Benzenesulfonamide derivatives of quinoxaline, pharmaceutical compositions thereof, and their use in methods for treating cancer

Abstract

Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of using these chemical entities, e.g., for treatment of cancer are described.

What is claimed is: 
     
         1 . A compound of Formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 10  are independently hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, or optionally substituted alkynyl; 
         R 9  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
         R 11  is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         provided that when R 10  is fluoro, then R 7  is not hydrogen, or R 8  is not hydrogen, or R 6  is not hydrogen, lower alkyl or halo. 
       
     
     
         2 . The compound or pharmaceutically acceptable salt of  claim 1 , wherein R 1  is hydrogen, cyano, halo, hydroxy, carboxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, or optionally substituted alkynyl. 
     
     
         3 . The compound or pharmaceutically acceptable salt of  claim 2 , wherein R 1  is hydrogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amino, optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     
     
         4 . The compound or pharmaceutically acceptable salt of  claim 3 , wherein R 1  is optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     
     
         5 . The compound or pharmaceutically acceptable salt of  claim 4 , wherein R 1  is optionally substituted morpholinyl, optionally substituted piperazinyl, optionally substituted imidazolyl, optionally substituted pyrazolyl, or optionally substituted pyridyl. 
     
     
         6 . The compound or pharmaceutically acceptable salt of any one of  claims 1  to  5  wherein R 2 , R 3 , R 4 , and R 5  are independently hydrogen, halo, optionally substituted alkoxy, or optionally substituted alkyl. 
     
     
         7 . The compound or pharmaceutically acceptable salt of any one of  claims 1  to  6  wherein R 6 , R 7 , R 8 , and R 10  are independently hydrogen, cyano, halo, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, or optionally substituted aminosulfonyl. 
     
     
         8 . The compound or pharmaceutically acceptable salt of  claim 7 , wherein R 6 , R 7 , R 8 , and R 10  are independently hydrogen, cyano, or halo. 
     
     
         9 . The compound or pharmaceutically acceptable salt of  claim 8 , wherein R 7  is halo. 
     
     
         10 . The compound or pharmaceutically acceptable salt of  claim 9 , wherein R 7  is fluoro. 
     
     
         11 . The compound or pharmaceutically acceptable salt of any one of  claims 1  to  10 , wherein R 9  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         12 . The compound or pharmaceutically acceptable salt of  claim 11 , wherein R 9  is optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         13 . The compound or pharmaceutically acceptable salt of  claim 12 , wherein R 9  is optionally substituted lower alkyl. 
     
     
         14 . The compound or pharmaceutically acceptable salt of any one of  claims 1  to  13 , wherein R 11  is hydrogen, optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         15 . The compound or pharmaceutically acceptable salt of  claim 14 , wherein R 11  is hydrogen or optionally substituted lower alkyl. 
     
     
         16 . The compound or pharmaceutically acceptable salt of  claim 15 , wherein R 11  is hydrogen. 
     
     
         17 . A compound or pharmaceutically acceptable salt chosen from the group consisting of:
 N-(3,4-difluoro-5-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-methylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-methoxyquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-phenylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(4-chlorophenyl)quinoxaline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(4-fluorophenyl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-imidazol-1-yl)quinoxaline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2-chloro-4,5-difluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(4-fluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-fluoro-5-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(4-fluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(2-methoxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(2-oxopiperazin-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-pyrazol-4-yl)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)cyclopropanesulfonamide,   N-(2,4,5-trifluoro-3-(3-(3-oxopiperazin-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(diethylamino)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-fluoroquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(3-(hydroxymethyl)morpholino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   4-Methyl-N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2,5-difluoro-4-(methylthio)-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-chloroquinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(3-(3-((2-(dimethylamino)ethyl)(methyl)amino)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-3-(3-cyanoquinoxaline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(methylamino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-aminoquinoxaline-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-phenylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-3-(3-(4-chlorophenyl)quinoxaline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(4-fluorophenyl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-imidazol-1-yl)quinoxaline-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(2-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(5-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(4-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(pyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(6-methylpyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(pyridin-4-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(piperazin-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-((2-aminoethyl)amino)quinoxaline-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-((2-hydroxyethyl)amino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-((2-methoxyethyl)amino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(2-methoxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4,5-difluoro-3-(3-(2-hydroxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(2-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(5-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(4-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(pyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(6-methylpyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(3-(pyridin-4-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-phenylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(4-chlorophenyl)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(4-fluorophenyl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-imidazol-1-yl)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(2-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(5-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(4-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(pyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(6-methylpyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(pyridin-4-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-3-(3-cyanoquinoxaline-6-carbonyl)-4-fluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-phenylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-3-(3-(4-chlorophenyl)quinoxaline-6-carbonyl)-4-fluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(4-fluorophenyl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-imidazol-1-yl)quinoxaline-6-carbonyl)-2-chloro-4-fluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(2-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(5-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(4-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(pyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-pyrazol-4-yl)quinoxaline-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,   N-(3-(3-(1H-pyrazol-3-yl)quinoxaline-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,   N-(3-(3-(1H-pyrazol-3-yl)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(3-(3-aminoquinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(methylamino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(2-hydroxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-(2-methoxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-((2-methoxyethyl)amino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-((2-aminoethyl)amino)quinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,   N-(2,4,5-trifluoro-3-(3-((2-hydroxyethyl)amino)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(6-methylpyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(pyridin-4-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3,4-difluoro-5-(quinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(3,4-difluoro-5-(3-methylquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-4,5-difluorophenyl)benzene sulfonamide,   N-(3,4-difluoro-5-(3-methoxyquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(3,4-difluoro-5-(quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(3,4-difluoro-5-(3-methylquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzene sulfonamide,   N-(3,4-difluoro-5-(3-methoxyquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4,5-trifluoro-3-(quinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2,4,5-trifluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)benzene sulfonamide,   N-(2,4,5-trifluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   3-fluoro-N-(2,4,5-trifluoro-3-(quinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   3-fluoro-N-(2,4,5-trifluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzene sulfonamide,   3-Fluoro-N-(2,4,5-trifluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2-chloro-4-fluoro-3-(quinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2-chloro-3-(3-cyanoquinoxaline-6-carbonyl)-4-fluorophenyl)benzene sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2-chloro-4-fluoro-3-(quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2-chloro-3-(3-cyanoquinoxaline-6-carbonyl)-4-fluorophenyl)-3-fluorobenzene sulfonamide,   and pharmaceutically acceptable salts thereof.   
     
