title: Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine derivatives as c-Met inhibitors.
abstract: Five novel 1H-pyrrolo[2,3-b]pyridine or 1H-pyrazolo[3,4-b]pyridine derivatives, with a methylene, sulfur, sulfoxide or cyclopropyl group as a linker, were designed, synthesized and biologically evaluated against c-Met and ALK. The development of these methods of compound synthesis may provide an important reference for the construction of novel 7-azaindole and 7-azaindazole derivatives with a single atom linker. The enzyme assay and cell assay in vitro showed that compound 9 displayed strong c-Met kinase inhibition with IC50 of 22.8nM, moderate ALK kinase inhibition, and strong cell inhibition with MKN-45 IC50 of 329nM and EBC-1 IC50 of 479nM. In order to find the better candidate compounds, compounds 8, 9 and 10 have been selected as tool compounds for further optimization.
authors.affiliation: School of Biological Engineering, Tianjin University of Science and Technology, #29, 13th Avenue, TEDA, Tianjin 300457, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: School of Biological Engineering, Tianjin University of Science and Technology, #29, 13th Avenue, TEDA, Tianjin 300457, China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Binjiang Pharma, Inc., #238 Baidi Road, Nankai District, Tianjin 300192, China.
authors.forename: Gongchao
authors.initials: G
authors.lastname: Huang
authors.affiliation: Tianjin Binjiang Pharma, Inc., #238 Baidi Road, Nankai District, Tianjin 300192, China.
authors.forename: Conghui
authors.initials: C
authors.lastname: Ji
authors.affiliation: School of Biological Engineering, Tianjin University of Science and Technology, #29, 13th Avenue, TEDA, Tianjin 300457, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Tianjin Binjiang Pharma, Inc., #238 Baidi Road, Nankai District, Tianjin 300192, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin Binjiang Pharma, Inc., #238 Baidi Road, Nankai District, Tianjin 300192, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, #238 Baidi Road, Nankai District, Tianjin 300192, China. Electronic address: tianhongqi@irm-cams.ac.cn.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Tian
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C478081:1H-pyrazolo(3,4-b)pyridine; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011758:Pyrroles; D019859:Proto-Oncogene Proteins c-met; C486292:pyrrolo(2, 3-b)pyridine
keywords: Azaindazole; Azaindole; Biological evaluation; Synthesis; c-Met inhibitor