2. Academic Validation
  3. Discovery and optimization of novel 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazones as c-Met kinase inhibitors

Discovery and optimization of novel 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazones as c-Met kinase inhibitors

  • Bioorg Med Chem. 2013 Sep 1;21(17):5246-60. doi: 10.1016/j.bmc.2013.06.026.
Baohui Qi 1,  Bin Mi,  Xin Zhai,  Ziyi Xu,  Xiaolong Zhang,  Zeru Tian,  Ping Gong
Affiliations

Affiliation

  • 1 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, PR China.
PMID: 23838381 DOI: 10.1016/j.bmc.2013.06.026
Abstract

A novel series of N(1)-(3-fluoro-4-(6,7-disubstituted-quinolin-4-yloxy)phenyl)-N(4)-arylidenesemicarbazide derivatives were synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against A549, HT-29, MKN-45 and MDA-MB-231 Cancer cell lines in vitro. Several potent compounds were further evaluated against three other Cancer cell lines (U87MG, NCI-H460 and SMMC7721). Most of compounds tested exhibited moderate to excellent activity. The studies of SARs identified the most promising compound 28 (c-Met IC50=1.4nM) as a c-Met kinase inhibitor. In this study, a promising compound 28 was identified, which displayed 2.1-, 3.3-, 48.4- and 3.6-fold increase against A549, HT-29, U87MG and NCI-H460 cell lines, respectively, compared with that of Foretinib.

Keywords

Anti-tumor; Kinase inhibitor; Quinoline; Semicarbazone; c-Met.

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