title: Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: synthesis and SAR study as tyrosine kinase c-Met inhibitors.
abstract: Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgw-atinib) with quinoxaline and pyrido[2,3-d]pyrimidine frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a-c possessing an O-linkage were inactive, whilst the N-linked analogues 15a-c retained c-Met inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b that showed an IC(50) value of 6.5 nM. Further structural modifications based on this compound were undergoing.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.forename: Qiufeng
authors.initials: Q
authors.lastname: Liu
authors.forename: TianTian
authors.initials: T
authors.lastname: Chen
authors.forename: Ailing
authors.initials: A
authors.lastname: Zhao
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yinchun
authors.initials: Y
authors.lastname: Ji
authors.forename: Qizheng
authors.initials: Q
authors.lastname: Yao
authors.forename: Yechun
authors.initials: Y
authors.lastname: Xu
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011810:Quinoxalines; D019859:Proto-Oncogene Proteins c-met