Substituted biphenyl compounds for the treatment of inflammation

Abstract

A class of substituted biphenyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula III: wherein each of R 11 through R 13 is independently selected from hydrido, halo, lower alkoxy, lower haloalkyl, amino, lower alkylamino, lower dialkylamino, and lower haloalkoxy; or wherein R 11 and R 12 together form —O(CH 2 ) n O—; wherein n is 1-2, inclusive; or a pharmaceutically-acceptable salt thereof.

What is claimed is:  
     
         1 . A compound of Formula I  
       
         
           
           
               
               
           
         
         wherein A is selected from aryl and heteroaryl, wherein A is optionally substituted with one or more radicals seleceted from alkyl, halo, alkoxy, alkylthio, cyano, haloalkyl, amino, alkylamino, carboxyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl and mercapto; wherein each of R 1  through R 4  is independently selected from hydrido, halo, and alkoxy; and wherein each of R 5  through R 9  is independently selected from hydrido, alkyl, halo, alkoxy, alkylthio, cyano, haloalkyl, amino, alkylamino, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, aminosulfonyl and alkylsulfonyl; or a pharmaceutically-acceptable salt thereof.  
       
     
     
         2 . Compound of  claim 1  wherein A is selected from phenyl, naphthyl, 5-membered heteroaryl and 6-membered heteroaryl, wherein A is optionally substituted with one or more radicals seleceted from lower alkyl, halo, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, amino, lower alkylamino, lower dialkylamino, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; wherein each of R 1  through R 4  is independently selected from hydrido and halo; or wherein R 2  and R 3  together form —O(CH 2 ) n O—; wherein n is 1 or 2, inclusive; and wherein each of R 5  through R 9  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, amino, lower alkylamino, lower dialkylamino, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl, mercapto, aminosulfonyl and lower alkylsulfonyl; or a pharmaceutically-acceptable salt thereof.  
     
     
         3 . Compound of  claim 2  wherein A is selected from phenyl, naphthyl, 5-membered heteroaryl and 6-membered heteroaryl, wherein A is optionally substituted with one or more radicals seleceted from lower alkyl, halo, lower alkoxy, lower haloalkyl and lower dialkylamino; wherein each of R 1  through R 4  is independently selected from hydrido and halo; or wherein R 2  and R 3  together form —O(CH 2 ) n O—; wherein n is 1 or 2, inclusive; wherein each of R 5 , R 6 , R 8  and R 9  is hydrido; and wherein R 7  is selected from aminosulfonyl and lower alkylsulfonyl; or a pharmaceutically-acceptable salt thereof.  
     
     
         4 . Compound of  claim 3  wherein A is selected from phenyl, naphthyl, 5-membered heteroaryl and 6-membered heteroaryl, wherein A is optionally substituted with one or more radicals seleceted from lower alkyl, halo, lower alkoxy, lower haloalkyl and lower dialkylamino; wherein each of R 1  through R 4  is independently selected from hydrido and halo; or wherein R 2  and R 3  together form —OCH 2 O—; and wherein R 7  is aminosulfonyl; or a pharmaceutically-acceptable salt thereof.  
     
     
         5 . Compound of  claim 4  wherein A is selected from phenyl, thienyl, furyl, pyrazolyl, pyrrolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, triazolyl and pyridyl, wherein A is optionally substituted with one or more radicals seleceted from methyl, ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, methylenedioxy, ethylenedioxy, fluoromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, dichloroethyl, dichlorofluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluoroethyl, difluoropropyl, dichloropropyl, N-ethyl-N-methylamino, N,N-dimethylamino and N,N-diethylamino; wherein each of R 1  through R 4  is independently selected from hydrido, fluoro, chloro and bromo; or wherein R 2  and R 3  together form —OCH 2 O—; wherein R 5 , R 6 , R 8  and R 9  are hydrido; and wherein R 7  is aminosulfonyl; or a pharmaceutically-acceptable salt thereof.  
     
