, herpes zoster). The prevalence in the United States of neuropathies associated with diabetes, herpes and amputation is estimated at 1.5 million. The worldwide prevalence of diabetic neuropathy alone is expected to reach 12 million by 2007. Nerve injury can result in both allodynia and hyperalgesia.

Current treatment of neuropathic pain involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and acetaminophen) and other analgesics as well as anticonvalsants (e.g., carbamazepine, gabapentin) and tricyclic antidepressants (e.g., amitryptiline). Effective treatment of pain with current therapies is limited by adverse effects and a lack of efficacy against all components of pain.

Current research is aimed at understanding the molecular and physiological components of pain processing to develop more effective analgesics (Levin, J. D., New Directions in Pain Research: Meeting Report Molecules to Maladies, Neuron 20:
649-654, 1998; Pastemak, G. W., The Central Questions in Pain Perception May Be Peripheral, PNAS 95:10354-10355, 1998).

The analgesic properties of cannabinoids have been known for many years and to many cultures. Cannabinoids are active in many pre-clinical models of pain, including neuropathic pain. Within the last few years, several endogenous cannabinoids, including the fatty acid amides arachidonylethanolamide (anandamide), and arachidonyl amino acids such as N-arachidonylglycine, homo-.gamma.-linolenyl-ethanolamide and docosatetraenyl-ethanolamide, as well as 2-arachidonyl-glycerol, have been shown to induce analgesia in laboratory animals (De Vane, W.A. et. al., Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptors, Science 258: 1946-1949, 1992; Hanus, L. et. al., Two New Unsaturated Fatty Acid Ethanolamides in Brain that Bind to the Cannabinoid Receptor, J. Med. Chem. 36: 3032-3034, 1993; Machoulam, R. et. al., Identification of an Endogenous 2-Monoglyceride, Present in Canine Gut, That Binds To Cannabinoid Receptors, Biochem. Pharmacol. 50: 83-90, 1995; Vogel, Z. et. al., Cannabinomimetic Behavioral Effects of and Adenylate Cyclase Inhibition By Two New Endogenous Anandamides, Eur. J. Pharmacol. 287: 145-152, 1995; Hargreaves, K. M. et al., Cannabinoids Reduce Hyperalgesia and Inflammation Via Interaction With Peripheral CB1 Receptors, Pain 75: 111-119, 1998; Rice,A. S. C., et. al., The Anti-Hyperalgesic Actions of the Cannabinoid Anandamide and the Putative CB2 Receptor Agonist Palmitoylethanolamide in Visceral and Somatic Inflammatory Pain, Pain 76:
189-199, 1998; Huang, S. M., et al., Identification of a New Class of Molecules, the Arachidonyl Amino Acids, and Characterization of One Member That Inhibits Pain, J. Biological Chemistry, 276: 46, 42639-42644, 2001). The ability of cannabinoid receptor antagonists and cannabinoid receptor antisense to induce hyperalgesia in animals suggests that endogenous cannabinoids regulate the nociceptive threshold (Hargreaves, K. M. et al., Hypoactivity of the Spinal Cannabinoid System Results in NMDA-Dependent Hyperalgesia, J. Neurosci. 18: 451-457, 1998; Piomelli, D. et. al., Control of Pain Initiation By Endogenous Cannabinoids, Nature 394: 277-281, 1998; Fields, H. L. et. al., An Analgesia Circuit Activated By Cannabinoids, Nature 395:
381-383, 1998). Elevation of levels of neuroactive fatty acid amides such as anandamide may provide a unique mechanism to achieve analgesia. The mechanisms by which endogenous cannabinoids are synthesized are not well understood; therefore, target for drugs aimed at increasing the synthesis of these compounds are slow to be identified.

Anandamide and the other identified endogenous cannabinoids are inactivated through a cleavage mechanism by a membrane-bound enzyme, fatty acid amide hydrolase (FAAH). FAAH, therefore, provides an important target for regulating the activity of endogenous cannabinoids. The inhibition of FAAH may elevate levels of anandamide or other endogenous cannabinoids to increase the nociceptive threshold. Furthermore, the inhibition of FAAH would also extend the therapeutic benefits of other cannabinoid agoinsts in the treatment of emesis, anxiety, feeding, behaviors, movement disorders, glaucoma, neuroprotection and cardiovascular disease.

SUMMARY OF THE INVENTION

Thus according to a first embodiment of the first aspect of the present invention are provided compounds of Formula (I) ##STR00001## and pharmaceutically acceptable salts and solvates thereof wherein

R.sup.1 are R.sup.2 are each independently H, C.sub.1-3alkyl or halo;

R.sup.3 is C.sub.1-C.sub.3alkyl or C.sub.3-7cycloalkyl;

A is C.sub.1-12alkylene or L; L is -phenyl-O--C.sub.1-4alkylene wherein said C.sub.1-4alkylene is attached to D; provided that if A is L, then D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; D is X(O)O, X(O)N(G'), HYC(O)O or HYC(O)ON.dbd.C(G'); X is C and is attached to A; Y is N and is attached to A; G is H, C.sub.1-5alkyl, C.sub.1-5haloalkyl, C.sub.3-7cycloalkyl, phenyl, --C.sub.1-2alkylene-phenyl, C-pyridyl or N-pyridyl, said phenyl or --C.sub.1-2alkylene-phenyl are each optionally and independently substituted with one or more of the same or different substituents selected from the group consisting of halo, NO.sub.2, CN, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl, hydroxy and C.sub.1-3alkoxy;

G' is H, C.sub.1-5alkyl or C.sub.1-5haloalkyl; wherein A--D is optionally interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene; wherein Z is O or S and is attached to A; J is CH and is attached to A, D and J'; J' is C.sub.1-4alkyl or phenyl; and provided that if A--D is interrpted with --Z-phenyl-, then A is C.sub.1-5alkylene; if A--D is not interrpted with --Z-phenyl-, then A is C.sub.5-12alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2are each H.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each halo.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each fluoro.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.3 is methyl.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.3is ethyl.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is L.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.3-10alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.7-10alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.4-8alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.5-7alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.8-9alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.9alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.6alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A is C.sub.1-4alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein D is X(O)O.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein D is X(O)N(G').

