2. Academic Validation
  3. Expanding the structural diversity of diarylureas as multi-target tyrosine kinase inhibitors

Expanding the structural diversity of diarylureas as multi-target tyrosine kinase inhibitors

  • Bioorg Med Chem. 2016 Feb 15;24(4):750-8. doi: 10.1016/j.bmc.2015.12.038.
Yuanyuan Shan 1,  Chen Wang 2,  Lin Zhang 2,  Jinfeng Wang 2,  Maoyi Wang 1,  Yalin Dong 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
  • 2 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China. Electronic address: dongyalin@mail.xjtu.edu.cn.
PMID: 26753815 DOI: 10.1016/j.bmc.2015.12.038
Abstract

Recently approved multi-target inhibitors of Receptor Tyrosine Kinases (RTKs) have significantly improved the clinical treatment of cancers. A series of N,N'-diarylureas incorporated with aromatic heterocycle have been designed, synthesized and evaluated as novel multi-target RTK inhibitors. The preliminary biological evaluation indicated that several compounds exhibited comparable potency with Sorafenib. Among them, compound 6f was identified as the most potent multikinase inhibitor of EGFR, VEGFR2/KDR/Flk-1 and FGFR1 with IC50 values of 14.83nM, 21.57nM, and 28.23nM, respectively. These compounds expanded the structural diversity of diarylureas as RTK inhibitors. The results demonstrated that compound 6f could be served as novel lead compound for further development of multi-target RTK inhibitors.

Keywords

Diarylurea; Inhibitor; Multi-target; Receptor tyrosine kinase; Structural diversity.

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