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

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 IC50 or Ki 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.

Graphical abstractA series of novel sulfonamides containing a single DFMP group were discovered to be potent inhibitors of PTP1B. Investigation of SAR led to the identification of compounds with IC50 or Ki values in the low nanomolar range.Figure optionsDownload full-size imageDownload as PowerPoint slide