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein D is HYC(O)O.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein D is HYC(O)ON.dbd.C(G').

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is C.sub.1-5alkyl.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is C.sub.3-7cycloalkyl.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is --C.sub.1-2alkylene-phenyl.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are optionally substituted with the same or different substituents selected from the group consisting of halo, CN, --C(O)O--C.sub.1-3alkyl, C.sub.1-3alkyl and C.sub.1-3alkoxy.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with halo, --C(O)O--C.sub.1-3-alkyl, C.sub.1-3alkyl or C.sub.1-3alkoxy.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with fluoro.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein G is phenyl or --C.sub.1-2alkylene-phenyl, said phenyl or phenyl of said --C.sub.1-2alkylene-phenyl are substituted with cyano.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A--D are not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A--D are interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A--D is interrupted with J--J'.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A--D is interrupted with --Z-phenyl- .

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein A--D is interrupted with --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.7-10alkylene, D is X(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.1-5alkylene, D is X(O)O and A--D is interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.7-10alkylene, D is X(O)N(G') and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3is C.sub.1-3alkyl, A is C.sub.1-5alkylene, D is X(O)N(G') and A--D is interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.7-10alkylene, D is HYC(O)O and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.1-5alkylene, D is HYC(O)O and A--D is interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.7-10alkylene, D is HYC(O)ON.dbd.C(G') and A--D is not interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided compounds of Formula (I) according to the first embodiment of the first aspect wherein R.sup.1 and R.sup.2 are each H, R.sup.3 is C.sub.1-3alkyl, A is C.sub.1-5alkylene, D is HYC(O)ON.dbd.C(G') and A--D is interrupted with J--J', --Z-phenyl- or --Z--C.sub.1-3alkylene.

According to another embodiment of the first aspect of the present invention are provided [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid tert-butyl ester; [6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid sec-butyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid benzyl ester; .[.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]c- arbonyl]oxime;.]. .Iadd.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylamino- carbonyl]oxime;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid methyl ester; .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-cyano-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-methoxy-phenyl ester; .[.[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl-carbamic acid methyl ester;.]. .Iadd.[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid methyl ester;.Iaddend. [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid ethyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,4-difluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-chloro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
4-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid o-tolyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-cyano-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
2,6-dimethoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid ethyl ester; .[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-y- l)hexyl]amino]carbonyl]oxime;.]. .Iadd.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)h- exylaminocarbonyl]oxime;.Iaddend. .[.2-Nitrobenzaldehye,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]- amino]carbonyl]oxime;.]. .Iadd.2-Nitrobenzaldehye, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbami- c acid 3,4-difluoro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 4-chloro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 3,4-difluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-chloro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 3-chloro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 2-fluoro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid 4-fluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl)}-carbamic acid 4-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2-fluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2,6-difluoro-phenyl ester; {4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-phenyl}-carbamic acid ethyl ester; [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Ethyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Isopropyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester or [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-1-phenyl-hexyl]-carbamic acid 2-fluoro-phenyl ester.

According to another embodiment of the first aspect of the present invention are provided [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; .[.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]c- arbonyl]oxime;.]. .Iadd.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylamino- carbonyl]oxime;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid cyclohexyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid methyl ester; .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
4-cyano-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid methyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,6-dimethoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
2-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid ethyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
4-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,4-difluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-chloro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid o-tolyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-cyano-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid isopropyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carba- mic acid 2-fluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid ethyl ester; .[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-y- l)hexyl]amino]carbonyl]oxime;.]. .Iadd.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)h- exylaminocarbonyl]oxime;.Iaddend. .[.2-Nitrobenzaldehye,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]- amino]carbonyl]oxime;.]. .Iadd.2-Nitrobenzaldehye, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Pryridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbam- ic acid 3,4-difluoro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 4-chloro-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 2-methoxy-phenyl ester; {4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-phenyl}-carbamic acid 3-chloro-phenyl ester; [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Ethyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; [1-Isopropyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; or [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-1-phenyl-hexyl]-carbamic acid 2-fluoro-phenyl ester.

According to another embodiment of the first aspect of the present invention are provided [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; .[.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]c- arbonyl]oxime;.]. .Iadd.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylamino- carbonyl]oxime;.Iaddend. .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-methoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
4-methoxy-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-cyano-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
2-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
2,4-difluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-chloro-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-methoxy-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-cyano-phenyl ester; [5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid
2,6-dimethoxy-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester; .[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-y- l)hexyl]amino]carbonyl]oxime;.]. .Iadd.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)h- exylaminocarbonyl]oxime;.Iaddend. .[.2-Nitrobenzaldehye,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]- amino]carbonyl]oxime;.]. .Iadd.2-Nitrobenzaldehye, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.4-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. .[.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime;.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime;.Ia- ddend. [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; or [1-Ethyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
2-fluoro-phenyl ester.

