Synthesis of sulfonamides incorporating piperazinyl-ureido moieties and their carbonic anhydrase I, II, IX and XII inhibitory activity

摘要

By using SLC-0111 (4-fluorophenylureido-benzenesulfonamide), a sulfonamide carbonic anhydraseud(CA, EC 4.2.1.1) inhibitor in Phase I clinical trials as an antitumor agent as lead molecule, a series ofudbenzenesulfonamide derivatives incorporating ureido moieties was synthesized. The new compoundsudcontain a 4-N-substituted piperazine fragment in which the ureido linker has been included, and wereudtested as inhibitors of the cytosolic human (h) hCA I and II isoforms, as well as the transmembrane,udtumor-associated enzymes hCA IX and XII. Depending on the substitution pattern at the piperazine ring,udlow nanomolar inhibitors were detected against all four isoforms, making the new class of sulfonamidesudof interest for various pharmacologic applications.