Benzenesulfonamide compounds and their use as therapeutic agents

Abstract

This invention is directed to benzenesulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy and/or epileptic seizure disorders.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         A is a direct bond or —(CH 2 ) m —C(R 4 )(R 5 )—(CH 2 ) n — where m and n are independently 0, 1, 2, 3 or 4; 
         q is 1, 2 or 3; 
         R 1  is an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted monocyclic heteroaryl or an optionally substituted bicyclic heteroaryl; 
         R 2  is an optionally substituted 5-membered N-heteroaryl or an optionally substituted 6-membered N-heteroaryl; 
         R 3  is —O—, —N(R 8 )— or —S(O) t — (where t is 0, 1 or 2); 
         R 4  and R 5  are each independently hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl, —R 9 —OR 10  or —R 9 —N(R 10 )R 11 ; 
         or R 4  and R 5 , together with the carbon to which they are attached, form an optionally substituted cycloalkyl or an optionally substituted heterocyclyl; 
         each R 6  is independently hydrogen, alkyl, halo, haloalkyl, cyano or —OR 12 ; 
         R 7  is alkyl, alkenyl, halo, haloalkyl, cyano or —OR 12 ; 
         each R 8 , R 10 , R 11  and R 12  is independently hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl; and 
         each R 9  is independently a direct bond or an optionally substituted straight or branched alkylene chain; 
         as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof; 
         or a pharmaceutically acceptable salt, solvate or prodrug thereof; 
         provided that: 
         (a) when A is a direct bond, R 1  is not optionally substituted cycloalkyl; 
         (b) when A is a direct bond and R 3  is —O— or —S(O) t — (where t is 0, 1 or 2), R 1  is not optionally substituted phenyl; 
         (c) when A is a direct bond and R 3  is —N(R 8 )—, R 1  is not optionally substituted phenyl or optionally substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazolyl; 
         (d) when A is —(CH 2 ) m —C(R 4 )(R 5 )—(CH 2 ) n —, where m and n are both 0 and R 4  and R 5  are both hydrogen, and R 3  is —O—, R 2  is not optionally substituted thiadiazolyl; and 
         (e) when A is direct bond and R 3  is —N(R 8 )—, R 1  is not an optionally substituted monocyclic heteroaryl. 
       
     
     
         2 . The compound of  claim 1  wherein R 3  is —O—, wherein the compound has the following formula (Ia): 
       
         
           
           
               
               
           
         
         wherein q, A, R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11  and R 12  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         3 . The compound of  claim 2  wherein A is a direct bond, wherein the compound has the following formula (Ia1): 
       
         
           
           
               
               
           
         
         wherein q, R 1 , R 2 , R 6  and R 7  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         4 . The compound of  claim 3  which is 5-chloro-2-fluoro-N-(thiazol-4-yl)-4-(4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yloxy)benzenesulfonamide. 
     
     
         5 . The compound of  claim 2  wherein A is —(CH 2 ) m —C(R 4 )(R 5 )—(CH 2 ) n —, wherein the compound has the following formula (Ia2): 
       
         
           
           
               
               
           
         
         wherein m, n, R 1 , R 2 , R 4 , R 5 , R 6  and R 7  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         6 . The compound of  claim 5  selected from:
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)oxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-3-chloro-4-(1-phenylethoxy)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 (S)-3-chloro-4-(1-phenylethoxy)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 (S)-3-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(isoquinolin-8-ylmethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-2,5-difluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-N-(thiazol-2-yl)-4-(2,2,2-trifluoro-1-phenylethoxy)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(5-chloro-2-fluorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(3,4-dichlorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(3-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-phenylethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(2-chlorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(3-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(2,6-difluorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(2,6-difluorophenyl)ethoxy)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((2-fluorobenzyl)oxy)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(2-chlorophenyl)ethoxy)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(5-chloro-2-fluorophenyl)ethoxy)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)oxy)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-2,6-difluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(1-phenylcyclopropoxy)-N-(thiazol-4-yl)benzenesulfonamide; and 
 (S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)propoxy)-N-(thiazol-4-yl)benzenesulfonamide. 
 