According to another embodiment of the first aspect of the present invention are provided [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester; .[.6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.]. .Iadd.[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester;.Iaddend. [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid
2,4-difluoro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester; [7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid
4-cyano-phenyl ester; [6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester; {6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester; or [1-Methyl-6-(2-methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester.

According to various embodiments of a second aspect of the present invention are provided pharmaceutical formulations comprising compounds of Formula (I) as defined herein.

According to various embodiments of a third aspect of the present invention are provided methods of treating conditions the treatment of which can be effected by the inhibition of FAAH by the administration of pharmaceutical compositions comprising compounds of Formula (I) as defined herein.

According to another embodiment of the third aspect of the present invention is provided a method of treating pain, more particularly chronic pain, acute pain and neuropathic pain by the administration of pharmaceutical compositions comprising compounds of Formula (I) as defined herein.

According to another embodiment of the third aspect of the present invention is provided a method of treating pain, more particularly chronic pain, acute pain and neuropathic pain by the administration of a pharmaceutical composition comprising ##STR00002## or salt or solvate thereof.

According to another embodiment of the third aspect of the present invention is provided a method of treating neuropathic pain by the administration of a pharmaceutical composition comprising ##STR00003## or salt or solvate thereof.

According to another embodiment of the third aspect of the present invention is provided a method of providing neuroprotection and contraception and yet further methods of psychomotor disorder, hypertension, cardiovascular disease, eating disorder, nausea, AIDS-related complex, glaucoma, inflammation, psoriasis and multiple sclerosis by the administration of pharmaceutical compositions comprising compounds of Formula (I) as defined herein. See Raphael Mechoulam, "Looking Back at Cannabis Research," Current Pharmaceutical Design, 2000, Vol. 6, No. 13, pp. 1313-1322 (p. 1319); Sumner H. Burstein, "Ajulemic Acid (CT3): A Potent Analog of the Acid Metabolites of THC," Current Pharmaceutical Design, 2000, Vol. 6, No. 13, pp. 1339-1345 (p.
1340); Vincenzo Di Marzo, et al., "Endocannabinoids: New Targets for Drug Development," Current Pharmaceutical Design, 2000, Vol. 6, No. 13, pp. 1361-1380 (p. 1362); and Sonya L. Palmer, et al., "Natural and Synthetic Endocannabinoids and Their Structure-Activity Relationships," Current Pharmaceutical Design, 2000, Vol. 6, No. 13, pp. 1381-1397 (p. 1386).

Other embodiments of the present invention may comprise a suitable combination of two or more of embodiments and/or aspects disclosed herein.

Yet other embodiments and aspects of the invention will be apparent according to the description provided below.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A illustrates results from a rat formalin model used for testing acute chemo-induced pain. The single asterisk (*) applies when p is less than 0.05.

FIG. 1B illustrates results from a rat formalin model used for testing chronic chemo-induced pain. The single asterisk (*) applies when p is less than 0.05.

FIG. 2 illustrates results from the Hargreaves Test used for measuring acute thermal pain. The single asterisk (*) applies when p is less than 0.05 whereas the double asterisk (**) applies when p is less than 0.01. n=6.

FIG. 3 illustrates results from the Chung Model used for measuring neuropathic pain. The single asterisk (*) applies when p is less than 0.05 whereas the double asterisk (**) applies when p is less than 0.01. n=9-10.

DETAILED DESCRIPTION OF THE INVENTION

The description of the invention herein should be construed in congruity with the laws and principles of chemical bonding. For example, when a moiety is optionally substituted and said substitution requires the removal of a hydrogen atom from the moiety to be substituted, the description of the moiety should be read to include the moiety with or without said hydrogen atom. As another example, if a variable is defined as a particular moiety or atom and is further defined to have value of 0 or some integer, the bond(s) attaching said moiety should be suitably removed in the event the variable equals 0. An embodiment or aspect which depends from another embodiment or aspect, will describe only the variables having values and provisos that differ from the embodiment or aspect from which it depends. It is to be understood that the present invention may include any and all possible stereoisomers, geometric isomers, diastereoisomers, enantiomers, anomers and optical isomers, unless a particular description specifies otherwise. As used herein, "halo" or "halogen" includes fluoro, chloro, bromo and iodo. As used herein, "alkyl" or "alkylene" includes straight or branched chain configurations.

The compounds of this invention can exist in the form of pharmaceutically acceptable salts. Such salts include addition salts with inorganic acids such as, for example, hydrochloric acid and sulfuric acid, and with organic acids such as, for example, acetic acid, citric acid, methanesulfonic acid, toluenesulfonic acid, tartaric acid and maleic acid. Further, in case the compounds of this invention contain an acidic group, the acidic group can exist in the form of alkali metal salts such as, for example, a potassium salt and a sodium salt; alkaline earth metal salts such as, for example, a magnesium salt and a calcium salt; and salts with organic bases such as a triethylammonium salt and an arginine salt. The compounds of the present invention may be hydrated or non-hydrated.

The compounds of this invention can be administered in such oral dosage forms as tablets, capsules (each of which includes sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups and emulsions. The compounds of this invention may also be administered intravenously, intraperitoneally, subcutaneously, or intramuscularly, all using dosage forms well known to those skilled in the pharmaceutical arts. The compounds can be administered alone, but generally will be administered with a pharmaceutical carrier selected upon the basis of the chosen route of administration and standard pharmaceutical practice. Compounds of this invention can also be administered in intranasal form by topical use of suitable intranasal vehicles, or by transdermal routes, using transdermal skin patches. When compounds of this invention are administered transdermally the dosage will be continuous throughout the dosage regimen.

