2. Academic Validation
  3. Discovery andw biological evaluation of novel 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety as c-Met kinase inhibitors

Discovery andw biological evaluation of novel 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety as c-Met kinase inhibitors

  • Bioorg Med Chem. 2014 Nov 15;22(22):6438-52. doi: 10.1016/j.bmc.2014.09.037.
Shunguang Zhou 1,  Huimin Liao 1,  Mingmei Liu 1,  Guobing Feng 1,  Baolin Fu 1,  Ruijuan Li 1,  Maosheng Cheng 1,  Yanfang Zhao 2,  Ping Gong 3
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 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: yanfangzhao@126.com.
  • 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: gongpinggp@126.com.
PMID: 25438768 DOI: 10.1016/j.bmc.2014.09.037
Abstract

A series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and five typical Cancer cell lines (A549, H460, HT-29, MKN-45 and U87MG). Most compounds showed moderate to excellent antiproliferative activity. In this study, a promising compound 34, with a c-Met IC50 value of 1.04nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The SAR analyses indicated that compounds with halogen group, especially fluoro group, at 4-position on the phenyl ring (moiety B) have potent antitumor activity, and methylation on the 5-atom linker played an important role in the c-Met enzymatic activity.

Keywords

1,2,3-Triazole-4-carboxamide; Antitumor activity; Quinoline derivatives; Receptor tyrosine kinase; c-Met.

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