688781-75-1Relevant articles and documents
Compound and application thereof in preparation of drugs for treating diseases caused by high expression of Flt3/c-Met kinase
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, (2020/12/29)
The invention belongs to the technical field of chemical drug synthesis, and provides a compound and application thereof in preparation of drugs for treating diseases caused by high expression of Flt3/cMet kinase. The compound provided by the invention is prepared by amidation reaction of an intermediate A and an intermediate B. The compound provided by the invention has a strong effect of inhibiting Flt3/cMet kinase. The invention also discloses application of the compound and salt, solvate or prodrug thereof, or application of a pharmaceutical composition composed of one of the compound, salt, hydrate, solvate and prodrug thereof and an excipient in preparation of drugs for treating diseases caused by abnormal high expression of Flt3/cMet kinase, and application in drugs for treating and/or preventing proliferative diseases or cancers.
Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor
Chen, Ting,Duan, Yongli,Huang, Shunmin,Liu, Huimin,Tang, Qidong,Xiong, Hehua,Zhang, Jianqing,Zheng, Pengwu
, (2019/12/25)
A series of pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC50 = 17 nM) was investigated the selectivity against Flt-3, c-Kit, VEGFR-2, ALK, PDGFR-β and RON. Structure-activity relationship studies indicated that hydrogen, fluorine atom, and mono-electron-withdrawing groups (mono-EWGs, such as R2 = F) on R, R1 and R2, respectively, were beneficial for the anti-proliferative activities of the target compounds. Besides, we have took further study on the combined mode between compound 34 and c-Met kinase through molecular docking.
Synthesis and bioevaluation and doking study of 1H-pyrrolo[2,3-b]pyridine derivatives bearing aromatic hydrazone moiety as c-Met inhibitors
Wang, Wenhui,Xu, Shan,Duan, Yongli,Liu, Xiaobo,Li, Xiaojing,Wang, Caolin,Zhao, Bingbing,Zheng, Pengwu,Zhu, Wufu
, p. 315 - 327 (2018/01/17)
Two series of aromatic hydrazone derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (7a–r, 8a–i, 12a–b, 13a–c, 16a–d and 17a–e) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7and PC-3). Two selected compounds (7c and 17e) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that targets compounds were selective for c-Met kinase. And the most promising compound 7c was further studied in terms of dose-dependent, time-dependent and cell apoptosis. Most of the compounds showed excellent cytotoxicity activity, especially the most promising compound 7c with the IC50 values of 0.82 ± 0.08 μM, 1.00 ± 0.11 μM, 0.93 ± 0.28 μM and 0.92 ± 0.17 μM against A549, HepG2, MCF-7 and PC-3 cell lines and 0.506 μM against c-Met kinase. Structure–activity relationships (SARs) and docking studies indicated that the activities of the phenyl hydrazone derivatives (7a–r and 8a–i) were superior to that of the heterocyclic hydrazone series (12a–b, 13a–c, 16a–d and 17a–e). What's more, the further studies indicated that the target compounds can induce apoptosis of A549 cells and arrest efficiently the cell cycle progression in G2/M phase of A549 cells.