     
         6 . Compound of  claim 5  selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 
 4-[2-(4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-fluoro-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-fluoro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,4-difluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-chlorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,4-dichlorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-trifluoromethylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-fluoro-4-trifluoromethylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-trifluoromethylphenyl)phenyl]benzenesulfonamide;  
 4-[2-[4-(N,N-dimethylamino)phenyl]phenyl]benzenesulfonamide;  
 4-[2-[3-fluoro-4-(N,N-dimethylamino)phenyl]phenyl]benzenesulfonamide;  
 4-[2-[3-chloro-4-(N,N-dimethylamino)phenyl]phenyl]benzenesulfonamide;  
 4-[6-(4-fluorophenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-(3,4-difluorophenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-(3-chloro-4-fluorophenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-[4-(N,N-dimethylamino)phenyl]-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-[4-(N,N-dimethylamino)-3-fluorophenyl]-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-[3-chloro-4-(N,N-dimethylamino)phenyl]-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-(3,5-difluoro-4-methylphenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-(3,5-dichloro-4-methylphenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-(3,5-difluoro-4-methoxyphenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[6-(3,5-dichloro-4-methoxyphenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3-fluoro-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4-difluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-fluoro-3-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-chlorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3-methylphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3-fluorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(3,4-dichlorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3-methoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-methoxy-3-methylphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4-dimethoxyphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-[4-(N,N-dimethylamino)phenyl]phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-[4-(N,N-dimethylamino)-3-methylphenyl]phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-[4-(N,N-dimethylamino)-3-fluorophenyl]phenyl]benzenesulfonamide;  
 4-[2-[3-chloro-4-(N,N-dimethylamino)phenyl]-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-[4-(N,N-dimethylamino)-3-methoxyphenyl]phenyl]benzenesulfonamide;  
 4-[2-(1,3-benzodioxol-5-yl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(5-methylpyridin-2-yl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(6-methylpyridin-3-yl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4,5-trimethylphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4-dimethylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,5-difluoro-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,5-dichloro-4-methylphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,5-dimethoxy-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,5-dimethyl-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,5-difluoro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4,5-trimethoxyphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,5-dimethyl-4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4,5-trifluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,5-dichloro-4-fluorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,5-dimethoxy-4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3,5-dimethylphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3,5-difluorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4,5-trichlorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-chloro-3,5-dimethoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-[3,5-dimethyl-4-(N,N-dimethylamino)phenyl]phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-[3,5-difluoro-4-(N,N-dimethylamino)phenyl]phenyl]benzenesulfonamide;  
 4-[2-[3,5-dichloro-4-(N,N-dimethylamino)phenyl]-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3-fluoro-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3-chloro-4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(4-methoxy-3-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3-fluoro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3-chloro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3,4-dimethoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(4-fluoro-3-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3,4-difluorophenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(3-chloro-4-fluorophenyl)phenyl]benzenesulfonamide; and  
 4-[2,3,4,5-tetrafluoro-6-(4-fluoro-3-methoxyphenyl)phenyl]benzenesulfonamide.  
 
     
     
         7 . Compound of  claim 5  selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 4-[4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl]benzenesulfonamide; 
 4-[2-(4-chloro-3-methylphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4-dimethylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-methoxy-3-methylphenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3,4-dimethoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(5-methylpyridin-2-yl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(6-methylpyridin-3-yl)phenyl]benzenesulfonamide;  
 4-[2-(3-Chloro-4-fluorophenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-chlorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-fluoro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[2-(4-trifluoromethylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2,3,4,5-tetrafluoro-6-(4-fluorophenyl)phenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl]benzenesulfonamide;  
 4-[6-(4-fluorophenyl)-1,3-benzodioxol-5-yl]benzenesulfonamide;  
 4-[4,5-difluoro-2-(4-methylphenyl)phenyl]benzenesulfonamide;  
 4-[2-(1,3-benzodioxol-5-yl)-4,5-difluorophenyl]benzenesulfonamide;  
 4-[2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl]benzenesulfonamide; and  
 4-[2-[3-chloro-4-(N,N-dimethylamino)phenyl]-4,5-difluorophenyl]benzenesulfonamide.  
 
