Phosphate transport inhibitors

A method of causing phosphate excretion and/or inhibiting phosphate absorption by administering to a subject in need thereof a safe and effective amount of a compound according to Formula (I):

• 4
• wherein:
• R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, acyl, aroyl, haloalkyl, halo, carboxy, carboalkoxy, carbamyl, alkylcarbamyl, arylcarbamyl, cyano, alkoxy, hydroxyl, phenylazo, amino, nitro, alkylamino, arylamino, arylalkylamino, acylamino, aroylamino, alkylthio, arylalkylthio, arylthio, alkysulfinyl, arylsulfinyl, arylalkylsulfinyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, sulfamyl, arylsulfonamido, and alkylsulfonamido;
• or the R1 moiety represents a fused ring forming a benzothiophene, naphthalene, quinoline, or isoquinoline with the ring it substitutes;
• or (R1)n and the ring it substitutes represents a heterocycle selected from the group consisting of thiophene, furan, pyridine, pyrimidine, and pyrazine, and benzo analogs thereof;
• and
• R3 is independently selected from the group consisting of alkyl, haloalkyl, R1 aryl and R1 aralkyl, and R1 substituted heterocycles selected from the group consisting of thiophene, furan, pyridine, pyrimidine, pyrazine, imidazole, isoxazole, thiadiazole, oxadiazole and thiazole, and benzo analogs thereof.

A method of treating chronic renal failure by inhibiting the phosphate transport system in a mammal in need thereof, by administering to a subject in need thereof a safe and effective amount of a compound a compound according to Formula (I):

• 5
• wherein:
• R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, acyl, aroyl, haloalkyl, halo, carboxy, carboalkoxy, carbamyl, alkylcarbamyl, arylcarbamyl, cyano, alkoxy, hydroxyl, phenylazo, amino, nitro, alkylamino, arylamino, arylalkylamino, acylamino, aroylamino, alkylthio, arylalkylthio, arylthio, alkysulfinyl, arylsulfinyl, arylalkylsulfinyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, sulfamyl, arylsulfonamido, and alkylsulfonamido;
• or the R1 moiety represents a fused ring forming a benzothiophene, naphthalene, quinoline, or isoquinoline with the ring it substitutes;
• or (R1)n and the ring it substitutes represents a heterocycle selected from the group consisting of thiophene, furan, pyridine, pyrimidine, and pyrazine, and benzo analogs thereof;
• and
• R3 is independently selected from the group consisting of alkyl, haloalkyl, R1 aryl and R1 aralkyl, R1 benzoaryl and R1 benzoaralkyl, and R1 substituted heterocycles selected from the group consisting of thiophene, furan, pyridine, pyrimidine, pyrazine, isoxazole, thiadiazole, oxadiazole, imidazole, and thiazole, and benzo analogs thereof.

A pharmaceutical composition comprising a compound selected from the group consisting of:

• 5-Bromo-N-(4-Bromophenyl)-2-(2-fluorophenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(5-chloro-2-thienylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3,3,3-trifluoroethylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3-chloro-2-fluorophenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3-chloropropylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(2-methylphenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(2-thienylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(2-methoxycarbonyl-3-thienylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(4-cyanophenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(methylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3-trifluoromethylphenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(4-methoxyphenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(phenylsulfonamido)benzamide and
• 5-Bromo-N-(4-Bromophenyl)-2-(4-bromophenylsulfonamido)benzamide;
• and a pharmaceutically acceptable carrier.
• N-phenyl-2-(3-trifluoromethylphenylsulfonamido)benzamide;
• 5-Methoxy-N-(3-trifluoromethylphenyl)-2-(4-chlorophenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(5-chloro-2-thienylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3,3,3-trifluoroethylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3-chloro-2-fluorophenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(3-chloropropylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(4-methoxyphenylsulfonamido)benzamide;
• 5-Bromo-N-(4-Bromophenyl)-2-(2-fluorophenylsulfonamido)benzamide;
• N-(4-Chlorophenyl)-2-(2-fluorophenylsulfonamido)benzamide;
• N-(4-Bromophenyl)-2-(3,3,3-trifluoroethylsulfonamido)benzamide;
• N-(4-Bromophenyl)-5-chloro-2-(3-chloro-2-fluorophenylsulfonamido)benzamide;
• N-(4-Chlorophenyl)-2-(3,4-dichlorophenylsulfonamido)benzamide;
• N-(4-Bromophenyl)-2-(2-thienylsulfonamido)benzamide;
• N-(4-Bromophenyl)-2-(2-methoxycarbonyl-3-thienylsulfonamido)benzamide;
• N-(3,4-Dichlorophenyl)-2-(2-fluorophenylsulfonamido)benzamide;
• N-(4-Chlorophenyl)-2-(3-trifluoromethylphenylsulfonamido)benzamide;
• 5-Bromo-N-(4-chlorophenyl)-2-(3,4-dichlorophenylsulfonamido)benzamide;
• N-(4-chlorophenyl)-2-(3,4-difluorophenylsulfonamido)benzamide;
• N-(4-Butoxyphenyl)-2-(3,4-difluorophenylsulfonamido)benzamide;
• N-(4-Chlorophenyl)-2-(3,5-dimethylisoxazole-4-sulfonamido)benzamide;
• N-(4-Chlorophenyl)-2-(2,1,3-benzothiadiazole-4-sulfonylamino)-benzamide;
• N-(3-Trifluoromethoxyphenyl)-2-(5-Bromo-thiophene-2-sulfonylamino)-benzamide;
• N-(4-Bromophenyl)-2-(phenylsulfonamido)benzamide and
• 5-Methoxy-N-(4-chlorophenyl)-2-(3-trifluoromethylphenylsulfonamido)benzamide.