Heterocyclo-substituted imidazoles for the treatment of inflammation

Abstract

A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (V), wherein R 3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy. aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R 4 is a radical selected from hydrido, alkyl and halo; and wherein R 13 and R 14 are independently selected from aryl and heterocyclo, wherein R 13 and R 14 are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R 13 and R 14 is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.

1 . A compound of Formula I  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently selected from aryl, cycloalkyl, cycloalkenyl and heterocyclo, wherein R 1  and R 2  are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, haloalkylsulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxcyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro;  
         wherein R 3  is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, cycloalkyloxy, cycloalkyloxyalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocycloalkylcarbonyl, cyanoalkyl, azidoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heterocyclo;  
         wherein R 4  is a radical selected from hydrido, alkyl and fluoro;  
         wherein R 5  is selected from hydroxyl and alkoxy; and  
         wherein R 6  is hydrido; or wherein R 5  and R 6  together form a double bond;  
         provided at least one of R 1  and R 2  is aryl substituted with alkylsulfonyl, haloalkylsulfonyl or aminosulfonyl;  
         or a pharmaceutically-acceptable salt thereof.  
       
     
     
         2 . Compound of  claim 1  wherein R 1  and R 2  are independently selected from phenyl, naphthyl, biphenyl, lower cycloalkyl, lower cycloalkenyl and heteroaryl, wherein R 1  and R 2  are optionally substituted at a substitutable position with one or more radicals independently selected from lower alkylsulfonyl, aminosulfonyl, lower haloalkylsulfonyl, halo, lower alkylthio, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkoxy, amino, lower alkylamino, arylamino and nitro; wherein R 3  is a radical selected from hydrido, lower alkyl, lower haloalkyl, lower aralkyl, lower heterocycloalkyl, acyl, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower cycloalkyloxy, lower cycloalkyloxyalkyl, lower cycloalkylthio, lower cycloalkylthioalkyl, lower cycloalkylsulfonyl, lower cycloalkylsulfonylalkyl, phenylsulfonyl, lower haloalkylsulfonyl, halo, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylcarbonyl, lower azidoalkyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower heterocycloalkylcarbonyl, lower cyanoalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower N-arylaminoalkyl, lower N-alkyl-N-arylaminoalkyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonyl, lower alkylthioalkyl, aminocarbonyl, lower alkylaminocarbonyl, lower alkylaminocarbonylalkyl, lower aralkoxy, lower aralkylthio, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroarylalkoxyalkyl, lower heteroarylalkylthioalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower arylthio, lower aryloxy, lower aralkylthioalkyl, lower aralkoxyalkyl, aryl selected from phenyl and naphthyl, and heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkylthio, lower alkylsulfonyl, lower alkyl, cyano, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl and lower haloalkoxy; wherein R 4  is a radical selected from hydrido, lower alkyl and fluoro; and wherein R 5  is selected from hydroxyl and lower alkoxy; wherein R 6  is hydrido; or wherein R 5  and R 6  together form a double bond; or a pharmaceutically-acceptable salt thereof.  
     
