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Synthesis and Antitumor Activity of Novel 4‐(2‐ F luorophenoxy)quinoline Derivatives Bearing the 4‐ O xo‐1,4‐dihydroquinoline‐3‐carboxamide Moiety
Author(s) -
Li Sai,
Jiang Rui,
Qin Mingze,
Liu Haicheng,
Zhang Guangyan,
Gong Ping
Publication year - 2013
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300029
Subject(s) - moiety , quinoline , chemistry , carboxamide , stereochemistry , biological activity , combinatorial chemistry , in vitro , biochemistry , organic chemistry
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 in vitro 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 21b , 21c , and 21i were further examined for their c‐Met kinase activity and exhibited strong efficacy with IC 50 values in the single‐digit nanomolar range, which was comparable with the positive control foretinib. The most promising compound 21c showed excellent cytostatic activity with IC 50 values from 0.01 to 0.53 µM against all tested cell lines, thus being 1.7–2.2 times more active than foretinib.