     
     
         7 . The compound of  claim 1  wherein R 3  is —N(R 8 )—, wherein the compound has the following formula (Ib): 
       
         
           
           
               
               
           
         
         wherein q, A, R 1 , R 2 , R 6 , R 7  and R 8  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         8 . The compound of  claim 7  wherein A is a direct bond, wherein the compound has the following formula (Ib1): 
       
         
           
           
               
               
           
         
         wherein q, R 1 , R 2 , R 6 , R 7  and R 8  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         9 . The compound of  claim 8  selected from:
 5-chloro-2-fluoro-4-((1-(pyridin-3-yl)propan-2-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-3-chloro-4-(2,3-dihydro-1H-inden-1-ylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 (S)-3-chloro-4-(2,3-dihydro-1H-inden-1-ylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1,2,3,4-tetrahydronaphthalen-1-ylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-(1,2,3,4-tetrahydronaphthalen-1-ylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-3-chloro-4-((5,6,7,8-tetrahydroquinolin-8-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((5,6,7,8-tetrahydroisoquinolin-8-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 5-chloro-2-fluoro-4-((5,6,7,8-tetrahydroisoquinolin-5-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 5-chloro-2-fluoro-4-((5,6,7,8-tetrahydroquinolin-5-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide formic acid salt 
 4-(((1R,3S)-3-(azetidin-1-yl)-2,3-dihydro-1H-inden-1-yl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-(((1R,3S)-3-(azetidin-1-yl)-2,3-dihydro-1H-inden-1-yl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; and 
 4-(((1S,3S)-3-(azetidin-1-yl)-2,3-dihydro-1H-inden-1-yl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide formate. 
 
     
     
         10 . The compound of  claim 7  wherein A is —(CH 2 ) m —C(R 4 )(R 5 )—(CH 2 ) n —, wherein the compound has the following formula (Ib2): 
       
         
           
           
               
               
           
         
         wherein m, n, R 1 , R 2 , R 4 , R 5 , R 6 , R 7  and R 8  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         11 . The compound of  claim 10  wherein R 2  is an optionally substituted 5-membered N-heteroaryl. 
     
     
         12 . The compound of  claim 11  wherein R 2  is selected from optionally substituted thiazolyl, optionally substituted thiadiazolyl, optionally substituted isoxazolyl, optionally substituted isothiazolyl or optionally substituted oxazolyl. 
     
     
         13 . The compound of  claim 12  wherein:
 R 1  is optionally substituted cycloalkyl; 
 or R 1  is aryl optionally substituted by one or more substituents selected from halo, alkyl, haloalkyl, optionally substituted cycloalkyl, cyano, —R 9 —OR 12 , —R 9 —N(R 10 )R 11 , —R 9 —N(R 10 )—R 13 —OR 12 , optionally substituted heterocyclyl and optionally substituted heteroaryl; 
 R 2  is optionally substituted thiazolyl; and 
 R 13  is a branched or straight alkylene chain. 
 
     
     
