A new way of synthesizing heterocyclic primary sulfonamide probes for carbonic anhydrase

An N,N-bis(p-methoxybenzyl)-protected a-acetyl-a-diazo-methane sulfonamide proved to be a useful building block for accessing new 5-methyl-1,2,3-thiadiazole-4-sulfonamide as well as methyl 3-sulfamoyl-1H-pyrazole-5-carboxylate. The latter was further subjected to N-alkylation and N-arylation reactions. All resulting compounds showed potent inhibition of I, II and particularly of cancer-related IX and XII isoforms of human carbonic anhydrase.

Automated summary

An N,N-bis(p-methoxybenzyl)-protected a-acetyl-a-diazo-methane sulfonamide was used as a useful building block for synthesizing new 5-methyl-1,2,3-thiadiazole-4-sulfonamide and methyl 3-sulfamoyl-1H-pyrazole-5-carboxylate. The latter underwent N-alkylation and N-arylation reactions. All resulting compounds exhibited potent inhibition against human carbonic anhydrase I, II, IX, and XII isoforms, particularly the cancer-related forms.