Design and Synthesis of Imidazolidine‐2,4‐Dione Derivatives as Selective Inhibitors by Targeting Protein Tyrosine Phosphatase‐1 B Over T ‐Cell Protein Tyrosine Phosphatase

Owing to its special role as a negative regulator in both insulin and leptin signaling, protein tyrosine phosphatase‐1 B ( PTP 1 B ) has drawn considerable attention as a target for treating type 2 diabetes and obesity. It, however, is a great challenge to discover inhibitors specific to each PTP due to the highly homologous. In this study, a series of compounds were discovered to inhibit PTP 1 B based on imidazolidine‐2,4‐dione by means of ‘core hopping’. A selective PTP 1 B inhibitor ( comp#h ) was identified, and molecular dynamics simulation and binding free energy calculation were carried out to propose the most likely binding mode of comp#h with PTP 1 B . The findings reported here may provide a new strategy in discovering selective and effective inhibitors for treating diabetes.