Biaryl ether sulfonamides and their use as therapeutic agents

The compound of claim 1 having the following formula (Ia):

The compound of claim 1 selected from:n4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyridazin-3-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(6-chloropyridazin-3-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyridin-2--yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(6-methylpyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(3-methylpyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-methylisoxazol-3-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(5-chloropyridin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(5-cyanopyridin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-(trifluoromethyl)pyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyridazin-4-yl)benzenesulfonamide;N-(5-(tert-butyl)isoxazol-3-yl)-4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(3-isopropyl-1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1-methyl-1H-tetrazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(4-(trifluoromethyl)pyrimidin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(3-(trifluoromethyl)pyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(3-chloropyridin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1-methyl-1H-pyrazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(2-methyl-2H-tetrazol-5-yl)benzenesulfonamide;N-(5-bromopyrimidin-2-yl)-4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(3,4-dimethylisoxazol-5-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(3-methyl-,1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(3-fluoropyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(4-(trifluoromethyl)pyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(4-chloropyridin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(4-methylpyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1-methyl-1H-1,2,4-triazol-3-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(5-chloropyrimidin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyrazin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(3-chloropyrazin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide; trifluoroacetate4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(pyridin-3-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(6-methoxypyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(3,5-dimethylisoxazol-4-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(5-methylpyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-N-(3-cyanopyridin-2-yl)-2,5-difluorobenzenesulfonamide;4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(6-(trifluoromethyl)pyridin-2-yl)benzenesulfonamide;4-(2-(3-aminoimidazo[1,2-a]pyridin-6-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;6-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)imidazo[1,2-a]pyridine-3-carboxamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(thiazol-4-yl)benzenesulfonamide;N-(5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)acetamide;4-(2-(benzo[d]oxazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)phenoxy)-2,5-difluor-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(2-aminobenzo[d]oxazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(2-aminobenzo[d]oxazol-6-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(3-(3-aminobenzo[d]isoxazol-5-yl)-2-oxopyridin-1(2H)-yl)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-((3-(3-aminobenzo[d]isoxazol-5-yl)pyridin-2-yl)oxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;5-(2-(4-((1H-pyrazol-1-yl)sulfonyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-amine;2-(2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-4,6-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,6-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-2,6-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-2,3-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-methoxyphenoxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate;4-(4-chloro-2-(3-(methylamino)benzo[d]isoxazol-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;tert-butyl (5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)carbamate;4-(2-(1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-fluorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(benzo[d][1,3]dioxol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-((3-(3-aminobenzo[d]isoxazol-5-yl)pyridin-2-yl)oxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(3-(3-aminobenzo[d]isoxazol-5-yl)-2-oxopyridin-1(2H)-yl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-6-bromo-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; and4-(4-chloro-2-(3-(dimethylamino)benzo[d]isoxazol-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide.

The compound of claim 1 selected from:n4-(4-chloro-2-(imidazo[1,2-a]pyrimidin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(imidazo[1,5-a]pyrazin-3-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(9-methyl-9H-purin-6-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(4-chloro-2-(9H-purin-9-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)-benzenesulfonamide;4-(4-chloro-2-(pyrazolo[1,5-a]pyrimidin-3-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-methyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;4-(2-(6-amino-9H-purin-9-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; and4-(2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,5-difluorobenzenesulfonamide.

A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1, as a stereoisomer, enantiomer or tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

A method of treating pain in a mammal-comprising administering to the mammal a compound of claim 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof.