Click chemistry‐based synthesis of new benzenesulfonamide derivatives bearing triazole ring as selective carbonic anhydrase II inhibitors

A series of 1,2,3-triazol-1-ylbenzenesulfonamide derivatives was designed, synthesized and their ability to inhibit several carbonic anhydrase isoforms was evaluated. The basis of our design is to hybridize the benzenesulfonamide moiety widely used as a zinc-binding group, a triazole ring as spacer with a tail of different substituted aryl moieties. The synthesis of these compounds was achieved using Cu(I)-mediated click chemistry between the azide containing the benzenesulfonamide pharmacophore and various aryl acetylenes or 1,6-heptadiyne through copper-catalyzed [3+2] cycloaddition reaction. The ability the new derivatives to inhibit four human carbonic anhydrase isoforms hCA I, II, IX, and XII was evaluated. All the compounds exhibited good potency and high selectivity towards isoforms hCA I and II more than isoforms hCA IX and XII, especially for the derivatives 3c and 3j that displayed K