     
     
         8 . Compound of  claim 5  where the compound is 4-[4,5-difluoro-2-(3-chloro-4-fluorophenyl)phenyl]benzenesulfonamide, or a pharmaceutically-acceptable salt thereof.  
     
     
         9 . Compound of  claim 5  where the compound is 4-[2-(3-chloro-4-methoxyphenyl)phenyl]benzenesulfonamide, or a pharmaceutically-acceptable salt thereof.  
     
     
         10 . Compound of  claim 3  wherein A is selected from phenyl, naphthyl, 5-membered heteroaryl and 6-membered heteroaryl, wherein A is optionally substituted with one or more radicals seleceted from lower alkyl, halo, lower alkoxy, lower haloalkyl and lower dialkylamino; wherein each of R 1  through R 4  is independently selected from hydrido and halo; or wherein R 2  and R 3  together form —OCH 2 O—; and wherein R 7  is lower alkylsulfonyl; or a pharmaceutically-acceptable salt thereof.  
     
     
         11 . Compound of  claim 10  wherein A is selected from phenyl, thienyl, furyl, pyrazolyl, pyrrolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, triazolyl and pyridyl, wherein A is optionally substituted with one or more radicals seleceted from methyl, ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, methylenedioxy, ethylenedioxy, fluoromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, dichloroethyl, dichlorofluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluoroethyl, difluoropropyl, dichloropropyl, N-ethyl-N-methylamino, N,N-dimethylamino and N,N-diethylamino; wherein each of R 1  through R 4  is independently selected from hydrido, fluoro, chloro and bromo; or wherein R 2  and R 3  together form —OCH 2 O—; wherein R 5 , R 6 , R 8  and R 9  are hydrido; and wherein R 7  is methylsulfonyl; or a pharmaceutically-acceptable salt thereof.  
     
     
         12 . Compound of  claim 11  selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 1,2-difluoro-4-(4-fluoro-3-methylphenyl)-5-[4-(methylsulfonyl)phenyl]benzene; 
 4-(4-chloro-3-methylphenyl)-1,2-difluoro-5-[4-(methylsulfonyl)phenyl]benzene;  
 1,2-difluoro-4-(3,4-dimethylphenyl)-5-[4-(methylsulfonyl)phenyl]benzene;  
 1,2-difluoro-4-(4-methoxy-3-methylpheny)-5-[4-(methylsulfonyl)phenyl]benzene;  
 1,2-difluoro-4-(3,4-dimethoxypheny)-5-[4-(methylsulfonyl)phenyl]benzene;  
 6-[4,5-difluoro-2-[4-(methylsulfonyl)phenyl]-2,3-dihydro-1,4-benzodioxin;  
 1,2-dichloro-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]benzene;  
 2-[4,5-difluoro-4′-(methylsulfonyl)-(1,1′-biphenyl)-2-yl]-5-methylpyridine;  
 5-[4,5-difluoro-4′-(methylsulfonyl)-(1,1′-biphenyl)-2-yl]-2-methylpyridine;  
 1-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]benzene;  
 1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl]benzene;  
 2-chloro-1-methoxy-4-[2-[4-(methylsulfonyl)phenyl]phenyl]benzene;  
 2-fluoro-1-methoxy-4-[2-[4-(methylsulfonyl)phenyl]phenyl]benzene;  
 2-chloro-1-fluoro-4-[2-[4-(methylsulfonyl)phenyl]phenyl]benzene;  
 5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-1,3-benzodioxole;  
 1,2-difluoro-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]benzene;  
 1,2-difluoro-4-(4-methylphenyl)-5-[4-(methylsulfonyl)phenyl]benzene;  
 1-(3-chloro-4-methoxyphenyl)-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene;  
 1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-[4-(methylsulfonyl)phenyl]benzene;  
 1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene;  
 1-(3,5-dichloro-4-methoxyphenyl)-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene;  
 1-(3,5-difluoro-4-methoxyphenyl)-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene;  
 5-[4,5-difluoro-2-[4-(methylsulfonyl)phenyl]phenyl]-1,3-benzodioxole;  
 1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene; and  
 2-chloro-4-[4,5-difluoro-2-[4-(methylsulfonyl)phenyl]phenyl]-N,N-dimethylbenzeneamine.  
 
