Synthesis and Antitumor Activity of Novel 4‐(2‐Fluorophenoxy)quinoline Derivatives Bearing the 4‐Oxo‐1, 4‐dihydroquinoline‐3‐carboxamide Moiety. Issue 7 (17th June 2013)

• Record Type: Journal Article
• Authors: Li, Sai; Jiang, Rui; Qin, Mingze; Liu, Haicheng; Zhang, Guangyan; Gong, Ping
• Is Part Of: Archiv der Pharmazie. Volume 346:Issue 7(2013:Jul.)
• Page Start: 521
• Page End: 533
• Publication Date: 2013-06-17
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201300029
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201300029-sec-0001" sec-type="section"> <p>A series of 4‐(2‐fluorophenoxy)quinoline derivatives bearing the 4‐oxo‐1, 4‐dihydroquinoline‐3‐carboxamide moiety were designed, synthesized, and evaluated for their <italic>in vitro</italic> antitumor activity against the H460, HT‐29, MKN‐45, U87MG, and SMMC‐7721 cancer cell lines. Most of the tested compounds showed potent activity and high selectivity toward the HT‐29 and MKN‐45 cell lines. Furthermore, compounds <bold>21b</bold>, <bold>21c</bold>, and <bold>21i</bold> were further examined for their c‐Met kinase activity and exhibited strong efficacy with IC₅₀ values in the single‐digit nanomolar range, which was comparable with the positive control foretinib. The most promising compound <bold>21c</bold> showed excellent cytostatic activity with IC₅₀ values from 0.01 to 0.53 µM against all tested cell lines, thus being 1.7–2.2 times more active than foretinib.</p> </sec> </abstract>