title: [Design, synthesis and biological evaluation of novel diaryl ethers bearing a pyrimidine motif as human Pin1 inhibitors].
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.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yue-Yue
authors.initials: YY
authors.lastname: Xi
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
authors.forename: Hong-Rui
authors.initials: HR
authors.lastname: Song
authors.forename: Bai-Ling
authors.initials: BL
authors.lastname: Xu
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004987:Ethers; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011743:Pyrimidines; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C030986:pyrimidine