The discovery of CA inhibition with sulfanilamide 4.1 by Mann and Keilin (1940) was the beginning of a great adventure that led to important drugs widely used to treat or prevent a multitude of diseases. Sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing, among others, antibacterial, antitumor, anticarbonic anhydrase (CA), diuretic, hypoglycemic, anti-thyroid or protease inhibitory activity (Northey 1948; Maren 1967; Scozzafava et al. 2003; Supuran et al. 2003; Owa and Nagasu 2000). The very simple sulfanilamide 4.1 lead molecule afforded the development of all these types of pharmacological agents that have a wide variety of biological actions, as exemplified later for the antibacterial agent sulfathiazole, the carbonic anhydrase inhibitor acetazolamide (clinically used for more than 45 years; Maren 1967), the widely used diuretic furosemide, the hypoglycemic agent glibenclamide, the anticancer sulfonamide indisulam (in advanced clinical trials), the aspartic HIV protease inhibitor amprenavir used to treat AIDS and HIV infection and the metalloprotease (MMP) inhibitors of the sulfonyl amino acid hydroxamate type (Scozzafava et al. 2003; Supuran et al. 2003; Supuran 2003; Supuran and Scozzafava 2000a, 2001, 2002a, 2002b; Figure 4.1).
SO2NH2 H S 22
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