The synthesis of novel pyrazole-3,4-dicarboxamides bearing 5-amino-1,3,4-thiadiazole-2-sulfonamide moiety with effective inhibitory activity against the isoforms of human cytosolic carbonic anhydrase I and II

• Pyrazole-3,4-dicarboxamides bearing sulfonamide moiety were synthesized.
• The inhibitory effect of the new compounds on CA I and II were investigated in vitro.
• 6, 11 and 15 have remarkable inhibitory effect on activities of CA isozymes.
• Almost all of the synthesized compounds have selective inhibition against CA II.

A series of 1-(3-substituted-phenyl)-5-phenyl-N3,N4-bis(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3,4-dicarboxamides (4–15) were synthesized. The structures of these pyrazole-sulfonamides were confirmed by FT-IR, 1H NMR, 13C NMR and elemental analysis methods. Human cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes (hCA I and II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of newly synthesized derivatives (4–15) were investigated in vitro on esterase activities of these isozymes. The Ki values were determined as 0.119–3.999 μM for hCA I and 0.084–0.878 μM for hCA II. The results showed that the compound 6 for hCA I and the compound 11 for hCA II had the highest inhibitory effect. Beside that, the compound 8 had the lowest inhibition effect on both isozymes.

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