Sulfenamido-sulfonamides as inhibitors of carbonic anhydrase isozymes I, II and IV

Reaction of 2-nitrophenyl- and 4-nitrophenylsulfenyl-chlorides with aromatic/heterocyclic sulfonamides containing a free amino group afforded sulfenamido-sulfonamides, which were inhibitors of the zinc enzyme carbonic anhydrase (CA). Oxidation of these derivatives with potassium permanganate in acetone led to the corresponding bis-sulfonamides. Good inhibition of three CA isozymes (CA I, II and IV, respectively) was observed with some of the new compounds, the bis-sulfonamides being more active than the sulfenamido-sulfonamides. A possible in vivo transformation of the last type of compounds, leading to an omeprazole-like gastric acid secretion inhibitor is also discussed.