title: Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold.
abstract: A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6-81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57-16 μM.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.affiliation: School of Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Dakuo
authors.initials: D
authors.lastname: Shi
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yinchun
authors.initials: Y
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. mygeng@simm.ac.cn.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. liyx417@fudan.edu.cn.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; C550356:N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D019859:Proto-Oncogene Proteins c-met