Carbonic anhydrase inhibitors: Synthesis of Schiff bases of hydroxybenzaldehydes with aromatic sulfonamides and their reactions with arylsulfonyl isocyanates - Part 90

Reaction of o- or p-hydroxybenzaldehydes with sulfanilamide, homosulfanilam ide and p-(2-aminoethyl)- benzene-sulfonamide afforded several new Schiff b ases which were subsequently derivatized at the phenolic hydroxy moiety by reaction with arylsulfonylisocyanates. The new arylsulfonylcarbamates obtai ned in this way possessed interesting inhibitory properties against three c arbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human, b = b ovine isozyme). All these new derivatives, the simple Schiff bases and the arylsulfonylcarbamates obtained as outlined above, were more inhibitory aga inst all isozymes as compared to the corresponding parent sulfonamide from which they were obtained. Generally, the p-hydroxybenzaldehyde derivatives were more active than the corresponding ortho isomers. An interesting behav ior was evidenced for some of the ortho-substituted arylsulfonylcarbamatosu lfonamides, which showed higher affinities for the isozyme hCA I, as compar ed to hCA II and bCA IV (generally hCA I is 10-1000 less sensitive to "norm al" sulfonamide inhibitors, such as acetazolamide, methazolamide or dorzola mide, as compared to hCA II). This make the new derivatives attractive lead s for designing isozyme I-specific inhibitors.