Discovery and structure–activity relationships of novel sulfonamides as potent PTP1B inhibitors

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A series of novel sulfonamides containing a single difluoromethylene-phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure–activity relationships around the scaffold were investigated, leading to the identification of compounds with IC 50 or K i values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively.