Synthesis and biological evaluation of pyrimidine derivatives as novel human Pin1 inhibitors

Publication date: Available online 15 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Guonan Cui, Jing Jin, Hualong Chen, Ran Cao, Xiaoguang Chen, Bailing Xu
Pin1 (Protein interacting with NIMA1) is a cis-trans isomerase and promotes the amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of Pin1 might be a novel strategy for developing anticancer agents. Herein, a series of pyrimidine derivatives were synthesized and their Pin1 inhibitory activities were evaluated. Among them, four compounds (2a, 2f, 2h and 2l) displayed potent inhibitory activities against Pin1 with IC50 values lower than 3 µM. This series of pyrimidine-based inhibitors presented time-dependent inhibition against Pin1. The structure-activity relationships on the 2-, 4- and 5-positions of the pyrimidine ring were analyzed in details, which would facilitate further exploration of new Pin1 inhibitors.

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