     
         3 . Compound of  claim 2  wherein R 1  and R 2  are independently selected from phenyl, naphthyl, biphenyl, cyclohexyl, cyclohexenyl, benzofuryl, benzodioxolyl, furyl, imidazolyl, thienyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, pyrimidinyl, isoquinolyl, quinolinyl, benzimidazolyl, indolyl, pyrazolyl and pyridyl, wherein R 1  and R 2  are optionally substituted at a substitutable position with one or more radicals independently selected from methylsulfonyl, aminosulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, fluoro, chloro, bromo, methylthio, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, trifluoromethoxy, amino, methylamnino, N,N-dimethylamino, phenylamino and nitro; wherein R 3  is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, benzyl, phenylethyl, phenylpropyl, furylmethyl, morpholinomethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridylmethyl, thienylmethyl, formyl, cyano, methoxy, ethoxy, propoxy, n-butoxy, methylthio, ethylthio, isopropylthio, methylsulfonyl, phenylsulfonyl, trifluoromethylsulfonyl, fluoro, chloro, bromo, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, isopropylthiomethyl, cyclohexylthiomethyl, benzyloxy, benzylthio, methylcarbonyl, ethylcarbonyl, phenylcarbonyl, azidomethyl, trifluoromethylcarbonyl, difluoromethylcarbonyl, fluoromethylcarbonyl, benzylcarbonyl, cyanomethyl, cyanobutyl, aminomethyl, methylaminomethyl, N-phenylaminomethyl, N-methyl-N-phenylaminomethyl, acetyl, propanoyl, butanoyl, methoxycarbonylmethyl, ethoxycarbonylethyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, isobutoxycarbonyl, carboxymethyl, carboxypropyl, aminocarbonyl, methylaminocarbonyl, N,N-diethylaminocarbonyl, N-methylaminocarbonylmethyl, pyridyloxy, pyridylthio, phenyloxy, 4-chlorophenoxy, furylmethoxy, furylmethylthio, 5-phenylpyridyl-2-methoxy, thienylmethoxy, quinolylmethoxy, pyridylmethoxy, thienylmethylthio, pyridylmethylthio, benzylthiomethyl, quinolylmethoxymethyl, furylbutoxyethyl, pyridyloxymethyl, pyridylmethoxymethyl, thienyloxyhexyl, thienylthiomethyl, pyridylthiohexyl, furyloxymethyl, furylmethylthiomethyl, quinolylmethylthioethyl, phenylthiomethyl, 2-chlorophenylthiomethyl, 2,6-dichlorophenylthiomethyl, 4-methylphenylthiomethyl, 2-isopropylphenylthiomethyl, 2-methylphenylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, 4-methylphenyloxymethyl, benzyloxymethyl, 4-methoxybenzyloxymethyl, naphthyl, phenyl, thienyl, furyl, pyridyl, wherein the thienyl, furyl, pyridyl and phenyl radicals are optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl and trifluoromethoxy; wherein R 4  is a radical selected from hydrido, methyl, ethyl, and fluoro; and wherein R 5  is selected from hydroxyl, methoxy, ethoxy, propoxy and n-butoxy; wherein R 6  is hydrido; or wherein R 5  and R 6  together form a double bond; or a pharmaceutically-acceptable salt thereof.  
     
     
         4 . A compound of Formula V  
       
         
           
           
               
               
           
         
         wherein R 3  is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R 4  is a radical selected from hydrido, alkyl and halo; and wherein R 13  and R 14  are independently selected from aryl and heterocyclo, wherein R 13  and R 14  are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R 13  and R 14  is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.  
       
     
     
         5 . Compound of  claim 4  wherein R 3  is a radical selected from hydrido, lower alkyl, lower haloalkyl, lower aralkyl, lower heterocycloalkyl, lower heteroaralkyl, acyl, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenylsulfonyl, lower haloalkylsulfonyl, halo, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylcarbonyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower cyanoalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower N-arylaminoalkyl, lower N-alkyl-N-arylaminoalkyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonyl, carboxyl, lower alkylthioalkyl, aminocarbonyl, lower alkylaminocarbonyl, lower alkylaminocarbonylalkyl, lower aralkoxy, lower aralkylthio, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroarylalkoxyalkyl, lower heteroarylalkylthioalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower arylthio, lower aryloxy, lower aralkylthioalkyl, lower aralkoxyalkyl, aryl selected from phenyl and naphthyl, 5 or 6 membered heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl and lower haloalkoxy; wherein R 4  is a radical selected from hydrido, lower alkyl and halo; and wherein R 13  and R 14  are independently selected from phenyl and heteroaryl, wherein R 13  and R 14  are optionally substituted at a substitutable position with one or more radicals independently selected from lower methylsulfonyl, aminosulfonyl, lower alkylthio, lower alkyl, lower haloalkyl, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, and lower haloalkoxy; or a pharmaceutically-acceptable salt thereof.  
     