     
         18 . A compound of Formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 10  are independently hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, or optionally substituted alkynyl; 
         R 9  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
         R 11  is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
       
     
     
         19 . The compound or pharmaceutically acceptable salt of  claim 18 , wherein R 7  and R 8  are hydrogen. 
     
     
         20 . The compound or pharmaceutically acceptable salt of  claim 18 , wherein R 1  is hydrogen, cyano, halo, hydroxy, carboxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, or optionally substituted alkynyl. 
     
     
         21 . The compound or pharmaceutically acceptable salt of  claim 20 , wherein R 1  is hydrogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amino, optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     
     
         22 . The compound or pharmaceutically acceptable salt of  claim 21 , wherein R 1  is optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl. 
     
     
         23 . The compound or pharmaceutically acceptable salt of  claim 22 , wherein R 1  is optionally substituted morpholinyl, optionally substituted piperazinyl, optionally substituted imidazolyl, optionally substituted pyrazolyl, or optionally substituted pyridyl. 
     
     
         24 . The compound or pharmaceutically acceptable salt of  claim 18 , wherein R 2 , R 3 , R 4 , and R 5  are independently hydrogen, halo, optionally substituted alkoxy, or optionally substituted alkyl. 
     
     
         25 . The compound or pharmaceutically acceptable salt of any one of  claims 18  to  24 , wherein R 6  and R 10  are independently halo. 
     
     
         26 . The compound or pharmaceutically acceptable salt of  claim 25 , wherein R 6  and R 10  are independently fluoro or chloro. 
     
     
         27 . The compound or pharmaceutically acceptable salt of  claim 26 , wherein R 6  is fluoro. 
     
     
         28 . The compound or pharmaceutically acceptable salt of  claim 26 , wherein R 10  is chloro. 
     
     
         29 . The compound or pharmaceutically acceptable salt of any one of  claims 18  to  24 , wherein R 9  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         30 . The compound or pharmaceutically acceptable salt of  claim 29 , wherein R 9  is optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         31 . The compound or pharmaceutically acceptable salt of  claim 30 , wherein R 9  is optionally substituted lower alkyl. 
     
     
         32 . The compound or pharmaceutically acceptable salt of any one of  claims 18  to  31 , wherein R 11  is hydrogen, optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         33 . The compound or pharmaceutically acceptable salt of  claim 32 , wherein R 11  is hydrogen or optionally substituted lower alkyl. 
     
     
         34 . The compound or pharmaceutically acceptable salt of  claim 33 , wherein R 11  is hydrogen. 
     