The dosage and dosage regimen and scheduling of a compounds of the present invention must in each case be carefully adjusted, utilizing sound professional judgment and considering the age, weight and condition of the recipient, the route of administration and the nature and extent of the disease condition. In accordance with good clinical practice, it is preferred to administer the instant compounds at a concentration level which will produce effective beneficial effects without causing any harmful or untoward side effects.

Compounds of the present invention may be synthesized according to the description provided below. Variables provided in the schema below are defined in accordance with the description of compounds of Formula (I) unless otherwise specified. ##STR00004##

The following Intermediates 1-13 may be used to synthesize Examples 1-51.

Intermediate 1

##STR00005##

2-Methyl-4,5-diphenyl-1H-imidazole: (Scheme 1, (A)) To a solution of benzil (3.0 g, 14 mmol) in glacial acetic acid (100 mL) was added ammonium acetate (22.2 g, 284 mmol) followed with acetaldehyde (1.26 g, 28 mmol). The resultant suspension was stirred at 100.degree. C. for 2.5 hours. After removal of most of solvent, the residue was dissolved in EtOAc. The precipitate ammonium acetate was filtered off. The filtrate was washed with 2N NaOH, H.sub.2O, and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: EtOAc/Hexanes). This compound was obtained as a white solid (0.96 g, 4.1 mmol, 29% yield): mp 232-235.degree. C.; MS m/e 235.0 (MH.sup.+); .sup.1H NMR (DMSO-d.sub.6) .delta.7.27 (br m, 10H), 2.33 (s, 3H); .sup.13C NMR (DMSO-d.sub.6) .delta.144.3, 128.7, 128.3, 127.8, 127.3, 126.3, and 14.0. Anal. Calcd for C.sub.16H.sub.14N.sub.2.0.12 H.sub.2O: C, 81.26; H, 6.07; N, 11.85. Found:C, 81.20; H,
6.03; N, 11.89.

Intermediate 2

##STR00006##

2-Ethyl-4,5-diphenyl-1H-imidazole: (Scheme 1, (A)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.30 (t, 3H), 2.72 (q, 2H), 7.44 (b, 10H), 12.02 (b, 1H); Mass Spec: 249.26 (MH.sup.+).

Intermediate 3

##STR00007##

4,5-Bis-(4-fluoro-phenyl)-2-methyl-1H-imidazole: (Scheme 1, (A)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.2.32 (s, 3H), 7.13 (t, 2H), 7.27 (t, 2H), 7.47 (m, 4H), 12.15 (b, 1H).

Intermediate 4

##STR00008##

7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid ethyl ester: (Scheme 1, (B)) To a solution of 2-methyl-4,5-diphenyl-1H-imidazole (0.20 g, 0.85 mmol) in DMF (6 mL) was added NaH (60% in mineral oil, 0.038 g, 0.94 mmol). The resulting mixture was stirred at rt for 10 min. The stirring continued for 2 hours after addition of ethyl 7-bromoheptanoate (0.21 g, 0.90 mmol). The reaction mixture was diluted with diethyl ether (30 mL), washed by water, and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: EtOAc/Hexanes). This compound was obtained as a colorless oil (0.24 g, 0.61 mmol, 72% yield): .sup.1H NMR (DMSO-d.sub.6) .delta.1.08 (m, 4H), 1.15
(t, J=7.2 Hz, 3H), 1.33 (m, 4H), 2.16 (t, J=6.6 Hz, 2H), 2.40 (s, 3H), 3.68 (t, J=7.8 Hz, 2H), 4.03 (q, J=4.5 Hz, 2H), 7.05)m, 1H), 7.13 (m, 2H), 7.34 (m, 4H), 7.48 (m, 3H); .sup.13C NMR (DMSO-d.sub.6) .delta.13.4, 14.4, 24.3, 25.7, 27.8, 29.6, 33.5,
43.3, 59.9, 125.8, 126.0, 128.1, 128.3, 128.8, 129.3, 131.1, 131.8, 135.2, 135.3, and 144.0. Anal. Calcd for C.sub.25H.sub.30N.sub.2O.sub.2: C, 76.89; H, 7.74; N, 7.17. Found: C, 76.33; H, 7.67, N, 6.85.

Intermediate 5

##STR00009##

8-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-octanoic acid ethyl ester: (Scheme 1, (B)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.06 (b, 6H), 1.20 (t, 3H), 1.42 (m, 4H), 2.22 (t, 2H), 2.49 (s, 3H), 3.70 (t, 2H), 4.06
(q, 2H), 7.16 (m, 3H), 7.35 (m, 4H), 7.51 (m, 3H). Mass Spec: 405.32 (MH.sup.+).

Intermediate 6

##STR00010##

6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexanoic acid ethyl ester: (Scheme 1, (B)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.13 (m, 2H), 1.17 (t, 3H), 1.43 (m, 4H), 2.15 (t, 2H), 2.40 (s, 3H), 3.70 (t, 2H), 4.04
(q, 2H), 7.13 (m, 3H), 7.47 (m, 4H), 7.54 (m, 3H). Mass Spec: 377.26 (MH.sup.+).

