title: Identification and synthesis of N'-(2-oxoindolin-3-ylidene)hydrazide derivatives against c-Met kinase.
abstract: A series of N'-(2-oxoindolin-3-ylidene)hydrazide derivatives were identified as moderately potent inhibitors against c-Met kinase by pharmacophore-based virtual screening and chemical synthesis methods. The structure-activity relationship (SAR) at various positions of the scaffold was investigated and its binding mode with c-Met kinase was analyzed by molecular modeling studies. In this study, two potent compounds D2 and D25, with IC(50) value at 1.3 μM and 2.2 μM against c-Met kinase respectively, were identified. Finally, based on the clues extracted from this study, future development for the optimization of this scaffold was discussed.
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Liang
authors.forename: Dengyou
authors.initials: D
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.forename: Limin
authors.initials: L
authors.lastname: Chen
authors.forename: Hengshuai
authors.initials: H
authors.lastname: Wang
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Kong
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D004789:Enzyme Activation / Q000187:drug effects; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D006834:Hydrazines; D007211:Indoles; D047428:Protein Kinase Inhibitors; C029424:hydrazine; D019859:Proto-Oncogene Proteins c-met