Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel protein tyrosine phosphatase IB inhibitors

摘要

A series of 5,7-dihydroxyflavanone derivatives were synthesized and identified as reversible and competitive protein tyrosine phosphatase (PTP) 1B inhibitors with IC_(50) values in the micromolar range. Compound 4k had the most potent in vitro inhibition activity against PTP1B (IC_(50) = 2.37 (+-)0.37 uM) and the greatest selectivity (3.7-fold) for PTP1B relative to T-cell protein tyrosine phosphatase. Cell-based studies revealed that 4k was membrane-permeable and enhanced insulin receptor tyrosine phosphorylation in CHO/hIR cells.