title: Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.
abstract: Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 μM in TR-FRET-based assay and IC50 value of 5.45 μM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.
authors.affiliation: Medicinal Chemistry Department, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China. yelb7909@163.com
authors.forename: Lianbao
authors.initials: L
authors.lastname: Ye
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ou
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Tian
authors.forename: Bangwei
authors.initials: B
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Binghong
authors.initials: B
authors.lastname: Feng
authors.forename: Hansen
authors.initials: H
authors.lastname: Lin
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zhang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; 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; D013329:Structure-Activity Relationship
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met
keywords: AQKULDWMVLPKPM-RQNOJGIXSA-N; ASSDAYRAIJUAKP-UHFFFAOYSA-N; Bioisosterism principles; IOEGMAJBPLCGLZ-RQNOJGIXSA-N; Indazole; Isomer; KFHKXMBLOGYCPH-OGESRWMOSA-N; KUZAYSZLNQTGIG-UHFFFAOYSA-N; LNULRIFOOHDLKU-UHFFFAOYSA-N; Molecular docking; QONCLFMRNBSJDL-UHFFFAOYSA-N; SGCGRBMTXZLJBR-OGESRWMOSA-N; Suzuki coupling reaction; VMWYPUTZWINMTO-UHFFFAOYSA-N; VXDNOGKPNKBTFZ-UHFFFAOYSA-N; c-Met inhibitor