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

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.

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

“…210o interacted with active site of hCA II by one hydrogen bond between Thr200 and SO 2 group. All three active compounds showed good binding score which was in agreement with their inhibitory action [41] (Scheme 22).…”

Diverse Biological Activities of 1,3,4-Thiadiazole Scaffold

“…Furthermore, among the two isoforms, hCA II was more effectively inhibited as compared with hCA I. Although all the synthesized derivatives displayed inhibition properties to some extent, two compounds, 44 and 45, displayed the highest inhibition in both I and II isoforms of hCA and can be considered as a potent hCA inhibitors [63] (Figure 9).…”

Design, synthesis, and biological activity of novel dithiocarbamate‐methylsulfonyl hybrids as carbonic anhydrase inhibitors

“…In addition, many studies brought to the literature in recent years have emphasized the strong CA inhibitory activity of this group. [ 15–24 ]…”

“…In addition, many studies brought to the literature in recent years have emphasized the strong CA inhibitory activity of this group. [15][16][17][18][19][20][21][22][23][24] Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. [25] In the context of contemporary medicinal chemistry and drug discovery, and particularly during lead optimization, isosterism and bioisosterism have been very active areas of research as their principles are directly applicable to structure optimization efforts.…”