title: Discovery of a novel 6,7-disubstituted-4-(2-fluorophenoxy)quinolines bearing 1,2,3-triazole-4-carboxamide moiety as potent c-Met kinase inhibitors.
abstract: A series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety were designed, synthesized and evaluated for their in vitro cytotoxic activities against four typical cancer cell lines (A549, H460, HT-29, and MKN-45). Most compounds showed moderate-to-excellent antiproliferative activity. Compounds 32, 36, 37, 45, 51, and 52 were further examined for their inhibitory activity against c-Met kinase. The promising compound 37, with a c-Met IC50 value of 2.27 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The analysis of their structure-activity relationships indicated that compounds with EWGs, especially chloro group, at 2-position on the phenyl ring (moiety B) have potent antitumor activity.
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Mingmei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Yunlei
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Weile
authors.initials: W
authors.lastname: Yin
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Shunguang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qian
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: yanfangzhao@126.com.
authors.forename: Yangfang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D011804:Quinolines; D014230:Triazoles; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Antitumor activity; Quinoline derivatives; Synthesis; c-Met