Design, synthesis and biological evaluation of c-Met kinase inhibitors bearing 2-oxo-1, 2-dihydroquinoline scaffold. Issue 18 (15th September 2016)

• Record Type: Journal Article
• Authors: Cui, Hong; Peng, Xia; Liu, Jian; Ma, Chunhua; Ji, Yinchun; Zhang, Wei; Geng, Meiyu; Li, Yingxia
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 18(2016)
• Page Start: 4483
• Page End: 4486
• Publication Date: 2016-09-15
• Subjects: c-Met -- Synthesis -- Antiproliferative activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.07.077
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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, namely1h and1n, stood out as the most potent c-Met inhibitors with IC50 s of 0.6 and 0.7 nM, respectively. And1a exhibited higher potency thanBMS-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.