Bicyclic and tricyclic thiophenes as protein tyrosine phosphatase 1B inhibitors

A novel pyridothiophene inhibitor of PTP1B was discovered by rational screening of phosphotyrosine mimics at high micromolar concentrations. The potency of this lead compound has been improved significantly by medicinal chemistry guided by X-ray crystallography and molecular modeling. Excellent consistency has been observed between structure–activity relationships and structural information from PTP1B-inhibitor complexes.

Novel bicyclic and tricyclic thiophene PTP1B inhibitors were discovered and optimized by structure-based design. Excellent consistency has been observed between structure–activity relationships and structural information from PTP1B-inhibitor complexes.Figure optionsDownload as PowerPoint slide