Intermediate 7

##STR00011##

8-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid ethyl ester: (Scheme 1, (B)) Prepared as described for the example above. .sup.1H NMR (DMSO-d.sub.6) .delta.1.08 (m, 4H), 1.15 (t, J=7.2 Hz, 3H), 1.33 (m, 7H), 2.16 (t, J=6.6 Hz, 2H), 2.71
(q, J=7.5 Hz), 3.68 (t, J=7.8 Hz, 2H), 4.03 (q, J=4.5 Hz, 2H), 7.05 (m, 1H), 7.13 (m, 2H), 7.34 (m, 4H), 7.48 (m, 3H). Anal. Calcd for C.sub.26H.sub.32N.sub.2O.sub.2: C, 77.19; H, 7.97; N, 6.92. Found: C, 77.06; H, 8.13; N, 6.89. Mass Spec: 405.2
(MH.sup.+).

Intermediate 8

##STR00012##

7-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-heptanoic acid ethyl ester: (Scheme 1, (B)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.09 (m, 4H), 1.17 (t, 3H), 1.38 (m, 4H), 2.19 (t, 2H), 2.39 (s, 3H), 3.6
(t, 2H), 4.05 (q, 2H), 7.03 (t, 2H), 7.36 (m, 4H), 7.41 (m, 2H). Mass Spec: 427.49 (MH.sup.+).

Intermediate 9

##STR00013##

7-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-heptanoic acid: (Scheme 1, (C)) To a solution of 7-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-heptanoic acid ethyl ester (1.9 g, 4.4 mmol) in EtOH (10 mL) was added NaOH (10 N, 2 mL, 20
mmol). The resulting mixture was stirred at rt for 1 hour, diluted with EtOAc (100 mL), washed by HCl (0.5 N), and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: MeOH/CH.sub.2Cl.sub.2). This compound was obtained as a white solid in HCl salt form (1.9 g, 4.3 mmol, 98% yield): .sup.1H NMR (DMSO): .delta.1.15 (m, 4H), 1.37 (t, 2H), 1.47 (t, 2H), 2.13 (t, 2H), 2.73 (s, 3H), 4.03 (t, 2H), 7.35 (t,2H), 7.45 (m, 4H),
7.57 (m, 2H), 12.1 (b, 1H).

Intermediate 10

##STR00014##

8-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid: (Scheme 1, (C)) Prepared as described for the example above. .sup.1H NMR (DMSO-d.sub.6) .delta.11.95 (br s, 1H), 7.56 (m, 3H), 7.46 (m, 2H), 7.38 (m, 2H), 7.28 (m, 3H), 3.83 (t, 2H, J=7.5
Hz), 2.67 (s, 3H), 2.09 (t, 2H, J=7.5 Hz), 1.38 (m, 2H), 1.25 (m, 2H), and 1.09 (m, 4H), .sup.13C NMR (DMSO-d.sub.6) .delta.174.5, 144.4, 131.3, 130.1, 129.6, 128,9, 128.8, 128.4, 128.1, 126.8, 44.3, 33.8, 29.4, 28.9, 25.6, 22.3 and 11.7. Anal. Calcd for C.sub.23H.sub.26N.sub.2O.sub.2.0.95 HCl.0.32 C.sub.6H.sub.14: C, 70.48; H, 7.46; N, 6.60. Found: C, 70.82; H, 7.08, N, 6.64.

Intermediate 11

##STR00015##

6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexanoic acid: (Scheme 1, (C)) Prepared as described for the example above. .sup.1H NMR DMSO): .delta.1.17 (m, 2H), 1.33 (m, 2H), 1.51 (m, 2H), 2.09 (t, 2H), 2.76 (s, 3H), 4.03 (t, 2H), 7.38 (m, 5H), 7.49
(m, 2H), 7.65 (m, 3H).

Intermediate 12

##STR00016##

8-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-octanoic acid: (Scheme 1, (C)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.07 (b, 6H), 1.39 (m, 2H), 1.48 (m, 2H), 2.15 (t, 2H), 2.72 (s, 3H), 3.92 (t, 2H), 7.35 (s, 5H), 7.52
(m, 2H), 7.606 (m, 3H), 12.1 (b, 1H). Anal. Calcd. for C.sub.24H.sub.28N.sub.2O.sub.2.0.982HCl. 0.59H2O: C, 68.16; H, 7.19; N, 6.62. Found: C, 68.00; H, 7.09; N, 6.81.

Intermediate 13

##STR00017##

8-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid: (Scheme 1, (C)) Prepared as described for the example above. .sup.1H NMR (DMSO-d.sub.6) .delta.11.95 (br s, 1H), 7.56 (m, 3H), 7.46 (m, 2H), 7.38 (m, 2H), 7.28 (m, 3H), 3.83 (t, 2H, J=7.5
Hz), 3.13 (q, J=7.8 Hz, 2H), 2.09 (t, 2H, J=7.5 Hz), 1.38 (m, 5H), 1.25 (m, 2H), and 1.09 (m, 4H). Anal. Calcd for C.sub.24H.sub.28N.sub.2O.sub.2.1.00HCl.0.44 C.sub.6H.sub.14: C, 68.44; H, 7.15; N, 6.65. Found: C, 68.43; H, 6.98; N, 6.53.