     
         6 . Compound of  claim 5  wherein R 3  is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, benzyl, phenylethyl, phenylpropyl, furylmethyl, morpholinomethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridylmethyl, thienylmethyl, formyl, cyano, methoxy, ethoxy, propoxy, n-butoxy, methylthio, ethylthio, isopropylthio, methylsulfonyl, phenylsulfonyl, trifluoromethylsulfonyl, fluoro, chloro, bromo, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, isopropylthiomethyl, cyclohexylthiomethyl, benzyloxy, benzylthio, methylcarbonyl, ethylcarbonyl, phenylcarbonyl, trifluoromethylcarbonyl, difluoromethylcarbonyl, fluoromethylcarbonyl, benzylcarbonyl, pyrrolidinylcarbonyl, cyanomethyl, cyanobutyl, aminomethyl, methylaminomethyl, N-phenylaminomethyl, N-methyl-N-phenylaminomethyl, acetyl, propanoyl, butanoyl, methoxycarbonylmethyl, ethoxycarbonylethyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, carboxyl, carboxymethyl, carboxypropyl, aminocarbonyl, methylaminocarbonyl, N,N-diethylaminocarbonyl, N-methoxy-N-methylaminocarbonyl, methylaminocarbonylmethyl, pyridyloxy, pyridylthio, phenyloxy, 4-chlorophenoxy, furylmethoxy, furylmethylthio, thienylmethoxy, quinolylmethoxy, pyridylmethoxy, 5-phenylpyridyl-2-methoxy, thienylmethylthio, pyridylmethylthio, quinolylmethoxymethyl, furylbutoxyethyl, pyridyloxymethyl, pyridylmethoxymethyl, thienyloxyhexyl, thienylthiomethyl, pyridylthiohexyl, furyloxymethyl, furylmethylthiomethyl, quinolylmethylthioethyl, phenylthiomethyl, 2-chlorophenylthiomethyl, 2,6-dichlorophenylthiomethyl, 4-methylphenylthiomethyl, 2-isopropylphenylthiomethyl, 2-methylphenylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, 4-methylphenyloxymethyl, benzyloxymethyl, 4-methoxybenzyloxymethyl, naphthyl, phenyl, thienyl, furyl, pyridyl, wherein the thienyl, furyl, pyridyl and phenyl radicals are optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl and trifluoromethoxy; wherein R 4  is a radical selected from hydrido, methyl, ethyl, fluoro, chloro and bromo; and wherein R 13  and R 14  are independently selected from phenyl, imidazolyl, thienyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, pyrazinyl, pyrimidinyl, isoquinolyl, quinolyl, indolyl, benzimidazolyl, pyrazolyl and pyridyl, wherein R 13  and R 14  are optionally substituted at a substitutable position with one or more radicals independently selected from methylsulfonyl, aminosulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, trifluoromethoxy, amino, methylamino, N,N-diethylamino, phenylamino and nitro; or a pharmaceutically-acceptable salt thereof.  
     
     
         7 . Compound of  claim 6  wherein R 3  is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl and 2-methylphenylthiomethyl; wherein R 4  is hydrido; wherein R 13  is phenyl optionally substituted with methylsulfonyl or aminosulfonyl; and wherein R 14  is selected from imidazolyl, thienyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, pyrimidinyl, quinolinyl, isoquinolyl, indolyl, benzimidazolyl, pyrazolyl and pyridyl, wherein R 14  is optionally substituted at a substitutable position with one or more radicals independently selected from methylthio, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, and trifluoromethoxy; or a pharmaceutically-acceptable salt thereof.  
     
     
         8 . Compound of  claim 4  selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 
 3-[4-[[(methylphenyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    3-[4-methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    4-[2-(6-methylpyrindin-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    4-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;    4-[2-(2-methylthiazol-4-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(4-methylpyrindin-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    3-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;    1-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]isoquinoline;    4-[2-(3-methylpyrindin-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]quinoline;    4-[2-(2-thienyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    3-bromo-5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;    1-[4-(methylsulfonyl)phenyl]-2-(3-pyridinyl)-1H-imidazole-4-carbonitrile;    2-(2-methyloxazol-4-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;    4-[2-(5-bromopyrindin-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    2-(5-methylpyridin-3-yl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-carbonitrile;    3-[4-difluoromethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    4-[4-cyano-2-(5-methylpyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(2-quinolinyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(3-methoxypyridin-5-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]isoquinoline;    2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyrazine;    2-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiazole;    1-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]-1H-indole;    4-[2-(4-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiophene;    3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiophene;    4-[2-(5-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-[2-(2-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    3-fluoro-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    3-chloro-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-[2-(5-fluoropyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(5-chloropyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    5-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-methoxy-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazo1-2-yl]pyridine;    5-methoxy-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-methoxy-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-chloro-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    5-chloro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-chloro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-fluoro-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-fluoro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-fluoro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-[2-(5-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(4-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(6-methoxypyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(5-methoxypyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(4-methoxypyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(6-chloropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(5-chloropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(4-chloropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(6-fluoropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(5-fluoropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(4-fluoropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    3-methoxy-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    3-[4-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    2-methylthio-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    3-[4-(difluoromethyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    4-[2-(5-methoxypyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[4-methyl-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(pyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[4-(4-fluorophenyl)-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-[6-(methylthio)pyridin-3-yl]-4-trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[4-(difluoromethyl)-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;    3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-[1-(4-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-methyl-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    4-[2-(6-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;    3-methyl-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;    2-methoxy-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine; and    2-[4-[4-fluorophenyl-1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine.    
     
