Owing to severe allergic reaction (anaphylaxis) and resistance shown by sulfonamide based CA inhibitors, non-classical or non-sulfonamide CA inhibitors are becoming center of attention to medicinal chemists. In this context, we herein report 30 newly non-sulfonamide CA inhibitors sulfocoumarin derivatives ( 5a-5ad ) have been designed, synthesis and investigated against hCA I, and II (cytosolic isozymes), as well as hCA IX and XII (trans-membrane, tumor associated enzymes). All compounds are clearly showed a prominent selectivity for the tumor associated isoenzymes hCA IX and XII over the cytosolic isoenzymes hCA I and II. Among all synthesized compounds, compound 5j and 5q are more potent and have better inhibition constant against hCA IX than standard AAZ with K i values 23.6 nM and 23.3 nM respectively whereas, all the other compounds are active under K i  = 920 nM against hCA IX and XII. Thus it gives a new perspective for the future development of non-sulfonamide derivatives as selective CAIs.