New synthetic methods of ureido-substituted benzenesulfonamides as carbonic anhydrase IX inhibitors

Human Carbonic anhydrase IX is often found to be over-expressed in solid tumors, and plays a role in helping cancer cells adapt and grow under Hypoxic conditions, by exacerbating the extracellular acidification which enables cancer cells to develop resistance against chemotherapy. Many molecules were studied as CAIX inhibitors. Ureido-Substituted benzenesulfonamides (UBSs) are promising CA IX inhibitors to be used in cancer treatments. (SLC-0111) is one of the (UBSs) that has shown tolerability and safety in patients previously Treated for tumors. The most common preparation method of these derivatives in the pharmaceutical industry is based on using toxic phosgene. (2-b), (SLC-0111), and (2-d) were synthesized by three phosgene-free methods of preparation in yields ranging between 30, 50, and 80% according to the used solvent.when acidic water is used as the solvent, impurities are formed as a result of a secondary reaction ,while, butanol is much suitable for synthesizing the desired compounds selectively.