EXAMPLE 1

##STR00018##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-fluoro-phenyl ester: (Scheme 1 (D)) To a suspension of 8-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid (11.3 g, 28.3 mmol) in a mixture of Et.sub.3N (10 g, 99 mmol) and toluene (200 mL) was added azide (11.0 g, 39.7 mmol). The resultant mixture was stirred at r.t. for 10 min. and then at 108.degree. C. under N.sub.2 for 90 min. After the mixture was cooled to r.t., 2-fluorophenol (3.8 g, 37 mmol) was added. The reaction mixture was stirred at r.t. for 10 min and then at 80.degree. C. for 1 h. The mixture was diluted with EtOAc, washed with H.sub.2O, and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: EtOAc/Hexanes). This compound was obtained as a white solid (7.3 g, 15.5 mmol, 55% yield): mp 129-131.degree. C.; .sup.1H NMR (DMSO-d.sub.6) .delta.7.85 (br s, 1H), 7.50 (m, 3H), 7.33 (m, 5H), 7.30-7.05 (m, 6H), 3.69
(t, 2H, J=4.8 Hz), 2.95 (dd, 2H, J=4.8, 3.6 Hz), 2.4 (s, 3H), 1.4 (m, 2H), 1.3 (m, 2H), 1.09 (m, 4H). Anal. Calcd for C.sub.29H.sub.30FN.sub.3O.sub.2: C, 73.86; H, 6.41; N, 8.91. Found: C, 73.63; H, 6.45; N, 8.81. Mass Spec: 472.2 (MH.sup.+).

EXAMPLE 2

##STR00019##

[6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid tert-butyl ester (Scheme 1, (D)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.04 (m, 4H), 1.28 (m, 7H), 1.35 (s, 9H), 2.79 (m, 4H), 3.68 (t, 2H), 7.08 (t,
1H), 7.16 (t, 2H), 7.36 (m, 4H), 7.51 (m, 3H). Anal. Calcd. for C28H37N3O2. 0.196 CH2Cl2. 0.4 C6H14: C, 73.68; H, 8.69; N, 8.43. Found: C, 73.81; H, 8.38; N, 8.19. Mass Spec: 448.2 (MH.sup.+).

EXAMPLE 3

##STR00020##

6-(2-Ethyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid sec-butyl ester: (Scheme 1, (D)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.0.84 (t, 3H), 1.03 (bs, 4H), 1.11 (d, J=6.27 Hz, 3H), 1.36 (t, 2H), 1.48 (m,
7H), 2.76 (q, 2H), 2.84 (q, 2H), 3.71 (t, 2H), 4.55 (m, 1H), 6.8 (t, 1H), 7.05 (m, 1H), 7.16 (t, 2H), 7.36 (m, 4H), 7.50 (m, 3H). Anal. Calcd. for C.sub.28H.sub.37N.sub.3O.sub.2. 0.17 CH.sub.2Cl.sub.2. 0.245 C.sub.6H.sub.14: C, 73.66; H, 8.50; N,
8.70. Found: C, 73.73; H, 8.19; N, 8.69. Mass Spec: 448.2 (MH.sup.+).

EXAMPLE 4

##STR00021##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-butyl ester: (Scheme 1, (D)) Prepared as described for the example above. Analytical HPLC 1.46 min (89%). Mass Spec: 454.3 (MH.sup.+).

EXAMPLE 5

##STR00022##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid benzyl ester: (Scheme 1 (D)) Prepared as described for the example above. This compound was purified by preparative HPLC (YMC 30.times.100 mm (5 uM packing), 10% MeOH/90% water/01% TFA as mobile phase A, 90% MeOH/10%water/0.1% TFA as mobile phase B). .sup.1H NMR (DMSO): .delta.1.067 (bs, 4H), 1.26 (t, 2H), 1.47 (t, 2H), 2.73 (s, 3H), 2.91 (q, 2H), 3.94 (t, 2H), 5.01 (s, 2H), 7.20 (m, 3H), 7.35 (m, 8H), 7.49 (m, 2H), 7.59 (d, J=6.69 mHz, 3H). Mass Spec: 468.17 (MH.sup.+).

EXAMPLE 6

##STR00023##

.[.2-Propanone, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino)carbonyl]oxime:.- ]. .Iadd.2-Propanone,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylami- nocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.11 (m, 4H), 1.30 (m, 2H), 1.50 (m, 2H), 1.92 (d, J=9.25 mHz, 6H), 2.74 (s, 3H), 2.96 (m, 2H), 3.94 (t, 2H), 7.29 (t, 1H), 7.39 (m, 2H), 7.41 (m, 3H), 7.49 (m, 2H), 7.61 (m, 2H). Mass Spec: 433.31 (MH.sup.+).

EXAMPLE 7

##STR00024##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid cyclohexyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.64 min (85%). Mass spec: 460.21 (MH.sup.+).

EXAMPLE 8

##STR00025##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid methyl ester: Prepared as described for the example above. Analytical HPLC 1.33 min. (80%). Mass spec: 392.12 (MH.sup.+).

EXAMPLE 9

##STR00026##

6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.50 min (83%). Mass Spec: 454.15 (MH.sup.+).

EXAMPLE 10

##STR00027##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-fluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.52 min (97%). Mass Spec: 472.09 (MH.sup.+).

EXAMPLE 11

##STR00028##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,4-difluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.54 min (96%). Mass Spec. 490.06 (MH.sup.+).

EXAMPLE 12

##STR00029##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-chloro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical 1.61 min (95%). Mass Spec: 488.02 (MH.sup.+).

EXAMPLE 13

##STR00030##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-methoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.51 min (96%). Mass Spec: 484.11 (MH.sup.+).

EXAMPLE 14

##STR00031##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid o-tolyl ester: (Scheme 1 (D)) Prepared as described for the example above. H Analytical HPLC 1.54 min (92%). Mass Spec: 468.11 (MH.sup.+).

EXAMPLE 15

##STR00032##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 4-cyano-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.46 min (94%). Mass Spec: 479.08 (MH.sup.+).

