Design and synthesis of benzenesulfonamide-linked imidazo[2,1-b][1,3,4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors

Article abstract of DOI:10.1002/ardp.202100028

A novel series of imidazothiadiazole-linked benzenesulfonamide derivatives (5a–t) was synthesized and subjected for screening against the four physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I, II, VA, and IX. The compounds selectively inhibited hCA I and II over hCA VA and IX. Furthermore, among the two cytosolic isoforms, hCA II was more effectively inhibited as compared with hCA I. The most active compounds were 5o with K_i = 0.246 μM and 5p with K_i = 0.376 μM against hCA II, whereas compound 5f showed good inhibition against both hCA I and II with K_i = 0.493 and 0.4 μM, respectively. This class of underexplored sulfonamides may be used to design isoform-selective CA inhibitors targeting enzymes of medicinal chemistry interest.