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

Article abstract of DOI:10.1016/j.bmcl.2005.06.061

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 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.