EXAMPLE 16

##STR00033##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2,6-dimethoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.43 min (94%). Mass Spec: 514.10 (MH.sup.+).

EXAMPLE 17

##STR00034##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 2-methoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.48 min (99%). Mass Spec: 484.12 (MH.sup.+).

EXAMPLE 18

##STR00035##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid methyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.41 min (98%). Mass Spec: 406.32 (MH.sup.+).

EXAMPLE 19

##STR00036##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid ethyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.49 min (95%). Mass Spec: 420.35 (MH.sup.+).

EXAMPLE 20

##STR00037##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.58 min (99%). Mass Spec: 468.32 (MH.sup.+).

EXAMPLE 21

##STR00038##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-fluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.60 min (98%). Mass Spec: 486.30 (MH.sup.+).

EXAMPLE 22

##STR00039##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-fluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.58 min (96%). Mass Spec: 486.31 (MH.sup.+).

EXAMPLE 23

##STR00040##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,4-difluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.61 min (90%). Mass Spec: 504.31 (MH.sup.+).

EXAMPLE 24

##STR00041##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-chloro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.68 min (90%). Mass Spec: 502.29 (MH.sup.+).

EXAMPLE 25

##STR00042##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-methoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.59 min (90%). Mass Spec: 498.33 (MH.sup.+).

EXAMPLE 26

##STR00043##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid o-tolyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.63 min (90%). Mass Spec: 482.33 (MH.sup.+).

EXAMPLE 27

##STR00044##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 4-cyano-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.53 min (90%). Mass Spec: 493.31 (MH.sup.+).

EXAMPLE 28

##STR00045##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2,6-dimethoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.53 min (96%). Mass Spec: 528.37 (MH.sup.+).

EXAMPLE 29

##STR00046##

[7-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-heptyl]-carbamic acid 2-methoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.57 min (90%). Mass Spec: 498.33 (MH.sup.+).

EXAMPLE 30

##STR00047##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid ethyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.36 min (98%). Mass Spec: 392.35 (MH.sup.+).

EXAMPLE 31

##STR00048##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.48 min (97%). Mass Spec: 440.36 (MH.sup.+).

EXAMPLE 32

##STR00049##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-fluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.51 min (97%). Mass Spec: 458.33 (MH.sup.+).

EXAMPLE 33

##STR00050##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,4-difluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.52 min (95%). Mass Spec: 476.32 (MH.sup.+).

EXAMPLE 34

##STR00051##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-fluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.48 min (98%). Mass Spec: 458.33 (MH.sup.+).

EXAMPLE 35

##STR00052##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-chloro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.62 min (98%). Mass Spec: 474.29 (MH.sup.+).

EXAMPLE 36

##STR00053##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-methoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.49 min (99%). Mass Spec: 470.35 (MH.sup.+).

EXAMPLE 37

##STR00054##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid o-tolyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.56 min (95%). Mass Spec: 454.36 (MH.sup.+).

EXAMPLE 38

##STR00055##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 4-cyano-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.44 min (99%). Mass Spec: 465.32 (MH.sup.+).

EXAMPLE 39

##STR00056##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2,6-dimethoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.44 min (99%). Mass Spec: 500.38 (MH.sup.+).

EXAMPLE 40

##STR00057##

[5-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-pentyl]-carbamic acid 2-methoxy-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.46 min (97%). Mass Spec: 470.34 (MH.sup.+).

EXAMPLE 41

##STR00058##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid 3,4-difluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.55 min (84%). Mass Spec: 490.32 (MH.sup.+).

EXAMPLE 42

##STR00059##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid isopropyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.47 min (83%). Mass Spec: 420.17 (MH.sup.+).

EXAMPLE 43

##STR00060##

{6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2-fluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.50 min (95%). Mass Spec: 508.29 (MH.sup.+).

EXAMPLE 44

##STR00061##

{6-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-imidazol-1-yl]-hexyl}-carbamic acid 2,6-difluoro-phenyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.50 min (85%). Mass Spec: 526.31 (MH.sup.+).

EXAMPLE 45

##STR00062##

[6-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-hexyl]-carbamic acid ethyl ester: (Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.40 min (82%). Mass Spec: 406.15 (MH.sup.+).

EXAMPLE 46

##STR00063##

.[.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime:.- ]. .Iadd.Benzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.48 min (89%). Mass Spec: 481.26 (MH.sup.+).

EXAMPLE 47

##STR00064##

.[.4-Fluorobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime:.- ]. .Iadd.4-Fluorobenzaldehyde,O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl- )hexylaminocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.58 min (87%). Mass Spec: 499.32 (MH.sup.+).

EXAMPLE 48

##STR00065##

.[.2-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime:.- ]. .Iadd.2-Nitrobenzaldehye, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.56 min (95%). Mass Spec: 526.3 (MH.sup.+).

EXAMPLE 49

##STR00066##

.[.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime:.- ]. .Iadd.3-Nitrobenzaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.57 min (83%). Mass Spec: 526.32 (MH.sup.+).

EXAMPLE 50

##STR00067##

.[.4-Nitrobenzaldehyde, O-{6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime:.- ]. .Iadd.4-Nitrobenzaldehyde, O-{6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.58 min (94%). Mass Spec: 526.29 (MH.sup.+).

EXAMPLE 51

##STR00068##

.[.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]amino]carbonyl]oxime:.- ]. .Iadd.3-Pyridinecarboxaldehyde, O-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexylaminocarbonyl]oxime: .Iaddend.(Scheme 1 (D)) Prepared as described for the example above. Analytical HPLC 1.24 min (94%). Mass Spec: 482.26 (MH.sup.+). ##STR00069##

The following Intermediates 14-20 may be used to synthesize Examples 52-74.

