Imidazole derivatives

Abstract

A CB2 receptor modulator comprising an imidazole derivative represented by the general formula (I): [wherein, R 1 represents optionally substituted lower alkyl or the like; R 2 represents optionally substituted cycloalkyl or the like; R 3 represents optionally substituted aryl or the like; and n represents an integer of 0 to 3] or a pharmaceutically acceptable salt thereof as an active ingredient, and the like are provided.

1 .- 27 . (canceled) 
     
     
         28 . A method for modulating a cannabinoid type 2 (CB2) receptor comprising contacting the CB2 receptor with an imidazole derivative represented by the general formula (I): 
       
         
           
           
               
               
           
         
       
       wherein R 1  represents optionally substituted lower alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted lower alkenyl, an optionally substituted aliphatic heterocyclic group, or an optionally substituted heteroaromatic group;
 R 2  represents optionally substituted cycloalkyl, an optionally substituted aliphatic heterocyclic group, optionally substituted aryl, or an optionally substituted heteroaromatic group; 
 R 3  represents optionally substituted aryl, an optionally substituted condensed aromatic hydrocarbon group, an optionally substituted heteroaromatic group, or optionally substituted vinyl; and 
 n represents an integer of 0 to 3; or a pharmaceutically acceptable salt thereof. 
 
     
     
         29 . The method according to  claim 28 , wherein the modulating the CB2 receptor is agonizing the CB2 receptor. 
     
     
         30 . A method for modulating a cannabinoid type 2 (CB2) receptor comprising contacting the CB2 receptor with an imidazole derivative represented by the general formula (IA): 
       
         
           
           
               
               
           
         
       
