- Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors
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A series of 4-(2-fluorophenoxy)quinoline derivatives containing an acylhydrazone moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and five cancer cell lines (A549, H460, HT-29, MKN-45, and U87MG). Most compounds showed weak to excellent antiproliferative activity. The most promising analog, 40 (c-Met IC50 Combining double low line 1.86 nM), displayed 1.3-, 6.8-, 1.5-, 3.5-fold increase against HT-29, H460, A549 and U87MG cell lines, respectively, compared with Foretinib. An analysis of structure-activity relationships revealed that an acylhydrazone scaffold with an unsubstituted sp2 hybridized carbon adjacent to the 4-CF3 phenyl ring is favorable for antitumor activity.
- Liao, Weike,Xu, Chen,Ji, Xiaohui,Hu, Gang,Ren, Lixiang,Liu, Yajing,Li, Ruijuan,Gong, Ping,Sun, Tiemin
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p. 508 - 518
(2015/01/09)
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- USE OF QSAR IN DESIGN OF ANTIINFLAMMATORY FLUORINATED ARYLALKANOIC ACIDS
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A series of 3-fluoro-4-alkoxyphenylalkanoic acids III was synthetized and their antiinflammatory activity and fibrinolytic capacity was evaluated.The suitable fluorinated derivative with better pharmacological profile than 3-chloro-4-benzyloxyphenylacetic acid (benzofenac) was selected.Experimental, biological activities of acids III were compared with those calculated by introducing the physico-chemical parameters into the formerly derived regression equations.Good coincidence was found out, as well as similarity of the regression equations derived for the originalseries of acids extended by the acids III.Lipophilicity of the acids under study was evaluated by partition thin-layer chromatography; the values of log P of benzyloxy derivatives IIIc-IIIf were lower than tabulated values - probably due to the intramolecular hydrophobic interactions of aromatic nuclei.
- Kuchar, Miroslav,Grimova, Jaroslava,Rejholec, Vaclav,Tomkova, Hana,Jelinkova, Magda,Holubek, Jiri
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p. 296 - 306
(2007/10/02)
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