2. Academic Validation
  3. Design, synthesis and biological evaluation of c-Met kinase inhibitors bearing 2-oxo-1,2-dihydroquinoline scaffold

Design, synthesis and biological evaluation of c-Met kinase inhibitors bearing 2-oxo-1,2-dihydroquinoline scaffold

  • Bioorg Med Chem Lett. 2016 Sep 15;26(18):4483-4486. doi: 10.1016/j.bmcl.2016.07.077.
Hong Cui 1,  Xia Peng 2,  Jian Liu 1,  Chunhua Ma 1,  Yinchun Ji 2,  Wei Zhang 1,  Meiyu Geng 3,  Yingxia Li 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
  • 2 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: mygeng@simm.ac.cn.
  • 4 School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: liyx417@fudan.edu.cn.
PMID: 27524312 DOI: 10.1016/j.bmcl.2016.07.077
Abstract

A series of 2-oxo-1,2-dihydroquinoline-containing c-Met inhibitors were designed, synthesized and evaluated for their in vitro activities targeting c-Met. Most compounds showed high potency against c-Met with IC50 values in the single-digit nM range. Among these compounds, two target compounds, namely 1h and 1n, stood out as the most potent c-Met inhibitors with IC50s of 0.6 and 0.7nM, respectively. And 1a exhibited higher potency than BMS-777607 did with respect to the inhibition of cell proliferation. The introduction of electron-donating substituent was favorable for the activities of the compounds to some extent. Furthermore, molecular docking studies also gave encouraging results that supported this work.

Keywords

Antiproliferative activity; Synthesis; c-Met.

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