     
     
         13 . A compound of Formula II  
       
         
           
           
               
               
           
         
         wherein A is selected from  
         
           
             
             
                 
                 
             
           
         
         wherein each of R 2  and R 3  is independently selected from hydrido and halo; or wherein R 2  and R 3  together form —OCH 2 O—; wherein each of R 10  through R 14  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, lower haloalkyl, and lower dialkylamino; or wherein R 11  and R 12  together form —O(CH 2 ) n O—; wherein n is 1-2, inclusive; and wherein R 7  is selected from lower alkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof.  
       
     
     
         14 . A compound of Formula III  
       
         
           
           
               
               
           
         
         wherein each of R 11  through R 13  is independently selected from hydrido, halo, lower alkoxy, lower haloalkyl, amino, lower alkylamino, lower dialkylamino, and lower haloalkoxy; or wherein R 11  and R 12  together form —O(CH 2 ) n O—; wherein n is 1-2, inclusive; or a pharmaceutically-acceptable salt thereof.  
       
     
     
         15 . A compound of Formula IV  
       
         
           
           
               
               
           
         
         wherein Y is CR 11  or N; wherein Z is CR 10  or N; wherein each of R 10  through R 12  is independently selected from hydrido and lower alkyl; wherein R 7  is aminosulfonyl or methylsulfonyl; provided one of Y and Z is N; 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 1;  or a pharmaceutically-acceptable salt thereof.  
     
     
         17 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 2;  or a pharmaceutically-acceptable salt thereof.  
     
     
         18 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 3;  or a pharmaceutically-acceptable salt thereof.  
     
     
         19 . 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.  
     
     
         20 . 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.  
     
     
         21 . 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.  
     
     
         22 . 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.  
     
     
         23 . 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.  
     
     
         24 . 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.  
     
     
         25 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 10;  or a pharmaceutically-acceptable salt thereof.  
     
     
         26 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 11;  or a pharmaceutically-acceptable salt thereof.  
     
     
         27 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 12;  or a pharmaceutically-acceptable salt thereof.  
     
     
         28 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 13;  or a pharmaceutically-acceptable salt thereof.  
     
     
         29 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 14;  or a pharmaceutically-acceptable salt thereof.  
     
     
         30 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of  claim 15;  or a pharmaceutically-acceptable salt thereof.  
     
     
         31 . 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.  
     
     
         32 . 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 2;  or a pharmaceutically-acceptable salt thereof.  
     
     
         33 . 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 3;  or a pharmaceutically-acceptable salt thereof.  
     
     
         34 . 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.  
     
     
         35 . 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.  
     
     
         36 . 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.  
     
     
         37 . 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.  
     
     
         38 . 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.  
     
     
         39 . 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.  
     
     
         40 . 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 10;  or a pharmaceutically-acceptable salt thereof.  
     
     
         41 . 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 11;  or a pharmaceutically-acceptable salt thereof.  
     
     
         42 . 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 12;  or a pharmaceutically-acceptable salt thereof.  
     
     
         43 . 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 13;  or a pharmaceutically-acceptable salt thereof.  
     
     
         44 . 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 14;  or a pharmaceutically-acceptable salt thereof.  
     
     
         45 . 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 15;  or a pharmaceutically-acceptable salt thereof.  
     
     
         46 . The method of  claim 31  for use in treatment of inflammation.  
     
     
         47 . The method of  claim 31  for use in treatment of an inflammation-associated disorder.  
     
     
         48 . The method of  claim 47  wherein the inflammation-associated disorder is arthritis.  
     
     
         49 . The method of  claim 47  wherein the inflammation-associated disorder is pain.  
     
     
         50 . The method of  claim 47  wherein the inflammation-associated disorder is fever.