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Discovery of novel 4-(2-fluorophenoxy)quinoline derivatives bearing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety as c-Met kinase inhibitors
- Source :
- Bioorganicmedicinal chemistry. 21(11)
- Publication Year :
- 2013
-
Abstract
- A series of novel 4-(2-fluorophenoxy)quinoline derivatives containing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG and SMMC-7721). All the prepared compounds showed moderate to excellent antiproliferative activity, and the analysis of their structure–activity relationships indicated that 2-chloro or 2-trifluoromethyl substituted phenyl group on the 1-position of cinnoline ring was more favorable for antitumor activity. In this study, a promising compound 33 , with a c-Met IC 50 value of 0.59 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor.
- Subjects :
- C-Met
medicine.drug_class
Stereochemistry
Clinical Biochemistry
Pharmaceutical Science
Carboxamide
Antineoplastic Agents
Biochemistry
Receptor tyrosine kinase
chemistry.chemical_compound
Inhibitory Concentration 50
Structure-Activity Relationship
Cell Line, Tumor
Drug Discovery
medicine
Phenyl group
Moiety
Humans
Anilides
Molecular Biology
Protein Kinase Inhibitors
Cinnoline
Cell Proliferation
biology
Kinase
Organic Chemistry
Quinoline
Proto-Oncogene Proteins c-met
Molecular Docking Simulation
Spectrometry, Fluorescence
chemistry
biology.protein
Quinolines
Molecular Medicine
Drug Screening Assays, Antitumor
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 21
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....75f306c906b62a859be2abb324e26d23