title: Design, synthesis and molecular docking studies of some novel spiro[indoline-3, 4'-piperidine]-2-ones as potential c-Met inhibitors.
abstract: Deregulation of receptor tyrosine kinase c-Met has been reported in human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of spiro[indoline-3, 4'-piperidine]-2-ones were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibitory effect on c-Met with IC(50) values of 0.0147-17 μM in TR-FRET-based assay and IC(50) values of 1.56-1400 μM in cell-based assay. Furthermore, our docking experiments verified the results and explained the molecular mechanism of eminent activities to c-Met.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. yelb7909@163.com
authors.forename: Lianbao
authors.initials: L
authors.lastname: Ye
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Tian
authors.forename: Zhonghuang
authors.initials: Z
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Zhengguang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Shanhe
authors.initials: S
authors.lastname: Wan
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhang
authors.forename: Pengjiu
authors.initials: P
authors.lastname: Yu
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zhang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wu
mesh_terms: D001665:Binding Sites; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D055808:Drug Discovery; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; C032727:piperidine; D019859:Proto-Oncogene Proteins c-met