         14 . The compound of  claim 13  selected from:
 (S)-5-chloro-4-((1-cyclohexylethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 3-chloro-4-(1-phenylpropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(1-phenylpropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-phenylpropylamino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-(1-phenylpropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-phenylpropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-4-(2-(dimethylamino)-1-phenylethylamino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-(1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(1-phenylcyclopropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-N-(thiazol-2-yl)-4-(3,3,3-trifluoro-1-phenylpropylamino)benzenesulfonamide; 
 (S)-5-bromo-2-fluoro-4-(1-phenylpropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-4-(1-(2-chlorophenyl)ethylamino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)propylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 3-chloro-4-(cyclopropyl(phenyl)methylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 3-chloro-4-(methyl(1-phenylpropyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-(4-fluorophenyl)ethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(2-morpholino-1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-2-fluoro-5-methyl-4-(1-phenylpropylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-3-chloro-4-(1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(1-(5,6,7,8-tetrahydronaphthalen-2-yl)propylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-3-chloro-4-(2-hydroxy-1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-N-(thiazol-2-yl)-4-(1-o-tolylpropylamino)benzenesulfonamide; 
 (R)-4-(2-(azetidin-1-yl)-1-phenylethylamino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-(1-(2-chlorophenyl)ethylamino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(1-phenylcyclobutylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(3-methyl-1-phenylbutylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(2-methoxy-1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-(2-methoxy-1-phenylethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 3-chloro-4-(1-phenylcyclobutylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-(1-phenylethylamino)-N-(thiazol-4-yl)benzenesulfonamide; 
 3-chloro-4-(3-phenyloxetan-3-ylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(naphthalen-1-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-N-(thiazol-2-yl)-4-((1-(3-(trifluoromethyl)phenyl)ethyl)amino)benzenesulfonamide; 
 (R)-3-chloro-N-(thiazol-2-yl)-4-((2,2,2-trifluoro-1-phenylethyl)amino)benzenesulfonamide formic acid salt; 
 (S)-5-chloro-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(3-chloro-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(3-bromophenyl)ethyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-3-chloro-2-fluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(4-chlorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(naphthalen-2-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-4-((2-cyanobenzyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-phenylcyclobutyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-phenylcyclopropyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-3,5-dichloro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-3-chloro-4-((1-phenylethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-2,5-difluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-2,6-difluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(4-fluorophenyl)cyclopropyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(3-fluorophenyl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(3-chlorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(3,5-dichlorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2,4-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(3,4-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((2-(dimethylamino)-1-phenylethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 (R)-5-chloro-4-((2-(dimethylamino)-1-phenylethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 (S)-4-((2-(azetidin-1-yl)-1-phenylethyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 (S)-5-chloro-4-((2-(3-fluoroazetidin-1-yl)-1-phenylethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 (S)-5-chloro-4-((2-(3,3-difluoroazetidin-1-yl)-1-phenylethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-((1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((2-morpholino-1-phenylethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 (S)-3-chloro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-chlorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((cyclopropyl(phenyl)methyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(3-fluorophenyl)cyclobutyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(2-fluorophenyl)cyclobutyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((3-methyl-1-phenylbutyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-((3-methyl-1-phenylbutyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-phenylbutyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-((dimethylamino)methyl)phenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-4-((1-(2-((dimethylamino)methyl)phenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 