title: Design, synthesis and biological evaluation of c-Met kinase inhibitors bearing 2-oxo-1,2-dihydroquinoline scaffold.
abstract: A series of 2-oxo-1,2-dihydroquinoline-containing c-Met inhibitors were designed, synthesized and evaluated for their in vitro activities targeting c-Met. Most compounds showed high potency against c-Met with IC50 values in the single-digit nM range. Among these compounds, two target compounds, namely 1h and 1n, stood out as the most potent c-Met inhibitors with IC50s of 0.6 and 0.7nM, respectively. And 1a exhibited higher potency than BMS-777607 did with respect to the inhibition of cell proliferation. The introduction of electron-donating substituent was favorable for the activities of the compounds to some extent. Furthermore, molecular docking studies also gave encouraging results that supported this work.
authors.affiliation: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cui
authors.affiliation: Division of Anti-Tumor 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: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
authors.affiliation: Division of Anti-Tumor 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, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: mygeng@simm.ac.cn.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.affiliation: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: liyx417@fudan.edu.cn.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D011804:Quinolines; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Antiproliferative activity; Synthesis; c-Met