By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by 1 H-NMR, 13 C-NMR and HRMS. Activities of the title compounds were evaluated on PTP1B and the homologous enzyme TCPTP by using a colorimetric assay. Most of the target compounds had

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... d activities against PTP1B. Among them, compound 29 (IC 50 = 0.91 ± 0.33 µM), characterized by a 5-(2,3-dichlorophenyl) isoxazole moiety, exhibited an activity about 14-fold higher than the lead compound LCA and a 4.2-fold selectivity over TCPTP. Compound 29 was identified as a competitive inhibitor of PTP1B with a K i value of 0.78 µM in enzyme kinetic studies. Molecules 2016, 21, 1722 2 of 11 in drug design when use the "scaffold hopping" method [15] . Additionally, stilbene is a common moiety found in many natural products endowed with antibacterial, antioxidative, antiproliferative or antidiabetic activities, such as resveratrol (6) , pinosylvin (7) and piceatannol (8) [16] [17] [18] [19] .