2. Academic Validation
  3. Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents

Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents

  • Bioorg Chem. 2022 Mar;120:105629. doi: 10.1016/j.bioorg.2022.105629.
Ju Liu 1,  Fang Liu 2,  Zhen Li 2,  Chunyan Li 3,  Shuang Wu 2,  Jiwei Shen 1,  Huan Wang 2,  Siyuan Du 2,  Hao Wei 2,  Yunlei Hou 4,  Shi Ding 5,  Ye Chen 6
Affiliations

Affiliations

  • 1 College of Pharmacy of Liaoning University, Shenyang, Liaoning 110036, PR China; API Engineering Technology Research Center of Liaoning Province, Shenyang, Liaoning 110036, PR China; Small Molecular Targeted Drug R&D Engineering Research Center of Liaoning Province, Shenyang, Liaoning 110036, PR China.
  • 2 College of Pharmacy of Liaoning University, Shenyang, Liaoning 110036, PR China.
  • 3 Shenyang Xingqi Pharmaceutical Co., Ltd, Shenyang, Liaoning 110164, PR China.
  • 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.
  • 5 College of Pharmacy of Liaoning University, Shenyang, Liaoning 110036, PR China; API Engineering Technology Research Center of Liaoning Province, Shenyang, Liaoning 110036, PR China; Small Molecular Targeted Drug R&D Engineering Research Center of Liaoning Province, Shenyang, Liaoning 110036, PR China. Electronic address: [email protected].
  • 6 College of Pharmacy of Liaoning University, Shenyang, Liaoning 110036, PR China; API Engineering Technology Research Center of Liaoning Province, Shenyang, Liaoning 110036, PR China; Small Molecular Targeted Drug R&D Engineering Research Center of Liaoning Province, Shenyang, Liaoning 110036, PR China. Electronic address: [email protected].
PMID: 35078047 DOI: 10.1016/j.bioorg.2022.105629
Abstract

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 Cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC50 value of 0.012 μM) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC50 values of 0.64 μM, 1.92 μM and 2.68 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities.

Keywords

4-Phenoxypyridine derivative; Antitumor activity; SARs study; Synthesis; c-Met inhibitor.

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