2. Academic Validation
  3. Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors

Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors

  • Eur J Med Chem. 2014 Nov 24:87:508-18. doi: 10.1016/j.ejmech.2014.09.095.
Weike Liao 1,  Chen Xu 1,  Xiaohui Ji 1,  Gang Hu 1,  Lixiang Ren 2,  Yajing Liu 1,  Ruijuan Li 1,  Ping Gong 3,  Tiemin Sun 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, PR China.
  • 2 Shenyang J & Health Bio-technic Development, Shenyang 110016, PR China.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, PR China. Electronic address: gongpinggp@126.com.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, PR China. Electronic address: suntiemin@126.com.
PMID: 25282672 DOI: 10.1016/j.ejmech.2014.09.095
Abstract

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 = 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 sp(2) hybridized carbon adjacent to the 4-CF3 phenyl ring is favorable for antitumor activity.

Keywords

Acylhydrazone; Quinoline derivatives; Synthesis; c-Met.

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