       wherein R 1A  represents lower alkyl which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy, or lower alkenyl which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy;
 R 2A  represents cycloalkyl which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl, or an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl; 
 R 3A  represents aryl which may have 1 to 5 substituents selected from the following substituent group A, a heteroaromatic group which may have 1 to 4 substituents selected from the following substituent group A, a condensed aromatic hydrocarbon group which may have 1 to 3 substituents selected from the following substituent group A and oxo, an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the following substituent group A and oxo, or vinyl which may have 1 to 3 substituents selected from the following substituent group A; 
 nA represents an integer of 1 to 3; 
 the substituent group A refers to a group consisting of (i) halogen, (ii) nitro, (iii) cyano, (iv) —OR 4  (wherein R 4  represents a hydrogen atom, lower alkyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, an aliphatic heterocyclic group which may be substituted with the following substituent D, lower alkanoyl which may be substituted with the following substituent B, or aroyl which may be substituted with the following substituent C), (v) —COR 6  (wherein R 6  represents a hydrogen atom, lower alkyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, or an aliphatic heterocyclic group which may be substituted with the following substituent D), (vi) —NR 7 R 8  (wherein R 7  and R 8  may be the same or different, and each represents a hydrogen atom, hydroxy, lower alkoxy which may be substituted with the following substituent B, amino, lower alkylamino which may be substituted with the following substituent B, lower alkyl which may be substituted with the following substituent B, lower alkenyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, an aliphatic heterocyclic group which may be substituted with the following substituent D, lower alkoxycarbonyl which may be substituted with the following substituent B, lower alkanoyl which may be substituted with the following substituent B, cycloalkylcarbonyl which may be substituted with the following substituent D, aralkylcarbonyl which may be substituted with the following substituent C, aroyl which may be substituted with the following substituent C, lower alkylsulfonyl which may be substituted with the following substituent B, cycloalkylsulfonyl which may be substituted with the following substituent D, aralkylsulfonyl which may be substituted with the following substituent C, arylsulfonyl which may be substituted with the following substituent C, lower alkylsulfamoyl which may be substituted with the following substituent B, di-lower alkylsulfamoyl which may be substituted with the following substituent B, carbamoyl, lower alkylcarbamoyl which may be substituted with the following substituent B, or di-lower alkylcarbamoyl which may be substituted with the following substituent B, or R 7  and R 8  are combined together with the adjacent nitrogen atom thereto and represent a nitrogen-containing heterocyclic group which may be substituted with the following substituent C), (vii) —C(═W)NR 9 R 10  (wherein W represents an oxygen atom or a sulfur atom, and R 9  and R 10  may be the same or different, and each represents a hydrogen atom, hydroxy, lower alkoxy which may be substituted with the following substituent B, amino, lower alkylamino which may be substituted with the following substituent B, lower alkyl which may be substituted with the following substituent B, lower alkenyl which may be substituted with the following substituent B, lower alkanoyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, or an aliphatic heterocyclic group which may be substituted with the following substituent D, or R 9  and R 10  are combined together with the adjacent nitrogen atom thereto and represent a nitrogen-containing heterocyclic group which may be substituted with the following substituent C), (viii) lower alkyl which may be substituted with the following substituent B, (ix) an aliphatic heterocyclic group which may be substituted with the following substituent D, (x) aralkyl which may be substituted with the following substituent C, (xi) aryl which may be substituted with the following substituent C, (xii) a heteroaromatic group which may be substituted with the following substituent C, (xiii) cycloalkyl which may be substituted with the following substituent D, (xiv) lower alkylsulfanyl which may be substituted with the following substituent B, (xv) lower alkylsulfinyl which may be substituted with the following substituent B, (xvi) lower alkylsulfonyl which may be substituted with the following substituent B, (xvii) lower alkylsulfamoyl which may be substituted with the following substituent B, (xviii) di-lower alkylsulfamoyl which may be substituted with the following substituent B, (xix) —C(═C(CN) 2 )R 13  (wherein R 13  represents lower alkyl), and (xx) —C(═NOR 14 )R 15  (wherein R 14  represents a hydrogen atom or lower alkyl, and R 15  represents lower alkyl); 
 the substituent B refers to 1 to 3 substituents selected from the group consisting of cyano; lower alkylsulfonyl; lower alkylsulfinyl; lower alkylsulfanyl; halogen; hydroxy; lower alkoxy; aralkyloxy; —NR 11 R 12  (wherein R 11  and R 12  may be the same or different, and each represents a hydrogen atom, lower alkyl, aralkyl, aryl, lower alkanoyl, lower alkoxycarbonyl, aroyl, lower alkylsulfonyl, or arylsulfonyl); a heteroaromatic group which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; and cycloalkyl which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; 
 the substituent C refers to 1 to 3 substituents selected from the group consisting of cyano; lower alkylsulfonyl; lower alkylsulfinyl; lower alkylsulfanyl; halogen; hydroxy; lower alkoxy; aralkyloxy; —NR 11 R 12  (wherein R 11  and R 12  have the same definitions as described above, respectively); a heteroaromatic group which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; aryl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; lower alkyl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy; and cycloalkyl which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; and 
 the substituent D refers to 1 to 3 substituents selected from the group consisting of oxo; cyano; lower alkylsulfonyl; lower alkylsulfinyl; lower alkylsulfanyl; halogen; hydroxy; lower alkoxy; aralkyloxy; —NR 11 R 12  (wherein R 11  and R 12  have the same definitions as described above, respectively); a heteroaromatic group which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; aryl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; lower alkyl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy; and cycloalkyl which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl) or a pharmaceutically acceptable salt thereof. 
 
     
     
         31 . The method according to  claim 30 , wherein modulating the CB2 receptor is agonizing the CB2 receptor. 
     
     
         32 . A method for treating and/or preventing a pain, the method comprising administering an imidazole derivative represented by the general formula (IA): 
       
         
           
           
               
               
           
         
       
