Design and synthesis of benzenesulfonamide‐linked imidazo[2, 1‐b][1, 3, 4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors. Issue 7 (24th March 2021)

• Record Type: Journal Article
• Authors: Swain, Baijayantimala; Aashritha, Kamtam; Singh, Priti; Angeli, Andrea; Kothari, Abhay; Sigalapalli, Dilep K.; Yaddanapudi, Venkata M.; Supuran, Claudiu T.; Arifuddin, Mohammed
• Is Part Of: Archiv der Pharmazie. Volume 354:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-24
• Subjects: carbonic anhydrase -- DABCO -- hCA I and II isoforms -- imidazothiadiazole -- sulfonamide; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202100028
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: 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. Abstract : A novel series of imidazothiadiazole‐linked benzenesulfonamide derivatives (5a –t ) was synthesized and subjected to screening for inhibitory activity against the human carbonic anhydrase (hCA) isoforms I, II, VA, and IX. Most of them displayed good potency and selectivity against the isoforms hCA I and II. Compounds 5o, 5p, and 5f may be taken as lead compounds for the further development of potent and selective hCA I and II inhibitors.