Synthesis and Carbonic Anhydrase Inhibition of Novel 2‐(4‐(Aryl)thiazole‐2‐yl)‐3a,4,7,7a‐tetrahydro‐1<i>H</i>‐4,7‐methanoisoindole‐1,3(2<i>H</i>)‐dione Derivatives

Abstract

Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO₂ ) and water to bicarbonate (HCO₃^- ) and protons (H⁺ ) and also plays an important role in biochemical and physiological processes. In this study, a number of novel 2-(4-(aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II). The structures of the new molecules 8a-i were confirmed by means of IR, ¹ H NMR, ¹³ C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with K_i values in the range of 27.07-37.80 nM against hCA I and in the range of 11.80-25.81 nM against hCA II. Our findings suggest that the new isoindolylthiazole derivatives have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor with K_i values of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.