title: Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.
abstract: Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC50of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: LingYun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Lianghui
authors.initials: L
authors.lastname: Si
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, P.O. Box 1110, Hefei, Anhui 230031, PR China; University of Science and Technology of China, Hefei, Anhui 230036, PR China. Electronic address: qsliu97@hmfl.ac.cn.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: jpzhou668@163.com.
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011725:Pyridines; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Cancer; Imidazopyridine derivatives; Molecular docking; c-Met kinase inhibitors