title: Discovery of novel 4-(2-fluorophenoxy)quinoline derivatives bearing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety as c-Met kinase inhibitors.
abstract: A series of novel 4-(2-fluorophenoxy)quinoline derivatives containing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG and SMMC-7721). All the prepared compounds showed moderate to excellent antiproliferative activity, and the analysis of their structure-activity relationships indicated that 2-chloro or 2-trifluoromethyl substituted phenyl group on the 1-position of cinnoline ring was more favorable for antitumor activity. In this study, a promising compound 33, with a c-Met IC50 value of 0.59 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor.
authors.affiliation: Key Lab of New Drug Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kewen
authors.initials: K
authors.lastname: Wang
authors.forename: Yali
authors.initials: Y
authors.lastname: Gao
authors.forename: Jianming
authors.initials: J
authors.lastname: Han
authors.forename: Bingbing
authors.initials: B
authors.lastname: Cui
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; 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* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C584668:N-(3-fluoro-4-(6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-4-oxo-1-(2-(trifluoromethyl)phenyl)-1,4-dihydrocinnoline-3-carboxamide; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D019859:Proto-Oncogene Proteins c-met