4-((2-((tert-butyl(methyl)amino)methyl)benzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-2,6-difluoro-4-((2-fluoro-6-(1-hydroxyethyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((tert-butyl(methyl)amino)methyl)-6-fluorobenzyl)amino)-2,3-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((methyl(tert-pentyl)amino)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(((cyclopropylmethyl)(methyl)amino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((tert-butylamino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((cyclobutylamino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((isobutyl(methyl)amino)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-(2-methylpyridin-4-yl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((cyclobutyl(methyl)amino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((tert-butyl(methyl)amino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((methyl(oxetan-3-yl)amino) methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((isopropyl(methyl)amino)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((1-methylazetidin-3-yl)oxy)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((diethylamino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((methyl((3-methyloxetan-3-yl)methyl)amino)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-(((2-methoxyethyl)(methyl)amino)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((dimethylamino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((2-fluoro-6-(methoxymethyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-(oxetan-3-ylmethoxy)phenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((1-(2-((dimethylamino)methyl)phenyl)cyclopropyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(5-(2,2-difluoroethyl)-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-((3-methyloxetan-3-yl)methoxy)phenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-3-cyano-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-2,6-difluoro-4-((1-(2-fluoro-5-methoxyphenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(5-cyano-2-fluorophenyl)ethyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((dimethylamino)methyl)benzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(2,5-difluorophenyl)ethyl)amino)-2,6-difluoro-N-(isoxazol-3-yl)benzenesulfonamide; 
 (S)-4-((1-(5-(difluoromethyl)-2-fluorophenyl)ethyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((1-phenylcyclopropyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-5-chloro-4-((1-(3-((dimethylamino)methyl)phenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-hydroxyphenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-(oxetan-3-yloxy)phenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-2,6-difluoro-4-((1-(2-fluoro-5-(methoxymethyl)phenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((2,5-difluorobenzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-(methoxymethyl)phenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-5-chloro-4-((1-(2,5-difluorophenyl)-2,2-difluoroethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((3,6-difluoro-2-(hydroxymethyl)benzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((2-chloro-6-methylbenzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((2-((dimethylamino)methyl)-6-fluorobenzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(5-cyano-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(3-((dimethylamino)methyl)phenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(5-(difluoromethoxy)-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-3-chloro-4-((1-(2,6-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((5-fluoro-2-methylbenzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-methoxyphenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(2,5-difluorophenyl)ethyl)amino)-5-ethyl-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((1-(2,5-difluorophenyl)cyclopropyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(2,5-difluorophenyl)ethyl)amino)-N-(thiazol-4-yl)-3-(trifluoromethyl)benzenesulfonamide; 
 (S)-3-chloro-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-fluorophenyl)ethyl)amino)-2-methyl-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-N-(thiazol-4-yl)-4-((1-(2,4,5-trifluorophenyl)ethyl)amino)benzenesulfonamide; 
 (S)-2,6-difluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((1-(2,4-difluorophenyl)cyclopropyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(5-cyclopropyl-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-N-(thiazol-2-yl)-4-((2,2,2-trifluoro-1-(2-fluorophenyl)ethyl)amino)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(3,5-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-chlorophenyl)propyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(2-fluorophenyl)cyclopropyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2,5-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2,5-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-N-(5-chlorothiazol-2-yl)-2-fluoro-4-((1-(2-fluorophenyl)ethyl)amino)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(5-fluorothiazol-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-N-(5-fluorothiazol-2-yl)-4-((1-phenylpropyl)amino)benzenesulfonamide; 
 (S)-3-chloro-4-((1-(2-chloro-6-fluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; and 
 (S)-5-chloro-4-((1-(2,5-difluorophenyl)ethyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide. 
 
