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

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• 作者：Yuanyuan Shan^a ; ^&dagger ; ; Chen Wang^b ; ^&dagger ; ; Lin Zhang^b ; Jinfeng Wang^b ; Maoyi Wang^a ; Yalin Dong^a ; ^{dongyalin@mail.xjtu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Diarylurea ; Multi-target ; Receptor tyrosine kinase ; Inhibitor ; Structural diversity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：24
• 期：4
• 页码：750-758
• 全文大小：3523 K

文摘

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, KDR and FGFR1 with IC₅₀ values of 14.83 nM, 21.57 nM, and 28.23 nM, 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.