title: Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors.
abstract: A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure-activity relationship studies indicated that electron-withdrawing groups (X=CF3, R(1)=F, R(2)=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.
authors.affiliation: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, 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: Yayi
authors.initials: Y
authors.lastname: Tu
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: 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.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Tu
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: School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Wu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
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; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; 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; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D014230:Triazoles; D019859:Proto-Oncogene Proteins c-met; C486292:pyrrolo(2, 3-b)pyridine
keywords: 1,2,3-Triazole; Antiproliferative activity; Pyrrolo[2,3-b]pyridine derivatives; Synthesis; c-Met