     
     
         15 . The compound of  claim 12  wherein:
 R 1  is aryl substituted with optionally substituted heterocyclylalkyl and optionally substituted by one or more substituents selected from halo, alkyl, haloalkyl, optionally substituted cycloalkyl, cyano, —R 9 —OR 12 , —R 9 —N(R 10 )R 11 , —R 9 —N(R 10 )—R 13 —OR 12 , optionally substituted heterocyclyl and optionally substituted heteroaryl; 
 R 2  is optionally substituted thiazolyl; and 
 R 13  is a branched or straight alkylene chain. 
 
     
     
         16 . The compound of  claim 13  selected from:
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 5-chloro-4-((2-((2,2-dimethylazetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2-azaspiro[3.3]heptan-2-yl)methyl)-6-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-chloro-6-((3-fluoroazetidin-1-yl)methyl)benzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2-fluoro-4-((2-fluoro-6-((3-fluoroazetidin-1-yl)methyl)benzyl)amino)-3-methyl-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-4-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 3-chloro-2-fluoro-4-((2-fluoro-6-((3-fluoroazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2-fluoro-4-((2-fluoro-6-((3-fluoroazetidin-1-yl)methyl)benzyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide; and 
 4-((2-((3-ethoxy-3-methylazetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((2-(1-(azetidin-1-yl)ethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-4-((2-(1-(azetidin-1-yl)ethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,3-difluoro-6-methyl-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)amino)-2,3,6-trifluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-chloro-6-((2,2-dimethylazetidin-1-yl)methyl)benzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2,2-dimethylazetidin-1-yl)methyl)-3-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((3-azabicyclo[3.1.0]hexan-3-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-((3-(2-methoxypropan-2-yl)azetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((1-azaspiro[3.3]heptan-1-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)amino)-2,3-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(2-(3,3-difluoroazetidin-1-yl)ethyl)benzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-methoxy-3-methylazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((5-azaspiro[2.3]hexan-5-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-(2-(3-fluoroazetidin-1-yl)ethyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2,2-dimethylazetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2-fluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((3-(difluoromethyl)azetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-fluoro-3-methylazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2,2-dimethylazetidin-1-yl)methyl)benzyl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-chloro-3-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-cyclopropylbenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-hydroxy-3-methylazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-ethylbenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-methylbenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2-fluoro-N-(thiazol-4-yl)-5-vinylbenzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-(pyrrolidin-1-ylmethyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-2,6-difluoro-4-((2-fluoro-6-((2-(methoxymethyl)pyrrolidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((1-oxa-6-azaspiro[3.4]octan-6-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((1-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((6-oxa-1-azaspiro[3.3]heptan-1-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-2,6-difluoro-4-((2-fluoro-6-((2-methylpyrrolidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((6-azaspiro[3.4]octan-6-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((1,1-difluoro-5-azaspiro[2.3]hexan-5-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (R)-2,6-difluoro-4-((2-fluoro-6-((3-fluoropyrrolidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-2,6-difluoro-4-((2-fluoro-6-((3-fluoropyrrolidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-methoxyazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-methylazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((3,3-dimethylazetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((4-methylpiperazin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((2-fluoro-5-(2-(3-fluoroazetidin-1-yl)ethyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3-fluorobenzyl)amino)-3-chloro-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((5-(2-(azetidin-1-yl)ethyl)-2-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-methoxybenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((5-(azetidin-1-ylmethyl)-2-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(2-(azetidin-1-yl)ethyl)benzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(5-(azetidin-1-ylmethyl)-2-fluorophenyl)ethyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-(piperidin-1-ylmethyl)phenyl)ethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 (S)-4-((1-(5-(2-(azetidin-1-yl)ethyl)-2-fluorophenyl)ethyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2-azaspiro[3.3]heptan-2-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,5-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-3-chloro-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2,2-dimethylazetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((2-((4,4-difluoropiperidin-1-yl)methyl)-6-fluorobenzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3,6-difluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)(methyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-4-((2-chloro-6-((6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl)benzyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2,6-diazaspiro[3.3]heptan-2-yl)methyl)-6-chlorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((2-fluoro-6-(morpholinomethyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-chlorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-fluoroazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((2-fluoro-6-((3-methoxyazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-6-chlorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-4,5-difluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-3-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((2-fluoro-6-((3-fluoroazetidin-1-yl)methyl)benzyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-chloro-3-fluorobenzyl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide 2,2,2-trifluoroacetate; and 
 4-((2-((3,3-dimethylazetidin-1-yl)methyl)-6-fluorobenzyl)amino)-2,3-difluoro-6-methyl-N-(thiazol-4-yl)benzenesulfonamide 2,2,2-trifluoroacetate. 
 
     
     
         17 . The compound of  claim 12  wherein:
 R 1  is aryl optionally substituted by one or more substituents selected from halo, alkyl, haloalkyl, optionally substituted cycloalkyl, cyano, —R 9 —OR 12 , —R 9 —N(R 10 )R 11 , —R 9 —N(R 10 )—R 13 —OR 12 , optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl and optionally substituted heteroaryl; 
 R 2  is optionally substituted thiadiazolyl, optionally substituted isothiazolyl, optionally substituted oxazolyl, optionally substituted isoxazolyl; and 
 R 13  is a branched or straight alkylene chain. 
 
