Synthesis and Characterization of New Ureido‐Containing Benzenesulfonamide Derivatives and Their Inhibition Effects on Carbonic Anhydrase Isoforms I, II, IX, and XII

Abstract Sulfonamides and urea derivatives possess significant biological effects in the medical field due to their inhibition of various enzymes, antimicrobial activities, and potential anticancer properties. These compounds are particularly noteworthy for their inhibition effects on different isozymes of carbonic anhydrase (CA) enzymes. In this study, using the tail‐approach strategy, new benzenesulfonamide derivatives ( 3 – 12 ) containing a urea group were synthesized based on carbamate compounds ( 1 – 2 ). The structures of the synthesized compounds were comprehensively characterized using FT‐IR, 13 C‐NMR, 1 H‐NMR, LC‐MS, and elemental analysis techniques. The new ureido‐containing benzenesulfonamide derivatives were tested in vitro on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. Among the investigated compounds for their inhibition effects on different isozymes of humacarbonic anhydrase (hCA) enzymes (hCA I, hCA II, and hCA IX), compounds 9 (K I  = 12.8 nM) and 12 (K I  = 16.3 nM) were found to have remarkable potential for inhibiting the hCA IX isozyme when compared to the standard inhibitor acetazolamide (AAZ) (K I  = 25.0 nM). Other compounds were found to exhibit moderate or weak inhibition effects on hCA enzymes. This study has identified compounds with affinity and selectivity toward different hCA isozymes. This series of compounds, with modifications, offers promising potential and insights for further development against hCA isozymes.