Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

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• 作者：Haofei Qi ; Ligong Chen ; Bingni Liu ; Xinran Wang ; Li Long ; Dengke Liu
• 关键词：ZKGGLVOJKMDYAK-UHFFFAOYSA-N
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 February, 2014
• 年：2014
• 卷：24
• 期：4
• 页码：1108-1110
• 全文大小：323 K

文摘

A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by ¹H NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-伪 and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC₅₀ values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib.