2. Academic Validation
  3. Discovery of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel, potent and selective c-Met kinase inhibitors: Synthesis, SAR study, and biological activity

Discovery of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel, potent and selective c-Met kinase inhibitors: Synthesis, SAR study, and biological activity

  • Eur J Med Chem. 2018 Apr 25:150:809-816. doi: 10.1016/j.ejmech.2018.03.049.
Li Zhang 1,  Jingyun Zhao 1,  Beichen Zhang 1,  Tao Lu 2,  Yadong Chen 3
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
  • 2 Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: lut163@163.com.
  • 3 Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China. Electronic address: ydchen@cpu.edu.cn.
PMID: 29602036 DOI: 10.1016/j.ejmech.2018.03.049
Abstract

A series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed, synthesized and evaluated for their biological activity. Most of these compounds showed potent activities against c-Met kinase and cell growth inhibition. The most promising compound, 7d, has the IC50 values of 2.02 and 88 nM to inhibit c-Met kinase activity and cell growth in the MKN45 cell line, respectively. In addition, 7d is highly selective to c-Met and exhibits over 2500-fold selective inhibition to 16 tyrosine kinases evaluated.

Keywords

Inhibitors; SAR; Synthesis; [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole; c-Met.

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