title: Design and Synthesis of Novel 4-Phenoxyquinolines Bearing 3-Hydrosulfonylacrylamido or 1H-Imidazole-4-carboxamido Scaffolds as c-Met Kinase Inhibitors.
abstract: A series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing (E)-3-hydrosulfonylacrylamido or 1H-imidazole-4-carboxamido moieties were designed, synthesized and evaluated for their cytotoxicity against A549, MKN-45, and HT-29 cancer cell lines in vitro. All the target compounds showed moderate to significant cytotoxic activity against the tested cells with IC50values ranging from 0.13 to 2.65 µM. Five of them were further examined for their inhibitory activity against c-Met kinase, which identified compound 30 as a promising agent (c-Met IC50= 1.52 nM) with IC50values of 0.24, 0.45, and 0.13 µM against HT-29, MKN-45, and A549 cells, respectively.
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xie
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Shuancheng
authors.initials: S
authors.lastname: Xi
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Tianfang
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhai
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D019859:Proto-Oncogene Proteins c-met
keywords: Antitumor activity; QSAR; Synthesis; c-Met inhibitors