2. Academic Validation
  3. Design and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives bearing an imidazolone moiety as c-Met kinase inhibitors

Design and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives bearing an imidazolone moiety as c-Met kinase inhibitors

  • Bioorg Med Chem. 2015 Aug 1;23(15):4410-4422. doi: 10.1016/j.bmc.2015.06.026.
Weike Liao 1,  Gang Hu 1,  Zhuang Guo 1,  Deyu Sun 2,  Lixia Zhang 1,  Yanxin Bu 1,  Yingxiu Li 1,  Yajing Liu 3,  Ping Gong 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
  • 2 Liaoning Cancer Hospital & Institute, 44 Xiaoheyan Road, Dadong District, PR China.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: lyjpharm@126.com.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China. Electronic address: gongpinggp@126.com.
PMID: 26169763 DOI: 10.1016/j.bmc.2015.06.026
Abstract

A series of 4-(2-fluorophenoxy)quinoline derivatives containing an imidazolone moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and four Cancer cell lines (A549, H460, HT-29 and MKN-45). Most compounds showed moderate to excellent activities in Enzyme and cellular assays. The most promising analog, 58 (c-Met IC50=1.42 nM), displayed 2.1-, 8.6-fold increase against H460, and MKN-45 cell lines, respectively, compared with foretinib. An analysis of structure-activity relationships revealed that an ortho substituted phenyl ring as well as an N-unsubstituted imidazolone linker is favorable for antitumor activity.

Keywords

Antitumor activity; Imidazolone-4-carboxamide; Quinoline derivatives; c-Met.

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