Synthesis and Antitumor Activity of Novel 4‐(2‐Fluorophenoxy)quinoline Derivatives Bearing the 4‐Oxo‐1,4‐dihydroquinoline‐3‐carboxamide Moiety
Authors:
- 17 June 2013
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 346 (7) , 521-533
Abstract
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 IC50 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 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.Keywords
This publication has 29 references indexed in Scilit:
- Structure-Based Design of Novel Class II c-Met Inhibitors: 1. Identification of Pyrazolone-Based DerivativesJournal of Medicinal Chemistry, 2012
- Structure-Based Design of Novel Class II c-Met Inhibitors: 2. SAR and Kinase Selectivity Profiles of the Pyrazolone SeriesJournal of Medicinal Chemistry, 2012
- Identification of a New Series of STAT3 Inhibitors by Virtual ScreeningACS Medicinal Chemistry Letters, 2010
- Small molecule c-Met kinase inhibitors: a review of recent patentsExpert Opinion on Therapeutic Patents, 2010
- N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitorsBioorganic & Medicinal Chemistry Letters, 2009
- Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine KinasesCancer Research, 2009
- 5-N-Methylated Quindoline Derivatives as Telomeric G-Quadruplex Stabilizing Ligands: Effects of 5-N Positive Charge on Quadruplex Binding Affinity and Cell ProliferationJournal of Medicinal Chemistry, 2008
- Structural insights into how irreversible inhibitors can overcome drug resistance in EGFRBioorganic & Medicinal Chemistry, 2008
- c-Met Inhibitors with Novel Binding Mode Show Activity against Several Hereditary Papillary Renal Cell Carcinoma-related MutationsJournal of Biological Chemistry, 2008
- Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]- and 4-(phenylamino)quinazolines as potent adenosine 5'-triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor.Journal of Medicinal Chemistry, 1995