title: Discovery of novel 7-azaindole derivatives bearing dihydropyridazine moiety as c-Met kinase inhibitors.
abstract: A series of 7-azaindole derivatives bearing the dihydropyridazine scaffold were synthesized and evaluated for their c-Met kinase inhibitory, and antiproliferative activity against 4 cancer cell lines (HT29, A549, H460, U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency. Compared to foretinib, the most promising analog 34 (c-Met IC50: 1.06 nM, a multitarget tyrosine kinase inhibitor) showed a 6.4-, 7.8-, and 3.2-fold increase in activity against HT29, A549, and H460 cell lines, respectively. Structure activity relationship studies indicated that mono-EWGs (such as R2= F) at 4-position of moiety D was a key factor in improving the antitumor activity.
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China. Electronic address: tangqidongcn@126.com.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Linxiao
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Duan
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Shunmin
authors.initials: S
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhi
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Jia
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Wufu
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Jiangxi Province Institute of Materia Medica, Nanchang 330000, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Luo
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China. Electronic address: zhengpw@126.com.
authors.forename: Pengwu
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology
chemical_list: C023422:7-azaindole dimer; D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: 7-Azaindole derivatives; Anti-tumor; Dihydropyridazine; Receptor tyrosine kinase; c-Met