63238-04-0Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors
Du, Lifei,Wang, Xiaoyu,Cui, Guonan,Xu, Bailing
supporting information, (2020/11/30)
Pin1 is a peptidyl prolyl cis-trans isomerase (PPIase) and inhibiting Pin1 is a potential way for discovering anti-tumor agents. With an aim to find potent Pin1 inhibitors with a novel scaffold, a series of thiazole derivatives with an alicyclic heterocycles on the 2-position were designed, synthesized and tested against human Pin1. Compound 9p bearing a 2-oxa-6-azaspiro [3,3] heptane moiety on the thiazole scaffold was identified as the most potent Pin1 inhibitor of this series with an IC50 value of 0.95 μM. The structure-activity relationship (SAR) and molecular modeling study indicated that introducing an alicyclic ring with an H-bond acceptor would be a viable way to improve the binding affinity.
Synthesis and Pin1 inhibitory activity of thiazole derivatives
Zhao, Hailong,Cui, Guonan,Jin, Jing,Chen, Xiaoguang,Xu, Bailing
, p. 5911 - 5920 (2016/11/09)
Pin1 (Protein interacting with NIMA1) is a peptidyl prolyl cis–trans isomerase (PPIase) which specifically catalyze the conformational conversion of the amide bond of pSer/Thr-Pro motifs in its substrate proteins and is a novel promising anticancer target. A series of new thiazole derivatives were designed and synthesized, and their inhibitory activities were measured against human Pin1 using a protease-coupled enzyme assay. Of all the tested compounds, a number of thiazole derivatives bearing an oxalic acid group at 4-position were found to be potent Pin1 inhibitors with IC50values at low micromolar level. The detailed structure–activity relationships were analyzed and the binding features of compound 10b (IC505.38 μM) was predicted using CDOCKER program. The results of this research would provide informative guidance for further optimizing thiazole derivatives as potent Pin1 inhibitors.