       wherein R 1A  represents lower alkyl which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy, or lower alkenyl which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy;
 R 2A  represents cycloalkyl which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl, or an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl; 
 R 3A  represents aryl which may have 1 to 5 substituents selected from the following substituent group A, a heteroaromatic group which may have 1 to 4 substituents selected from the following substituent group A, a condensed aromatic hydrocarbon group which may have 1 to 3 substituents selected from the following substituent group A and oxo, an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the following substituent group A and oxo, or vinyl which may have 1 to 3 substituents selected from the following substituent group A; 
 nA represents an integer of 1 to 3; 
 the substituent group A refers to a group consisting of (i) halogen, (ii) nitro, (iii) cyano, (iv) —OR 4  (wherein R 4  represents a hydrogen atom, lower alkyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, an aliphatic heterocyclic group which may be substituted with the following substituent D, lower alkanoyl which may be substituted with the following substituent B, or aroyl which may be substituted with the following substituent C), (v) —COR 6  (wherein R 6  represents a hydrogen atom, lower alkyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, or an aliphatic heterocyclic group which may be substituted with the following substituent D), (vi) —NR 7 R 8  (wherein R 7  and R 8  may be the same or different, and each represents a hydrogen atom, hydroxy, lower alkoxy which may be substituted with the following substituent B, amino, lower alkylamino which may be substituted with the following substituent B, lower alkyl which may be substituted with the following substituent B, lower alkenyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, an aliphatic heterocyclic group which may be substituted with the following substituent D, lower alkoxycarbonyl which may be substituted with the following substituent B, lower alkanoyl which may be substituted with the following substituent B, cycloalkylcarbonyl which may be substituted with the following substituent D, aralkylcarbonyl which may be substituted with the following substituent C, aroyl which may be substituted with the following substituent C, lower alkylsulfonyl which may be substituted with the following substituent B, cycloalkylsulfonyl which may be substituted with the following substituent D, aralkylsulfonyl which may be substituted with the following substituent C, arylsulfonyl which may be substituted with the following substituent C, lower alkylsulfamoyl which may be substituted with the following substituent B, di-lower alkylsulfamoyl which may be substituted with the following substituent B, carbamoyl, lower alkylcarbamoyl which may be substituted with the following substituent B, or di-lower alkylcarbamoyl which may be substituted with the following substituent B, or R 7  and R 8  are combined together with the adjacent nitrogen atom thereto and represent a nitrogen-containing heterocyclic group which may be substituted with the following substituent C), (vii) —C(═W)NR 9 R 10  (wherein W represents an oxygen atom or a sulfur atom, and R 9  and R 10  may be the same or different, and each represents a hydrogen atom, hydroxy, lower alkoxy which may be substituted with the following substituent B, amino, lower alkylamino which may be substituted with the following substituent B, lower alkyl which may be substituted with the following substituent B, lower alkenyl which may be substituted with the following substituent B, lower alkanoyl which may be substituted with the following substituent B, cycloalkyl which may be substituted with the following substituent D, aralkyl which may be substituted with the following substituent C, aryl which may be substituted with the following substituent C, a heteroaromatic group which may be substituted with the following substituent C, or an aliphatic heterocyclic group which may be substituted with the following substituent D, or R 9  and R 10  are combined together with the adjacent nitrogen atom thereto and represent a nitrogen-containing heterocyclic group which may be substituted with the following substituent C), (viii) lower alkyl which may be substituted with the following substituent B, (ix) an aliphatic heterocyclic group which may be substituted with the following substituent D, (x) aralkyl which may be substituted with the following substituent C, (xi) aryl which may be substituted with the following substituent C, (xii) a heteroaromatic group which may be substituted with the following substituent C, (xiii) cycloalkyl which may be substituted with the following substituent D, (xiv) lower alkylsulfanyl which may be substituted with the following substituent B, (xv) lower alkylsulfinyl which may be substituted with the following substituent B, (xvi) lower alkylsulfonyl which may be substituted with the following substituent B, (xvii) lower alkylsulfamoyl which may be substituted with the following substituent B, (xviii) di-lower alkylsulfamoyl which may be substituted with the following substituent B, (xix) —C(═C(CN) 2 )R 13  (wherein R 13  represents lower alkyl), and (xx) —C(═NOR 14 )R 15  (wherein R 14  represents a hydrogen atom or lower alkyl, and R 15  represents lower alkyl); 
 the substituent B refers to 1 to 3 substituents selected from the group consisting of cyano; lower alkylsulfonyl; lower alkylsulfinyl; lower alkylsulfanyl; halogen; hydroxy; lower alkoxy; aralkyloxy; —NR 11 R 12  (wherein R 11  and R 12  may be the same or different, and each represents a hydrogen atom, lower alkyl, aralkyl, aryl, lower alkanoyl, lower alkoxycarbonyl, aroyl, lower alkylsulfonyl, or arylsulfonyl); a heteroaromatic group which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; and cycloalkyl which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; 
 the substituent C refers to 1 to 3 substituents selected from the group consisting of cyano; lower alkylsulfonyl; lower alkylsulfinyl; lower alkylsulfanyl; halogen; hydroxy; lower alkoxy; aralkyloxy; —NR 11 R 12  (wherein R 11  and R 12  have the same definitions as described above, respectively); a heteroaromatic group which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; aryl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; lower alkyl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy; and cycloalkyl which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; and 
 the substituent D refers to 1 to 3 substituents selected from the group consisting of oxo; cyano; lower alkylsulfonyl; lower alkylsulfinyl; lower alkylsulfanyl; halogen; hydroxy; lower alkoxy; aralkyloxy; —NR 11 R 12  (wherein R 11  and R 12  have the same definitions as described above, respectively); a heteroaromatic group which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl; aryl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, lower alkoxy, and lower alkyl; lower alkyl which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy; and cycloalkyl which may have 1 to 3 substituents selected from the group consisting of halogen, oxo, hydroxy, lower alkoxy, and lower alkyl) or a pharmaceutically acceptable salt thereof. 
 
