Design, synthesis and biological evaluation of novel diaryl ethers bearing a pyrimidine motif as human Pin1 inhibitors.
- Author:
Yueyue XI
;
Jing JIN
;
Yan SUN
;
Xiaoguang CHEN
;
Hongrui SONG
;
Bailing XU
- Publication Type:Journal Article
- From:
Acta Pharmaceutica Sinica
2013;48(8):1266-72
- CountryChina
- Language:Chinese
-
Abstract:
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.