     
         35 . A compound or pharmaceutically acceptable salt chosen from the group consisting of:
 N-(2-chloro-4-fluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-3-(3-cyanoquinoxaline-6-carbonyl)-4-fluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-phenylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2-chloro-3-(3-(4-chlorophenyl)quinoxaline-6-carbonyl)-4-fluorophenyl)propane-1-sulfonamide,   N-(2-chloro-4-fluoro-3-(3-(4-fluorophenyl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-imidazol-1-yl)quinoxaline-6-carbonyl)-2-chloro-4-fluorophenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(quinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2,4-difluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-2,4-difluorophenyl)benzene sulfonamide,   N-(2,4-difluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)benzene sulfonamide,   N-(2,4-difluoro-3-(quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-2,4-difluorophenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-(piperazin-1-yl)quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-(2-hydroxyethoxy)quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-(2-methoxyethoxy)quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(3-(3-(1H-pyrazol-4-yl)quinoxaline-6-carbonyl)-2,4-difluorophenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(3-(pyridin-3-yl)quinoxaline-6-carbonyl)phenyl)-3-fluorobenzene sulfonamide,   N-(2,4-difluoro-3-(quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-methylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-cyanoquinoxaline-6-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-methoxyquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(piperazin-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(2-methoxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(2-hydroxyethoxy)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-phenylquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(4-chlorophenyl)quinoxaline-6-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(4-fluorophenyl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-imidazol-1-yl)quinoxaline-6-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(2-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(5-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(4-methyl-1H-imidazol-1-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(3-(3-(1H-pyrazol-4-yl)quinoxaline-6-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(pyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   N-(2,4-difluoro-3-(3-(6-methylpyridin-3-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide, and   N-(2,4-difluoro-3-(3-(pyridin-4-yl)quinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide,   and pharmaceutically acceptable salts thereof.   
     
     
         36 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound or pharmaceutically acceptable salt of any one of  claims 1  to  35 . 
     
     
         37 . A pharmaceutical composition of  claim 36  wherein the composition is formulated in a form which is a tablet, capsule, powder, liquid, suspension, suppository, or aerosol. 
     
     
         38 . A packaged pharmaceutical composition comprising a pharmaceutical composition of  claim 36  or  37  and instructions for using the composition to treat a subject suffering from cancer. 
     
     
         39 . A method of treating cancer in a subject which comprises administering to a subject in need thereof a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of  claims 1  to  38 . 
     
     
         40 . The method of  claim 39  wherein the cancer is colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, thyroid cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chondroma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, thyroid cancer, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, non-small cell lung cancer, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, acute lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia); chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia); and polycythemia vera, lymphoma (Hodgkin's disease and non-Hodgkin's disease), multiple myeloma, Waldenstrom's macroglobulinemia, or heavy chain disease. 
     
     
         41 . The method of  claim 40 , wherein the cancer is melanoma. 
     
     
         42 . The method of  claim 41 , wherein the melanoma is unresectable or metastatic melanoma. 
     
     
         43 . The method of  claim 40 , wherein the cancer is non-small cell lung cancer. 
     
     
         44 . The method of  claim 40 , wherein the cancer is colon cancer. 
     
     
         45 . The method of  claim 40 , wherein the cancer is thyroid cancer. 
     
     
         46 . The method of  claim 40 , wherein the cancer is ovarian cancer. 
     
     
         47 . A method of treating a disorder mediated by Raf in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of  claims 1  to  35 . 
     
     
         48 . A method of treating a disorder in a subject in need thereof, comprising:
 a. determining the presence or absence of a BRAF mutation in a biological sample isolated from the subject; and   b. if a BRAF mutation is determined to be present in the subject, administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of  claims 1  to  35 .   
     
     
         49 . The method of  claim 48 , wherein the BRAF mutation is in codon 600. 
     
     
         50 . The method of  claim 48 , wherein the BRAF mutation is V600E. 
     
     
         51 . The method of  claim 48 , wherein determining the presence of absence of the BRAF mutation comprises amplifying BRAF nucleic acid from the biological sample and sequencing the amplified nucleic acid. 
     
     
         52 . The method of  claim 48 , wherein determining the presence of absence of the BRAF mutation comprises detecting a mutant BRAF polypeptide in the biological sample using a binding agent to a mutant BRAF polypeptide. 
     
     
         53 . The method of  claim 52 , wherein the binding agent is an antibody. 
     
     
         54 . The method of  claim 48 , wherein the biological sample is isolated from a tumor of the subject. 
     
     
         55 . The method of any one of  claims 47 - 54 , wherein the disorder is cancer. 
     
     
         56 . The method of  claim 55 , wherein the cancer is colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, thyroid cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chondroma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, non-small cell lung cancer, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, acute lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia); chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia); and polycythemia vera, lymphoma (Hodgkin's disease and non-Hodgkin's disease), multiple myeloma, Waldenstrom's macroglobulinemia, or heavy chain disease. 
     
     
         57 . The method of  claim 56 , wherein the cancer is melanoma. 
     
     
         58 . The method of  claim 57 , wherein the melanoma is unresectable or metastatic melanoma. 
     
     
         59 . The method of  claim 56 , wherein the cancer is non-small cell lung cancer. 
     
     
         60 . The method of  claim 56 , wherein the cancer is colon cancer. 
     
     
         61 . The method of  claim 56 , wherein the cancer is thyroid cancer. 
     
     
         62 . The method of  claim 56 , wherein the cancer is ovarian cancer. 
     
     
         63 . The method of any one of  claims 39 - 62 , further comprising administering an additional anti-cancer and/or cytotoxic agent.