School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
Bioorg Med Chem Lett. 2014 Feb 15;24(4):1108-10. doi: 10.1016/j.bmcl.2014.01.003. Epub 2014 Jan 13.
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 (1)H NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-α 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.
一系列新型帕唑帕尼衍生物，7a-m，通过对帕唑帕尼中末端苯环和吲唑环的修饰设计和合成。所有合成化合物的结构均通过（1）H NMR 和 MS 得到确认。它们对 VEGFR-2、PDGFR-α 和 c-kit 酪氨酸激酶的抑制活性进行了评估。所有化合物均表现出一定的激酶抑制活性，其中化合物 7l 对 VEGFR-2 的抑制活性最强，IC50 值为 12 nM。此外，化合物 7c、7d 和 7m 对三种酪氨酸激酶的抑制活性与帕唑帕尼相当，而化合物 7f 的抑制效果优于帕唑帕尼。