     
     
         33 . The method according to  claim 30 , wherein R 1A  is lower alkyl which may have 1 to 3 substituents selected from the group consisting of halogen, hydroxy, and lower alkoxy. 
     
     
         34 . The method according to  claim 30 , wherein R 1A  is lower alkyl. 
     
     
         35 . The method according to  claim 30 , wherein R 1A  is tert-butyl. 
     
     
         36 . The method according to  claim 30 , wherein R 2A  is cycloalkyl which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl. 
     
     
         37 . The method according to  claim 30 , wherein R 2A  is an aliphatic heterocyclic group which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl. 
     
     
         38 . The method according to  claim 37 , wherein the aliphatic heterocyclic group is an oxygen-containing aliphatic heterocyclic group. 
     
     
         39 . The method according to  claim 37 , wherein the aliphatic heterocyclic group is an aliphatic heterocyclic group represented by the following formula (X): 
       
         
           
           
               
               
           
         
         (wherein Z represents an oxygen atom or a sulfur atom, and n1 and n2 independently represent an integer of 0 to 3). 
       
     
     
         40 . The method according to  claim 30 , wherein R 2A  is cyclohexyl which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl, or 4-tetrahydropyranyl which may have 1 to 3 substituents selected from the group consisting of cyano, halogen, hydroxy, lower alkoxy, lower alkyl, oxo, lower alkoxycarbonyl, and aralkyl. 
     
     
         41 . The method according to  claim 30 , wherein R 3A  is aryl which has 1 to 5 substituents selected from the substituent group A. 
     
     
         42 . The method according to  claim 30 , wherein R 3A  is a heteroaromatic group which may have 1 to 5 substituents selected from the substituent group A. 
     
     
         43 . The method according to  claim 30 , wherein R 3A  is vinyl which has 1 to 3 substituents selected from the substituent group A. 
     
     
         44 . The method according to  claim 30 , wherein the substituent group A is a group consisting of cyano, —COR 6  (wherein R 6  has the same definition as described above), —NR 7 R 8  (wherein R 7  and R 8  have the same definitions as described above, respectively), and —C(═O)NR 9 R 10  (wherein R 9  and R 10  have the same definitions as described above, respectively). 
     
     
         45 . The method according to  claim 30 , wherein the substituent group A is a group consisting of —NR 7 R 8  (wherein R 7  and R 8  have the same definitions as described above, respectively) and —C(═O)NR 9 R 10  (wherein R 9  and R 19  have the same definitions as described above, respectively). 
     
     
         46 . The method according to  claim 30 , wherein nA is 1. 
     
     
         47 . A method for modulating a cannabinoid type 2 (CB2) receptor comprising contacting the CB2 receptor with an imidazole derivative selected from the group consisting of:
 5-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N,N-diethyl-2-fluorobenzamide;   3-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N,N-diethylbenzamide;   3-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N-ethyl-N-methylbenzamide;   5-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N,N-diethylnicotinamide;   4-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylthiophene-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N,N-diethylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-methyl-N-propylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N,N-dimethylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(4-fluorotetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(4-fluorotetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N,N-dimethylpyrazine-2-carboxamide and   5-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-methyl-N-(2,2,2-trifluoroethyl)isoxazole-3-carboxamide;   or a pharmaceutically acceptable salt thereof.   
     
     
         48 . The method according to  claim 47 , wherein modulating the CB2 receptor is agonizing the CB2 receptor. 
     
     
         49 . A method for treating and/or preventing a pain, the method comprising administering an imidazole derivative selected from the group consisting of:
 5-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N,N-diethyl-2-fluorobenzamide;   3-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N,N-diethylbenzamide;   3-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N-ethyl-N-methylbenzamide;   5-(2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl)-N,N-diethylnicotinamide;   4-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylthiophene-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N,N-diethylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-methyl-N-propylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N,N-dimethylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(4-fluorotetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylpyrazine-2-carboxamide;   6-[2-tert-Butyl-1-(4-fluorotetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N,N-dimethylpyrazine-2-carboxamide and   5-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-methyl-N-(2,2,2-trifluoroethyl)isoxazole-3-carboxamide;   or a pharmaceutically acceptable salt thereof.