ABSTRACT
The first sulfonamide (sulphonamide) compound of clinical importance, prontosil rubrum, was synthesized in Germany in 1932 and first used as a chemotherapeutic agent in 1935, initiating a new era in the treatment of infections. It was soon shown that the therapeutic action of this compound depended on its breakdown in the body into an inactive dye and an antibacterial substance called sulfanilamide (p-amino-benzene sulfonamide), which had been synthesized in 1908. Subsequently, by manipulating chemical side chains, several thousand sulfonamides were synthesized, and some of these have clinical uses other than for chemotherapy, such as the oral hypoglycemic agent tolbutamide. It was observed that sulfanilamide could cause metabolic acidosis and act as a diuretic, and this was later shown to be due to its sulfamoyl group. Subsequent chemical manipulations of sulfanilamide led to the development of the sulfamoyl diuretics, such as the carbonic anhydrase inhibitors (e.g. acetazolamide), the thiazides, and frusemide (Feit, 1975). The history of the sulfonamides has been reviewed by Lerner (1991).