     
         9 . Compound of  claim 7  selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 
 3-[4-[[(methylphenyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    4-[2-(pyrindin-3-yl)-4-[[(methylphenyl)thio]methyl]-1H-imidazol-1-yl]benzenesulfonamide;    3-[4-methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    4-[2-(6-methylpyrindin-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    4-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;    4-[2-(4-methylpyrindin-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    3-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;    1-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]isoquinoline;    4-[2-(3-methylpyrindin-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]quinoline;    4-[2-(2-thienyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    3-bromo-5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;    1-[4-(methylsulfonyl)phenyl]-2-(3-pyridinyl)-1H-imidazole-4-carbonitrile;    2-(2-methyloxazol-4-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;    4-[2-(5-bromopyrindin-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    2-(5-methylpyridin-3-yl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-carbonitrile;    3-[4-difluoromethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;    4-[4-difluoromethyl-2-(pyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[4-cyano-2-(pyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[4-cyano-2-(5-methylpyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(2-quinolinyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    1-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]-1H-pyrazole;    4-[2-(1-methyl-1H-pyrazol-4-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    2-(1-methyl-1H-imidazol-4-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;    4-[2-(1-methyl-1H-imidazol-4-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    2-(1-methyl-1H-imidazol-5-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;    4-[2-(1-methyl-1H-imidazol-5-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    2-(1-methyl-1H-imidazol-2-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;    4-[2 -(1-methyl-1H-imidazol-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    1-[4-(methylsulfonyl)phenyl]-2-(4-methylthiazol-2-yl)-4-trifluoromethyl-1H-imidazole;    4-[2-(4-methylthiazol-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    1-[4-(methylsulfonyl)phenyl]-2-(2-methylthiazol-5-yl)-4-trifluoromethyl-1H-imidazole;    4-[2-(2-methylthiazol-5-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    5-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]isoxazole;    4-[2-(5-methylisoxazol-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyrimidine;    4-[2-(5-pyrimidinyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;    4-[2-(pyrazin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide; and    4-[2-(quinol-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide.    
     
     
         10 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 1;  or a pharmaceutically-acceptable salt thereof.  
     
     
         11 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 4;  or a pharmaceutically-acceptable salt thereof.  
     
     
         12 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 5;  or a pharmaceutically-acceptable salt thereof.  
     
     
         13 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 6;  or a pharmaceutically-acceptable salt thereof.  
     
     
         14 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 7;  or a pharmaceutically-acceptable salt thereof.  
     
     
         15 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 8;  or a pharmaceutically-acceptable salt thereof.  
     
     
         16 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 9;  or a pharmaceutically-acceptable salt thereof.  
     
     
         17 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 1;  or a pharmaceutically-acceptable salt thereof.  
     
     
         18 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 4;  or a pharmaceutically-acceptable salt thereof.  
     
     
         19 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 5;  or a pharmaceutically-acceptable salt thereof.  
     
     
         20 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 6;  or a pharmaceutically-acceptable salt thereof.  
     
     
         21 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 7;  or a pharmaceutically-acceptable salt thereof.  
     
     
         22 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 8;  or a pharmaceutically-acceptable salt thereof.  
     
     
         23 . A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising treating the subject having or susceptible to said disorder with a therapeutically-effective amount of a compound of  claim 9;  or a pharmaceutically-acceptable salt thereof.  
     
     
         24 . The method of  claim 18  for use in treatment of inflammation.  
     
     
         25 . The method of  claim 18  for use in treatment of an inflammation-associated disorder.  
     
     
         26 . The method of  claim 25  wherein the inflammation-associated disorder is arthritis.  
     
     
         27 . The method of  claim 25  wherein the inflammation-associated disorder is pain.  
     
     
         28 . The method of  claim 25  wherein the inflammation-associated disorder is fever.  
     
     
         29 . A process of making a compound of the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-acceptable salt thereof, wherein R 3  is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R 4  is a radical selected from hydrido, alkyl and halo; and wherein R 14  is selected from aryl and heterocyclo, wherein R 14  is optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; 
 said method comprising the steps of forming a (protected sulfonyl)benzenamine, treating said (protected sulfonyl)benzenamine first with a base and then with a nitrile to form an amidine, treating said amidine with a haloketone derivative in the presence of a base to form a hydroxyimidazole, forming a (protected sulfonylphenyl)imidazole by dehydrating said hydroxyimidazole, and forming said compounds by deprotecting said (protected sulfonylphenyl)imidazole.