     
     
         18 . The compound of  claim 17  selected from:
 3-chloro-4-(1-phenylpropylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 (R)-3-chloro-4-(1-phenylpropylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 (S)-3-chloro-4-(1-phenylpropylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 3-chloro-4-(1-phenylethylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 2,5-difluoro-4-(1-phenylpropylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 4-(benzylamino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 3-chloro-4-(2-phenylpropylamino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((3-fluoro-3-methylazetidin-1-yl)methyl)benzyl)amino)-N-(isoxazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2-fluoro-N-(isoxazol-3-yl)-5-methylbenzenesulfonamide; 
 2,6-difluoro-4-((2-fluoro-6-((isopropyl(methyl)amino)methyl)benzyl)amino)-N-(isoxazol-3-yl)benzenesulfonamide; 
 2,3-difluoro-4-((2-fluoro-6-(pyrrolidin-1-ylmethyl)benzyl)amino)-N-(isoxazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(isothiazol-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)amino)-2,6-difluoro-N-(5-methylisoxazol-3-yl)benzenesulfonamide; 
 4-((2-((tert-butyl(methyl)amino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(isothiazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(isothiazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,6-difluoro-3-methyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-3-chloro-2,6-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(isoxazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,6-difluoro-N-(isoxazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-5-chloro-2-fluoro-N-(isoxazol-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(isoxazol-3-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2,5-difluorophenyl)ethyl)amino)-2-fluoro-N-(oxazol-2-yl)benzenesulfonamide; and 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2-fluoro-N-(isoxazol-3-yl)-3-methylbenzenesulfonamide 2,2,2-trifluoroacetate. 
 
     
     
         19 . The compound of  claim 10  wherein:
 R 1  is an optionally substituted aryl; and 
 R 2  is an optionally substituted 6-membered N-heteroaryl. 
 
     
     
         20 . The compound of  claim 19  wherein R 2  is selected from optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyridazinyl and optionally substituted pyrazinyl. 
     
     
         21 . The compound of  claim 20  selected from:
 5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)-4-(1-phenylpropylamino)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluorophenyl)ethyl)amino)-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-chlorophenyl)ethyl)amino)-2-fluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)-4-((1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)benzenesulfonamide 2,2,2-trifluoroacetate; 
 4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)amino)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(pyridazin-3-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,6-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,6-difluoro-3-methyl-N-(pyrimidin-4-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2-fluoro-N-(6-fluoropyridin-2-yl)-5-methylbenzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(pyridin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-2,6-difluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)-6-fluorobenzyl)amino)-5-chloro-2-fluoro-N-(pyridazin-3-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-chlorophenyl)ethyl)amino)-2-fluoro-N-(2-(trifluoromethyl)pyrimidin-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-chlorophenyl)ethyl)amino)-2-fluoro-N-(6-methylpyrimidin-4-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2-fluoro-N-(pyrazin-2-yl)benzenesulfonamide; 
 (R)-5-chloro-4-((1-(5-chloro-2-fluorophenyl)-2,2,2-trifluoroethyl)amino)-2-fluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 (S)-4-((1-(2,5-difluorophenyl)ethyl)amino)-2,6-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 (S)-4-((1-(2-chloro-5-fluorophenyl)propyl)amino)-2,6-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 (S)-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2,6-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(2-fluorophenyl)cyclopropyl)amino)-N-(pyrimidin-4-yl)benzenesulfonamide; 
 5-chloro-4-((1-(2,5-difluorophenyl)cyclopropyl)amino)-2-fluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 (S)-3-chloro-4-((1-(2-chlorophenyl)ethyl)amino)-2-fluoro-N-(pyrimidin-4-yl)benzenesulfonamide; 
 (S)-4-((1-(5-chloro-2-fluorophenyl)ethyl)amino)-2-fluoro-5-methyl-N-(pyrimidin-4-yl)benzenesulfonamide; 
 (S)-4-((1-(2,5-difluorophenyl)ethyl)amino)-N-(pyrimidin-4-yl)-3-(trifluoromethyl)benzenesulfonamide; 
 4-((2-(azetidin-1-ylmethyl)benzyl)amino)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; 
 (S)-5-chloro-4-((1-(2-chlorophenyl)propyl)amino)-2-fluoro-N-(pyrimidin-4-yl)benzenesulfonamide; and 
 (S)-5-chloro-2-fluoro-4-((1-(2-fluorophenyl)propyl)amino)-N-(6-fluoropyridin-2-yl)benzenesulfonamide. 
 
