Synthesis and biological evaluation of novel (E)-N'-benzylidene hydrazides as novel c-Met inhibitors through fragment based virtual screening

Content Provider	Scilit
Author	Liang, Jing-Wei Li, Shi-Long Wang, Shan Li, Wan-Qiu Meng, Fan-Hao
Copyright Year	2020
Description	C-Met plays a crucial role in the development and progression of neoplastic disease. Type II c-Met inhibitors recognise the inactive DFG-out conformation of the kinase, result in better anti-tumour effects due to synergistic effect against the other kinases. According to our previous works, an (E)-N'-benzylidene group was selected as the initial fragment. Two series of (E)-N'-benzylidene hydrazides were designed by fragment growth method. The inhibitory activities were in vitro investigated against c-Met and VEGFR-2. Compound 10b exhibited the most potent inhibitory activity against the c-Met inhibitor $(IC_{50}$ = 0.37 nM). Compound 11b exhibited multi-target c-Met kinase inhibitory activity as a potential type II c-Met inhibitor $(IC_{50}$ = 3.41 nM against c-Met; 25.34 nM against VEGFR-2). The two compounds also demonstrate the feasibility of fragment-based virtual screening method for drug discovery.
Related Links	https://www.tandfonline.com/doi/pdf/10.1080/14756366.2019.1702655?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968643/pdf
Ending Page	477
Page Count	10
Starting Page	468
ISSN	14756366
e-ISSN	14756374
DOI	10.1080/14756366.2019.1702655
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Issue Number	1
Volume Number	35
Language	English
Publisher	Informa UK Limited
Publisher Date	2020-01-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Enzyme Inhibition and Medicinal Chemistry Medicinal Chemistry Virtual Screening C-met Inhibitor Qsar Benzylidene Hydrazides
Content Type	Text
Resource Type	Article
Subject	Medicine Drug Discovery Pharmacology