Effect of hydrophobic extension of aryl enaminones and pyrazole-linked compounds combined with sulphonamide, sulfaguanidine, or carboxylic acid functionalities on carbonic anhydrase inhibitory potency and selectivity.

Design and synthesis of three novel series of aryl enaminones (- and -) and pyrazole () linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid functionalities were reported as carbonic anhydrase inhibitors (CAIs) using the "tail approach" strategy in their design to achieve the most variable amino acids in the middle/outer rims of the hCAs active site. The synthesised compounds were assessed for their inhibitory activity against the following human (h) isoforms, hCA I, II, IX, and XII using stopped-flow CO hydrase assay. Enaminone sulphonamide derivatives (-) potently inhibited the target tumour-associated isoforms hCA IX and hCA XII (KIs 26.