Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) belongs to peptidyl-prolyl cis-trans isomerase (PPIase) and is a novel promising anticancer target. Based on the lead structure of benzophenone, a series of novel diarylether derivatives containing a pyrimidine ring were designed and synthesized. The inhibitory activities on Pin1 of compounds 5a-5d and 6a-6i were evaluated by a protease-coupled enzyme assay. Of all the evaluated compounds, 6 compounds displayed inhibitory activities. Molecular docking was performed using FlexX algorithm to explore the binding mode of the active molecules.
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