Intermediate 14

##STR00070##

1-(5-Bromo-pentyl)-2-methyl-4,5-diphenyl-1H-imidazole: (Scheme 2 (E)) To a solution of 2-Methyl-4,5-diphenyl-1H-imidazole (2.0 g, 8.5 mmol) and 1,5-dibromopentane (3.01 g, 12.7 mmol) in DMF (100 mL) was added NaH (60% in mineral oil, 0.50 g, 12.7
mmol). The resulting mixture was stirred at rt for 1 hour, quenched by addition of water, extracted by CH.sub.2Cl.sub.2, washed by water, and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: EtOAc/Hexanes). This compound was obtained as a pale yellow oil (2.2 g, 5.7 mmol, 67% yield): .sup.1H NMR (DMSO): .delta.1.20 (m, 2H), 1.47 (m, 2H), 1.64 (m, 2H), 2.41 (s, 3H), 3.45 (t, 2H), 3.72 (t, 2H), 7.16 (m, 3H), 7.31
(m, 4H), 7.55 (t, 3H). Mass Spec: 384.57 (MH.sup.+).

Intermediate 15

##STR00071##

1-(6-Bromo-hexyl)-2-methyl-4,5-diphenyl-1H-imidazole: (Scheme 2 (E)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.2 (m, 4H), 1.5 (m, 2H), 1.75 (m, 2H), 2.5 (s, 3H), 3.4 (t, 2H), 3.69 (t, 2H), 7.14 (m, 3H), 7.36 (m,
4H), 7.516 (m, 3H). Mass Spec: 399.14 (MH.sup.+).

Intermediate 16

##STR00072##

1-(3-Bromo-propyl)-2-methyl-4,5-diphenyl-1H-imidazole: (Scheme 2 (E)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.99 (m, 2H), 2.43 (s, 3H), 3.39 (t, 2H), 3.88 (t, 2H), 7.17 (m, 3H), 7.35 (m, 4H), 7.53 (m, 3H), Mass Spec: 356.59 (MH.sup.+).

Intermediate 17

##STR00073##

4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-benzoic acid ethyl ester: (Scheme 2 (H)) To a solution of 1-(3-Bromo-propyl)-2-methyl-4,5-diphenyl-1H-imidazole (0.80 g, 2.2 mmol) and ethyl 4-hydroxybenzoate (1.20 g, 7.2 mmol) in DMF (30 mL) was added K.sub.2CO.sub.3 (0.40 g, 2.9 mmol). The resulting mixture was stirred at 55.degree. C. for 1 hour, quenched by addition of water, extracted by EtOAc, washed by water, and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: EtOAc/Hexanes). This compound was obtained as a pale yellow gum (0.92 g, 2.0 mmol, 94% yield): .sup.1H NMR (DMSO): .delta.1.32 (t, 3H), 1.85 (m, 2H), 2.402 (s, 3H), 3.87 (m, 4H), 4.28
(q, 2H), 6.89 (d, J=8.82 Hz, 2H), 7.143 (m, 3H), 7.36 (m, 4H), 7.46 (m, 3H), 7.82 (d, J=8.85 mHz, 2H). Mass spec: 441.28 (MH.sup.+).

Intermediate 18

##STR00074##

4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxy]-benzoic acid ethyl ester: (Scheme 2 (H)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.1.31 (t, 3H), 2.5 (s, 3H), 4.07 (m, 2H), 4.15 (m, 2H), 4.26 (q, 2H), 6.91 (d, J=8.88 mHz, 2H), 7.16 (m, 3H), 7.33 (d, J=7.56 mHz, 2H), 7.41 (m, 2H), 7.53 (m, 3H), 7.85 (d, J=8.85 mHz, 2H).

Intermediate 19

##STR00075##

4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-benzoic acid: (Scheme 2 (I)) To a solution of 4-[3-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-propoxy]-benzoic acid ethyl ester (0.80 g, 1.8 mmol) in EtOH (20 mL) was added NaOH (10 N, 4.0 mL, 40.0
mmol). The resulting mixture was stirred at rt for 3 hours, diluted with water, acidified to pH.about.1 using 1N HCl, extracted by CH.sub.2Cl.sub.2, and then was dried over MgSO.sub.4. After filtration and concentration in vacuo, the residue was purified by flash chromatography (SiO.sub.2: MeOH/CH.sub.2Cl.sub.2). This compound was obtained as a white dry foam in HCl salt form (0.80 g, 1.8 mmol, 99% yield): .sup.1H NMR (DMSO): .delta.1.93 (m, 2H), 2.67 (s, 3H), 3.97 (t, 2H), 4.13 (t, 2H), 6.85
(d, J=8.82 mHz, 2H), 7.33 (s, 5H), 7.43 (m, 2H), 7.55 (m, 3H), 7.86 (d, J=8.82 mHz, 2H), 12.64 (b, 1H).

Intermediate 20

##STR00076##

4-[2-(2-Methyl-4,5-diphenyl-imidazol-1-yl)-ethoxyl-benzoic acid: (Scheme 2 (I)) Prepared as described for the example above. .sup.1H NMR (DMSO): .delta.2.82 (s, 3H), 4.19 (m, 2H), 4.39 (m, 2H), 6.93 (d, J=8.85 mHz, 2H), 7.359 (m, 5H), 7.54 (m,
2H), 7.61 (m, 3H),