Novel Taurinamide‐Based Compounds as Carbonic Anhydrase Inhibitors

A series of taurinamide‐based amides 1–19 were investigated for their effects on human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms I, II, VA, VII, IX, and XII, which are all relevant for biomedical applications. According to inhibition data, most of the derivatives displayed affinity and selectivity for the hCA I isoform over the other isoforms tested, and compounds 1 , 2 , 4 , 8 , and 9 emerged as potent nanomolar inhibitors of hCA I and hCA IX, exhibiting K I values in the range of 0.65–0.83 and 0.59–0.96 µM, respectively (asetazolamide K I = 0.25 for CA I and K I = 0.03 M for hCA IX). The X‐ray structures of 15 and 18 in complex with hCA II provided detailed insights into the binding mode and molecular determinants. Substitution patterns were found to have a tuning effect on both affinity and selectivity toward specific isoforms, thus providing valuable insights for the design of new CA inhibitors.