title: Novel 5-(benzyloxy)pyridin-2(1H)-one derivatives as potent c-Met inhibitors.
abstract: A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. Various amides and benzoimidazoles at C-3 position were investigated. A potent compound 12b with a c-Met IC50 of 12nM was identified. This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases. The binding model 12b with c-Met was disclosed by docking analysis.
authors.affiliation: State Key Laboratory of Drug Research, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China.
authors.forename: Dengyou
authors.initials: D
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Liang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.forename: Xianjie
authors.initials: X
authors.lastname: Chen
authors.forename: YinChun
authors.initials: Y
authors.lastname: Ji
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011728:Pyridones; D019859:Proto-Oncogene Proteins c-met