     
     
         22 . The compound of  claim 10  wherein R 1  is an optionally substituted monocyclic heteroaryl or an optionally substituted bicyclic heteroaryl. 
     
     
         23 . The compound of  claim 22  selected from:
 5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)-4-((isoquinolin-8-ylmethyl)amino)benzenesulfonamide; 
 (S)-5-chloro-2-fluoro-4-((1-(isoquinolin-8-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (R)-5-chloro-2-fluoro-4-((1-(isoquinolin-8-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-(isoquinolin-8-ylmethylamino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(pyridin-3-yl)propan-2-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(pyridin-3-yl)propyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((1-(pyridin-4-yl)propyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 3-chloro-4-((1-(pyridin-2-yl)propyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 (S)-3-chloro-4-((1-(pyridin-2-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 3-chloro-4-((1-(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide; 
 5-chloro-2-fluoro-4-((isoquinolin-8-ylmethyl)amino)-N-(thiazol-4-yl)benzenesulfonamide 2,2,2-trifluoroacetate; 
 (R)-5-chloro-2-fluoro-4-((1-(pyridin-3-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide formic acid salt; 
 5-chloro-2-fluoro-4-(((6-fluoro-1H-indol-7-yl)methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide; and 
 5-chloro-2-fluoro-4-(((6-fluoro-1H-indazol-7-yl)methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide. 
 
     
     
         24 . The compound of  claim 1  wherein R 3  is —S(O) t — (where t is 0, 1 or 2), wherein the compound has the following formula (Ic): 
       
         
           
           
               
               
           
         
         wherein q, t, A, R 1 , R 2 , R 6  and R 7  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         25 . The compound of  claim 24  wherein A is a direct bond, wherein the compound has the following formula (Ic1): 
       
         
           
           
               
               
           
         
         wherein q, t, R 1 , R 2 , R 6  and R 7  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         26 . The compound of  claim 24  wherein A is —(CH 2 ) m —C(R 4 )(R 5 )—(CH 2 ) n —, wherein the compound has the following formula (Ic2): 
       
         
           
           
               
               
           
         
         wherein m, n, t, R 1 , R 2 , R 4 , R 5 , R 6  and R 7  are each as defined above in  claim 1 ; as an individual stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
       
     
     
         27 . The compound of  claim 26  which is (S)-5-chloro-2-fluoro-4-((1-phenylethyl)thio)-N-(thiazol-2-yl)benzenesulfonamide. 
     
     
         28 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of  claim 1 , as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         29 . A method of treating a disease or a condition associated with Na V 1.6 activity in a mammal wherein the disease or condition is epilepsy and/or epileptic seizure disorder and wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of  claim 1 , as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         30 . A method of decreasing ion flux through Na V 1.6 in a mammalian cell, wherein the method comprises contacting the cell with a compound of  claim 1 , as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         31 . A method of selectively inhibiting a first voltage-gated sodium channel over a second voltage-gated sodium channel in a mammal, wherein the method comprises administering to the mammal a modulating amount of a compound of  claim 1 , as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         32 . The method of  claim 31  wherein the first voltage-gated sodium channel is Na V 1.6. 
     
     
         33 . The method of  claim 32  wherein the second voltage-gated sodium channel is Na V 1.5. 
     
     
         34 . The method of  claim 32  wherein the second voltage-gated sodium channel is Na V 1.1.